Contacting authors to retrieve individual patient data study protocol for a randomized controlled trial

BACKGROUND: Individual patient data (IPD) meta-analysis is considered the "gold standard" for exploring the effectiveness of interventions in different subgroups of patients. However, obtaining IPD is time-consuming and contact with the researchers responsible for the original trials is usually required. To date, there are no studies evaluating different strategies to optimize the process for retrieval of IPD from such researchers. Our aim is to examine the impact of providing incentives to the researchers responsible for the trials eligible for a meta-analysis to submit their IPD.METHODS/DESIGN: We updated our previously published systematic reviews for type 1 diabetes mellitus comparing long- and intermediate-acting insulin regimens (from January 2013 to June 2015) and for Alzheimer's dementia comparing cognitive enhancers (from January 2015 to May 2015). Eligible were randomized controlled trials (RCTs) fulfilling the eligibility criteria of the systematic reviews. We will randomly allocate authors of the reports of these RCTs into an intervention or control group. Those allocated to the intervention group will be contacted by email, mail, and phone, and will be asked to provide the IPD from their RCT and will be given a financial incentive. Those allocated to the control group will be contacted by email, mail, and phone, but will not receive a financial incentive. Our primary outcome will be the proportion of authors who provide the IPD. The secondary outcomes will be the time to return the dataset (defined as the period between the information request and the authors' response with the dataset), and completeness of data. We will compare the response rates in the two groups using the odds ratio and the corresponding 95 % confidence interval. We will also use binary logistic regression and cox regression analyses to examine whether different RCT characteristics, such as study size and sponsor information, influence the probability of providing IPD and the time needed to share the data.DISCUSSION: This study will determine whether a financial incentive affects response rates when seeking IPD from the original researchers. We will disseminate our findings in an open access scientific journal and present results at national and international conferences.TRIAL REGISTRATION: This trial is registered in Clinical Trials.gov, ID number NCT02569411 . Date of registration 5 October 2015.</p

An Unusual Michael-Induced Skeletal Rearrangement of a Bicyclo[3.3.1]nonane Framework of Phloroglucinols to a Novel Bioactive Bicyclo[3.3.0]octane

A novel skeletal rearrangement of bicyclo[3.3.1]nonane-2,4,9-trione (16) to an unprecedented highly functionalized bicyclo[3.3.0]octane system (17), induced by an intramolecular Michael addition, is presented. This novel framework was found to be similarly active to hyperforin (1), against PC-3 cell lines. A mechanistic study was examined in detail, proposing a number of cascade transformations. Also, reactivity of the Δ7,10-double bond was examined under several conditions to explain the above results

„Τῇ καλλίστῃ”: Do Najpiękniejszej. Ceremonia wyboru cesarskiej żony na dworze bizantyńskim (788–882)

Beauty pageants were used as a ceremonial mechanism during the Byzantine Empire to select the emperor’s bride. This practice aimed to maintain the mystique surrounding Constantinople’s rulers and prevent local elites from gaining undue influence. These contests were exclusively held for the emperor’s firstborn sons during their initial marriages, and they aimed to identify the most beautiful and virtuous women to become empresses, adding magnificence to royal weddings. Primary Byzantine sources indicate that these contests took place between 788 and 882, with the first one officially held by Irene for her son Constantine VI. The criteria used to determine the winner were based on a combination of factors: age, appearance, demeanour, ideal facial features, graceful movements and gait, and modest posture. The Roman emperor could only be matched by a woman possessing the corresponding qualifications and, above all, the most appreciated virtue of the time – beauty. Only the most beautiful woman had the privilege of standing beside the emperor. The two symbols used to seal the bride’s choice were the golden apple and the golden ring. The Byzantine bridal pageants exerted their enchanting influence on the subjects of the empire during and after their existence. Even the ecclesiastical world was captivated by their glamour, and the most intriguing information about them can be found in the saints’ chronicles. This study aims to explore the portrayal of these bride shows in primary Byzantine sources and other contemporary scholars. Furthermore, it examines the impact of this custom on politics and the reasons behind its eventual extinction.W Cesarstwie Bizantyńskim wyłonienie żony cesarza odbywało się w formie konkursu piękności, który stanowił jeden z elementów ogólnej mistyki otaczającej władców Konstantynopola i ich dwór oraz zapobiegał zdobywaniu przez lokalne elity nadmiernych wpływów w otoczeniu władcy państwa. Konkursy te, organizowane wyłącznie dla pierwszych zaślubin pierworodnych synów cesarza, wyłaniały najpiękniejsze i najbardziej cnotliwe kobiety do roli przyszłej cesarzowej. Ceremoniał tego zwyczaju podnosił rangę cesarskich ślubów. Oryginalne źródła bizantyńskie wskazują, że konkursy te odbywały się w latach 788–882, a pierwszy z nich został oficjalnie zorganizowany przez Irenę dla jej syna Konstantyna VI. Kryteria stosowane do wyłonienia zwycięzcy opierały się na kombinacji czynników: wieku, wyglądu, postawy, idealnych rysów twarzy, pełnych wdzięku ruchów i chodu oraz skromnej postawy. Rzymskiemu cesarzowi mogła dorównać jedynie kobieta posiadająca odpowiednie kwalifikacje, a przede wszystkim najbardziej cenioną cnotę tamtych czasów – urodę. Tylko najpiękniejsza&nbsp;kobieta miała przywilej stanąć u boku cesarza. Dwa symbole używane do przypieczętowania wyboru panny młodej to złote jabłko i złoty pierścień. Bizantyńskie konkursy piękności wywierały czarujący wpływ na poddanych cesarstwa w trakcie i po ich istnieniu. Nawet świat kościelny był urzeczony ich blaskiem, a najbardziej intrygujące informacje na ich temat można znaleźć w kronikach świętych. Celem artykułu jest zaprezentowanie sposobu przedstawiania tej ceremonii w oryginalnych źródłach bizantyńskich oraz we współczesnej historiografii. Ponadto zostaną omówione wpływy tego zwyczaju na politykę oraz okoliczności jego zniknięcia

What guidance are researchers given on how to present network meta-analyses to end-users such as policymakers and clinicians? A systematic review

© 2014 Sullivan et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.Introduction: Network meta-analyses (NMAs) are complex methodological approaches that may be challenging for non-technical end-users, such as policymakers and clinicians, to understand. Consideration should be given to identifying optimal approaches to presenting NMAs that help clarify analyses. It is unclear what guidance researchers currently have on how to present and tailor NMAs to different end-users. Methods: A systematic review of NMA guidelines was conducted to identify guidance on how to present NMAs. Electronic databases and supplementary sources were searched for NMA guidelines. Presentation format details related to sample formats, target audiences, data sources, analysis methods and results were extracted and frequencies tabulated. Guideline quality was assessed following criteria developed for clinical practice guidelines. Results: Seven guidelines were included. Current guidelines focus on how to conduct NMAs but provide limited guidance to researchers on how to best present analyses to different end-users. None of the guidelines provided reporting templates. Few guidelines provided advice on tailoring presentations to different end-users, such as policymakers. Available guidance on presentation formats focused on evidence networks, characteristics of individual trials, comparisons between direct and indirect estimates and assumptions of heterogeneity and/or inconsistency. Some guidelines also provided examples of figures and tables that could be used to present information. Conclusions: Limited guidance exists for researchers on how best to present NMAs in an accessible format, especially for non-technical end-users such as policymakers and clinicians. NMA guidelines may require further integration with end-users' needs, when NMAs are used to support healthcare policy and practice decisions. Developing presentation formats that enhance understanding and accessibility of NMAs could also enhance the transparency and legitimacy of decisions informed by NMAs.The Canadian Institute of Health Research (CIHR) Drug Safety and Effectiveness Network (Funding reference number – 116573)

Integrated Management of European Cherry Fruit Fly Rhagoletis cerasi (L.): Situation in Switzerland and Europe

Abstract: The European cherry fruit fly, Rhagoletis cerasi (L.) (Diptera: Tephritidae), is a highly destructive pest. The low tolerance for damaged fruit requires preventive insecticide treatments for a marketable crop. The phase-out of old insecticides threatens cherry production throughout the European Union (EU). Consequently, new management techniques and tools are needed. With the increasing number of dwarf tree orchards covered against rain to avoid fruit splitting, crop netting has become a viable, cost-effective method of cherry fruit fly control. Recently, a biocontrol method using the entomopathogenic fungus Beauveria bassiana has been developed for organic agriculture. However, for most situations, there is still a lack of efficient and environmentally sound insecticides to control this pest. This review summarizes the literature from over one hundred years of research on R. cerasi with focus on the biology and history of cherry fruit fly control as well as on antagonists and potential biocontrol organisms. We will present the situation of cherry fruit fly regulation in different European countries, give recommendations for cherry fruit fly control, show gaps in knowledge and identify future research opportunities

An investigation of the impact of using different methods for network meta-analysis: A protocol for an empirical evaluation

BACKGROUND: Network meta-analysis, a method to synthesise evidence from multiple treatments, has increased in popularity in the past decade. Two broad approaches are available to synthesise data across networks, namely, arm- and contrast-synthesis models, with a range of models that can be fitted within each. There has been recent debate about the validity of the arm-synthesis models, but to date, there has been limited empirical evaluation comparing results using the methods applied to a large number of networks. We aim to address this gap through the re-analysis of a large cohort of published networks of interventions using a range of network meta-analysis methods. METHODS: We will include a subset of networks from a database of network meta-analyses of randomised trials that have been identified and curated from the published literature. The subset of networks will include those where the primary outcome is binary, the number of events and participants are reported for each direct comparison, and there is no evidence of inconsistency in the network. We will re-analyse the networks using three contrast-synthesis methods and two arm-synthesis methods. We will compare the estimated treatment effects, their standard errors, treatment hierarchy based on the surface under the cumulative ranking (SUCRA) curve, the SUCRA value, and the between-trial heterogeneity variance across the network meta-analysis methods. We will investigate whether differences in the results are affected by network characteristics and baseline risk. DISCUSSION: The results of this study will inform whether, in practice, the choice of network meta-analysis method matters, and if it does, in what situations differences in the results between methods might arise. The results from this research might also inform future simulation studies

Accounting for heterogeneity in meta-analysis using a multiplicative model—an empirical study

In meta-analysis, the random-effects model is often used to account for heterogeneity. The model assumes that heterogeneity has an additive effect on the variance of effect sizes. An alternative model, which assumes multiplicative heterogeneity, has been little used in the medical statistics community, but is widely used by particle physicists. In this paper, we compare the two models using a random sample of 448 meta-analyses drawn from the Cochrane Database of Systematic Reviews. In general, differences in goodness of fit are modest. The multiplicative model tends to give results that are closer to the null, with a narrower confidence interval. Both approaches make different assumptions about the outcome of the meta-analysis. In our opinion, the selection of the more appropriate model will often be guided by whether the multiplicative model's assumption of a single effect size is plausible. Copyright © 2016 John Wiley & Sons, Ltd

Methods to estimate the between-study variance and its uncertainty in meta-analysis

Meta‐analyses are typically used to estimate the overall/mean of an outcome of interest. However, inference about between‐study variability, which is typically modelled using a between‐study variance parameter, is usually an additional aim. The DerSimonian and Laird method, currently widely used by default to estimate the between‐study variance, has been long challenged. Our aim is to identify known methods for estimation of the between‐study variance and its corresponding uncertainty, and to summarise the simulation and empirical evidence that compares them. We identified 16 estimators for the between‐study variance, seven methods to calculate confidence intervals, and several comparative studies. Simulation studies suggest that for both dichotomous and continuous data the estimator proposed by Paule and Mandel and for continuous data the restricted maximum likelihood estimator are better alternatives to estimate the between‐study variance. Based on the scenarios and results presented in the published studies, we recommend the Q‐profile method and the alternative approach based on a ‘generalised Cochran between‐study variance statistic’ to compute corresponding confidence intervals around the resulting estimates. Our recommendations are based on a qualitative evaluation of the existing literature and expert consensus. Evidence‐based recommendations require an extensive simulation study where all methods would be compared under the same scenarios. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd

Sequential change detection and monitoring of temporal trends in random-effects meta-analysis

Temporal changes in magnitude of effect sizes reported in many areas of research are a threat to the credibility of the results and conclusions of meta-analysis. Numerous sequential methods for meta-analysis have been proposed to detect changes and monitor trends in effect sizes so that meta-analysis can be updated when necessary and interpreted based on the time it was conducted. The difficulties of sequential meta-analysis under the random-effects model are caused by dependencies in increments introduced by the estimation of the heterogeneity parameter τ2. In this paper we propose the use of a retrospective CUSUM-type test with bootstrap critical values. This method allows retrospective analysis of the past trajectory of cumulative effects in random-effects meta-analysis, and its visualisation on a chart similar to CUSUM chart. Simulation results show that the new method demonstrates good control of Type I error regardless of the number or size of the studies and the amount of heterogeneity. Application of the new method is illustrated on two examples of medical meta-analyses

Interventions for treating cavitated or dentine carious lesions

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To determine the clinical and cost-effectiveness of interventions (non-selective, selective or stepwise carious tissue removal, sealing of carious lesions using sealant materials or preformed metal crowns, or NRCC) to treat carious lesions conventionally considered to require restorations (cavitated or micro-cavitated lesions, or occlusal lesions that are clinically non-cavitated but clinically/radiographically extend into dentine) in primary or permanent teeth with vital (sensitive) pulps.</p