Evaluating heterogeneity in cumulative meta-analyses

BACKGROUND: Recently developed measures such as I(2 )and H allow the evaluation of the impact of heterogeneity in conventional meta-analyses. There has been no examination of the development of heterogeneity in the context of a cumulative meta-analysis. METHODS: Cumulative meta-analyses of five smoking cessation interventions (clonidine, nicotine replacement therapy using gum and patch, physician advice and acupuncture) were used to calculate I(2 )and H. These values were plotted by year of publication, control event rate and sample size to trace the development of heterogeneity over these covariates. RESULTS: The cumulative evaluation of heterogeneity varied according to the measure of heterogeneity used and the basis of cumulation. Plots produced from the calculations revealed areas of heterogeneity useful in the consideration of potential sources for further study. CONCLUSION: The examination of heterogeneity in conjunction with summary effect estimates in a cumulative meta-analysis offered valuable insight into the evolution of variation. Such information is not available in the context of conventional meta-analysis and has the potential to lead to the development of a richer picture of the effectiveness of interventions

Subgroup effects despite homogeneous heterogeneity test results

Background. Statistical tests of heterogeneity are very popular in meta-analyses, as heterogeneity might indicate subgroup effects. Lack of demonstrable statistical heterogeneity, however, might obscure clinical heterogeneity, meaning clinically relevant subgroup effects. Methods. A qualitative, visual method to explore the potential for subgroup effects was provided by a modification of the forest plot, i.e., adding a vertical axis indicating the proportion of a subgroup variable in the individual trials. Such a plot was used to assess the potential for clinically relevant subgroup effects and was illustrated by a clinical example on the effects of antibiotics in children with acute otitis media. Results. Statistical tests did not indicate heterogeneity in the meta-analysis on the effects of amoxicillin on acute otitis media (Q = 3.29, p = 0.51; I2 = 0%; T2 = 0). Nevertheless, in a modified forest plot, in which the individual trials were ordered by the proportion of children with bilateral otitis, a clear relation between bilaterality and treatment effects was observed (which was also found in an individual patient data meta-analysis of the included trials: p-value for interaction 0.021). Conclusions. A modification of the forest plot, by including an additional (vertical) axis indicating the proportion of a certain subgroup variable, is a qualitative, visual, and easy-to-interpret method to explore potential subgroup effects in studies included in meta-analyse

An empirical study using permutation-based resampling in meta-regression

<p>Abstract</p> <p>Background</p> <p>In meta-regression, as the number of trials in the analyses decreases, the risk of false positives or false negatives increases. This is partly due to the assumption of normality that may not hold in small samples. Creation of a distribution from the observed trials using permutation methods to calculate <it>P </it>values may allow for less spurious findings. Permutation has not been empirically tested in meta-regression. The objective of this study was to perform an empirical investigation to explore the differences in results for meta-analyses on a small number of trials using standard large sample approaches verses permutation-based methods for meta-regression.</p> <p>Methods</p> <p>We isolated a sample of randomized controlled clinical trials (RCTs) for interventions that have a small number of trials (herbal medicine trials). Trials were then grouped by herbal species and condition and assessed for methodological quality using the Jadad scale, and data were extracted for each outcome. Finally, we performed meta-analyses on the primary outcome of each group of trials and meta-regression for methodological quality subgroups within each meta-analysis. We used large sample methods and permutation methods in our meta-regression modeling. We then compared final models and final <it>P </it>values between methods.</p> <p>Results</p> <p>We collected 110 trials across 5 intervention/outcome pairings and 5 to 10 trials per covariate. When applying large sample methods and permutation-based methods in our backwards stepwise regression the covariates in the final models were identical in all cases. The <it>P </it>values for the covariates in the final model were larger in 78% (7/9) of the cases for permutation and identical for 22% (2/9) of the cases.</p> <p>Conclusions</p> <p>We present empirical evidence that permutation-based resampling may not change final models when using backwards stepwise regression, but may increase <it>P </it>values in meta-regression of multiple covariates for relatively small amount of trials.</p

Rounding of low serum creatinine levels and consequent impact on accuracy of bedside estimates of renal function in cancer patients

To compare glomerular filtration rate measured by technetium-99m ([Tc(99m)]) DTPA clearance with estimated creatinine clearance (CrCl) (Cockcroft and Gault (C&G) method) in patients with serum creatinine (Scr) levels 100 ml min(-1). This work indicates that when bedside estimates of renal function are calculated using the C&G formula actual Scr should be used first to estimate CrCl. If the resultant CrCl is </=100 ml min(-1), then the Scr should be rounded up to 0.06 mmol l(-1) and CrCl recalculated. Further assessment of this approach is warranted in a larger cohort of patients

What’s in a surname? Physique, aptitude, and sports type comparisons between Tailors and Smiths

Combined heredity of surnames and physique, coupled with past marriage patterns and trade-specific physical aptitude and selection factors, may have led to differential assortment of bodily characteristics among present-day men with specific trade-reflecting surnames (Tailor vs. Smith). Two studies reported here were partially consistent with this genetic-social hypothesis, first proposed by Bäumler (1980). Study 1 (N = 224) indicated significantly higher self-rated physical aptitude for prototypically strength-related activities (professions, sports, hobbies) in a random sample of Smiths. The counterpart effect (higher aptitude for dexterity-related activities among Tailors) was directionally correct, but not significant, and Tailor-Smith differences in basic physique variables were not significant. Study 2 examined two large datasets (Austria/Germany combined, and UK: N = 7001 and 20532) of men’s national high-score lists for track-and-field events requiring different physiques. In both datasets, proportions of Smiths significantly increased from light-stature over medium-stature to heavy-stature sports categories. The predicted counterpart effect (decreasing prevalences of Tailors along these categories) was not supported. Related prior findings, implicit egotism as an alternative interpretation of the evidence, and directions for further inquiry are discussed in conclusion

X-Ray Repair Cross-Complementing Group 1 (XRCC1) Genetic Polymorphisms and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis

Background: Recently, there have been a number of studies on the association between XRCC1 polymorphisms and childhood acute lymphoblastic leukemia (ALL) risk. However, the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effects of XRCC1 variants on childhood ALL risk. Methods: A meta-analysis was performed to examine the association between XRCC1 polymorphisms (Arg399Gln, Arg194Trp, and Arg280His) and childhood ALL risk. We critically reviewed 7 studies with a total of 880 cases and 1311 controls for Arg399Gln polymorphism, 3 studies with a total of 345 cases and 554 controls for Arg280His polymorphism, and 6 studies with a total of 783 cases and 1180 controls for Arg194Trp polymorphism, respectively. Odds ratio (OR) and its 95% confidence interval (CI) were used. Results: Significant association between XRCC1 Arg399Gln polymorphism and childhood ALL risk was observed in total population analyses (OR additive model = 1.501, 95 % CI 1.112–2.026, P OR = 0.008; OR dominant model = 1.316, 95 % CI = 1.104–1.569, POR = 0.002) and Asian subgroup analyses (ORadditive model = 2.338, 95%CI = 1.254–4.359, POR = 0.008; ORdominant model = 2.108, 95%CI = 1.498–2.967, POR = 0.000). No association was detected in Caucasians, Metizo and mixed populations. Ethnicity was considered as a significant source of heterogeneity in the meta-regression model. For the other two XRCC1 polymorphisms, no association with childhood ALL risk was found

Study of CP violation in Dalitz-plot analyses of B0 --> K+K-KS, B+ --> K+K-K+, and B+ --> KSKSK+

We perform amplitude analyses of the decays $B^0 \to K^+K^-K^0_S$, $B^+ \rightarrow K^+K^-K^+$, and $B^+ \to K^0_S K^0_S K^+$, and measure CP-violating parameters and partial branching fractions. The results are based on a data sample of approximately $470\times 10^6$ $B\bar{B}$ decays, collected with the BABAR detector at the PEP-II asymmetric-energy $B$ factory at the SLAC National Accelerator Laboratory. For $B^+ \to K^+K^-K^+$, we find a direct CP asymmetry in $B^+ \to \phi(1020)K^+$ of $A_{CP}= (12.8\pm 4.4 \pm 1.3)$, which differs from zero by $2.8 \sigma$. For $B^0 \to K^+K^-K^0_S$, we measure the CP-violating phase $\beta_{\rm eff} (\phi(1020)K^0_S) = (21\pm 6 \pm 2)^\circ$. For $B^+ \to K^0_S K^0_S K^+$, we measure an overall direct CP asymmetry of $A_{CP} = (4 ^{+4}_{-5} \pm 2)$. We also perform an angular-moment analysis of the three channels, and determine that the $f_X(1500)$ state can be described well by the sum of the resonances $f_0(1500)$, $f_2^{\prime}(1525)$, and $f_0(1710)$.Comment: 35 pages, 68 postscript figures. v3 - minor modifications to agree with published versio

Interpreting Meta-Analyses of Genome-Wide Association Studies

Meta-analysis is an increasingly popular tool for combining multiple genome-wide association studies in a single analysis to identify associations with small effect sizes. The effect sizes between studies in a meta-analysis may differ and these differences, or heterogeneity, can be caused by many factors. If heterogeneity is observed in the results of a meta-analysis, interpreting the cause of heterogeneity is important because the correct interpretation can lead to a better understanding of the disease and a more effective design of a replication study. However, interpreting heterogeneous results is difficult. The standard approach of examining the association p-values of the studies does not effectively predict if the effect exists in each study. In this paper, we propose a framework facilitating the interpretation of the results of a meta-analysis. Our framework is based on a new statistic representing the posterior probability that the effect exists in each study, which is estimated utilizing cross-study information. Simulations and application to the real data show that our framework can effectively segregate the studies predicted to have an effect, the studies predicted to not have an effect, and the ambiguous studies that are underpowered. In addition to helping interpretation, the new framework also allows us to develop a new association testing procedure taking into account the existence of effect

Jet energy measurement with the ATLAS detector in proton-proton collisions at root s=7 TeV

The jet energy scale and its systematic uncertainty are determined for jets measured with the ATLAS detector at the LHC in proton-proton collision data at a centre-of-mass energy of √s = 7TeV corresponding to an integrated luminosity of 38 pb-1. Jets are reconstructed with the anti-kt algorithm with distance parameters R=0. 4 or R=0. 6. Jet energy and angle corrections are determined from Monte Carlo simulations to calibrate jets with transverse momenta pT≥20 GeV and pseudorapidities {pipe}η{pipe}<4. 5. The jet energy systematic uncertainty is estimated using the single isolated hadron response measured in situ and in test-beams, exploiting the transverse momentum balance between central and forward jets in events with dijet topologies and studying systematic variations in Monte Carlo simulations. The jet energy uncertainty is less than 2. 5 % in the central calorimeter region ({pipe}η{pipe}<0. 8) for jets with 60≤pT<800 GeV, and is maximally 14 % for pT<30 GeV in the most forward region 3. 2≤{pipe}η{pipe}<4. 5. The jet energy is validated for jet transverse momenta up to 1 TeV to the level of a few percent using several in situ techniques by comparing a well-known reference such as the recoiling photon pT, the sum of the transverse momenta of tracks associated to the jet, or a system of low-pT jets recoiling against a high-pT jet. More sophisticated jet calibration schemes are presented based on calorimeter cell energy density weighting or hadronic properties of jets, aiming for an improved jet energy resolution and a reduced flavour dependence of the jet response. The systematic uncertainty of the jet energy determined from a combination of in situ techniques is consistent with the one derived from single hadron response measurements over a wide kinematic range. The nominal corrections and uncertainties are derived for isolated jets in an inclusive sample of high-pT jets. Special cases such as event topologies with close-by jets, or selections of samples with an enhanced content of jets originating from light quarks, heavy quarks or gluons are also discussed and the corresponding uncertainties are determined. © 2013 CERN for the benefit of the ATLAS collaboration

Tea Consumption Enhances Endothelial-Dependent Vasodilation; a Meta-Analysis

Background: Tea consumption is associated with a lower risk of cardiovascular disease including stroke. Direct effects of tea components on the vasculature, particularly the endothelium, may partly explain this association. Objective: We performed a meta-analysis of controlled human intervention studies on the effect of tea on flow-mediated dilation (FMD) of the brachial artery, a measurement of endothelial function, which is suggested to be associated with cardiovascular risk. Methods: Human intervention studies were identified by systematic search of the databases Medline, Embase, Chemical Abstracts and Biosis through March 2009 and by hand-searching related articles. Studies were selected based on predefined criteria: intervention with tea as the sole experimental variable, placebo-controlled design, and no missing data on FMD outcome or its variability. A random effects model was used to calculate the pooled overall effect on FMD due to the intake of tea. The impact of various subject and treatment characteristics was investigated in the presence of heterogeneity. Results: In total, 9 studies from different research groups were included with 15 relevant study arms. The overall absolute increase in FMD of tea vs. placebo was 2.6 % of the arterial diameter (95 % CI: 1.8-3.3%; P-value,0.001) for a median daily dose of 500 mL of tea (2–3 cups). This is a relative increase of approximately 40 % compared to the average FMD of 6.3% measured under placebo or baseline conditions. There was significant heterogeneity between studies (P-value,0.001) tha