Overall Odds Ratio Research Articles

The risk of bilobectomy compared with lobectomy: a retrospective analysis of a series of matched cases and controls

Bilobectomy is considered to be a risky procedure due to space mismatch between the pleural space and the remnant lung. The objective of this study was to evaluate if postoperative complications related or not to size mismatch are more frequent after bilobectomy compared with right lobectomy cases. Retrospective case-control study on a series of matched non-small-cell lung cancer patients. Cases were patients who underwent right bilobectomy (upper and middle or lower and middle) and controls, patients who underwent right upper or lower lobectomy. Cases and controls were matched by propensity scoring according to site, age, ppoFEV1, type of postoperative management (intensive physiotherapy or not), cardiac comorbidity and pT status. We selected two primary outcomes for comparison: occurrence of any cardiorespiratory complication and occurrence of any complication related to space discrepancies. For the latter, all complicated case records were reviewed and two blinded observers agreed on the probability of each complication to be related to space discrepancies. Agreement was measured by the κ statistic. The overall odds ratio (OR) and 95% confidence interval (CI) for each outcome were calculated on 2 × 2 tables for the whole population and for cases with upper or lower resections. The study included 689 patients: 572 right lobectomy (419 upper and 153 lower) and 117 bilobectomy cases (30 upper and middle and 87 lower and middle). The overall mortality rate of the series was 2.03% (14/689), and cardiorespiratory complications were recorded in 14.4% (99/689) and space-related complications in 19.59% (135/689) cases. Both observers agreed on space-related complications in 86% of the 135 cases (κ: 0.72). After matching, 234 cases entered the study (117 with right lobectomy, including 83 lower and 34 upper, and 117 with bilobectomy, including 87 lower and 30 upper). The prevalence of cardiorespiratory complications was higher after lower and middle lobectomy compared with lower lobectomy (P = 0.0002; OR: 7.96, 95% CI: 2.19-43.16). No differences were found in death rates or in space-related complications between groups of lobectomy and bilobectomy cases. This study failed to demonstrate a higher space-related complication rate in bilobectomy cases but cardiorespiratory complications were statistically higher after lower and middle lobectomy compared with lower lobectomy in matched cases.

The SH2B1 obesity locus and abnormal glucose homeostasis: Lack of evidence for association from a meta-analysis in individuals of European ancestry

Background/AimsThe development of type 2 diabetes (T2D) is influenced both by environmental and by genetic determinants. Obesity is an important risk factor for T2D, mostly mediated by obesity-related insulin resistance. Obesity and insulin resistance are also modulated by the genetic milieu; thus, genes affecting risk of obesity and insulin resistance might also modulate risk of T2D.Recently, 32 loci have been associated with body mass index (BMI) by genome-wide studies, including one locus on chromosome 16p11 containing the SH2B1 gene. Animal studies have suggested that SH2B1 is a physiological enhancer of the insulin receptor and humans with rare deletions or mutations at SH2B1 are obese with a disproportionately high insulin resistance. Thus, the role of SH2B1 in both obesity and insulin resistance makes it a strong candidate for T2D. However, published data on the role of SH2B1 variability on the risk for T2D are conflicting, ranging from no effect at all to a robust association. MethodsThe SH2B1 tag SNP rs4788102 (SNP, single nucleotide polymorphism) was genotyped in 6978 individuals from six studies for abnormal glucose homeostasis (AGH), including impaired fasting glucose, impaired glucose tolerance or T2D, from the GENetics of Type 2 Diabetes in Italy and the United States (GENIUS T2D) consortium. Data from these studies were then meta-analyzed, in a Bayesian fashion, with those from DIAGRAM+ (n = 47,117) and four other published studies (n = 39,448). ResultsVariability at the SH2B1 obesity locus was not associated with AGH either in the GENIUS consortium (overall odds ratio (OR) = 0.96; 0.89–1.04) or in the meta-analysis (OR = 1.01; 0.98–1.05). ConclusionOur data exclude a role for the SH2B1 obesity locus in the modulation of AGH.

The VDR gene FokI polymorphism and ovarian cancer risk

The polymorphism of vitamin D receptor (VDR) gene is demonstrated to affect the activity of its encoding protein and the subsequent downstream effects mediated by vitamin D. Mutations in VDR gene FokI have been suggested in the development of various cancers. Whether the polymorphism of the VDR gene FokI confers risk to ovarian cancer still remains controversial across the published studies in different ethnicity. The aim of this meta-analysis was to determine the role of VDR gene FokI variant in the susceptibility to ovarian cancer. Six publications with 14 individual case-control studies involving a total of 10,964 subjects were finally included into our study after a comprehensive literature search of the PubMed, Embase, Web of Science, and Wanfang databases. The strength of the association between the VDR gene FokI polymorphism and ovarian cancer risk was estimated under the allelic (T vs. C), homozygous (TT vs. CC), additive (CT vs. CC), recessive (TT vs. CC + CT), and dominant (CT + TT vs. CC) gene models. The overall odds ratios (ORs) for the contrast models of T vs. C, TT vs. CC, CT vs. CC, and CT + TT vs. CC indicated that the VDR gene FokI variant was related to an increased risk of ovarian cancer (OR(T vs. C) = 1.09, 95 % confidence interval (CI) 1.03-1.15, P(OR) = 0.004; OR(TT vs. CC) = 1.17, 95 % CI 1.04-1.32, P(OR) = 0.011; OR(CT vs. CC) = 1.10, 95 % CI 1.01-1.20, P(OR) = 0.027; OR(CT + TT vs. CC) = 1.12, 95 % CI 1.03-1.21, P(OR) = 0.007). The stratified analysis among the Caucasians also identified a significant association between the VDR gene FokI polymorphism and the susceptibility to ovarian cancer. The present meta-analysis with large available published data has revealed that the VDR gene FokI polymorphism confers susceptibility to ovarian cancer, particularly among the Caucasian population.

Association between the receptor for advanced glycation end products gene polymorphisms and coronary artery disease

Receptor for advanced glycation end products (RAGE) is a cell-surface molecule member of the immunoglobulin superfamily and thought to play a critical role in diabetic atherosclerosis. A growing body of studies has been conducted to determine the extent to which the variants of RAGE gene influence the risk of coronary artery disease (CAD). However, these have reported conflicting results. To investigate this inconsistency, we performed a comprehensive meta-analysis on the associations between the RAGE -374T/A, -429T/C, and Gly82Ser polymorphisms and the risk of CAD. A total of 4,402 cases and 6,081 controls from 17 published case-control studies were included. The overall odds ratio (OR) of CAD was 0.99 (95 % CI 0.87-1.13), 1.06 (95 % CI 0.95-1.18) and 1.12 (95 % CI 0.90-1.39) for -374A, -429C, and the minor S allele of the Gly82Ser polymorphism, respectively. Similarly, no significant results were observed for these polymorphisms using dominant model. However, when stratified by diabetic/non-diabetic status of the CAD patients, we found significant association among Caucasian type two diabetic CAD patients with the -374A allele [OR 1.39, 95 % CI 1.10-1.76, P(Z) = 0.006], while no association was detected between the -374T/A polymorphism and non-diabetic CAD in Caucasians [OR 0.79, 95 % CI 0.58-1.07, P(Z) = 0.13]. In conclusion, this meta-analysis suggested that possession of the -374A allele may be a risk factor in CAD among Caucasian patients with type two diabetes.

Comment on Song et al.: associations between the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism and susceptibility to psoriasis and psoriatic arthritis: a meta-analysis

We read with great interest the recent meta-analysis by the Song et al. on the associations between the major histocompatibility complex class I chain-related gene A transmembrane (MICA-TM) polymorphism and susceptibility to psoriasis and psoriatic arthritis (PsA) [1]. Their metaanalysis suggested a significant association of the MICATM A9 allele with psoriasis and PsA in the entire study population. In subgroup analyses, it revealed that the MICA-TM A9 allele was associated with PsA susceptibility in Europeans and psoriasis risk in Asians. The findings of this meta-analysis seem interesting; however, we would like to raise two concerns. First, the relative small number of included subjects in their meta-analysis limits the statistical power to achieve a definitive conclusion. According to Table 2 of their paper, the total number of all study patients and controls was 2002 and 1933, respectively. When the subjects were subdivided into different ethnic groups, the sample number of each group was even small. In Europeans, the total number of included cases and controls was 617 and 633, respectively, whereas in Asians, the number was 1,288 and 1,050, respectively. Therefore, it seems unlikely that the metaanalysis draws a definitive conclusion with such a small number of subjects. Discussion for the influence of subject number on the final conclusion may be necessary. Second, between-study heterogeneity was found among several analyses, which may result in bias for the estimates of the overall odds ratios (ORs). For example, heterogeneity was found among the analysis for the MICA-TM A9 allele association with psoriasis and PsA in all study subjects and Europeans (P = 0.002 and P = 0.018, respectively), and among the analysis for PsA in the entire population and Europeans (P = 0.042 and P = 0.046, respectively). It is noted that even in the analysis restricted to Europeans, heterogeneity appeared. Some possible sources, including study design, source of controls, mean age, percent of men, and genotyping method may account for it. It would be valuable if the authors could investigate sources of heterogeneity or give some discussion for this issue, rather than just conduct a combined analysis under a random-effects model. Collectively, future investigations should be conducted using large sample numbers to establish a more definitive conclusion, especially in Europeans. If the above-mentioned remarks could be taken into account in their metaanalysis, a better analysis and explanation for the results may be achieved.

Relationship Between theHLA-B*1502Allele and Carbamazepine-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis

The US Food and Drug Administration recommends screening for the HLA-B*1502 allele before initiation of carbamazepine therapy in patients of Asian ancestry, but there remains unclear evidence of a relationship between HLA-B*1502 and Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) among carbamazepine users, especially in some racial/ethnic populations. To determine the relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN. A comprehensive search of the following data sources was performed without language restriction from the inception of the database until January 8, 2013: EMBASE, PubMed, clinicaltrials.gov, Cochrane Library, IPA (International Pharmaceutical Abstracts), HuGENet (Human Genome Epidemiology Network), and CINAHL (Cumulative Index to Nursing and Allied Health Literature), and the reference lists of identified studies. Inclusion criteria were studies that investigated the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN and that reported sufficient data for calculating the frequency of HLA-B*1502 carriers among cases and controls. The search yielded 525 articles, of which 16 met the inclusion criteria. The studies included 227 SJS or TEN cases, 602 matched control subjects, and 2949 population control subjects. Two reviewers independently extracted the following data: study design, eligibility criteria, diagnostic criteria, patient demographics, genotype distribution, HLA-B genotyping technique, selection of cases and controls, dosage of carbamazepine and duration of use, and results of Hardy-Weinberg equilibrium in the control group. The Newcastle-Ottawa Scale was used to assess the quality of studies. The overall odds ratios (ORs) with corresponding 95% CIs were calculated using a random-effects model. The primary analysis was based on matched control studies. Subgroup analyses by race/ethnicity were also performed. The primary outcome was carbamazepine-induced SJS and TEN. The outcome measure is given as an overall OR. The summary OR for the relationship between HLA-B*1502 and carbamazepine-induced SJS and TEN was 79.84 (95% CI, 28.45-224.06). Racial/ethnic subgroup analyses yielded similar findings for Han-Chinese (115.32; 18.17-732.13), Thais (54.43; 16.28-181.96), and Malaysians (221.00; 3.85-12 694.65). Among individuals of white or Japanese race/ethnicity, no patients with SJS or TEN were carriers of the HLA-B*1502 allele. We found a strong relationship between the HLA-B*1502 allele and carbamazepine-induced SJS and TEN in Han-Chinese, Thai, and Malaysian populations. HLA-B*1502 screening in patients requiring carbamazepine therapy is warranted.

Maternal smoking during pregnancy and neural tube defects in offspring: a meta-analysis

This study aims to examine the association between maternal smoking during pregnancy and neural tube defects (NTDs) in offspring. We retrieved published studies on the association between maternal smoking during pregnancy and NTDs risk in offspring. Meta-analysis was applied to calculate the overall odds ratios (ORs) and their 95% confidence intervals (CIs). The publication bias was assessed by the Egger's regression asymmetry test and Begg's rank correlation test. The overall effect of maternal smoking during pregnancy on NTDs was 1.03 (OR = 1.03, 95% CI = 0.80-1.33). When subgroup analysis was conducted by geographic regions, the overall effects were 1.39 (OR = 1.39, 95% CI = 1.18-1.64), 0.88 (OR = 0.88, 95% CI = 0.66-1.17) in Europe and USA; when subgroup analysis was conducted by NTDs types, the overall effect was 1.55 (OR = 1.55, 95% CI = 1.06-2.26) for spina bifida. Women who smoked during pregnancy had mildly elevated risk of having infants with NTDs.

Association of IFIH1 rs1990760 polymorphism with susceptibility to autoimmune diseases: A meta-analysis

Published data on the association between the IFIH1 rs1990760 polymorphism and multiple autoimmune diseases are controversial and inconclusive. To more precisely estimate the association between the IFIH1 rs1990760 polymorphism and susceptibility to autoimmune diseases, a meta-analysis was conducted. Studies examining the association of the IFIH1 rs1990760 polymorphism with autoimmune diseases were exhaustively searched using PubMed, Web of Science and a review of the references. A total of 19 studies with 26 comparisons including 8 type 1 diabetes (T1D), 5 systemic lupus erythematosus (SLE), 5 Graves’ disease (GD), 2 multiple scleorosis (MS), 2 rheumatoid arthritis (RA), 2 Hashimoto's thyroiditis (HT), 2 autoimmune Addison’s disease (AAD) were available for this meta-analysis. Meta-analysis was performed for genotype T/T + T/C (dominant model), genotype T/T (recessive model) and T-allele in fixed or random-effects models. The overall odds ratios (ORs) and 95% confidence intervals (CIs) for T-allele were T1D (OR = 1.184, 95% CI = 1.142–1.229), SLE (OR = 1.143, 95% CI = 1.073–1.217), MS (OR = 1.181, 95% CI = 1.062–1.313) and RA (OR = 1.115, 95% CI = 1.004–1.239), respectively. For T1D and SLE, significant association was observed in the population of European ancestry, but not in the Asian population. This meta-analysis demonstrates that the IFIH1 rs1990760 T-allele confers susceptibility to T1D, SLE, MS and RA and suggests that the IFIH1 rs1990760 polymorphism might have no effect on GD and AAD. Our result provides further evidence for the notion of common gene underlying multiple autoimmune diseases.

Outcomes of Single-Row Versus Double-Row Arthroscopic Rotator Cuff Repair: A Systematic Review and Meta-Analysis of Current Evidence

Our purpose was to perform a systematic review and meta-analysis of the clinical outcomes of single-row versus double-row repair. An electronic search was performed using PubMed, EMBASE, and the Cochrane Library up to September 30, 2012. Studies that met the inclusion and exclusion criteria were assessed for quality of methodology. The primary analysis included Level I evidence from studies examining single-row versus double-row repair. The second meta-analysis and subgroup analysis were performed for evidence Levels I, II, and III. The primary analysis of studies providing 6 Level I randomized controlled trials showed no clinically significant differences in Constant scores, University of California, Los Angeles (UCLA), and American Shoulder and Elbow Surgeons (ASES) scores between double-row and single-row rotator cuff repair. The overall odds ratio (OR) of intact rotator cuff tendon healing was 1.93 in patients treated with double-row versus single-row repair, and the difference was significant. The results of the second meta-analysis including evidence Levels I, II, and III were similar to those of the primary analysis. In the subgroup with tears less than 3 cm, there was no statistically significant difference between the groups with regard to shoulder functional score and structure integrity. A statistically significant benefit of double-row repair in the ASES and UCLA scores was observed in the subgroup with tears greater than 3 cm; however, these differences were not clinically significant. The OR for tendon healing was found to be more favorable for double-row repair than for single-row repair in the subgroup with tears greater than 3 cm. Double-row repair provides a significantly higher rate of intact tendon healing than does single-row repair, and this advantage was mainly reflected in patients with large or massive tears. However, this benefit did not translate into clinically confirmed functional improvement. Thus, the double-row technique should be used only in carefully selected patients. Level III, systematic review of Levels I, II, and III studies.

Genetic variants in TERT–CLPTM1L genetic region associated with several types of cancer: A meta-analysis

BackgroundTERT–CLPTM1L genomic region has been extensively associated with several types of cancer. However, results were inconsistent. We performed this meta-analysis to estimate the association between TERT (rs2736100, rs2736098), as well as CLPTM1L (rs402710, rs401681) polymorphisms and cancer risk. MethodsElectronic search in PubMed, EMBASE and China National Knowledge Infrastructure (CNKI) was conducted to select the studies. Studies containing available genotype frequencies of those 4 polymorphisms were chosen, and overall odds ratio (OR) with 95% confidence interval (CI) was used to assess the association. ResultsThe final meta-analysis included 16 published case–control studies. Increased cancer risk was found between TERT-rs2736100, as well as CLPTM1L-rs402710 and cancer susceptibility. In addition, we found an increased risk of cancer in both rs2736098 and rs401681 homozygous variant genetic model. ConclusionsThis meta-analysis suggested that TERT–CLPTM1L genomic region was associated with increased risk of cancer. To validate the association between these polymorphisms and cancer susceptibility, further studies with larger participants are needed.

Personalised risk communication for informed decision making about taking screening tests

There is a trend towards greater patient involvement in healthcare decisions. Although screening is usually perceived as good for the health of the population, there are risks associated with the tests involved. Achieving both adequate involvement of consumers and informed decision making are now seen as important goals for screening programmes. Personalised risk estimates have been shown to be effective methods of risk communication. To assess the effects of personalised risk communication on informed decision making by individuals taking screening tests. We also assess individual components that constitute informed decisions. Two authors searched the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 3, 2012), MEDLINE (OvidSP), EMBASE (OvidSP), CINAHL (EbscoHOST) and PsycINFO (OvidSP) without language restrictions. We searched from 2006 to March 2012. The date ranges for the previous searches were from 1989 to December 2005 for PsycINFO and from 1985 to December 2005 for other databases. For the original version of this review, we also searched CancerLit and Science Citation Index (March 2001). We also reviewed the reference lists and conducted citation searches of included studies and other systematic reviews in the field, to identify any studies missed during the initial search. Randomised controlled trials incorporating an intervention with a 'personalised risk communication element' for individuals undergoing screening procedures, and reporting measures of informed decisions and alsocognitive, affective, or behavioural outcomes addressing the decision by such individuals, of whether or not to undergo screening. Two authors independently assessed each included trial for risk of bias, and extracted data. We extracted data about the nature and setting of interventions, and relevant outcome data. We used standard statistical methods to combine data using RevMan version 5, including analysis according to different levels of detail of personalised risk communication, different conditions for screening, and studies based only on high-risk participants rather than people at 'average' risk. We included 41 studies involving 28,700 people. Nineteen new studies were identified in this update, adding to the 22 studies included in the previous two iterations of the review. Three studies measured informed decision with regard to the uptake of screening following personalised risk communication as a part of their intervention. All of these three studies were at low risk of bias and there was strong evidence that the interventions enhanced informed decision making, although with heterogeneous results. Overall 45.2% (592/1309) of participants who received personalised risk information made informed choices, compared to 20.2% (229/1135) of participants who received generic risk information. The overall odds ratios (ORs) for informed decision were 4.48 (95% confidence interval (CI) 3.62 to 5.53 for fixed effect) and 3.65 (95% CI 2.13 to 6.23 for random effects). Nine studies measured increase in knowledge, using different scales. All of these studies showed an increase in knowledge with personalised risk communication. In three studies the interventions showed a trend towards more accurate risk perception, but the evidence was of poor quality. Four out of six studies reported non-significant changes in anxiety following personalised risk communication to the participants. Overall there was a small non-significant decrease in the anxiety scores. Most studies (32/41) measured the uptake of screening tests following interventions. Our results (OR 1.15 (95% CI 1.02 to 1.29)) constitute low quality evidence, consistent with a small effect, that personalised risk communication in which a risk score was provided (6 studies) or the participants were given their categorised risk (6 studies), increases uptake of screening tests. There is strong evidence from three trials that personalised risk estimates incorporated within communication interventions for screening programmes enhance informed choices. However the evidence for increasing the uptake of such screening tests with similar interventions is weak, and it is not clear if this increase is associated with informed choices. Studies included a diverse range of screening programmes. Therefore, data from this review do not allow us to draw conclusions about the best interventions to deliver personalised risk communication for enhancing informed decisions. The results are dominated by findings from the topic area of mammography and colorectal cancer. Caution is therefore required in generalising from these results, and particularly for clinical topics other than mammography and colorectal cancer screening.

Association of the ADRA2A polymorphisms with the risk of type 2 diabetes: A meta-analysis

ObjectivesResults from the published studies on the association of ADRA2A (adrenoceptor alpha 2A) variants with type 2 diabetes (T2D) are conflicting and call for further assessment. The aim of this meta-analysis was to quantitatively summarize the effects of the two recently reported ADRA2A single nucleotide polymorphisms (SNPs) rs553668 and rs10885122 on T2D risk. Design and methodsWe searched all the publications about the association between the ADRA2A SNPs and T2D from PubMed and ISI database updated on September 2012. Meta-analysis of the overall odds ratios (ORs) with 95% confidence intervals (CIs) was calculated by using the software STATA 11.0. ResultsTwelve studies with 40,828 subjects from seven eligible papers were included in the meta-analysis. Overall, the present meta-analysis failed to support a positive association between ADRA2A SNPs (rs553668 and rs10885122) and susceptibility to T2D (OR=1.05, p=0.17, 95% CI: 0.98, 1.12; and OR=1.06, p=0.11, 95% CI: 0.99, 1.13; respectively). However, in the subgroup analysis by ethnicity, the significant association between rs553668 and the risk of T2D was obtained in Europeans under the recessive genetic model (OR=1.36, p=0.02, 95% CI: 1.05, 1.76). ConclusionsThis meta-analysis suggested that the AA genotype of rs553668 in ADRA2A might be a genetic risk factor that increases T2D susceptibility in Europeans. However, rs10885122 was unlikely substantially contribute to T2D susceptibility.

The genetics of Henoch–Schönlein purpura: a systematic review and meta-analysis

Henoch-Schönlein purpura (HSP) is the most common form of systemic vasculitis of unknown etiology. This study aimed at reviewing published studies investigating the association of genetic polymorphisms with HSP and its severity. We systematically reviewed all published data on genetic risk factors for HSP by searching MEDLINE. We also performed a meta-analysis of association studies of HLA-DRB1-01, 07, and 11, angiotensin I-converting enzyme (ACE) insertion/deletion (I/D) polymorphism. We identified 45 studies investigating polymorphisms in 39 genes in association with HSP and/or its severity. Most of these genes are involved in immunological and/or inflammatory responses or vasomotor regulation. Most results were negative. The most convincing finding is the association of HLA-DRB1 01, 07, and 11 with HSP susceptibility. The overall odds ratios (ORs) for the three loci were significant for HSP: HLA-DRB1 01 (OR = 1.805, 95 % CI 1.259-2.588, p = 0.0012); HLA-DRB1 07 (OR = 0.671, 95 % CI 0.469-0.961, p = 0.058); HLA-DRB1 11 (OR = 2.001, 95 % CI 1.50-2.67, p = 0.027). Genetic regulation of endothelial function, such as polymorphisms in genes coding rennin-angiotensin system (RAS) components, endothelial nitric oxide synthases, Inter-Cellular Adhesion Molecule 1, and vascular endothelial growth factor, could also confer effect on HSP. In addition, MEFV, whose mutations cause familial Mediterranean fever, could be an important candidate gene for HSP. Further large studies are required to investigate the association between genetic polymorphisms and HSP. Alternative approaches, such as genome-wide association study, are necessary to help to identify genetic risks for HSP.

Meta-analysis demonstrates association of the TGF-β1 gene -C509T polymorphism with susceptibility to IgA nephropathy in European but not in Asian populations

There are conflicting reports associating the TGF-β1 gene -C509T polymorphism with susceptibility to IgA nephropathy. We investigated this association through a meta-analysis. Case-control studies were searched up to January 2012; the genotype frequencies in the control group were found to be consistent with Hardy-Weinberg equilibrium. Publication bias was tested by funnel plot and the Egger regression test. Eight studies, comprising 1364 cases and 1483 controls, were included. Significant heterogeneity was observed (χ² = 18.29, P = 0.01). Under the random-effects model, the overall odds ratio (OR) was 1.01 [95% confidence interval (95%CI) = 0.74-1.38; P = 0.94]. In the subgroup analysis based on ethnicities, no significant effect was observed in the Asian descent groups (five comparisons, OR = 0.78; 95%CI = 0.53-1.15; moderate heterogeneity between studies). However, an association was observed in the European descent groups (OR = 1.5; 95%CI = 1.15-1.96; P = 0.003; no significant heterogeneity between studies). There was no evidence of publication bias according to funnel plot and the Egger regression test (a = -2.16, P = 0.23). There was heterogeneity between studies and no clear evidence of an association between the TGF-β1 gene -C509T polymorphism and susceptibility to IgA nephropathy in the worldwide population. Subgroup analysis suggests that the TGF-β1 gene -C509T polymorphism would not be a risk factor for IgA nephropathy in Asians but might play a role in Europeans. More studies are required for definitive conclusions.

Optimized dose of imatinib for treatment of gastrointestinal stromal tumors: A meta‐analysis

To investigate the efficacy and safety of standard-dose versus high-dose imatinib. After a systematic review of English language articles, five studies including 2008 patients were eligible for the meta-analysis. Data extracted from each study were synthesized into overall odds ratios (OR). The overall OR for the high dose vs standard dose was 1.19 (95% CI 1.00-1.42) and the Z-score for the overall effect was 1.93 (P = 0.054), suggesting that high-dose imatinib added no survival benefits. The dose-related toxicity was also assessed in the same way. The rates of rash, hemorrhage, nausea, vomiting and taste disturbance increased as dose increased (P < 0.05), whereas the incidence of headache, abdominal pain, edema, fatigue, anemia, infection, muscle cramp and constipation was nearly identical and showed no significant difference. Imatinib at a standard dose produces a similar effect to that at a high dose. The severity of the toxicity is associated with the dose of imatinib. However, larger and randomized studies are needed to draw definitive conclusions.

A meta-analysis of an association between the XRCC1 polymorphisms and gliomas risk

The associations of the X-ray repair cross complementing group 1 (XRCC1) gene single nucleotide polymorphisms (SNPs) Arg194Trp, Arg280His, Arg399Gln with the risk of gliomas have been studied recently, but contradictions exist whether the XRCC1 SNPs were a risk factor. We examined these associations by performing a meta-analyse. Nine studies tested the associations between XRCC1 SNPs and gliomas were retrieved. Overall odds ratios (ORs) and corresponding 95 % confidence intervals were estimated using genetic models. Heterogeneity and publication bias were evaluated. The pooled OR for Arg194Trp TT versus CC were significant, which was 2.208 (95 % CI: 1.099, 4.435; P = 0.026), but it was non-significant after removal of the studies which deviated from the Hardy-Weinberg equilibrium (HWE). The pooled OR for Arg399Gln AA+GA versus GG of genotype methods subgroup and the low study appraisal score subgroup were significant in the stratification analysis, but the meta-regression results were non-significance. No significant associations were found between the Arg280His SNPs and gliomas' risk. There was no evidence of publication bias. We conclude that SNPs in XRCC1 are not associated with the risk of gliomas. We should do more work on the relevant variants like those in TERT, RTEL1, EGFR, CDKN2A, CCDC26, and PHLDB1 and their products rather than the XRCC1. More GWAS will also need to involve sufficiently larger study populations along with analysis of tumor or gender subtypes in order to assess these risks.

PAI-1 promoter 4G/5G polymorphism (rs1799768) contributes to tumor susceptibility: Evidence from meta-analysis

Plasminogen activator inhibitor-1 (PAI-1), belonging to the urokinase plasminogen activation (uPA) system, is involved in cancer development and progression. The PAI-1 promoter 4G/5G polymorphism was shown to contribute to genetic susceptibility to cancer, although the results were inconsistent. To assess this relationship more precisely, a meta-analysis was performed. The electronic databases PubMed, Scopus, Web of Science and Chinese National Knowledge Infrastructure (CNKI) were searched; data were extracted and analyzed independently by two reviewers. Ultimately, 21 eligible case-control studies with a total of 8,415 cancer cases and 9,208 controls were included. The overall odds ratio (OR) with its 95% confidence interval (CI) showed a statistically significant association between the PAI-1 promoter 4G/5G polymorphism and cancer risk (4G/4G vs. 5G/5G: OR=1.25, 95% CI=1.07–1.47, Pheterogeneity=0.001; 4G/4G vs. 4G/5G+5G/5G: OR=1.10, 95% CI=1.03–1.17, Pheterogeneity=0.194; 4G/4G+4G/5G vs. 5G/5G: OR=1.17, 95% CI=1.01–1.35, Pheterogeneity=0.041). In further subgroup analyses, the increased risk of cancer was observed in a subgroup of Caucasians with regards to endometrial cancer. Our meta-analysis suggests that the PAI-1 4G/5G polymorphism most likely contributes to susceptibility to cancer, particularly in Caucasians. Furthermore, the 4G allele may be associated with an increased risk of endometrial cancer.

The association between apolipoprotein E gene polymorphisms and essential hypertension: a meta-analysis of 45 studies including 13 940 cases and 16 364 controls

The apolipoprotein E single-nucleotide polymorphisms are among the potential candidate genes that may serve as modulators in susceptibility to essential hypertension. In an effort to clarify earlier inconclusive results, we performed a meta-analysis of population-based case-control genetic association studies. Random-effects methods were applied on summary data in order to combine the results of the individual studies. We identified in total 45 studies, including 13 940 hypertensive cases and 16 364 controls. The contrast of E4 carriers versus non-carriers yielded an overall odds ratio (OR) of 1.16 (95% confidence interval (CI): 1.02, 1.31), whereas the contrast of E4 allele versus the others in a subtotal of 6617 cases and 7330 controls, yielded an OR of 1.39 (95% CI: 1.12, 1.72). There was moderate evidence of publication bias in both contrasts, which was eliminated after excluding studies not in Hardy-Weinberg equilibrium. Subgroup analyses revealed that significant estimates arose from studies on Asian populations, as opposed to the Caucasian ones. Furthermore, no evidence of publication bias was demonstrated in the comparisons within this subgroup. Our results are consistent with recent meta-analyses but show that the association is weaker than that has been previously demonstrated. Further studies are needed in order to fully address questions about the etiological mechanism of the particular association, as well as to study the effect in populations of African descent.

Erectile Dysfunction and Cardiovascular Events in Diabetic Men: A Meta-analysis of Observational Studies

BackgroundSeveral studies have shown that erectile dysfunction (ED) influences the risk of cardiovascular events (CV events). However, a meta-analysis of the overall risk of CV events associated with ED in patients with diabetes has not been performed.Methodology/Principal FindingsWe searched MEDLINE and the Cochrane Library for pertinent articles (including references) published between 1951 and April 22, 2012. English language reports of original observational cohort studies and cross-sectional studies were included. Pooled effect estimates were obtained by random effects meta-analysis.A total of 3,791 CV events were reported in 3 cohort studies and 9 cross-sectional studies (covering 22,586 subjects). Across the cohort studies, the overall odds ratio (OR) of diabetic men with ED versus those without ED was 1.74 (95% confidence interval [CI]: 1.34–2.27; P<0.001) for CV events and 1.72 (95% CI: 1.5–1.98; P<0.001) for coronary heart disease (CHD). The funnel plot, Begg's test, and Egger's test did not show evidence of publication bias (all P>0.05). Moreover, meta-regression analysis found no relationship between the method used to assess ED (questionnaire or interview), mean age, mean hemoglobin A1c, mean body mass index, or mean duration of diabetes and the risk of CV events or CHD. In the cross-sectional studies, the OR of diabetic men with ED versus those without ED was 3.39 (95% CI: 2.58–4.44; P<0.001) for CV events (N = 9), 3.43 (95% CI: 2.46–4.77; P<0.001) for CHD (N = 7), and 2.63 (95% CI: 1.41–4.91; P = 0.002) for peripheral vascular disease (N = 5).Conclusion/SignificanceED was associated with an increased risk of CV events in diabetic patients. Prevention and early detection of cardiovascular disease are important in the management of diabetes, especially in view of the rapid increase in its prevalence.

The Overall Odds Ratio as an Intuitive Effect Size Index for Multiple Logistic Regression

This study used Monte Carlo simulation to examine the properties of the overall odds ratio (OOR), which was recently introduced as an index for overall effect size in multiple logistic regression. It was found that the OOR was relatively independent of study base rate and performed better than most commonly used R-square analogs in indexing model strength. The authors also illustrate and test a jackknife procedure to correct for the bias in the OOR and estimate its standard error. An example applying the OOR to evaluate logistic regression models predicting organizational turnover is provided. The authors discuss implications and offer recommendations for using the OOR to quantify and compare the effectiveness of logistic regression models in applied research.