Comparison of noninferiority margins reported in protocols and publications showed incomplete and inconsistent reporting.

OBJECTIVES To compare noninferiority margins defined in study protocols and trial registry records with margins reported in subsequent publications. STUDY DESIGN AND SETTING Comparison of protocols of noninferiority trials submitted 2001 to 2005 to ethics committees in Switzerland and The Netherlands with corresponding publications and registry records. We searched MEDLINE via PubMed, the Cochrane Controlled Trials Register (Cochrane Library issue 01/2012), and Google Scholar in September 2013 to identify published reports, and the International Clinical Trials Registry Platform of the World Health Organization in March 2013 to identify registry records. Two readers recorded the noninferiority margin and other data using a standardized data-abstraction form. RESULTS The margin was identical in study protocol and publication in 43 (80%) of 54 pairs of study protocols and articles. In the remaining pairs, reporting was inconsistent (five pairs, 9%), or the noninferiority margin was either not reported in the publication (five pairs, 9%) or not defined in the study protocol (one pair). The confidence interval or the exact P-value required to judge whether the result was compatible with noninferior, inferior, or superior efficacy was reported in 43 (80%) publications. Complete and consistent reporting of both noninferiority margin and confidence interval (or exact P-value) was present in 39 (72%) protocol-publication pairs. Twenty-nine trials (54%) were registered in trial registries, but only one registry record included the noninferiority margin. CONCLUSION The reporting of noninferiority margins was incomplete and inconsistent with study protocols in a substantial proportion of published trials, and margins were rarely reported in trial registries.

A systematic review and meta-analysis of factors associated with anthelmintic resistance in sheep.

BACKGROUND Anthelmintic drugs have been widely used in sheep as a cost-effective means for gastro-intestinal nematode (GIN) control. However, growing anthelmintic resistance (AHR) has created a compelling need to identify evidence-based management recommendations that reduce the risk of further development and impact of AHR. OBJECTIVE To identify, critically assess, and synthesize available data from primary research on factors associated with AHR in sheep. METHODS Publications reporting original observational or experimental research on selected factors associated with AHR in sheep GINs and published after 1974, were identified through two processes. Three electronic databases (PubMed, Agricola, CAB) and Web of Science (a collection of databases) were searched for potentially relevant publications. Additional publications were identified through consultation with experts, manual search of references of included publications and conference proceedings, and information solicited from small ruminant practitioner list-serves. Two independent investigators screened abstracts for relevance. Relevant publications were assessed for risk of systematic bias. Where sufficient data were available, random-effects Meta-Analyses (MAs) were performed to estimate the pooled Odds Ratio (OR) and 95% Confidence Intervals (CIs) of AHR for factors reported in ≥2 publications. RESULTS Of the 1712 abstracts screened for eligibility, 131 were deemed relevant for full publication review. Thirty publications describing 25 individual studies (15 observational studies, 7 challenge trials, and 3 controlled trials) were included in the qualitative synthesis and assessed for systematic bias. Unclear (i.e. not reported, or unable to assess) or high risk of selection bias and confounding bias was found in 93% (14/15) and 60% (9/15) of the observational studies, respectively, while unclear risk of selection bias was identified in all of the trials. Ten independent studies were included in the quantitative synthesis, and MAs were performed for five factors. Only high frequency of treatment was a significant risk factor (OR=4.39; 95% CI=1.59, 12.14), while the remaining 4 variables were marginally significant: mixed-species grazing (OR=1.63; 95% CI=0.66, 4.07); flock size (OR=1.02; 95% CI=0.97, 1.07); use of long-acting drug formulations (OR=2.85; 95% CI=0.79, 10.24); and drench-and-shift pasture management (OR=4.08; 95% CI=0.75, 22.16). CONCLUSIONS While there is abundant literature on the topic of AHR in sheep GINs, few studies have explicitly investigated the association between putative risk or protective factors and AHR. Consequently, several of the current recommendations on parasite management are not evidence-based. Moreover, many of the studies included in this review had a high or unclear risk of systematic bias, highlighting the need to improve study design and/or reporting of future research carried out in this field.

School-age children show a bias toward fantasy classifications after playing a platform game

We investigated the influence of playing a video game on children’s ability to distinguish between fantasy and reality. School-age children played a platform game for 15 min and then performed a fantasy/reality distinction task in which they were to judge whether images (from the platform game and from other games) were fantasy images or reality images. Unlike those in the control group (who played a memory game), the children in the experimental group showed a response bias toward mistakenly classifying reality images from the video game as fantasy images (as determined by means of an analysis based on signal detection theory). We conclude that playing the video game exerted a short-term influence on children’s ability to distinguish between fantasy and reality.

Reporting standards for studies of diagnostic test accuracy in dementia: The STARDdem Initiative.

OBJECTIVE To provide guidance on standards for reporting studies of diagnostic test accuracy for dementia disorders. METHODS An international consensus process on reporting standards in dementia and cognitive impairment (STARDdem) was established, focusing on studies presenting data from which sensitivity and specificity were reported or could be derived. A working group led the initiative through 4 rounds of consensus work, using a modified Delphi process and culminating in a face-to-face consensus meeting in October 2012. The aim of this process was to agree on how best to supplement the generic standards of the STARD statement to enhance their utility and encourage their use in dementia research. RESULTS More than 200 comments were received during the wider consultation rounds. The areas at most risk of inadequate reporting were identified and a set of dementia-specific recommendations to supplement the STARD guidance were developed, including better reporting of patient selection, the reference standard used, avoidance of circularity, and reporting of test-retest reliability. CONCLUSION STARDdem is an implementation of the STARD statement in which the original checklist is elaborated and supplemented with guidance pertinent to studies of cognitive disorders. Its adoption is expected to increase transparency, enable more effective evaluation of diagnostic tests in Alzheimer disease and dementia, contribute to greater adherence to methodologic standards, and advance the development of Alzheimer biomarkers.

Pelvic floor muscle activation and strength components influencing female urinary continence and stress incontinence: A systematic review

AIMS A better understanding of pelvic floor muscle (PFM) activation and strength components is a prerequisite to get better insight in PFM contraction mechanisms and develop more specific PFM-training regimens for female stress urinary incontinence (SUI) patients. The aim of this systematic review (2012:CRD42012002547) was to evaluate and summarize existing studies investigating PFM activation and strength components influencing female continence and SUI. METHODS PubMed, EMBASE, and Cochrane databases were systematically searched for literature from January 1980 to November 2013 for cross-sectional studies comparing female SUI patients with healthy controls and intervention studies with SUI patients reporting on the association between PFM activation and strength components and urine loss. Trial characteristics, evaluated PFM components, their definitions, measurement methods, study outcomes, as well as quality measures, based on the Cochrane risk of bias tool, were independently extracted. The high heterogeneity of the retrieved data made pooling of results impossible and therefore restricted the analysis to a systematic review. RESULTS Cross-sectional studies showed group differences in favor of the continent women compared to SUI patients for PFM activation or PFM maximal strength, mean strength or sustained contraction. All intervention studies showed an improvement of PFM strength and decrease in urine loss in SUI patients after physical therapy. CONCLUSIONS Higher PFM activation and strength components influence female continence positively. This systematic review underscored the need for a standardized PFM components' terminology (similar to rehabilitation and training science), standardized test procedures and well matched diagnostic instruments. Neurourol. Urodynam. © 2014 Wiley Periodicals, Inc.

8p23 beta-defensin copy number determination by single-locus pseudogene-based paralog ratio tests risk bias due to low-frequency sequence variations.

BACKGROUND The copy number variation (CNV) in beta-defensin genes (DEFB) on human chromosome 8p23 has been proposed to contribute to the phenotypic differences in inflammatory diseases. However, determination of exact DEFB CN is a major challenge in association studies. Quantitative real-time PCR (qPCR), paralog ratio tests (PRT) and multiplex ligation-dependent probe amplification (MLPA) have been extensively used to determine DEFB CN in different laboratories, but inter-method inconsistencies were observed frequently. In this study we asked which one is superior among the three methods for DEFB CN determination. RESULTS We developed a clustering approach for MLPA and PRT to statistically correlate data from a single experiment. Then we compared qPCR, a newly designed PRT and MLPA for DEFB CN determination in 285 DNA samples. We found MLPA had the best convergence and clustering results of the raw data and the highest call rate. In addition, the concordance rates between MLPA or PRT and qPCR (32.12% and 37.99%, respectively) were unacceptably low with underestimated CN by qPCR. Concordance rate between MLPA and PRT (90.52%) was high but PRT systematically underestimated CN by one in a subset of samples. In these samples a sequence variant which caused complete PCR dropout of the respective DEFB cluster copies was found in one primer binding site of one of the targeted paralogous pseudogenes. CONCLUSION MLPA is superior to PRT and even more to qPCR for DEFB CN determination. Although the applied PRT provides in most cases reliable results, such a test is particularly sensitive to low-frequency sequence variations preferably accumulating in loci like pseudogenes which are most likely not under selective pressure. In the light of the superior performance of multiplex assays, the drawbacks of such single PRTs could be overcome by combining more test markers.

How narcissistic self-construction sabotages their relationships: Accuracy and bias in partner perception

Trapped by their superordinate goal to maintain a grandiose self, narcissists navigate their relationships wishing to re-assure themselves of their specialness and superiority, using strategies bound to fail. Dyadic analyses of diary data (14 days, 83 couples) showed that narcissists focus on their partners’ shortcomings, becoming experts at detecting negative forms of support, while simultaneously minimizing their partner’s positive intentions. Partners of narcissists, in contrast, appear to have a positive bias in ongoing relationships and seem to compensate for some of the narcissists’ shortcomings. Narcissists’ focus on their own selfconstruction purposes also extends to their parenting roles. In a retrospective study, narcissistic mothers were found to demand superior performance, desiring to show-off their child, yet concurrently attributing their child’s success to themselves. They also exercise psychological control and role-reversal, requiring the child to cater to their needs, and to admire them, while simultaneously oblivious to their child’s needs and desires.

Strengthening the Reporting of Observational Studies in Epidemiology for respondent-driven sampling studies: "STROBE-RDS" statement.

OBJECTIVES Respondent-driven sampling (RDS) is a new data collection methodology used to estimate characteristics of hard-to-reach groups, such as the HIV prevalence in drug users. Many national public health systems and international organizations rely on RDS data. However, RDS reporting quality and available reporting guidelines are inadequate. We carried out a systematic review of RDS studies and present Strengthening the Reporting of Observational Studies in Epidemiology for RDS Studies (STROBE-RDS), a checklist of essential items to present in RDS publications, justified by an explanation and elaboration document. STUDY DESIGN AND SETTING We searched the MEDLINE (1970-2013), EMBASE (1974-2013), and Global Health (1910-2013) databases to assess the number and geographical distribution of published RDS studies. STROBE-RDS was developed based on STROBE guidelines, following Guidance for Developers of Health Research Reporting Guidelines. RESULTS RDS has been used in over 460 studies from 69 countries, including the USA (151 studies), China (70), and India (32). STROBE-RDS includes modifications to 12 of the 22 items on the STROBE checklist. The two key areas that required modification concerned the selection of participants and statistical analysis of the sample. CONCLUSION STROBE-RDS seeks to enhance the transparency and utility of research using RDS. If widely adopted, STROBE-RDS should improve global infectious diseases public health decision making.

Brain systems underlying encounter expectancy bias in spider phobia.

Spider-phobic individuals are characterized by exaggerated expectancies to be faced with spiders (so-called encounter expectancy bias). Whereas phobic responses have been linked to brain systems mediating fear, little is known about how the recruitment of these systems relates to exaggerated expectancies of threat. We used fMRI to examine spider-phobic and control participants while they imagined visiting different locations in a forest after having received background information about the likelihood of encountering different animals (spiders, snakes, and birds) at these locations. Critically, imagined encounter expectancies modulated brain responses differently in phobics as compared with controls. Phobics displayed stronger negative modulation of activity in the lateral prefrontal cortex, precuneus, and visual cortex by encounter expectancies for spiders, relative to snakes or birds (within-participants analysis); these effects were not seen in controls. Between-participants correlation analyses within the phobic group further corroborated the hypothesis that these phobia-specific modulations may underlie irrationality in encounter expectancies (deviations of encounter expectancies from objective background information) in spider phobia; the greater the negative modulation a phobic participant displayed in the lateral prefrontal cortex, precuneus, and visual cortex, the stronger was her bias in encounter expectancies for spiders. Interestingly, irrationality in expectancies reflected in frontal areas relied on right rather than left hemispheric deactivations. Our data accord with the idea that expectancy biases in spider phobia may reflect deficiencies in cognitive control and contextual integration that are mediated by right frontal and parietal areas.

Varying expectancies and attention bias in phobic and non-phobic individuals.

Phobic individuals display an attention bias to phobia-related information and biased expectancies regarding the likelihood of being faced with such stimuli. Notably, although attention and expectancy biases are core features in phobia and anxiety disorders, these biases have mostly been investigated separately and their causal impact has not been examined. We hypothesized that these biases might be causally related. Spider phobic and low spider fearful control participants performed a visual search task in which they specified whether the deviant animal in a search array was a spider or a bird. Shorter reaction times (RTs) for spiders than for birds in this task reflect an attention bias toward spiders. Participants' expectancies regarding the likelihood of these animals being the deviant in the search array were manipulated by presenting verbal cues. Phobics were characterized by a pronounced and persistent attention bias toward spiders; controls displayed slower RTs for birds than for spiders only when spider cues had been presented. More important, we found RTs for spider detections to be virtually unaffected by the expectancy cues in both groups, whereas RTs for bird detections showed a clear influence of the cues. Our results speak to the possibility that evolution has formed attentional systems that are specific to the detection of phylogenetically salient stimuli such as threatening animals; these systems may not be as penetrable to variations in (experimentally induced) expectancies as those systems that are used for the detection of non-threatening stimuli. In sum, our findings highlight the relation between expectancies and attention engagement in general. However, expectancies may play a greater role in attention engagement in safe environments than in threatening environments.

Evidence for an encounter expectancy bias in fear of spiders.

Whereas research has demonstrated that phobic or fearful individuals overestimate the likelihood of incurring aversive consequences from an encounter with feared stimuli, it has not yet been systematically investigated whether these individuals also overestimate the likelihood (i.e., the frequency) of such encounters. In the current study, spider-fearful and control participants were presented with background information that allowed them to estimate the overall likelihood that different kinds of animals (spiders, snakes, or birds) would be encountered. Spider-fearful participants systematically overestimated the likelihood of encountering a spider with respect to the likelihood of encountering a snake or a bird. No such expectancy bias was observed in control participants. The results thus strengthen our idea that there indeed exist two different types of expectancy bias in high fear and phobia that can be related to different components of the fear response. A conscientious distinction and examination of these two types of expectancy bias are of potential interest for therapeutic applications.