The effect of publication bias on the Q test and assessment of heterogeneity

One of the main goals of meta-analysis is to test for and estimate the heterogeneity of effect sizes. We examined the effect of publication bias on the Q test and assessments of heterogeneity as a function of true heterogeneity, publication bias, true effect size, number of studies, and variation of sample sizes. The present study has two main contributions and is relevant to all researchers conducting meta-analysis. First, we show when and how publication bias affects the assessment of heterogeneity. The expected values of heterogeneity measures H² and I² were analytically derived, and the power and Type I error rate of the Q test were examined in a Monte Carlo simulation study. Our results show that the effect of publication bias on the Q test and assessment of heterogeneity is large, complex, and nonlinear. Publication bias can both dramatically decrease and increase heterogeneity in true effect size, particularly if the number of studies is large and population effect size is small. We therefore conclude that the Q test of homogeneity and heterogeneity measures H² and I² are generally not valid when publication bias is present. Our second contribution is that we introduce a web application, Q-sense, which can be used to determine the impact of publication bias on the assessment of heterogeneity within a certain meta-analysis and to assess the robustness of the meta-analytic estimate to publication bias. Furthermore, we apply Q-sense to 2 published meta-analyses, showing how publication bias can result in invalid estimates of effect size and heterogeneity. (PsycINFO Database Record (c) 2018 APA, all rights reserved)

Role of therapeutic drug monitoring in pulmonary infections : use and potential for expanded use of dried blood spot samples

Respiratory tract infections are among the most common infections in men. We reviewed literature to document their pharmacological treatments, and the extent to which therapeutic drug monitoring (TDM) is needed during treatment. We subsequently examined potential use of dried blood spots as sample procedure for TDM. TDM was found to be an important component of clinical care for many (but not all) pulmonary infections. For gentamicin, linezolid, voriconazole and posaconazole dried blood spot methods and their use in TDM were already evident in literature. For glycopeptides, beta-lactam antibiotics and fluoroquinolones it was determined that development of a dried blood spot (DBS) method could be useful. This review identifies specific antibiotics for which development of DBS methods could support the optimization of treatment of pulmonary infections

Publication bias examined in meta-analyses from psychology and medicine: A meta-meta-analysis

<div><p>Publication bias is a substantial problem for the credibility of research in general and of meta-analyses in particular, as it yields overestimated effects and may suggest the existence of non-existing effects. Although there is consensus that publication bias exists, how strongly it affects different scientific literatures is currently less well-known. We examined evidence of publication bias in a large-scale data set of primary studies that were included in 83 meta-analyses published in Psychological Bulletin (representing meta-analyses from psychology) and 499 systematic reviews from the Cochrane Database of Systematic Reviews (CDSR; representing meta-analyses from medicine). Publication bias was assessed on all homogeneous subsets (3.8% of all subsets of meta-analyses published in Psychological Bulletin) of primary studies included in meta-analyses, because publication bias methods do not have good statistical properties if the true effect size is heterogeneous. Publication bias tests did not reveal evidence for bias in the homogeneous subsets. Overestimation was minimal but statistically significant, providing evidence of publication bias that appeared to be similar in both fields. However, a Monte-Carlo simulation study revealed that the creation of homogeneous subsets resulted in challenging conditions for publication bias methods since the number of effect sizes in a subset was rather small (median number of effect sizes equaled 6). Our findings are in line with, in its most extreme case, publication bias ranging from no bias until only 5% statistically nonsignificant effect sizes being published. These and other findings, in combination with the small percentages of statistically significant primary effect sizes (28.9% and 18.9% for subsets published in Psychological Bulletin and CDSR), led to the conclusion that evidence for publication bias in the studied homogeneous subsets is weak, but suggestive of mild publication bias in both psychology and medicine.</p></div

Triple-marker cardiac MRI detects sequential tissue changes of healing myocardium after a hydrogel-based therapy

Regenerative therapies based on injectable biomaterials, hold an unparalleled potential for treating myocardial ischemia. Yet, noninvasive evaluation of their efficacy has been lagging behind. Here, we report the development and longitudinal application of multiparametric cardiac magnetic resonance imaging (MRI) to evaluate a hydrogel-based cardiac regenerative therapy. A pH-switchable hydrogel was loaded with slow releasing insulin growth factor 1 and vascular endothelial growth factor, followed by intramyocardial injection in a mouse model of ischemia reperfusion injury. Longitudinal cardiac MRI assessed three hallmarks of cardiac regeneration: angiogenesis, resolution of fibrosis and (re)muscularization after infarction. The multiparametric approach contained dynamic contrast enhanced MRI that measured improved vessel features by assessing fractional blood volume and permeability*surface area product, T1-mapping that displayed reduced fibrosis, and tagging MRI that showed improved regional myocardial strain in hydrogel treated infarcts. Finally, standard volumetric MRI demonstrated improved left ventricular functioning in hydrogel treated mice followed over time. Histology confirmed MR-based vessel features and fibrotic measurements. Our novel triple-marker strategy enabled detection of ameliorated regeneration in hydrogel treated hearts highlighting the translational potential of these longitudinal MRI approaches

Guest Editorial : Special issue on advanced computing for image-guided intervention

Editorial Guest Editorial: Special issue on advanced computing for image-guided intervention In the past years, we have witnessed a growing number of applications of minimally invasive or non-invasive interventions in clinical practice, where imaging is playing an essential role for the success of both diagnosis and therapy. Particularly, advanced signal and image processing algorithms are receiving increasing attention, which aim to provide accurate and reliable information directly to physicians. We have seen the applications of these technologies during all stages of an intervention, including preoperational planning, intra-operational guidance and post-operational verification. For this special issue, we have received a significant number of submissions from both academia and industry, out of which we have carefully selected eleven articles with outstanding quality. These articles have covered the topics of anatomic structure identification and tracking, image registration, data visualization and newly emerging applications. In [1] have addressed the image registration problem between preand post-radiated MRI to facilitate the evaluation of the therapeutic response after External Beam Radiation Treatment (EBRT) for the prostate cancer. A different approach has been employed by We have also included three papers on ultrasound-guided image interventions. In We have included in this special issue two papers on tissue characterization from endoscopic images. Nawarathna et al. have proposed in With the increasing use of various imaging modalities in image-guided intervention and therapy, how to optimally present and visualize the data becomes also an important issue. In [10], the authors have addressed the use of autostereoscopic volumetric visualization of the patient&apos;s anatomy, which has the potential to be combined with augmented reality. The paper especially addresses the latency problem in the visualization chain, and a few improvements have been proposed. A new adjacent application has been presented in In summary, we have seen from submissions to this special issue a growing interest in applying advanced signal and image processing technologies to image-guided interventions. The submissions have covered a wide range of clinical applications using various imaging modalities. Image feature extraction remains to be an important subject and it has to be specifically designed to suit the needs for specific applications. Learning-based approaches have also attracted a lot of attention, especially in applications requiring automatic tissue characterization and classification. We are also very happy to have received new emerging applications which are able to extend the traditional interventional imaging into greater application areas. Acknowledgments We would like to thank all the reviewers who have helped to peer-review the submitted papers and their constructive comments are well appreciated

Longitudinal analysis of varicella-zoster virus-specific antibodies in systemic lupus erythematosus:No association with subclinical viral reactivations or lupus disease activity

Systemic lupus erythematosus (SLE) patients are at high risk of herpes zoster. Previously, we found increased immunoglobulin (Ig)G levels against varicella-zoster virus (VZV) in SLE patients compared to controls, while antibody levels against diphtheria and cellular immunity to VZV were decreased. We aimed to test our hypothesis that increased VZV-IgG levels in SLE result from subclinical VZV reactivations, caused by stress because of lupus disease activity or immunosuppressive drug use. Methods Antibody levels to VZV (IgG, IgA, IgM), total IgG and VZV-DNA were longitudinally determined in the serum of 34 SLE patients, using enzyme-linked immunosorbent assay and polymerase chain reaction. Clinical data were retrieved from medical records. Reactivation of VZV was defined as an at least fivefold rise in VZV-IgG or presence of VZV-IgM or VZV-DNA. Generalized estimating equations (GEE) were used to longitudinally analyse associations between antibody levels, lupus disease activity and medication use. Systemic Lupus Erythematosus Disease Activity Index, anti-double-stranded DNA and complement levels were used as indicators of lupus disease activity. Results A VZV reactivation was determined in 11 patients (33%). In at least five of them, herpes zoster was clinically overt. No association between SLE disease activity or medication use and VZV-specific antibody levels was found. There was a weak association between total IgG and VZV-IgG. Conclusions Our results indicate that increased VZV-IgG levels in SLE do not result from frequent subclinical VZV reactivations, and are not associated with lupus disease activity. Increased VZV-IgG can only partially be explained by hypergammaglobulinaemia

Efficacy of Antibiotic Suppressive Therapy in Patients with a Prosthetic Joint Infection

Introduction: For chronic prosthetic joint infections (PJI), complete removal of the infected prosthesis is necessary in order to cure the infection. Unfortunately, a subgroup of patients is not able to undergo a revision surgery due to high surgical risk. Alternatively, these patients can be treated with antibiotic suppressive therapy (AST) to suppress the infection. Aim: To evaluate the efficacy and tolerability of AST. Methods: We retrospectively collected data (period 2009-2015) from patients with a PJI (of hip, knee or shoulder) who were treated with AST at the University Medical Center Groningen, the Netherlands. AST was defined as antibiotic treatment for PJI that was started after the usual 3 months of antibiotic treatment. The time of follow-up was defined from the time point AST was started. Treatment was considered as failed, when the patient still experienced joint pain, when surgical intervention (debridement, removal, arthrodesis or amputation) was needed to control the infection and/or when death occurred due to the infection. Results: We included 21 patients with a median age of 67 years (range 21 - 88) and with a median follow-up of 21 months (range 3 - 81). Coagulase negative staphylococci (CNS) (n=6), S. aureus (n=6) and polymicrobial flora (n=4) were the most frequently found causative pathogens. Most patients with CNS and S. aureus were treated with minocycline (67%) and clindamycin (83%) as AST, respectively. Overall, treatment was successful in 67% of patients. Failure was due to persistent joint pain (n=1), surgical intervention because of an uncontrolled infection (n=3), and death due the infection (n=3). We observed a treatment success of 90% in patients with a 'standard' prosthesis (n=11), compared to only 50% in patients with a tumor-prosthesis (n=10). Also, treatment was successful in 83% of patients with a CNS as causative microorganism for the infection, compared to 50% in patients with a S. aureus. Patients who failed on AST had a higher ESR in comparison to patients with a successful treatment (mean 73 ± 25SD versus 32 ± 19SD mm/hour (p = 0.007), respectively. 43% of patients experienced side effects and led to a switch of antibiotic treatment or a dose adjustment in almost all of these patients. Conclusions: Removal of the implant remains first choice in patients with chronic PJI. However, AST is a reasonable alternative treatment option in a subgroup of patients with a PJI who are no candidate for revision surgery, in particular in patients with a 'standard' prosthesis and/or CNS as the causative micro-organism

New approaches for the assessment of vessel sizes in quantitative (cardio-)vascular X-ray analysis

This paper presents new approaches for the assessment of the arterial and reference diameters in (cardio-)vascular X-ray images, designed to overcome the problems experienced in conventional quantitative coronary and vascular angiography approaches. In single or “straight” vessel segments, the arterial and reference diameter directions were made independent of each other in order to be able to measure the minimal lumen diameter (MLD) more accurately, especially in curved vessel segments. For ostial segments, an extension of this approach was used, to allow measurement of ostial lesions in sidebranches more proximal than using conventional methods. Furthermore, two new bifurcation approaches were developed. The validation study shows that the straight segment approach results in significant smaller MLDs (on average 0.032 mm) and the ostial approach achieves on average an increase in %DS of 3.8% and an increase in lesion length of 0.59 mm due to loosening the directional constraint. The validation of our new bifurcation approaches in phantom data as well as clinical data shows only small differences between pre- and post-intervention measurements of the reference diameters outside the bifurcation core (errors smaller than 0.06 mm) and the bifurcation core area (errors smaller than 1.4% for phantom data). In summary, these new approaches have led to further improvements in the quantitative analyses of (cardio-)vascular X-ray angiographies