ALE Meta-Analysis of Schizophrenics Performing the N-Back Task

NASA Astrophysics Data System (ADS)

Harrell, Zachary

2010-10-01

MRI/fMRI has already proven itself as a valuable tool in the diagnosis and treatment of many illnesses of the brain, including cognitive problems. By exploiting the differences in magnetic susceptibility between oxygenated and deoxygenated hemoglobin, fMRI can measure blood flow in various regions of interest within the brain. This can determine the level of brain activity in relation to motor or cognitive functions and provide a metric for tissue damage or illness symptoms. Structural imaging techniques have shown lesions or deficiencies in tissue volumes in schizophrenics corresponding to areas primarily in the frontal and temporal lobes. These areas are currently known to be involved in working memory and attention, which many schizophrenics have trouble with. The ALE (Activation Likelihood Estimation) Meta-Analysis is able to statistically determine the significance of brain area activations based on the post-hoc combination of multiple studies. This process is useful for giving a general model of brain function in relation to a particular task designed to engage the affected areas (such as working memory for the n-back task). The advantages of the ALE Meta-Analysis include elimination of single subject anomalies, elimination of false/extremely weak activations, and verification of function/location hypotheses.

A meta-analysis of neuroimaging studies on divergent thinking using activation likelihood estimation.

PubMed

Wu, Xin; Yang, Wenjing; Tong, Dandan; Sun, Jiangzhou; Chen, Qunlin; Wei, Dongtao; Zhang, Qinglin; Zhang, Meng; Qiu, Jiang

2015-07-01

In this study, an activation likelihood estimation (ALE) meta-analysis was used to conduct a quantitative investigation of neuroimaging studies on divergent thinking. Based on the ALE results, the functional magnetic resonance imaging (fMRI) studies showed that distributed brain regions were more active under divergent thinking tasks (DTTs) than those under control tasks, but a large portion of the brain regions were deactivated. The ALE results indicated that the brain networks of the creative idea generation in DTTs may be composed of the lateral prefrontal cortex, posterior parietal cortex [such as the inferior parietal lobule (BA 40) and precuneus (BA 7)], anterior cingulate cortex (ACC) (BA 32), and several regions in the temporal cortex [such as the left middle temporal gyrus (BA 39), and left fusiform gyrus (BA 37)]. The left dorsolateral prefrontal cortex (BA 46) was related to selecting the loosely and remotely associated concepts and organizing them into creative ideas, whereas the ACC (BA 32) was related to observing and forming distant semantic associations in performing DTTs. The posterior parietal cortex may be involved in the semantic information related to the retrieval and buffering of the formed creative ideas, and several regions in the temporal cortex may be related to the stored long-term memory. In addition, the ALE results of the structural studies showed that divergent thinking was related to the dopaminergic system (e.g., left caudate and claustrum). Based on the ALE results, both fMRI and structural MRI studies could uncover the neural basis of divergent thinking from different aspects (e.g., specific cognitive processing and stable individual difference of cognitive capability). © 2015 Wiley Periodicals, Inc.

Different patterns and development characteristics of processing written logographic characters and alphabetic words: an ALE meta-analysis.

PubMed

Zhu, Linlin; Nie, Yaoxin; Chang, Chunqi; Gao, Jia-Hong; Niu, Zhendong

2014-06-01

The neural systems for phonological processing of written language have been well identified now, while models based on these neural systems are different for different language systems or age groups. Although each of such models is mostly concordant across different experiments, the results are sensitive to the experiment design and intersubject variability. Activation likelihood estimation (ALE) meta-analysis can quantitatively synthesize the data from multiple studies and minimize the interstudy or intersubject differences. In this study, we performed two ALE meta-analysis experiments: one was to examine the neural activation patterns of the phonological processing of two different types of written languages and the other was to examine the development characteristics of such neural activation patterns based on both alphabetic language and logographic language data. The results of our first meta-analysis experiment were consistent with the meta-analysis which was based on the studies published before 2005. And there were new findings in our second meta-analysis experiment, where both adults and children groups showed great activation in the left frontal lobe, the left superior/middle temporal gyrus, and the bilateral middle/superior occipital gyrus. However, the activation of the left middle/inferior frontal gyrus was found increase with the development, and the activation was found decrease in the following areas: the right claustrum and inferior frontal gyrus, the left inferior/medial frontal gyrus, the left middle/superior temporal gyrus, the right cerebellum, and the bilateral fusiform gyrus. It seems that adults involve more phonological areas, whereas children involve more orthographic areas and semantic areas. Copyright © 2013 Wiley Periodicals, Inc.

Specifying the core network supporting episodic simulation and episodic memory by activation likelihood estimation.

PubMed

Benoit, Roland G; Schacter, Daniel L

2015-08-01

It has been suggested that the simulation of hypothetical episodes and the recollection of past episodes are supported by fundamentally the same set of brain regions. The present article specifies this core network via Activation Likelihood Estimation (ALE). Specifically, a first meta-analysis revealed joint engagement of expected core-network regions during episodic memory and episodic simulation. These include parts of the medial surface, the hippocampus and parahippocampal cortex within the medial temporal lobes, and the temporal and inferior posterior parietal cortices on the lateral surface. Both capacities also jointly recruited additional regions such as parts of the bilateral dorsolateral prefrontal cortex. All of these core regions overlapped with the default network. Moreover, it has further been suggested that episodic simulation may require a stronger engagement of some of the core network's nodes as well as the recruitment of additional brain regions supporting control functions. A second ALE meta-analysis indeed identified such regions that were consistently more strongly engaged during episodic simulation than episodic memory. These comprised the core-network clusters located in the left dorsolateral prefrontal cortex and posterior inferior parietal lobe and other structures distributed broadly across the default and fronto-parietal control networks. Together, the analyses determine the set of brain regions that allow us to experience past and hypothetical episodes, thus providing an important foundation for studying the regions' specialized contributions and interactions. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perceiving emotional expressions in others: Activation likelihood estimation meta-analyses of explicit evaluation, passive perception and incidental perception of emotions.

PubMed

Dricu, Mihai; Frühholz, Sascha

2016-12-01

We conducted a series of activation likelihood estimation (ALE) meta-analyses to determine the commonalities and distinctions between separate levels of emotion perception, namely incidental perception, passive perception, and explicit evaluation of emotional expressions. Pooling together more than 180 neuroimaging experiments using facial, vocal or body expressions, our results are threefold. First, explicitly evaluating the emotions of others recruits brain regions associated with the sensory processing of expressions, such as the inferior occipital gyrus, middle fusiform gyrus and the superior temporal gyrus, and brain regions involved in low-level and high-level mindreading, namely the posterior superior temporal sulcus, the inferior frontal cortex and dorsomedial frontal cortex. Second, we show that only the sensory regions were also consistently active during the passive perception of emotional expressions. Third, we show that the brain regions involved in mindreading were active during the explicit evaluation of both facial and vocal expressions. We discuss these results in light of the existing literature and conclude by proposing a cognitive model for perceiving and evaluating the emotions of others. Copyright © 2016 Elsevier Ltd. All rights reserved.

Common and distinct neural correlates of personal and vicarious reward: A quantitative meta-analysis

PubMed Central

Morelli, Sylvia A.; Sacchet, Matthew D.; Zaki, Jamil

2015-01-01

Individuals experience reward not only when directly receiving positive outcomes (e.g., food or money), but also when observing others receive such outcomes. This latter phenomenon, known as vicarious reward, is a perennial topic of interest among psychologists and economists. More recently, neuroscientists have begun exploring the neuroanatomy underlying vicarious reward. Here we present a quantitative whole-brain meta-analysis of this emerging literature. We identified 25 functional neuroimaging studies that included contrasts between vicarious reward and a neutral control, and subjected these contrasts to an activation likelihood estimate (ALE) meta-analysis. This analysis revealed a consistent pattern of activation across studies, spanning structures typically associated with the computation of value (especially ventromedial prefrontal cortex) and mentalizing (including dorsomedial prefrontal cortex and superior temporal sulcus). We further quantitatively compared this activation pattern to activation foci from a previous meta-analysis of personal reward. Conjunction analyses yielded overlapping VMPFC activity in response to personal and vicarious reward. Contrast analyses identified preferential engagement of the nucleus accumbens in response to personal as compared to vicarious reward, and in mentalizing-related structures in response to vicarious as compared to personal reward. These data shed light on the common and unique components of the reward that individuals experience directly and through their social connections. PMID:25554428

An Activation Likelihood Estimation Meta-Analysis Study of Simple Motor Movements in Older and Young Adults

PubMed Central

Turesky, Ted K.; Turkeltaub, Peter E.; Eden, Guinevere F.

2016-01-01

The functional neuroanatomy of finger movements has been characterized with neuroimaging in young adults. However, less is known about the aging motor system. Several studies have contrasted movement-related activity in older versus young adults, but there is inconsistency among their findings. To address this, we conducted an activation likelihood estimation (ALE) meta-analysis on within-group data from older adults and young adults performing regularly paced right-hand finger movement tasks in response to external stimuli. We hypothesized that older adults would show a greater likelihood of activation in right cortical motor areas (i.e., ipsilateral to the side of movement) compared to young adults. ALE maps were examined for conjunction and between-group differences. Older adults showed overlapping likelihoods of activation with young adults in left primary sensorimotor cortex (SM1), bilateral supplementary motor area, bilateral insula, left thalamus, and right anterior cerebellum. Their ALE map differed from that of the young adults in right SM1 (extending into dorsal premotor cortex), right supramarginal gyrus, medial premotor cortex, and right posterior cerebellum. The finding that older adults uniquely use ipsilateral regions for right-hand finger movements and show age-dependent modulations in regions recruited by both age groups provides a foundation by which to understand age-related motor decline and motor disorders. PMID:27799910

Functional magnetic resonance imaging during emotion recognition in social anxiety disorder: an activation likelihood meta-analysis

PubMed Central

Hattingh, Coenraad J.; Ipser, J.; Tromp, S. A.; Syal, S.; Lochner, C.; Brooks, S. J.; Stein, D. J.

2012-01-01

Background: Social anxiety disorder (SAD) is characterized by abnormal fear and anxiety in social situations. Functional magnetic resonance imaging (fMRI) is a brain imaging technique that can be used to demonstrate neural activation to emotionally salient stimuli. However, no attempt has yet been made to statistically collate fMRI studies of brain activation, using the activation likelihood-estimate (ALE) technique, in response to emotion recognition tasks in individuals with SAD. Methods: A systematic search of fMRI studies of neural responses to socially emotive cues in SAD was undertaken. ALE meta-analysis, a voxel-based meta-analytic technique, was used to estimate the most significant activations during emotional recognition. Results: Seven studies were eligible for inclusion in the meta-analysis, constituting a total of 91 subjects with SAD, and 93 healthy controls. The most significant areas of activation during emotional vs. neutral stimuli in individuals with SAD compared to controls were: bilateral amygdala, left medial temporal lobe encompassing the entorhinal cortex, left medial aspect of the inferior temporal lobe encompassing perirhinal cortex and parahippocampus, right anterior cingulate, right globus pallidus, and distal tip of right postcentral gyrus. Conclusion: The results are consistent with neuroanatomic models of the role of the amygdala in fear conditioning, and the importance of the limbic circuitry in mediating anxiety symptoms. PMID:23335892

Neurological soft signs are not "soft" in brain structure and functional networks: evidence from ALE meta-analysis.

PubMed

Zhao, Qing; Li, Zhi; Huang, Jia; Yan, Chao; Dazzan, Paola; Pantelis, Christos; Cheung, Eric F C; Lui, Simon S Y; Chan, Raymond C K

2014-05-01

Neurological soft signs (NSS) are associated with schizophrenia and related psychotic disorders. NSS have been conventionally considered as clinical neurological signs without localized brain regions. However, recent brain imaging studies suggest that NSS are partly localizable and may be associated with deficits in specific brain areas. We conducted an activation likelihood estimation meta-analysis to quantitatively review structural and functional imaging studies that evaluated the brain correlates of NSS in patients with schizophrenia and other psychotic disorders. Six structural magnetic resonance imaging (sMRI) and 15 functional magnetic resonance imaging (fMRI) studies were included. The results from meta-analysis of the sMRI studies indicated that NSS were associated with atrophy of the precentral gyrus, the cerebellum, the inferior frontal gyrus, and the thalamus. The results from meta-analysis of the fMRI studies demonstrated that the NSS-related task was significantly associated with altered brain activation in the inferior frontal gyrus, bilateral putamen, the cerebellum, and the superior temporal gyrus. Our findings from both sMRI and fMRI meta-analyses further support the conceptualization of NSS as a manifestation of the "cerebello-thalamo-prefrontal" brain network model of schizophrenia and related psychotic disorders.

The neural basis of audiomotor entrainment: an ALE meta-analysis

PubMed Central

Chauvigné, Léa A. S.; Gitau, Kevin M.; Brown, Steven

2014-01-01

Synchronization of body movement to an acoustic rhythm is a major form of entrainment, such as occurs in dance. This is exemplified in experimental studies of finger tapping. Entrainment to a beat is contrasted with movement that is internally driven and is therefore self-paced. In order to examine brain areas important for entrainment to an acoustic beat, we meta-analyzed the functional neuroimaging literature on finger tapping (43 studies) using activation likelihood estimation (ALE) meta-analysis with a focus on the contrast between externally-paced and self-paced tapping. The results demonstrated a dissociation between two subcortical systems involved in timing, namely the cerebellum and the basal ganglia. Externally-paced tapping highlighted the importance of the spinocerebellum, most especially the vermis, which was not activated at all by self-paced tapping. In contrast, the basal ganglia, including the putamen and globus pallidus, were active during both types of tapping, but preferentially during self-paced tapping. These results suggest a central role for the spinocerebellum in audiomotor entrainment. We conclude with a theoretical discussion about the various forms of entrainment in humans and other animals. PMID:25324765

Are numbers grounded in a general magnitude processing system? A functional neuroimaging meta-analysis.

PubMed

Sokolowski, H Moriah; Fias, Wim; Bosah Ononye, Chuka; Ansari, Daniel

2017-10-01

It is currently debated whether numbers are processed using a number-specific system or a general magnitude processing system, also used for non-numerical magnitudes such as physical size, duration, or luminance. Activation likelihood estimation (ALE) was used to conduct the first quantitative meta-analysis of 93 empirical neuroimaging papers examining neural activation during numerical and non-numerical magnitude processing. Foci were compiled to generate probabilistic maps of activation for non-numerical magnitudes (e.g. physical size), symbolic numerical magnitudes (e.g. Arabic digits), and nonsymbolic numerical magnitudes (e.g. dot arrays). Conjunction analyses revealed overlapping activation for symbolic, nonsymbolic and non-numerical magnitudes in frontal and parietal lobes. Contrast analyses revealed specific activation in the left superior parietal lobule for symbolic numerical magnitudes. In contrast, small regions in the bilateral precuneus were specifically activated for nonsymbolic numerical magnitudes. No regions in the parietal lobes were activated for non-numerical magnitudes that were not also activated for numerical magnitudes. Therefore, numbers are processed using both a generalized magnitude system and format specific number regions. Copyright © 2017 Elsevier Ltd. All rights reserved.

Social cognition and the cerebellum: a meta-analysis of over 350 fMRI studies.

PubMed

Van Overwalle, Frank; Baetens, Kris; Mariën, Peter; Vandekerckhove, Marie

2014-02-01

This meta-analysis explores the role of the cerebellum in social cognition. Recent meta-analyses of neuroimaging studies since 2008 demonstrate that the cerebellum is only marginally involved in social cognition and emotionality, with a few meta-analyses pointing to an involvement of at most 54% of the individual studies. In this study, novel meta-analyses of over 350 fMRI studies, dividing up the domain of social cognition in homogeneous subdomains, confirmed this low involvement of the cerebellum in conditions that trigger the mirror network (e.g., when familiar movements of body parts are observed) and the mentalizing network (when no moving body parts or unfamiliar movements are present). There is, however, one set of mentalizing conditions that strongly involve the cerebellum in 50-100% of the individual studies. In particular, when the level of abstraction is high, such as when behaviors are described in terms of traits or permanent characteristics, in terms of groups rather than individuals, in terms of the past (episodic autobiographic memory) or the future rather than the present, or in terms of hypothetical events that may happen. An activation likelihood estimation (ALE) meta-analysis conducted in this study reveals that the cerebellum is critically implicated in social cognition and that the areas of the cerebellum which are consistently involved in social cognitive processes show extensive overlap with the areas involved in sensorimotor (during mirror and self-judgments tasks) as well as in executive functioning (across all tasks). We discuss the role of the cerebellum in social cognition in general and in higher abstraction mentalizing in particular. We also point out a number of methodological limitations of some available studies on the social brain that hamper the detection of cerebellar activity. © 2013 Elsevier Inc. All rights reserved.

Exposure to subliminal arousing stimuli induces robust activation in the amygdala, hippocampus, anterior cingulate, insular cortex and primary visual cortex: a systematic meta-analysis of fMRI studies.

PubMed

Brooks, S J; Savov, V; Allzén, E; Benedict, C; Fredriksson, R; Schiöth, H B

2012-02-01

Functional Magnetic Resonance Imaging (fMRI) demonstrates that the subliminal presentation of arousing stimuli can activate subcortical brain regions independently of consciousness-generating top-down cortical modulation loops. Delineating these processes may elucidate mechanisms for arousal, aberration in which may underlie some psychiatric conditions. Here we are the first to review and discuss four Activation Likelihood Estimation (ALE) meta-analyses of fMRI studies using subliminal paradigms. We find a maximum of 9 out of 12 studies using subliminal presentation of faces contributing to activation of the amygdala, and also a significantly high number of studies reporting activation in the bilateral anterior cingulate, bilateral insular cortex, hippocampus and primary visual cortex. Subliminal faces are the strongest modality, whereas lexical stimuli are the weakest. Meta-analyses independent of studies using Regions of Interest (ROI) revealed no biasing effect. Core neuronal arousal in the brain, which may be at first independent of conscious processing, potentially involves a network incorporating primary visual areas, somatosensory, implicit memory and conflict monitoring regions. These data could provide candidate brain regions for the study of psychiatric disorders associated with aberrant automatic emotional processing. Copyright © 2011 Elsevier Inc. All rights reserved.

Neural Networks Involved in Adolescent Reward Processing: An Activation Likelihood Estimation Meta-Analysis of Functional Neuroimaging Studies

PubMed Central

Silverman, Merav H.; Jedd, Kelly; Luciana, Monica

2015-01-01

Behavioral responses to, and the neural processing of, rewards change dramatically during adolescence and may contribute to observed increases in risk-taking during this developmental period. Functional MRI (fMRI) studies suggest differences between adolescents and adults in neural activation during reward processing, but findings are contradictory, and effects have been found in non-predicted directions. The current study uses an activation likelihood estimation (ALE) approach for quantitative meta-analysis of functional neuroimaging studies to: 1) confirm the network of brain regions involved in adolescents’ reward processing, 2) identify regions involved in specific stages (anticipation, outcome) and valence (positive, negative) of reward processing, and 3) identify differences in activation likelihood between adolescent and adult reward-related brain activation. Results reveal a subcortical network of brain regions involved in adolescent reward processing similar to that found in adults with major hubs including the ventral and dorsal striatum, insula, and posterior cingulate cortex (PCC). Contrast analyses find that adolescents exhibit greater likelihood of activation in the insula while processing anticipation relative to outcome and greater likelihood of activation in the putamen and amygdala during outcome relative to anticipation. While processing positive compared to negative valence, adolescents show increased likelihood for activation in the posterior cingulate cortex (PCC) and ventral striatum. Contrasting adolescent reward processing with the existing ALE of adult reward processing (Liu et al., 2011) reveals increased likelihood for activation in limbic, frontolimbic, and striatal regions in adolescents compared with adults. Unlike adolescents, adults also activate executive control regions of the frontal and parietal lobes. These findings support hypothesized elevations in motivated activity during adolescence. PMID:26254587

Event-related fMRI studies of episodic encoding and retrieval: meta-analyses using activation likelihood estimation.

PubMed

Spaniol, Julia; Davidson, Patrick S R; Kim, Alice S N; Han, Hua; Moscovitch, Morris; Grady, Cheryl L

2009-07-01

The recent surge in event-related fMRI studies of episodic memory has generated a wealth of information about the neural correlates of encoding and retrieval processes. However, interpretation of individual studies is hampered by methodological differences, and by the fact that sample sizes are typically small. We submitted results from studies of episodic memory in healthy young adults, published between 1998 and 2007, to a voxel-wise quantitative meta-analysis using activation likelihood estimation [Laird, A. R., McMillan, K. M., Lancaster, J. L., Kochunov, P., Turkeltaub, P. E., & Pardo, J. V., et al. (2005). A comparison of label-based review and ALE meta-analysis in the stroop task. Human Brain Mapping, 25, 6-21]. We conducted separate meta-analyses for four contrasts of interest: episodic encoding success as measured in the subsequent-memory paradigm (subsequent Hit vs. Miss), episodic retrieval success (Hit vs. Correct Rejection), objective recollection (e.g., Source Hit vs. Item Hit), and subjective recollection (e.g., Remember vs. Know). Concordance maps revealed significant cross-study overlap for each contrast. In each case, the left hemisphere showed greater concordance than the right hemisphere. Both encoding and retrieval success were associated with activation in medial-temporal, prefrontal, and parietal regions. Left ventrolateral prefrontal cortex (PFC) and medial-temporal regions were more strongly involved in encoding, whereas left superior parietal and dorsolateral and anterior PFC regions were more strongly involved in retrieval. Objective recollection was associated with activation in multiple PFC regions, as well as multiple posterior parietal and medial-temporal areas, but not hippocampus. Subjective recollection, in contrast, showed left hippocampal involvement. In summary, these results identify broadly consistent activation patterns associated with episodic encoding and retrieval, and subjective and objective recollection, but also subtle differences among these processes.

Voxel-Based Morphometry ALE meta-analysis of Bipolar Disorder

NASA Astrophysics Data System (ADS)

Magana, Omar; Laird, Robert

2012-03-01

A meta-analysis was performed independently to view the changes in gray matter (GM) on patients with Bipolar disorder (BP). The meta-analysis was conducted on a Talairach Space using GingerALE to determine the voxels and their permutation. In order to achieve the data acquisition, published experiments and similar research studies were uploaded onto the online Voxel-Based Morphometry database (VBM). By doing so, coordinates of activation locations were extracted from Bipolar disorder related journals utilizing Sleuth. Once the coordinates of given experiments were selected and imported to GingerALE, a Gaussian was performed on all foci points to create the concentration points of GM on BP patients. The results included volume reductions and variations of GM between Normal Healthy controls and Patients with Bipolar disorder. A significant amount of GM clusters were obtained in Normal Healthy controls over BP patients on the right precentral gyrus, right anterior cingulate, and the left inferior frontal gyrus. In future research, more published journals could be uploaded onto the database and another VBM meta-analysis could be performed including more activation coordinates or a variation of age groups.

Task modulated brain connectivity of the amygdala: a meta-analysis of psychophysiological interactions.

PubMed

Di, Xin; Huang, Jia; Biswal, Bharat B

2017-01-01

Understanding functional connectivity of the amygdala with other brain regions, especially task modulated connectivity, is a critical step toward understanding the role of the amygdala in emotional processes and the interactions between emotion and cognition. The present study performed coordinate-based meta-analysis on studies of task modulated connectivity of the amygdala which used psychophysiological interaction (PPI) analysis. We first analyzed 49 PPI studies on different types of tasks using activation likelihood estimation (ALE) meta-analysis. Widespread cortical and subcortical regions showed consistent task modulated connectivity with the amygdala, including the medial frontal cortex, bilateral insula, anterior cingulate, fusiform gyrus, parahippocampal gyrus, thalamus, and basal ganglia. These regions were in general overlapped with those showed coactivations with the amygdala, suggesting that these regions and amygdala are not only activated together, but also show different levels of interactions during tasks. Further analyses with subsets of PPI studies revealed task specific functional connectivities with the amygdala that were modulated by fear processing, face processing, and emotion regulation. These results suggest a dynamic modulation of connectivity upon task demands, and provide new insights on the functions of the amygdala in different affective and cognitive processes. The meta-analytic approach on PPI studies may offer a framework toward systematical examinations of task modulated connectivity.

Introspective Minds: Using ALE Meta-Analyses to Study Commonalities in the Neural Correlates of Emotional Processing, Social & Unconstrained Cognition

PubMed Central

Schilbach, Leonhard; Bzdok, Danilo; Timmermans, Bert; Fox, Peter T.; Laird, Angela R.; Vogeley, Kai; Eickhoff, Simon B.

2012-01-01

Previous research suggests overlap between brain regions that show task-induced deactivations and those activated during the performance of social-cognitive tasks. Here, we present results of quantitative meta-analyses of neuroimaging studies, which confirm a statistical convergence in the neural correlates of social and resting state cognition. Based on the idea that both social and unconstrained cognition might be characterized by introspective processes, which are also thought to be highly relevant for emotional experiences, a third meta-analysis was performed investigating studies on emotional processing. By using conjunction analyses across all three sets of studies, we can demonstrate significant overlap of task-related signal change in dorso-medial prefrontal and medial parietal cortex, brain regions that have, indeed, recently been linked to introspective abilities. Our findings, therefore, provide evidence for the existence of a core neural network, which shows task-related signal change during socio-emotional tasks and during resting states. PMID:22319593

The first taste is always with the eyes: a meta-analysis on the neural correlates of processing visual food cues.

PubMed

van der Laan, L N; de Ridder, D T D; Viergever, M A; Smeets, P A M

2011-03-01

Food selection is primarily guided by the visual system. Multiple functional neuro-imaging studies have examined the brain responses to visual food stimuli. However, the results of these studies are heterogeneous and there still is uncertainty about the core brain regions involved in the neural processing of viewing food pictures. The aims of the present study were to determine the concurrence in the brain regions activated in response to viewing pictures of food and to assess the modulating effects of hunger state and the food's energy content. We performed three Activation Likelihood Estimation (ALE) meta-analyses on data from healthy normal weight subjects in which we examined: 1) the contrast between viewing food and nonfood pictures (17 studies, 189 foci), 2) the modulation by hunger state (five studies, 48 foci) and 3) the modulation by energy content (seven studies, 86 foci). The most concurrent brain regions activated in response to viewing food pictures, both in terms of ALE values and the number of contributing experiments, were the bilateral posterior fusiform gyrus, the left lateral orbitofrontal cortex (OFC) and the left middle insula. Hunger modulated the response to food pictures in the right amygdala and left lateral OFC, and energy content modulated the response in the hypothalamus/ventral striatum. Overall, the concurrence between studies was moderate: at best 41% of the experiments contributed to the clusters for the contrast between food and nonfood. Therefore, future research should further elucidate the separate effects of methodological and physiological factors on between-study variations. Copyright © 2010 Elsevier Inc. All rights reserved.

Is there a neuroanatomical basis of the vulnerability to suicidal behavior? A coordinate-based meta-analysis of structural and functional MRI studies

PubMed Central

van Heeringen, Kees; Bijttebier, Stijn; Desmyter, Stefanie; Vervaet, Myriam; Baeken, Chris

2014-01-01

Objective: We conducted meta-analyses of functional and structural neuroimaging studies comparing adolescent and adult individuals with a history of suicidal behavior and a psychiatric disorder to psychiatric controls in order to objectify changes in brain structure and function in association with a vulnerability to suicidal behavior. Methods: Magnetic resonance imaging studies published up to July 2013 investigating structural or functional brain correlates of suicidal behavior were identified through computerized and manual literature searches. Activation foci from 12 studies encompassing 475 individuals, i.e., 213 suicide attempters and 262 psychiatric controls were subjected to meta-analytical study using anatomic or activation likelihood estimation (ALE). Result: Activation likelihood estimation revealed structural deficits and functional changes in association with a history of suicidal behavior. Structural findings included reduced volumes of the rectal gyrus, superior temporal gyrus and caudate nucleus. Functional differences between study groups included an increased reactivity of the anterior and posterior cingulate cortices. Discussion: A history of suicidal behavior appears to be associated with (probably interrelated) structural deficits and functional overactivation in brain areas, which contribute to a decision-making network. The findings suggest that a vulnerability to suicidal behavior can be defined in terms of a reduced motivational control over the intentional behavioral reaction to salient negative stimuli. PMID:25374525

White matter and schizophrenia: A meta-analysis of voxel-based morphometry and diffusion tensor imaging studies.

PubMed

Vitolo, Enrico; Tatu, Mona Karina; Pignolo, Claudia; Cauda, Franco; Costa, Tommaso; Ando', Agata; Zennaro, Alessandro

2017-12-30

Voxel-based morphometry (VBM) and diffusion tensor imaging (DTI) are the most implemented methodologies to detect alterations of both gray and white matter (WM). However, the role of WM in mental disorders is still not well defined. We aimed at clarifying the role of WM disruption in schizophrenia and at identifying the most frequently involved brain networks. A systematic literature search was conducted to identify VBM and DTI studies focusing on WM alterations in patients with schizophrenia compared to control subjects. We selected studies reporting the coordinates of WM reductions and we performed the anatomical likelihood estimation (ALE). Moreover, we labeled the WM bundles with an anatomical atlas and compared VBM and DTI ALE-scores of each significant WM tract. A total of 59 studies were eligible for the meta-analysis. WM alterations were reported in 31 and 34 foci with VBM and DTI methods, respectively. The most occurred WM bundles in both VBM and DTI studies and largely involved in schizophrenia were long projection fibers, callosal and commissural fibers, part of motor descending fibers, and fronto-temporal-limbic pathways. The meta-analysis showed a widespread WM disruption in schizophrenia involving specific cerebral circuits instead of well-defined regions. Copyright © 2017 Elsevier B.V. All rights reserved.

Common and distinct networks underlying reward valence and processing stages: A meta-analysis of functional neuroimaging studies

PubMed Central

Liu, Xun; Hairston, Jacqueline; Schrier, Madeleine; Fan, Jin

2011-01-01

To better understand the reward circuitry in human brain, we conducted activation likelihood estimation (ALE) and parametric voxel-based meta-analyses (PVM) on 142 neuroimaging studies that examined brain activation in reward-related tasks in healthy adults. We observed several core brain areas that participated in reward-related decision making, including the nucleus accumbens (NAcc), caudate, putamen, thalamus, orbitofrontal cortex (OFC), bilateral anterior insula, anterior (ACC) and posterior (PCC) cingulate cortex, as well as cognitive control regions in the inferior parietal lobule and prefrontal cortex (PFC). The NAcc was commonly activated by both positive and negative rewards across various stages of reward processing (e.g., anticipation, outcome, and evaluation). In addition, the medial OFC and PCC preferentially responded to positive rewards, whereas the ACC, bilateral anterior insula, and lateral PFC selectively responded to negative rewards. Reward anticipation activated the ACC, bilateral anterior insula, and brain stem, whereas reward outcome more significantly activated the NAcc, medial OFC, and amygdala. Neurobiological theories of reward-related decision making should therefore distributed and interrelated representations of reward valuation and valence assessment into account. PMID:21185861

How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies.

PubMed

Ma, Ning; Dinges, David F; Basner, Mathias; Rao, Hengyi

2015-02-01

Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. © 2015 Associated Professional Sleep Societies, LLC.

How Acute Total Sleep Loss Affects the Attending Brain: A Meta-Analysis of Neuroimaging Studies

PubMed Central

Ma, Ning; Dinges, David F.; Basner, Mathias; Rao, Hengyi

2015-01-01

Study Objectives: Attention is a cognitive domain that can be severely affected by sleep deprivation. Previous neuroimaging studies have used different attention paradigms and reported both increased and reduced brain activation after sleep deprivation. However, due to large variability in sleep deprivation protocols, task paradigms, experimental designs, characteristics of subject populations, and imaging techniques, there is no consensus regarding the effects of sleep loss on the attending brain. The aim of this meta-analysis was to identify brain activations that are commonly altered by acute total sleep deprivation across different attention tasks. Design: Coordinate-based meta-analysis of neuroimaging studies of performance on attention tasks during experimental sleep deprivation. Methods: The current version of the activation likelihood estimation (ALE) approach was used for meta-analysis. The authors searched published articles and identified 11 sleep deprivation neuroimaging studies using different attention tasks with a total of 185 participants, equaling 81 foci for ALE analysis. Results: The meta-analysis revealed significantly reduced brain activation in multiple regions following sleep deprivation compared to rested wakefulness, including bilateral intraparietal sulcus, bilateral insula, right prefrontal cortex, medial frontal cortex, and right parahippocampal gyrus. Increased activation was found only in bilateral thalamus after sleep deprivation compared to rested wakefulness. Conclusion: Acute total sleep deprivation decreases brain activation in the fronto-parietal attention network (prefrontal cortex and intraparietal sulcus) and in the salience network (insula and medial frontal cortex). Increased thalamic activation after sleep deprivation may reflect a complex interaction between the de-arousing effects of sleep loss and the arousing effects of task performance on thalamic activity. Citation: Ma N, Dinges DF, Basner M, Rao H. How acute total sleep loss affects the attending brain: a meta-analysis of neuroimaging studies. SLEEP 2015;38(2):233–240. PMID:25409102

Neuroanatomical and neurofunctional markers of social cognition in autism spectrum disorder.

PubMed

Patriquin, Michelle A; DeRamus, Thomas; Libero, Lauren E; Laird, Angela; Kana, Rajesh K

2016-11-01

Social impairments in autism spectrum disorder (ASD), a hallmark feature of its diagnosis, may underlie specific neural signatures that can aid in differentiating between those with and without ASD. To assess common and consistent patterns of differences in brain responses underlying social cognition in ASD, this study applied an activation likelihood estimation (ALE) meta-analysis to results from 50 neuroimaging studies of social cognition in children and adults with ASD. In addition, the group ALE clusters of activation obtained from this was used as a social brain mask to perform surface-based cortical morphometry (SBM) in an empirical structural MRI dataset collected from 55 ASD and 60 typically developing (TD) control participants. Overall, the ALE meta-analysis revealed consistent differences in activation in the posterior superior temporal sulcus at the temporoparietal junction, middle frontal gyrus, fusiform face area (FFA), inferior frontal gyrus (IFG), amygdala, insula, and cingulate cortex between ASD and TD individuals. SBM analysis showed alterations in the thickness, volume, and surface area in individuals with ASD in STS, insula, and FFA. Increased cortical thickness was found in individuals with ASD, the IFG. The results of this study provide functional and anatomical bases of social cognition abnormalities in ASD by identifying common signatures from a large pool of neuroimaging studies. These findings provide new insights into the quest for a neuroimaging-based marker for ASD. Hum Brain Mapp 37:3957-3978, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A quantitative meta-analysis and review of motor learning in the human brain

PubMed Central

Hardwick, Robert M.; Rottschy, Claudia; Miall, R. Chris; Eickhoff, Simon B.

2013-01-01

Neuroimaging studies have improved our understanding of which brain structures are involved in motor learning. Despite this, questions remain regarding the areas that contribute consistently across paradigms with different task demands. For instance, sensorimotor tasks focus on learning novel movement kinematics and dynamics, while serial response time task (SRTT) variants focus on sequence learning. These differing task demands are likely to elicit quantifiably different patterns of neural activity on top of a potentially consistent core network. The current study identified consistent activations across 70 motor learning experiments using activation likelihood estimation (ALE) meta-analysis. A global analysis of all tasks revealed a bilateral cortical–subcortical network consistently underlying motor learning across tasks. Converging activations were revealed in the dorsal premotor cortex, supplementary motor cortex, primary motor cortex, primary somatosensory cortex, superior parietal lobule, thalamus, putamen and cerebellum. These activations were broadly consistent across task specific analyses that separated sensorimotor tasks and SRTT variants. Contrast analysis indicated that activity in the basal ganglia and cerebellum was significantly stronger for sensorimotor tasks, while activity in cortical structures and the thalamus was significantly stronger for SRTT variants. Additional conjunction analyses then indicated that the left dorsal premotor cortex was activated across all analyses considered, even when controlling for potential motor confounds. The highly consistent activation of the left dorsal premotor cortex suggests it is a critical node in the motor learning network. PMID:23194819

What you see is what you eat: an ALE meta-analysis of the neural correlates of food viewing in children and adolescents.

PubMed

van Meer, Floor; van der Laan, Laura N; Adan, Roger A H; Viergever, Max A; Smeets, Paul A M

2015-01-01

Food cues are omnipresent and may enhance overconsumption. In the last two decades the prevalence of childhood obesity has increased dramatically all over the world, largely due to overconsumption. Understanding children's neural responses to food may help to develop better interventions for preventing or reducing overconsumption. We aimed to determine which brain regions are concurrently activated in children/adolescents in response to viewing food pictures, and how these relate to adult findings. Two activation likelihood estimation (ALE) meta-analyses were performed: one with studies in normal weight children/adolescents (aged 8-18, 8 studies, 137 foci) and one with studies in normal weight adults (aged 18-45, 16 studies, 178 foci). A contrast analysis was performed for children/adolescents vs. adults. In children/adolescents, the most concurrent clusters were in the left lateral orbitofrontal cortex (OFC), the bilateral fusiform gyrus, and the right superior parietal lobule. In adults, clusters in similar areas were found. Although the number of studies for a direct statistical comparison between the groups was relatively low, there were indications that children/adolescents may not activate areas important for cognitive control. Overall, the number of studies that contributed to the significant clusters was moderate (6-75%). In summary, the brain areas most consistently activated in children/adolescents by food viewing are part of the appetitive brain network and overlap with those found in adults. However, the age range of the children studied was rather broad. This study offers important recommendations for future research; studies making a direct comparison between adults and children in a sufficiently narrow age range would further elucidate how neural responses to food cues change during development. Copyright © 2014 Elsevier Inc. All rights reserved.

Identifying environmental sounds: a multimodal mapping study

PubMed Central

Tomasino, Barbara; Canderan, Cinzia; Marin, Dario; Maieron, Marta; Gremese, Michele; D'Agostini, Serena; Fabbro, Franco; Skrap, Miran

2015-01-01

Our environment is full of auditory events such as warnings or hazards, and their correct recognition is essential. We explored environmental sounds (ES) recognition in a series of studies. In study 1 we performed an Activation Likelihood Estimation (ALE) meta-analysis of neuroimaging experiments addressing ES processing to delineate the network of areas consistently involved in ES processing. Areas consistently activated in the ALE meta-analysis were the STG/MTG, insula/rolandic operculum, parahippocampal gyrus and inferior frontal gyrus bilaterally. Some of these areas truly reflect ES processing, whereas others are related to design choices, e.g., type of task, type of control condition, type of stimulus. In study 2 we report on 7 neurosurgical patients with lesions involving the areas which were found to be activated by the ALE meta-analysis. We tested their ES recognition abilities and found an impairment of ES recognition. These results indicate that deficits of ES recognition do not exclusively reflect lesions to the right or to the left hemisphere but both hemispheres are involved. The most frequently lesioned area is the hippocampus/insula/STG. We made sure that any impairment in ES recognition would not be related to language problems, but reflect impaired ES processing. In study 3 we carried out an fMRI study on patients (vs. healthy controls) to investigate how the areas involved in ES might be functionally deregulated because of a lesion. The fMRI evidenced that controls activated the right IFG, the STG bilaterally and the left insula. We applied a multimodal mapping approach and found that, although the meta-analysis showed that part of the left and right STG/MTG activation during ES processing might in part be related to design choices, this area was one of the most frequently lesioned areas in our patients, thus highlighting its causal role in ES processing. We found that the ROIs we drew on the two clusters of activation found in the left and in the right STG overlapped with the lesions of at least 4 out of the 7 patients' lesions, indicating that the lack of STG activation found for patients is related to brain damage and is crucial for explaining the ES deficit. PMID:26539096

Grey matter alterations in migraine: A systematic review and meta-analysis.

PubMed

Jia, Zhihua; Yu, Shengyuan

2017-01-01

To summarize and meta-analyze studies on changes in grey matter (GM) in patients with migraine. We aimed to determine whether there are concordant structural changes in the foci, whether structural changes are concordant with functional changes, and provide further understanding of the anatomy and biology of migraine. We searched PubMed and Embase for relevant articles published between January 1985 and November 2015, and examined the references within relevant primary articles. Following exclusion of unsuitable studies, meta-analysis were performed using activation likelihood estimation (ALE). Eight clinical studies were analyzed for structural changes, containing a total of 390 subjects (191 patients and 199 controls). Five functional studies were enrolled, containing 93 patients and 96 controls. ALE showed that the migraineurs had concordant decreases in the GM volume (GMV) in the bilateral inferior frontal gyri, the right precentral gyrus, the left middle frontal gyrus and the left cingulate gyrus. GMV decreases in right claustrum, left cingulated gyrus, right anterior cingulate, amygdala and left parahippocampal gyrus are related to estimated frequency of headache attack . Activation was found in the somatosensory, cingulate, limbic lobe, basal ganglia and midbrain in migraine patients. GM changes in migraineurs may indicate the mechanism of pain processing and associated symptoms. Changes in the frontal gyrus may predispose a person to pain conditions. The limbic regions may be accumulated damage due to the repetitive occurrence of pain-related processes. Increased activation in precentral gyrus and cingulate opposed to GMV decrease might suggest increased effort duo to disorganization of these areas and/or the use of compensatory strategies involving pain processing in migraine. Knowledge of these structural and functional changes may be useful for monitoring disease progression as well as for therapeutic interventions.

Decoding fMRI events in sensorimotor motor network using sparse paradigm free mapping and activation likelihood estimates.

PubMed

Tan, Francisca M; Caballero-Gaudes, César; Mullinger, Karen J; Cho, Siu-Yeung; Zhang, Yaping; Dryden, Ian L; Francis, Susan T; Gowland, Penny A

2017-11-01

Most functional MRI (fMRI) studies map task-driven brain activity using a block or event-related paradigm. Sparse paradigm free mapping (SPFM) can detect the onset and spatial distribution of BOLD events in the brain without prior timing information, but relating the detected events to brain function remains a challenge. In this study, we developed a decoding method for SPFM using a coordinate-based meta-analysis method of activation likelihood estimation (ALE). We defined meta-maps of statistically significant ALE values that correspond to types of events and calculated a summation overlap between the normalized meta-maps and SPFM maps. As a proof of concept, this framework was applied to relate SPFM-detected events in the sensorimotor network (SMN) to six motor functions (left/right fingers, left/right toes, swallowing, and eye blinks). We validated the framework using simultaneous electromyography (EMG)-fMRI experiments and motor tasks with short and long duration, and random interstimulus interval. The decoding scores were considerably lower for eye movements relative to other movement types tested. The average successful rate for short and long motor events were 77 ± 13% and 74 ± 16%, respectively, excluding eye movements. We found good agreement between the decoding results and EMG for most events and subjects, with a range in sensitivity between 55% and 100%, excluding eye movements. The proposed method was then used to classify the movement types of spontaneous single-trial events in the SMN during resting state, which produced an average successful rate of 22 ± 12%. Finally, this article discusses methodological implications and improvements to increase the decoding performance. Hum Brain Mapp 38:5778-5794, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Decoding fMRI events in Sensorimotor Motor Network using Sparse Paradigm Free Mapping and Activation Likelihood Estimates

PubMed Central

Tan, Francisca M.; Caballero-Gaudes, César; Mullinger, Karen J.; Cho, Siu-Yeung; Zhang, Yaping; Dryden, Ian L.; Francis, Susan T.; Gowland, Penny A.

2017-01-01

Most fMRI studies map task-driven brain activity using a block or event-related paradigm. Sparse Paradigm Free Mapping (SPFM) can detect the onset and spatial distribution of BOLD events in the brain without prior timing information; but relating the detected events to brain function remains a challenge. In this study, we developed a decoding method for SPFM using a coordinate-based meta-analysis method of Activation Likelihood Estimation (ALE). We defined meta-maps of statistically significant ALE values that correspond to types of events and calculated a summation overlap between the normalized meta-maps and SPFM maps. As a proof of concept, this framework was applied to relate SPFM-detected events in the Sensorimotor Network (SMN) to six motor function (left/right fingers, left/right toes, swallowing and eye blinks). We validated the framework using simultaneous Electromyography-fMRI experiments and motor tasks with short and long duration, and random inter-stimulus interval. The decoding scores were considerably lower for eye movements relative to other movement types tested. The average successful rate for short and long motor events was 77 ± 13% and 74 ± 16% respectively, excluding eye movements. We found good agreement between the decoding results and EMG for most events and subjects, with a range in sensitivity between 55 and 100%, excluding eye movements. The proposed method was then used to classify the movement types of spontaneous single-trial events in the SMN during resting state, which produced an average successful rate of 22 ± 12%. Finally, this paper discusses methodological implications and improvements to increase the decoding performance. PMID:28815863

The neuroplastic effect of working memory training in healthy volunteers and patients with schizophrenia: Implications for cognitive rehabilitation.

PubMed

Li, Xu; Xiao, Ya-hui; Zhao, Qing; Leung, Ada W W; Cheung, Eric F C; Chan, Raymond C K

2015-08-01

We conducted an activation likelihood estimation (ALE) meta-analysis to quantitatively review the existing working memory (WM) training studies that investigated neural activation changes both in healthy individuals and patients with schizophrenia. ALE analysis of studies in healthy individuals indicates a widespread distribution of activation changes with WM training in the frontal and parietal regions, especially the dorsolateral prefrontal cortex, the medial frontal cortex and the precuneus, as well as subcortical regions such as the insula and the striatum. WM training is also accompanied by activation changes in patients with schizophrenia, mainly in the dorsolateral prefrontal cortex, the precuneus and the fusiform gyrus. Our results demonstrate that WM training is accompanied by changes in neural activation patterns in healthy individuals, which may provide the basis for understanding neuroplastic changes in patients with schizophrenia. Copyright © 2015 Elsevier Ltd. All rights reserved.

Perception of affective and linguistic prosody: an ALE meta-analysis of neuroimaging studies

PubMed Central

Brown, Steven

2014-01-01

Prosody refers to the melodic and rhythmic aspects of speech. Two forms of prosody are typically distinguished: ‘affective prosody’ refers to the expression of emotion in speech, whereas ‘linguistic prosody’ relates to the intonation of sentences, including the specification of focus within sentences and stress within polysyllabic words. While these two processes are united by their use of vocal pitch modulation, they are functionally distinct. In order to examine the localization and lateralization of speech prosody in the brain, we performed two voxel-based meta-analyses of neuroimaging studies of the perception of affective and linguistic prosody. There was substantial sharing of brain activations between analyses, particularly in right-hemisphere auditory areas. However, a major point of divergence was observed in the inferior frontal gyrus: affective prosody was more likely to activate Brodmann area 47, while linguistic prosody was more likely to activate the ventral part of area 44. PMID:23934416

ALE meta-analysis on facial judgments of trustworthiness and attractiveness.

PubMed

Bzdok, D; Langner, R; Caspers, S; Kurth, F; Habel, U; Zilles, K; Laird, A; Eickhoff, Simon B

2011-01-01

Faces convey a multitude of information in social interaction, among which are trustworthiness and attractiveness. Humans process and evaluate these two dimensions very quickly due to their great adaptive importance. Trustworthiness evaluation is crucial for modulating behavior toward strangers; attractiveness evaluation is a crucial factor for mate selection, possibly providing cues for reproductive success. As both dimensions rapidly guide social behavior, this study tests the hypothesis that both judgments may be subserved by overlapping brain networks. To this end, we conducted an activation likelihood estimation meta-analysis on 16 functional magnetic resonance imaging studies pertaining to facial judgments of trustworthiness and attractiveness. Throughout combined, individual, and conjunction analyses on those two facial judgments, we observed consistent maxima in the amygdala which corroborates our initial hypothesis. This finding supports the contemporary paradigm shift extending the amygdala's role from dominantly processing negative emotional stimuli to processing socially relevant ones. We speculate that the amygdala filters sensory information with evolutionarily conserved relevance. Our data suggest that such a role includes not only "fight-or-flight" decisions but also social behaviors with longer term pay-off schedules, e.g., trustworthiness and attractiveness evaluation. © Springer-Verlag 2010

Stuttering as a trait or state - an ALE meta-analysis of neuroimaging studies.

PubMed

Belyk, Michel; Kraft, Shelly Jo; Brown, Steven

2015-01-01

Stuttering is a speech disorder characterised by repetitions, prolongations and blocks that disrupt the forward movement of speech. An earlier meta-analysis of brain imaging studies of stuttering (Brown et al., 2005) revealed a general trend towards rightward lateralization of brain activations and hyperactivity in the larynx motor cortex bilaterally. The present study sought not only to update that meta-analysis with recent work but to introduce an important distinction not present in the first study, namely the difference between 'trait' and 'state' stuttering. The analysis of trait stuttering compares people who stutter (PWS) with people who do not stutter when behaviour is controlled for, i.e., when speech is fluent in both groups. In contrast, the analysis of state stuttering examines PWS during episodes of stuttered speech compared with episodes of fluent speech. Seventeen studies were analysed using activation likelihood estimation. Trait stuttering was characterised by the well-known rightward shift in lateralization for language and speech areas. State stuttering revealed a more diverse pattern. Abnormal activation of larynx and lip motor cortex was common to the two analyses. State stuttering was associated with overactivation in the right hemisphere larynx and lip motor cortex. Trait stuttering was associated with overactivation of lip motor cortex in the right hemisphere but underactivation of larynx motor cortex in the left hemisphere. These results support a large literature highlighting laryngeal and lip involvement in the symptomatology of stuttering, and disambiguate two possible sources of activation in neuroimaging studies of persistent developmental stuttering. © 2014 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Localising semantic and syntactic processing in spoken and written language comprehension: an Activation Likelihood Estimation meta-analysis.

PubMed

Rodd, Jennifer M; Vitello, Sylvia; Woollams, Anna M; Adank, Patti

2015-02-01

We conducted an Activation Likelihood Estimation (ALE) meta-analysis to identify brain regions that are recruited by linguistic stimuli requiring relatively demanding semantic or syntactic processing. We included 54 functional MRI studies that explicitly varied the semantic or syntactic processing load, while holding constant demands on earlier stages of processing. We included studies that introduced a syntactic/semantic ambiguity or anomaly, used a priming manipulation that specifically reduced the load on semantic/syntactic processing, or varied the level of syntactic complexity. The results confirmed the critical role of the posterior left Inferior Frontal Gyrus (LIFG) in semantic and syntactic processing. These results challenge models of sentence comprehension highlighting the role of anterior LIFG for semantic processing. In addition, the results emphasise the posterior (but not anterior) temporal lobe for both semantic and syntactic processing. Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.

A coordinate-based ALE functional MRI meta-analysis of brain activation during verbal fluency tasks in healthy control subjects

PubMed Central

2014-01-01

Background The processing of verbal fluency tasks relies on the coordinated activity of a number of brain areas, particularly in the frontal and temporal lobes of the left hemisphere. Recent studies using functional magnetic resonance imaging (fMRI) to study the neural networks subserving verbal fluency functions have yielded divergent results especially with respect to a parcellation of the inferior frontal gyrus for phonemic and semantic verbal fluency. We conducted a coordinate-based activation likelihood estimation (ALE) meta-analysis on brain activation during the processing of phonemic and semantic verbal fluency tasks involving 28 individual studies with 490 healthy volunteers. Results For phonemic as well as for semantic verbal fluency, the most prominent clusters of brain activation were found in the left inferior/middle frontal gyrus (LIFG/MIFG) and the anterior cingulate gyrus. BA 44 was only involved in the processing of phonemic verbal fluency tasks, BA 45 and 47 in the processing of phonemic and semantic fluency tasks. Conclusions Our comparison of brain activation during the execution of either phonemic or semantic verbal fluency tasks revealed evidence for spatially different activation in BA 44, but not other regions of the LIFG/LMFG (BA 9, 45, 47) during phonemic and semantic verbal fluency processing. PMID:24456150

The "handwriting brain": a meta-analysis of neuroimaging studies of motor versus orthographic processes.

PubMed

Planton, Samuel; Jucla, Mélanie; Roux, Franck-Emmanuel; Démonet, Jean-François

2013-01-01

Handwriting is a modality of language production whose cerebral substrates remain poorly known although the existence of specific regions is postulated. The description of brain damaged patients with agraphia and, more recently, several neuroimaging studies suggest the involvement of different brain regions. However, results vary with the methodological choices made and may not always discriminate between "writing-specific" and motor or linguistic processes shared with other abilities. We used the "Activation Likelihood Estimate" (ALE) meta-analytical method to identify the cerebral network of areas commonly activated during handwriting in 18 neuroimaging studies published in the literature. Included contrasts were also classified according to the control tasks used, whether non-specific motor/output-control or linguistic/input-control. These data were included in two secondary meta-analyses in order to reveal the functional role of the different areas of this network. An extensive, mainly left-hemisphere network of 12 cortical and sub-cortical areas was obtained; three of which were considered as primarily writing-specific (left superior frontal sulcus/middle frontal gyrus area, left intraparietal sulcus/superior parietal area, right cerebellum) while others related rather to non-specific motor (primary motor and sensorimotor cortex, supplementary motor area, thalamus and putamen) or linguistic processes (ventral premotor cortex, posterior/inferior temporal cortex). This meta-analysis provides a description of the cerebral network of handwriting as revealed by various types of neuroimaging experiments and confirms the crucial involvement of the left frontal and superior parietal regions. These findings provide new insights into cognitive processes involved in handwriting and their cerebral substrates. Copyright © 2013 Elsevier Ltd. All rights reserved.

Using coordinate-based meta-analyses to explore structural imaging genetics.

PubMed

Janouschek, Hildegard; Eickhoff, Claudia R; Mühleisen, Thomas W; Eickhoff, Simon B; Nickl-Jockschat, Thomas

2018-05-05

Imaging genetics has become a highly popular approach in the field of schizophrenia research. A frequently reported finding is that effects from common genetic variation are associated with a schizophrenia-related structural endophenotype. Genetic contributions to a structural endophenotype may be easier to delineate, when referring to biological rather than diagnostic criteria. We used coordinate-based meta-analyses, namely the anatomical likelihood estimation (ALE) algorithm on 30 schizophrenia-related imaging genetics studies, representing 44 single-nucleotide polymorphisms at 26 gene loci investigated in 4682 subjects. To test whether analyses based on biological information would improve the convergence of results, gene ontology (GO) terms were used to group the findings from the published studies. We did not find any significant results for the main contrast. However, our analysis enrolling studies on genotype × diagnosis interaction yielded two clusters in the left temporal lobe and the medial orbitofrontal cortex. All other subanalyses did not yield any significant results. To gain insight into possible biological relationships between the genes implicated by these clusters, we mapped five of them to GO terms of the category "biological process" (AKT1, CNNM2, DISC1, DTNBP1, VAV3), then five to "cellular component" terms (AKT1, CNNM2, DISC1, DTNBP1, VAV3), and three to "molecular function" terms (AKT1, VAV3, ZNF804A). A subsequent cluster analysis identified representative, non-redundant subsets of semantically similar terms that aided a further interpretation. We regard this approach as a new option to systematically explore the richness of the literature in imaging genetics.

Perception of affective and linguistic prosody: an ALE meta-analysis of neuroimaging studies.

PubMed

Belyk, Michel; Brown, Steven

2014-09-01

Prosody refers to the melodic and rhythmic aspects of speech. Two forms of prosody are typically distinguished: 'affective prosody' refers to the expression of emotion in speech, whereas 'linguistic prosody' relates to the intonation of sentences, including the specification of focus within sentences and stress within polysyllabic words. While these two processes are united by their use of vocal pitch modulation, they are functionally distinct. In order to examine the localization and lateralization of speech prosody in the brain, we performed two voxel-based meta-analyses of neuroimaging studies of the perception of affective and linguistic prosody. There was substantial sharing of brain activations between analyses, particularly in right-hemisphere auditory areas. However, a major point of divergence was observed in the inferior frontal gyrus: affective prosody was more likely to activate Brodmann area 47, while linguistic prosody was more likely to activate the ventral part of area 44. © The Author (2013). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

Speech perception in autism spectrum disorder: An activation likelihood estimation meta-analysis.

PubMed

Tryfon, Ana; Foster, Nicholas E V; Sharda, Megha; Hyde, Krista L

2018-02-15

Autism spectrum disorder (ASD) is often characterized by atypical language profiles and auditory and speech processing. These can contribute to aberrant language and social communication skills in ASD. The study of the neural basis of speech perception in ASD can serve as a potential neurobiological marker of ASD early on, but mixed results across studies renders it difficult to find a reliable neural characterization of speech processing in ASD. To this aim, the present study examined the functional neural basis of speech perception in ASD versus typical development (TD) using an activation likelihood estimation (ALE) meta-analysis of 18 qualifying studies. The present study included separate analyses for TD and ASD, which allowed us to examine patterns of within-group brain activation as well as both common and distinct patterns of brain activation across the ASD and TD groups. Overall, ASD and TD showed mostly common brain activation of speech processing in bilateral superior temporal gyrus (STG) and left inferior frontal gyrus (IFG). However, the results revealed trends for some distinct activation in the TD group showing additional activation in higher-order brain areas including left superior frontal gyrus (SFG), left medial frontal gyrus (MFG), and right IFG. These results provide a more reliable neural characterization of speech processing in ASD relative to previous single neuroimaging studies and motivate future work to investigate how these brain signatures relate to behavioral measures of speech processing in ASD. Copyright © 2017 Elsevier B.V. All rights reserved.

Connectivity and functional profiling of abnormal brain structures in pedophilia

PubMed Central

Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-01-01

Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

Connectivity and functional profiling of abnormal brain structures in pedophilia.

PubMed

Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

Rostral and caudal prefrontal contribution to creativity: a meta-analysis of functional imaging data

PubMed Central

Gonen-Yaacovi, Gil; de Souza, Leonardo Cruz; Levy, Richard; Urbanski, Marika; Josse, Goulven; Volle, Emmanuelle

2013-01-01

Creativity is of central importance for human civilization, yet its neurocognitive bases are poorly understood. The aim of the present study was to integrate existing functional imaging data by using the meta-analysis approach. We reviewed 34 functional imaging studies that reported activation foci during tasks assumed to engage creative thinking in healthy adults. A coordinate-based meta-analysis using Activation Likelihood Estimation (ALE) first showed a set of predominantly left-hemispheric regions shared by the various creativity tasks examined. These regions included the caudal lateral prefrontal cortex (PFC), the medial and lateral rostral PFC, and the inferior parietal and posterior temporal cortices. Further analyses showed that tasks involving the combination of remote information (combination tasks) activated more anterior areas of the lateral PFC than tasks involving the free generation of unusual responses (unusual generation tasks), although both types of tasks shared caudal prefrontal areas. In addition, verbal and non-verbal tasks involved the same regions in the left caudal prefrontal, temporal, and parietal areas, but also distinct domain-oriented areas. Taken together, these findings suggest that several frontal and parieto-temporal regions may support cognitive processes shared by diverse creativity tasks, and that some regions may be specialized for distinct types of processes. In particular, the lateral PFC appeared to be organized along a rostro-caudal axis, with rostral regions involved in combining ideas creatively and more posterior regions involved in freely generating novel ideas. PMID:23966927

Modeling motor connectivity using TMS/PET and structural equation modeling

PubMed Central

Laird, Angela R.; Robbins, Jacob M.; Li, Karl; Price, Larry R.; Cykowski, Matthew D.; Narayana, Shalini; Laird, Robert W.; Franklin, Crystal; Fox, Peter T.

2010-01-01

Structural equation modeling (SEM) was applied to positron emission tomographic (PET) images acquired during transcranial magnetic stimulation (TMS) of the primary motor cortex (M1hand). TMS was applied across a range of intensities, and responses both at the stimulation site and remotely connected brain regions covaried with stimulus intensity. Regions of interest (ROIs) were identified through an activation likelihood estimation (ALE) meta-analysis of TMS studies. That these ROIs represented the network engaged by motor planning and execution was confirmed by an ALE meta-analysis of finger movement studies. Rather than postulate connections in the form of an a priori model (confirmatory approach), effective connectivity models were developed using a model-generating strategy based on improving tentatively specified models. This strategy exploited the experimentally-imposed causal relations: (1) that response variations were caused by stimulation variations, (2) that stimulation was unidirectionally applied to the M1hand region, and (3) that remote effects must be caused, either directly or indirectly, by the M1hand excitation. The path model thus derived exhibited an exceptional level of goodness (χ2=22.150, df = 38, P = 0.981, TLI=1.0). The regions and connections derived were in good agreement with the known anatomy of the human and primate motor system. The model-generating SEM strategy thus proved highly effective and successfully identified a complex set of causal relationships of motor connectivity. PMID:18387823

Meta-epidemiologic study showed frequent time trends in summary estimates from meta-analyses of diagnostic accuracy studies.

PubMed

Cohen, Jérémie F; Korevaar, Daniël A; Wang, Junfeng; Leeflang, Mariska M; Bossuyt, Patrick M

2016-09-01

To evaluate changes over time in summary estimates from meta-analyses of diagnostic accuracy studies. We included 48 meta-analyses from 35 MEDLINE-indexed systematic reviews published between September 2011 and January 2012 (743 diagnostic accuracy studies; 344,015 participants). Within each meta-analysis, we ranked studies by publication date. We applied random-effects cumulative meta-analysis to follow how summary estimates of sensitivity and specificity evolved over time. Time trends were assessed by fitting a weighted linear regression model of the summary accuracy estimate against rank of publication. The median of the 48 slopes was -0.02 (-0.08 to 0.03) for sensitivity and -0.01 (-0.03 to 0.03) for specificity. Twelve of 96 (12.5%) time trends in sensitivity or specificity were statistically significant. We found a significant time trend in at least one accuracy measure for 11 of the 48 (23%) meta-analyses. Time trends in summary estimates are relatively frequent in meta-analyses of diagnostic accuracy studies. Results from early meta-analyses of diagnostic accuracy studies should be considered with caution. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of Estimates between Cohort and Case-Control Studies in Meta-Analyses of Therapeutic Interventions: A Meta-Epidemiological Study.

PubMed

Lanza, Amy; Ravaud, Philippe; Riveros, Carolina; Dechartres, Agnes

2016-01-01

Observational studies are increasingly being used for assessing therapeutic interventions. Case-control studies are generally considered to have greater risk of bias than cohort studies, but we lack evidence of differences in effect estimates between the 2 study types. We aimed to compare estimates between cohort and case-control studies in meta-analyses of observational studies of therapeutic interventions by using a meta-epidemiological study. We used a random sample of meta-analyses of therapeutic interventions published in 2013 that included both cohort and case-control studies assessing a binary outcome. For each meta-analysis, the ratio of estimates (RE) was calculated by comparing the estimate in case-control studies to that in cohort studies. Then, we used random-effects meta-analysis to estimate a combined RE across meta-analyses. An RE < 1 indicated that case-control studies yielded larger estimates than cohort studies. The final analysis included 23 meta-analyses: 138 cohort and 133 case-control studies. Treatment effect estimates did not significantly differ between case-control and cohort studies (combined RE 0.97 [95% CI 0.86-1.09]). Heterogeneity was low, with between-meta-analysis variance τ2 = 0.0049. Estimates did not differ between case-control and prospective or retrospective cohort studies (RE = 1.05 [95% CI 0.96-1.15] and RE = 0.99 [95% CI, 0.83-1.19], respectively). Sensitivity analysis of studies reporting adjusted estimates also revealed no significant difference (RE = 1.03 [95% CI 0.91-1.16]). Heterogeneity was also low for these analyses. We found no significant difference in treatment effect estimates between case-control and cohort studies assessing therapeutic interventions.

Comparison of variance estimators for meta-analysis of instrumental variable estimates

PubMed Central

Schmidt, AF; Hingorani, AD; Jefferis, BJ; White, J; Groenwold, RHH; Dudbridge, F

2016-01-01

Abstract Background: Mendelian randomization studies perform instrumental variable (IV) analysis using genetic IVs. Results of individual Mendelian randomization studies can be pooled through meta-analysis. We explored how different variance estimators influence the meta-analysed IV estimate. Methods: Two versions of the delta method (IV before or after pooling), four bootstrap estimators, a jack-knife estimator and a heteroscedasticity-consistent (HC) variance estimator were compared using simulation. Two types of meta-analyses were compared, a two-stage meta-analysis pooling results, and a one-stage meta-analysis pooling datasets. Results: Using a two-stage meta-analysis, coverage of the point estimate using bootstrapped estimators deviated from nominal levels at weak instrument settings and/or outcome probabilities ≤ 0.10. The jack-knife estimator was the least biased resampling method, the HC estimator often failed at outcome probabilities ≤ 0.50 and overall the delta method estimators were the least biased. In the presence of between-study heterogeneity, the delta method before meta-analysis performed best. Using a one-stage meta-analysis all methods performed equally well and better than two-stage meta-analysis of greater or equal size. Conclusions: In the presence of between-study heterogeneity, two-stage meta-analyses should preferentially use the delta method before meta-analysis. Weak instrument bias can be reduced by performing a one-stage meta-analysis. PMID:27591262

Implicit timing activates the left inferior parietal cortex.

PubMed

Wiener, Martin; Turkeltaub, Peter E; Coslett, H Branch

2010-11-01

Coull and Nobre (2008) suggested that tasks that employ temporal cues might be divided on the basis of whether these cues are explicitly or implicitly processed. Furthermore, they suggested that implicit timing preferentially engages the left cerebral hemisphere. We tested this hypothesis by conducting a quantitative meta-analysis of eleven neuroimaging studies of implicit timing using the activation-likelihood estimation (ALE) algorithm (Turkeltaub, Eden, Jones, & Zeffiro, 2002). Our analysis revealed a single but robust cluster of activation-likelihood in the left inferior parietal cortex (supramarginal gyrus). This result is in accord with the hypothesis that the left hemisphere subserves implicit timing mechanisms. Furthermore, in conjunction with a previously reported meta-analysis of explicit timing tasks, our data support the claim that implicit and explicit timing are supported by at least partially distinct neural structures. Copyright © 2010 Elsevier Ltd. All rights reserved.

The Role of the Amygdala in Facial Trustworthiness Processing: A Systematic Review and Meta-Analyses of fMRI Studies.

PubMed

Santos, Sara; Almeida, Inês; Oliveiros, Bárbara; Castelo-Branco, Miguel

2016-01-01

Faces play a key role in signaling social cues such as signals of trustworthiness. Although several studies identify the amygdala as a core brain region in social cognition, quantitative approaches evaluating its role are scarce. This review aimed to assess the role of the amygdala in the processing of facial trustworthiness, by analyzing its amplitude BOLD response polarity to untrustworthy versus trustworthy facial signals under fMRI tasks through a Meta-analysis of effect sizes (MA). Activation Likelihood Estimation (ALE) analyses were also conducted. Articles were retrieved from MEDLINE, ScienceDirect and Web-of-Science in January 2016. Following the PRISMA statement guidelines, a systematic review of original research articles in English language using the search string "(face OR facial) AND (trustworthiness OR trustworthy OR untrustworthy OR trustee) AND fMRI" was conducted. The MA concerned amygdala responses to facial trustworthiness for the contrast Untrustworthy vs. trustworthy faces, and included whole-brain and ROI studies. To prevent potential bias, results were considered even when at the single study level they did not survive correction for multiple comparisons or provided non-significant results. ALE considered whole-brain studies, using the same methodology to prevent bias. A summary of the methodological options (design and analysis) described in the articles was finally used to get further insight into the characteristics of the studies and to perform a subgroup analysis. Data were extracted by two authors and checked independently. Twenty fMRI studies were considered for systematic review. An MA of effect sizes with 11 articles (12 studies) showed high heterogeneity between studies [Q(11) = 265.68, p < .0001; I2 = 95.86%, 94.20% to 97.05%, with 95% confidence interval, CI]. Random effects analysis [RE(183) = 0.851, .422 to .969, 95% CI] supported the evidence that the (right) amygdala responds preferentially to untrustworthy faces. Moreover, two ALE analyses performed with 6 articles (7 studies) identified the amygdala, insula and medial dorsal nuclei of thalamus as structures with negative correlation with trustworthiness. Six articles/studies showed that posterior cingulate and medial frontal gyrus present positive correlations with increasing facial trustworthiness levels. Significant effects considering subgroup analysis based on methodological criteria were found for experiments using spatial smoothing, categorization of trustworthiness in 2 or 3 categories and paradigms which involve both explicit and implicit tasks. Significant heterogeneity between studies was found in MA, which might have arisen from inclusion of studies with smaller sample sizes and differences in methodological options. Studies using ROI analysis / small volume correction methods were more often devoted specifically to the amygdala region, with some results reporting uncorrected p-values based on mainly clinical a priori evidence of amygdala involvement in these processes. Nevertheless, we did not find significant evidence for publication bias. Our results support the role of amygdala in facial trustworthiness judgment, emphasizing its predominant role during processing of negative social signals in (untrustworthy) faces. This systematic review suggests that little consistency exists among studies' methodology, and that larger sample sizes should be preferred.

Dissociations of cognitive inhibition, response inhibition, and emotional interference: Voxelwise ALE meta-analyses of fMRI studies.

PubMed

Hung, Yuwen; Gaillard, Schuyler L; Yarmak, Pavel; Arsalidou, Marie

2018-06-19

Inhibitory control is the stopping of a mental process with or without intention, conceptualized as mental suppression of competing information because of limited cognitive capacity. Inhibitory control dysfunction is a core characteristic of many major psychiatric disorders. Inhibition is generally thought to involve the prefrontal cortex; however, a single inhibitory mechanism is insufficient for interpreting the heterogeneous nature of human cognition. It remains unclear whether different dimensions of inhibitory processes-specifically cognitive inhibition, response inhibition, and emotional interference-rely on dissociated neural systems. We conducted systematic meta-analyses of fMRI studies in the BrainMap database supplemented by PubMed using whole-brain activation likelihood estimation. A total of 66 study experiments including 1,447 participants and 987 foci revealed that while the left anterior insula was concordant in all inhibitory dimensions, cognitive inhibition reliably activated specific dorsal frontal inhibitory system, engaging dorsal anterior cingulate, dorsolateral prefrontal cortex, and parietal areas, whereas emotional interference reliably implicated a ventral inhibitory system, involving the ventral surface of the inferior frontal gyrus and the amygdala. Response inhibition showed concordant clusters in the fronto-striatal system, including the dorsal anterior cingulate region and extended supplementary motor areas, the dorsal and ventral lateral prefrontal cortex, basal ganglia, midbrain regions, and parietal regions. We provide an empirically derived dimensional model of inhibition characterizing neural systems underlying different aspects of inhibitory mechanisms. This study offers a fundamental framework to advance current understanding of inhibition and provides new insights for future clinical research into disorders with different types of inhibition-related dysfunctions. © 2018 Wiley Periodicals, Inc.

Approximate Confidence Intervals for Moment-Based Estimators of the Between-Study Variance in Random Effects Meta-Analysis

ERIC Educational Resources Information Center

Jackson, Dan; Bowden, Jack; Baker, Rose

2015-01-01

Moment-based estimators of the between-study variance are very popular when performing random effects meta-analyses. This type of estimation has many advantages including computational and conceptual simplicity. Furthermore, by using these estimators in large samples, valid meta-analyses can be performed without the assumption that the treatment…

Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry.

PubMed

Faggion, Clovis Mariano; Wu, Yun-Chun; Scheidgen, Moritz; Tu, Yu-Kang

2015-01-01

Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association.

Predictive distributions were developed for the extent of heterogeneity in meta-analyses of continuous outcome data.

PubMed

Rhodes, Kirsty M; Turner, Rebecca M; Higgins, Julian P T

2015-01-01

Estimation of between-study heterogeneity is problematic in small meta-analyses. Bayesian meta-analysis is beneficial because it allows incorporation of external evidence on heterogeneity. To facilitate this, we provide empirical evidence on the likely heterogeneity between studies in meta-analyses relating to specific research settings. Our analyses included 6,492 continuous-outcome meta-analyses within the Cochrane Database of Systematic Reviews. We investigated the influence of meta-analysis settings on heterogeneity by modeling study data from all meta-analyses on the standardized mean difference scale. Meta-analysis setting was described according to outcome type, intervention comparison type, and medical area. Predictive distributions for between-study variance expected in future meta-analyses were obtained, which can be used directly as informative priors. Among outcome types, heterogeneity was found to be lowest in meta-analyses of obstetric outcomes. Among intervention comparison types, heterogeneity was lowest in meta-analyses comparing two pharmacologic interventions. Predictive distributions are reported for different settings. In two example meta-analyses, incorporating external evidence led to a more precise heterogeneity estimate. Heterogeneity was influenced by meta-analysis characteristics. Informative priors for between-study variance were derived for each specific setting. Our analyses thus assist the incorporation of realistic prior information into meta-analyses including few studies. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

Insensitive Munitions Modeling Improvement Efforts

DTIC Science & Technology

2010-10-01

LLNL) ALE3D . Report Documentation Page Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to...codes most commonly used by munition designers are CTH and the SIERRA suite of codes produced by Sandia National Labs (SNL) and ALE3D produced by... ALE3D , a LLNL developed code, is also used by various DoD participants. It was however, designed differently than either CTH or Sierra. ALE3D is a

Effect of Risk of Bias on the Effect Size of Meta-Analytic Estimates in Randomized Controlled Trials in Periodontology and Implant Dentistry

PubMed Central

Faggion, Clovis Mariano; Wu, Yun-Chun; Scheidgen, Moritz; Tu, Yu-Kang

2015-01-01

Background Risk of bias (ROB) may threaten the internal validity of a clinical trial by distorting the magnitude of treatment effect estimates, although some conflicting information on this assumption exists. Objective The objective of this study was evaluate the effect of ROB on the magnitude of treatment effect estimates in randomized controlled trials (RCTs) in periodontology and implant dentistry. Methods A search for Cochrane systematic reviews (SRs), including meta-analyses of RCTs published in periodontology and implant dentistry fields, was performed in the Cochrane Library in September 2014. Random-effect meta-analyses were performed by grouping RCTs with different levels of ROBs in three domains (sequence generation, allocation concealment, and blinding of outcome assessment). To increase power and precision, only SRs with meta-analyses including at least 10 RCTs were included. Meta-regression was performed to investigate the association between ROB characteristics and the magnitudes of intervention effects in the meta-analyses. Results Of the 24 initially screened SRs, 21 SRs were excluded because they did not include at least 10 RCTs in the meta-analyses. Three SRs (two from periodontology field) generated information for conducting 27 meta-analyses. Meta-regression did not reveal significant differences in the relationship of the ROB level with the size of treatment effect estimates, although a trend for inflated estimates was observed in domains with unclear ROBs. Conclusion In this sample of RCTs, high and (mainly) unclear risks of selection and detection biases did not seem to influence the size of treatment effect estimates, although several confounders might have influenced the strength of the association. PMID:26422698

Active life expectancy from annual follow-up data with missing responses.

PubMed

Izmirlian, G; Brock, D; Ferrucci, L; Phillips, C

2000-03-01

Active life expectancy (ALE) at a given age is defined as the expected remaining years free of disability. In this study, three categories of health status are defined according to the ability to perform activities of daily living independently. Several studies have used increment-decrement life tables to estimate ALE, without error analysis, from only a baseline and one follow-up interview. The present work conducts an individual-level covariate analysis using a three-state Markov chain model for multiple follow-up data. Using a logistic link, the model estimates single-year transition probabilities among states of health, accounting for missing interviews. This approach has the advantages of smoothing subsequent estimates and increased power by using all follow-ups. We compute ALE and total life expectancy from these estimated single-year transition probabilities. Variance estimates are computed using the delta method. Data from the Iowa Established Population for the Epidemiologic Study of the Elderly are used to test the effects of smoking on ALE on all 5-year age groups past 65 years, controlling for sex and education.

Does the inclusion of grey literature influence estimates of intervention effectiveness reported in meta-analyses?

PubMed

McAuley, L; Pham, B; Tugwell, P; Moher, D

2000-10-07

The inclusion of only a subset of all available evidence in a meta-analysis may introduce biases and threaten its validity; this is particularly likely if the subset of included studies differ from those not included, which may be the case for published and grey literature (unpublished studies, with limited distribution). We set out to examine whether exclusion of grey literature, compared with its inclusion in meta-analysis, provides different estimates of the effectiveness of interventions assessed in randomised trials. From a random sample of 135 meta-analyses, we identified and retrieved 33 publications that included both grey and published primary studies. The 33 publications contributed 41 separate meta-analyses from several disease areas. General characteristics of the meta-analyses and associated studies and outcome data at the trial level were collected. We explored the effects of the inclusion of grey literature on the quantitative results using logistic-regression analyses. 33% of the meta-analyses were found to include some form of grey literature. The grey literature, when included, accounts for between 4.5% and 75% of the studies in a meta-analysis. On average, published work, compared with grey literature, yielded significantly larger estimates of the intervention effect by 15% (ratio of odds ratios=1.15 [95% CI 1.04-1.28]). Excluding abstracts from the analysis further compounded the exaggeration (1.33 [1.10-1.60]). The exclusion of grey literature from meta-analyses can lead to exaggerated estimates of intervention effectiveness. In general, meta-analysts should attempt to identify, retrieve, and include all reports, grey and published, that meet predefined inclusion criteria.

Meta-analyses of Adverse Effects Data Derived from Randomised Controlled Trials as Compared to Observational Studies: Methodological Overview

PubMed Central

Golder, Su; Loke, Yoon K.; Bland, Martin

2011-01-01

Background There is considerable debate as to the relative merits of using randomised controlled trial (RCT) data as opposed to observational data in systematic reviews of adverse effects. This meta-analysis of meta-analyses aimed to assess the level of agreement or disagreement in the estimates of harm derived from meta-analysis of RCTs as compared to meta-analysis of observational studies. Methods and Findings Searches were carried out in ten databases in addition to reference checking, contacting experts, citation searches, and hand-searching key journals, conference proceedings, and Web sites. Studies were included where a pooled relative measure of an adverse effect (odds ratio or risk ratio) from RCTs could be directly compared, using the ratio of odds ratios, with the pooled estimate for the same adverse effect arising from observational studies. Nineteen studies, yielding 58 meta-analyses, were identified for inclusion. The pooled ratio of odds ratios of RCTs compared to observational studies was estimated to be 1.03 (95% confidence interval 0.93–1.15). There was less discrepancy with larger studies. The symmetric funnel plot suggests that there is no consistent difference between risk estimates from meta-analysis of RCT data and those from meta-analysis of observational studies. In almost all instances, the estimates of harm from meta-analyses of the different study designs had 95% confidence intervals that overlapped (54/58, 93%). In terms of statistical significance, in nearly two-thirds (37/58, 64%), the results agreed (both studies showing a significant increase or significant decrease or both showing no significant difference). In only one meta-analysis about one adverse effect was there opposing statistical significance. Conclusions Empirical evidence from this overview indicates that there is no difference on average in the risk estimate of adverse effects of an intervention derived from meta-analyses of RCTs and meta-analyses of observational studies. This suggests that systematic reviews of adverse effects should not be restricted to specific study types. Please see later in the article for the Editors' Summary PMID:21559325

Estimating eruption temperature from thermal emission spectra of lava fountain activity in the Erta'Ale (Ethiopia) volcano lava lake: Implications for observing Io's volcanoes

USGS Publications Warehouse

Davies, Ashley G.; Keszthelyi, Laszlo P.; McEwen, Alfred S.

2011-01-01

We have analysed high-spatial-resolution and high-temporal-resolution temperature measurements of the active lava lake at Erta'Ale volcano, Ethiopia, to derive requirements for measuring eruption temperatures at Io's volcanoes. Lava lakes are particularly attractive targets because they are persistent in activity and large, often with ongoing lava fountain activity that exposes lava at near-eruption temperature. Using infrared thermography, we find that extracting useful temperature estimates from remote-sensing data requires (a) high spatial resolution to isolate lava fountains from adjacent cooler lava and (b) rapid acquisition of multi-color data. Because existing spacecraft data of Io's volcanoes do not meet these criteria, it is particularly important to design future instruments so that they will be able to collect such data. Near-simultaneous data at more than two relatively short wavelengths (shorter than 1 μm) are needed to constrain eruption temperatures. Resolving parts of the lava lake or fountains that are near the eruption temperature is also essential, and we provide a rough estimate of the required image scale.

The Role of the Amygdala in Facial Trustworthiness Processing: A Systematic Review and Meta-Analyses of fMRI Studies

PubMed Central

Oliveiros, Bárbara

2016-01-01

Background Faces play a key role in signaling social cues such as signals of trustworthiness. Although several studies identify the amygdala as a core brain region in social cognition, quantitative approaches evaluating its role are scarce. Objectives This review aimed to assess the role of the amygdala in the processing of facial trustworthiness, by analyzing its amplitude BOLD response polarity to untrustworthy versus trustworthy facial signals under fMRI tasks through a Meta-analysis of effect sizes (MA). Activation Likelihood Estimation (ALE) analyses were also conducted. Data sources Articles were retrieved from MEDLINE, ScienceDirect and Web-of-Science in January 2016. Following the PRISMA statement guidelines, a systematic review of original research articles in English language using the search string “(face OR facial) AND (trustworthiness OR trustworthy OR untrustworthy OR trustee) AND fMRI” was conducted. Study selection and data extraction The MA concerned amygdala responses to facial trustworthiness for the contrast Untrustworthy vs. trustworthy faces, and included whole-brain and ROI studies. To prevent potential bias, results were considered even when at the single study level they did not survive correction for multiple comparisons or provided non-significant results. ALE considered whole-brain studies, using the same methodology to prevent bias. A summary of the methodological options (design and analysis) described in the articles was finally used to get further insight into the characteristics of the studies and to perform a subgroup analysis. Data were extracted by two authors and checked independently. Data synthesis Twenty fMRI studies were considered for systematic review. An MA of effect sizes with 11 articles (12 studies) showed high heterogeneity between studies [Q(11) = 265.68, p < .0001; I2 = 95.86%, 94.20% to 97.05%, with 95% confidence interval, CI]. Random effects analysis [RE(183) = 0.851, .422 to .969, 95% CI] supported the evidence that the (right) amygdala responds preferentially to untrustworthy faces. Moreover, two ALE analyses performed with 6 articles (7 studies) identified the amygdala, insula and medial dorsal nuclei of thalamus as structures with negative correlation with trustworthiness. Six articles/studies showed that posterior cingulate and medial frontal gyrus present positive correlations with increasing facial trustworthiness levels. Significant effects considering subgroup analysis based on methodological criteria were found for experiments using spatial smoothing, categorization of trustworthiness in 2 or 3 categories and paradigms which involve both explicit and implicit tasks. Limitations Significant heterogeneity between studies was found in MA, which might have arisen from inclusion of studies with smaller sample sizes and differences in methodological options. Studies using ROI analysis / small volume correction methods were more often devoted specifically to the amygdala region, with some results reporting uncorrected p-values based on mainly clinical a priori evidence of amygdala involvement in these processes. Nevertheless, we did not find significant evidence for publication bias. Conclusions and implications of key findings Our results support the role of amygdala in facial trustworthiness judgment, emphasizing its predominant role during processing of negative social signals in (untrustworthy) faces. This systematic review suggests that little consistency exists among studies’ methodology, and that larger sample sizes should be preferred. PMID:27898705

A Meta-Meta-Analysis: Empirical Review of Statistical Power, Type I Error Rates, Effect Sizes, and Model Selection of Meta-Analyses Published in Psychology

ERIC Educational Resources Information Center

Cafri, Guy; Kromrey, Jeffrey D.; Brannick, Michael T.

2010-01-01

This article uses meta-analyses published in "Psychological Bulletin" from 1995 to 2005 to describe meta-analyses in psychology, including examination of statistical power, Type I errors resulting from multiple comparisons, and model choice. Retrospective power estimates indicated that univariate categorical and continuous moderators, individual…

Is creative insight task-specific? A coordinate-based meta-analysis of neuroimaging studies on insightful problem solving.

PubMed

Shen, Wangbing; Yuan, Yuan; Liu, Chang; Zhang, Xiaojiang; Luo, Jing; Gong, Zhe

2016-12-01

The question of whether creative insight varies across problem types has recently come to the forefront of studies of creative cognition. In the present study, to address the nature of creative insight, the coordinate-based activation likelihood estimation (ALE) technique was utilized to individually conduct three quantitative meta-analyses of neuroimaging experiments that used the compound remote associate (CRA) task, the prototype heuristic (PH) task and the Chinese character chunk decomposition (CCD) task. These tasks were chosen because they are frequently used to uncover the neurocognitive correlates of insight. Our results demonstrated that creative insight reliably activates largely non-overlapping brain regions across task types, with the exception of some shared regions: the CRA task mainly relied on the right parahippocampal gyrus, the superior frontal gyrus and the inferior frontal gyrus; the PH task primarily depended on the right middle occipital gyrus (MOG), the bilateral superior parietal lobule/precuneus, the left inferior parietal lobule, the left lingual gyrus and the left middle frontal gyrus; and the CCD task activated a broad cerebral network consisting of most dorsolateral and medial prefrontal regions, frontoparietal regions and the right MOG. These results provide the first neural evidence of the task dependence of creative insight. The implications of these findings for resolving conflict surrounding the different theories of creative cognition and for defining insight as a set of heterogeneous processes are discussed. Copyright © 2016 Elsevier B.V. All rights reserved.

Neuroanatomical correlates of negative emotionality-related traits: A systematic review and meta-analysis.

PubMed

Mincic, Adina M

2015-10-01

Two central traits present in the most influential models of personality characterize the response to positive and, respectively, negative emotional events. Negative emotionality (NE)-related traits are linked to vulnerability to mood and anxiety disorders; this has fuelled a special interest in examining stable differences in brain morphology associated to these traits. Structural imaging methods including voxel-based morphometry, cortical thickness analysis and diffusion tensor imaging (DTI) have yielded inconclusive and sometimes contradictory results. This review summarizes the findings reported to date through these methods and discusses them in relation to the functional imaging results. To detect topographic convergence between studies showing positive and, respectively, negative grey matter associations with NE-traits, activation likelihood estimation (ALE) meta-analyses of VBM studies were performed. Individuals scoring high on NE-related traits show consistent morphological differences in a left-lateralized circuit: higher grey matter volume (GMV) in amygdala and anterior parahippocampal gyrus and lower GMV in the orbitofrontal cortex extending into perigenual anterior cingulate cortex. Most DTI studies indicate reduced white matter integrity in various brain regions and tracts, particularly in the uncinate fasciculus and in cingulum bundle. These results show that the behavioural phenotype associated to NE traits is reflected in structural differences within the cortico-limbic system, suggesting alterations in information processing and transmission. The results are discussed from the perspective of neuron-glia interactions. Future directions are outlined based on recent developments in structural imaging techniques. Copyright © 2015 Elsevier Ltd. All rights reserved.

Neuroimaging of Reading Intervention: A Systematic Review and Activation Likelihood Estimate Meta-Analysis

PubMed Central

Barquero, Laura A.; Davis, Nicole; Cutting, Laurie E.

2014-01-01

A growing number of studies examine instructional training and brain activity. The purpose of this paper is to review the literature regarding neuroimaging of reading intervention, with a particular focus on reading difficulties (RD). To locate relevant studies, searches of peer-reviewed literature were conducted using electronic databases to search for studies from the imaging modalities of fMRI and MEG (including MSI) that explored reading intervention. Of the 96 identified studies, 22 met the inclusion criteria for descriptive analysis. A subset of these (8 fMRI experiments with post-intervention data) was subjected to activation likelihood estimate (ALE) meta-analysis to investigate differences in functional activation following reading intervention. Findings from the literature review suggest differences in functional activation of numerous brain regions associated with reading intervention, including bilateral inferior frontal, superior temporal, middle temporal, middle frontal, superior frontal, and postcentral gyri, as well as bilateral occipital cortex, inferior parietal lobules, thalami, and insulae. Findings from the meta-analysis indicate change in functional activation following reading intervention in the left thalamus, right insula/inferior frontal, left inferior frontal, right posterior cingulate, and left middle occipital gyri. Though these findings should be interpreted with caution due to the small number of studies and the disparate methodologies used, this paper is an effort to synthesize across studies and to guide future exploration of neuroimaging and reading intervention. PMID:24427278

Nonindependence and sensitivity analyses in ecological and evolutionary meta-analyses.

PubMed

Noble, Daniel W A; Lagisz, Malgorzata; O'dea, Rose E; Nakagawa, Shinichi

2017-05-01

Meta-analysis is an important tool for synthesizing research on a variety of topics in ecology and evolution, including molecular ecology, but can be susceptible to nonindependence. Nonindependence can affect two major interrelated components of a meta-analysis: (i) the calculation of effect size statistics and (ii) the estimation of overall meta-analytic estimates and their uncertainty. While some solutions to nonindependence exist at the statistical analysis stages, there is little advice on what to do when complex analyses are not possible, or when studies with nonindependent experimental designs exist in the data. Here we argue that exploring the effects of procedural decisions in a meta-analysis (e.g. inclusion of different quality data, choice of effect size) and statistical assumptions (e.g. assuming no phylogenetic covariance) using sensitivity analyses are extremely important in assessing the impact of nonindependence. Sensitivity analyses can provide greater confidence in results and highlight important limitations of empirical work (e.g. impact of study design on overall effects). Despite their importance, sensitivity analyses are seldom applied to problems of nonindependence. To encourage better practice for dealing with nonindependence in meta-analytic studies, we present accessible examples demonstrating the impact that ignoring nonindependence can have on meta-analytic estimates. We also provide pragmatic solutions for dealing with nonindependent study designs, and for analysing dependent effect sizes. Additionally, we offer reporting guidelines that will facilitate disclosure of the sources of nonindependence in meta-analyses, leading to greater transparency and more robust conclusions. © 2017 John Wiley & Sons Ltd.

Aloe vera extract functionalized zinc oxide nanoparticles as nanoantibiotics against multi-drug resistant clinical bacterial isolates.

PubMed

Ali, Khursheed; Dwivedi, Sourabh; Azam, Ameer; Saquib, Quaiser; Al-Said, Mansour S; Alkhedhairy, Abdulaziz A; Musarrat, Javed

2016-06-15

ZnO nanoparticles (ZnONPs) were synthesised through a simple and efficient biogenic synthesis approach, exploiting the reducing and capping potential of Aloe barbadensis Miller (A. vera) leaf extract (ALE). ALE-capped ZnO nanoparticles (ALE-ZnONPs) were characterized using UV-Vis spectroscopy, X-ray diffraction (XRD), Fourier transform infrared (FTIR) spectroscopy, scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), and transmission electron microscopy (TEM) analyses. XRD analysis provided the average size of ZnONPs as 15 nm. FTIR spectral analysis suggested the role of phenolic compounds, terpenoids and proteins present in ALE, in nucleation and stability of ZnONPs. Flow cytometry and atomic absorption spectrophotometry (AAS) data analyses revealed the surface binding and internalization of ZnONPs in Gram +ve (Staphylococcus aureus) and Gram -ve (Escherichia coli) cells, respectively. Significant antibacterial activity of ALE-ZnONPs was observed against extended spectrum beta lactamases (ESBL) positive E. coli, Pseudomonas aeruginosa, and methicillin resistant S. aureus (MRSA) clinical isolates exhibiting the MIC and MBC values of 2200, 2400 μg/ml and 2300, 2700 μg/ml, respectively. Substantial inhibitory effects of ALE-ZnONPs on bacterial growth kinetics, exopolysaccharides and biofilm formation, unequivocally suggested the antibiotic and anti-biofilm potential. Overall, the results elucidated a rapid, environmentally benign, cost-effective, and convenient method for ALE-ZnONPs synthesis, for possible applications as nanoantibiotics or drug carriers. Copyright © 2016 Elsevier Inc. All rights reserved.

Neural Bases Of Food Perception: Coordinate-Based Meta-Analyses Of Neuroimaging Studies In Multiple Modalities

PubMed Central

Huerta, Claudia I; Sarkar, Pooja R; Duong, Timothy Q.; Laird, Angela R; Fox, Peter T

2013-01-01

Objective The purpose of this study was to compare the results of the three food-cue paradigms most commonly used for functional neuroimaging studies to determine: i) commonalities and differences in the neural response patterns by paradigm; and, ii) the relative robustness and reliability of responses to each paradigm. Design and Methods functional magnetic resonance imaging (fMRI) studies using standardized stereotactic coordinates to report brain responses to food cues were identified using on-line databases. Studies were grouped by food-cue modality as: i) tastes (8 studies); ii) odors (8 studies); and, iii) images (11 studies). Activation likelihood estimation (ALE) was used to identify statistically reliable regional responses within each stimulation paradigm. Results Brain response distributions were distinctly different for the three stimulation modalities, corresponding to known differences in location of the respective primary and associative cortices. Visual stimulation induced the most robust and extensive responses. The left anterior insula was the only brain region reliably responding to all three stimulus categories. Conclusions These findings suggest visual food-cue paradigm as promising candidate for imaging studies addressing the neural substrate of therapeutic interventions. PMID:24174404

Impact of a grout curtain on groundwater regime in karst: the example of the Ðale reservoir (Croatia)

NASA Astrophysics Data System (ADS)

Bonacci, Ognjen; Roje-Bonacci, Tanja

2010-05-01

Construction of grout curtains in karst terrains is primarily connected with dams and reservoirs. Their role is to increase watertightness and prevent progressive erosion. In this presentation hourly continuous measurement of groundwater level in two deep piezometers near the Đale reservoir is analysed. The Đale reservoir in the Cetina River began operation in 1989. The total length of the grout curtain is 3.9 km. It spreads 120 m bellow the Đale dam. First analysed piezometer A is drilled in the interior part of the system, between the reservoir and the grout curtain, while the second one B is located in its external part. Distance between them is 200 m. In natural conditions, prior the grout curtain construction, groundwater level fluctuation in both of them was similar (practically the same). Construction of the grout curtain extremely changed groundwater behaviour in each of them. During the six month of continuous monitoring, differences between groundwater levels in them range between +19.86 m (groundwater in B is lower than in A) and -12.77 m (groundwater in A is lower than in B). During the 77% of analysed period the groundwater level in interior piezometer A is higher than the groundwater level in external piezometer B. In other 23% of analysed period the groundwater level in outside piezometer B is higher than in inside A. The construction of the grout curtain caused unnaturally high hydrostatic gradients, which can accelerate the dissolutional expansion of karst fractures. As a result, unbearable leakage of the reservoir Đale can occur over its lifetime. Careful analyses of groundwater level behaviour discover some other very important characteristics of karst underground morphology.

Grey literature in meta-analyses.

PubMed

Conn, Vicki S; Valentine, Jeffrey C; Cooper, Harris M; Rantz, Marilyn J

2003-01-01

In meta-analysis, researchers combine the results of individual studies to arrive at cumulative conclusions. Meta-analysts sometimes include "grey literature" in their evidential base, which includes unpublished studies and studies published outside widely available journals. Because grey literature is a source of data that might not employ peer review, critics have questioned the validity of its data and the results of meta-analyses that include it. To examine evidence regarding whether grey literature should be included in meta-analyses and strategies to manage grey literature in quantitative synthesis. This article reviews evidence on whether the results of studies published in peer-reviewed journals are representative of results from broader samplings of research on a topic as a rationale for inclusion of grey literature. Strategies to enhance access to grey literature are addressed. The most consistent and robust difference between published and grey literature is that published research is more likely to contain results that are statistically significant. Effect size estimates of published research are about one-third larger than those of unpublished studies. Unfunded and small sample studies are less likely to be published. Yet, importantly, methodological rigor does not differ between published and grey literature. Meta-analyses that exclude grey literature likely (a) over-represent studies with statistically significant findings, (b) inflate effect size estimates, and (c) provide less precise effect size estimates than meta-analyses including grey literature. Meta-analyses should include grey literature to fully reflect the existing evidential base and should assess the impact of methodological variations through moderator analysis.

Estimating eruption temperature from thermal emission spectra of lava fountain activity in the Erta'Ale (Ethiopia) volcano lava lake: Implications for observing Io's volcanoes

USGS Publications Warehouse

Davies, A.G.; Keszthelyi, L.; McEwen, A.S.

2011-01-01

We have analysed high-spatial-resolution and high-temporal-resolution temperature measurements of the active lava lake at Erta'Ale volcano, Ethiopia, to derive requirements for measuring eruption temperatures at Io's volcanoes. Lava lakes are particularly attractive targets because they are persistent in activity and large, often with ongoing lava fountain activity that exposes lava at near-eruption temperature. Using infrared thermography, we find that extracting useful temperature estimates from remote-sensing data requires (a) high spatial resolution to isolate lava fountains from adjacent cooler lava and (b) rapid acquisition of multi-color data. Because existing spacecraft data of Io's volcanoes do not meet these criteria, it is particularly important to design future instruments so that they will be able to collect such data. Near-simultaneous data at more than two relatively short wavelengths (shorter than 1 ??m) are needed to constrain eruption temperatures. Resolving parts of the lava lake or fountains that are near the eruption temperature is also essential, and we provide a rough estimate of the required image scale. ?? 2011 by the American Geophysical Union.

Comparison of intervention effects in split-mouth and parallel-arm randomized controlled trials: a meta-epidemiological study

PubMed Central

2014-01-01

Background Split-mouth randomized controlled trials (RCTs) are popular in oral health research. Meta-analyses frequently include trials of both split-mouth and parallel-arm designs to derive combined intervention effects. However, carry-over effects may induce bias in split- mouth RCTs. We aimed to assess whether intervention effect estimates differ between split- mouth and parallel-arm RCTs investigating the same questions. Methods We performed a meta-epidemiological study. We systematically reviewed meta- analyses including both split-mouth and parallel-arm RCTs with binary or continuous outcomes published up to February 2013. Two independent authors selected studies and extracted data. We used a two-step approach to quantify the differences between split-mouth and parallel-arm RCTs: for each meta-analysis. First, we derived ratios of odds ratios (ROR) for dichotomous data and differences in standardized mean differences (∆SMD) for continuous data; second, we pooled RORs or ∆SMDs across meta-analyses by random-effects meta-analysis models. Results We selected 18 systematic reviews, for 15 meta-analyses with binary outcomes (28 split-mouth and 28 parallel-arm RCTs) and 19 meta-analyses with continuous outcomes (28 split-mouth and 28 parallel-arm RCTs). Effect estimates did not differ between split-mouth and parallel-arm RCTs (mean ROR, 0.96, 95% confidence interval 0.52–1.80; mean ∆SMD, 0.08, -0.14–0.30). Conclusions Our study did not provide sufficient evidence for a difference in intervention effect estimates derived from split-mouth and parallel-arm RCTs. Authors should consider including split-mouth RCTs in their meta-analyses with suitable and appropriate analysis. PMID:24886043

Neural signatures of lexical tone reading.

PubMed

Kwok, Veronica P Y; Wang, Tianfu; Chen, Siping; Yakpo, Kofi; Zhu, Linlin; Fox, Peter T; Tan, Li Hai

2015-01-01

Research on how lexical tone is neuroanatomically represented in the human brain is central to our understanding of cortical regions subserving language. Past studies have exclusively focused on tone perception of the spoken language, and little is known as to the lexical tone processing in reading visual words and its associated brain mechanisms. In this study, we performed two experiments to identify neural substrates in Chinese tone reading. First, we used a tone judgment paradigm to investigate tone processing of visually presented Chinese characters. We found that, relative to baseline, tone perception of printed Chinese characters were mediated by strong brain activation in bilateral frontal regions, left inferior parietal lobule, left posterior middle/medial temporal gyrus, left inferior temporal region, bilateral visual systems, and cerebellum. Surprisingly, no activation was found in superior temporal regions, brain sites well known for speech tone processing. In activation likelihood estimation (ALE) meta-analysis to combine results of relevant published studies, we attempted to elucidate whether the left temporal cortex activities identified in Experiment one is consistent with those found in previous studies of auditory lexical tone perception. ALE results showed that only the left superior temporal gyrus and putamen were critical in auditory lexical tone processing. These findings suggest that activation in the superior temporal cortex associated with lexical tone perception is modality-dependent. © 2014 Wiley Periodicals, Inc.

Meta-Analysis of Functional Neuroimaging and Cognitive Control Studies in Schizophrenia: Preliminary Elucidation of a Core Dysfunctional Timing Network

PubMed Central

Alústiza, Irene; Radua, Joaquim; Albajes-Eizagirre, Anton; Domínguez, Manuel; Aubá, Enrique; Ortuño, Felipe

2016-01-01

Timing and other cognitive processes demanding cognitive control become interlinked when there is an increase in the level of difficulty or effort required. Both functions are interrelated and share neuroanatomical bases. A previous meta-analysis of neuroimaging studies found that people with schizophrenia had significantly lower activation, relative to normal controls, of most right hemisphere regions of the time circuit. This finding suggests that a pattern of disconnectivity of this circuit, particularly in the supplementary motor area, is a trait of this mental disease. We hypothesize that a dysfunctional temporal/cognitive control network underlies both cognitive and psychiatric symptoms of schizophrenia and that timing dysfunction is at the root of the cognitive deficits observed. The goal of our study was to look, in schizophrenia patients, for brain structures activated both by execution of cognitive tasks requiring increased effort and by performance of time perception tasks. We conducted a signed differential mapping (SDM) meta-analysis of functional neuroimaging studies in schizophrenia patients assessing the brain response to increasing levels of cognitive difficulty. Then, we performed a multimodal meta-analysis to identify common brain regions in the findings of that SDM meta-analysis and our previously-published activation likelihood estimate (ALE) meta-analysis of neuroimaging of time perception in schizophrenia patients. The current study supports the hypothesis that there exists an overlap between neural structures engaged by both timing tasks and non-temporal cognitive tasks of escalating difficulty in schizophrenia. The implication is that a deficit in timing can be considered as a trait marker of the schizophrenia cognitive profile. PMID:26925013

Meta-analysis of the effect of road work zones on crash occurrence.

PubMed

Theofilatos, Athanasios; Ziakopoulos, Apostolos; Papadimitriou, Eleonora; Yannis, George; Diamandouros, Konstantinos

2017-11-01

There is strong evidence that work zones pose increased risk of crashes and injuries. The two most common risk factors associated with increased crash frequencies are work zone duration and length. However, relevant research on the topic is relatively limited. For that reason, this paper presents formal meta-analyses of studies that have estimated the relationship between the number of crashes and work zone duration and length, in order to provide overall estimates of those effects on crash frequencies. All studies presented in this paper are crash prediction models with similar specifications. According to the meta-analyses and after correcting for publication bias when it was considered appropriate, the summary estimates of regression coefficients were found to be 0.1703 for duration and 0.862 for length. These effects were significant for length but not for duration. However, the overall estimate of duration was significant before correcting for publication bias. Separate meta-analyses on the studies examining both duration and length was also carried out in order to have rough estimates of the combined effects. The estimate of duration was found to be 0.953, while for length was 0.847. Similar to previous meta-analyses the effect of duration after correcting for publication bias is not significant, while the effect of length was significant at a 95% level. Meta-regression findings indicate that the main factors influencing the overall estimates of the beta coefficients are study year and region for duration and study year and model specification for length. Copyright © 2017 Elsevier Ltd. All rights reserved.

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research.

PubMed

Schmucker, Christine M; Blümle, Anette; Schell, Lisa K; Schwarzer, Guido; Oeller, Patrick; Cabrera, Laura; von Elm, Erik; Briel, Matthias; Meerpohl, Joerg J

2017-01-01

A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04-1.28 and 1.34, 95% CI 1.09-1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data.

Systematic review finds that study data not published in full text articles have unclear impact on meta-analyses results in medical research

PubMed Central

Blümle, Anette; Schell, Lisa K.; Schwarzer, Guido; Oeller, Patrick; Cabrera, Laura; von Elm, Erik; Briel, Matthias; Meerpohl, Joerg J.

2017-01-01

Background A meta-analysis as part of a systematic review aims to provide a thorough, comprehensive and unbiased statistical summary of data from the literature. However, relevant study results could be missing from a meta-analysis because of selective publication and inadequate dissemination. If missing outcome data differ systematically from published ones, a meta-analysis will be biased with an inaccurate assessment of the intervention effect. As part of the EU-funded OPEN project (www.open-project.eu) we conducted a systematic review that assessed whether the inclusion of data that were not published at all and/or published only in the grey literature influences pooled effect estimates in meta-analyses and leads to different interpretation. Methods and findings Systematic review of published literature (methodological research projects). Four bibliographic databases were searched up to February 2016 without restriction of publication year or language. Methodological research projects were considered eligible for inclusion if they reviewed a cohort of meta-analyses which (i) compared pooled effect estimates of meta-analyses of health care interventions according to publication status of data or (ii) examined whether the inclusion of unpublished or grey literature data impacts the result of a meta-analysis. Seven methodological research projects including 187 meta-analyses comparing pooled treatment effect estimates according to different publication status were identified. Two research projects showed that published data showed larger pooled treatment effects in favour of the intervention than unpublished or grey literature data (Ratio of ORs 1.15, 95% CI 1.04–1.28 and 1.34, 95% CI 1.09–1.66). In the remaining research projects pooled effect estimates and/or overall findings were not significantly changed by the inclusion of unpublished and/or grey literature data. The precision of the pooled estimate was increased with narrower 95% confidence interval. Conclusions Although we may anticipate that systematic reviews and meta-analyses not including unpublished or grey literature study results are likely to overestimate the treatment effects, current empirical research shows that this is only the case in a minority of reviews. Therefore, currently, a meta-analyst should particularly consider time, effort and costs when adding such data to their analysis. Future research is needed to identify which reviews may benefit most from including unpublished or grey data. PMID:28441452

The heterogeneity statistic I(2) can be biased in small meta-analyses.

PubMed

von Hippel, Paul T

2015-04-14

Estimated effects vary across studies, partly because of random sampling error and partly because of heterogeneity. In meta-analysis, the fraction of variance that is due to heterogeneity is estimated by the statistic I(2). We calculate the bias of I(2), focusing on the situation where the number of studies in the meta-analysis is small. Small meta-analyses are common; in the Cochrane Library, the median number of studies per meta-analysis is 7 or fewer. We use Mathematica software to calculate the expectation and bias of I(2). I(2) has a substantial bias when the number of studies is small. The bias is positive when the true fraction of heterogeneity is small, but the bias is typically negative when the true fraction of heterogeneity is large. For example, with 7 studies and no true heterogeneity, I(2) will overestimate heterogeneity by an average of 12 percentage points, but with 7 studies and 80 percent true heterogeneity, I(2) can underestimate heterogeneity by an average of 28 percentage points. Biases of 12-28 percentage points are not trivial when one considers that, in the Cochrane Library, the median I(2) estimate is 21 percent. The point estimate I(2) should be interpreted cautiously when a meta-analysis has few studies. In small meta-analyses, confidence intervals should supplement or replace the biased point estimate I(2).

Gray matter atrophy in narcolepsy: An activation likelihood estimation meta-analysis.

PubMed

Weng, Hsu-Huei; Chen, Chih-Feng; Tsai, Yuan-Hsiung; Wu, Chih-Ying; Lee, Meng; Lin, Yu-Ching; Yang, Cheng-Ta; Tsai, Ying-Huang; Yang, Chun-Yuh

2015-12-01

The authors reviewed the literature on the use of voxel-based morphometry (VBM) in narcolepsy magnetic resonance imaging (MRI) studies via the use of a meta-analysis of neuroimaging to identify concordant and specific structural deficits in patients with narcolepsy as compared with healthy subjects. We used PubMed to retrieve articles published between January 2000 and March 2014. The authors included all VBM research on narcolepsy and compared the findings of the studies by using gray matter volume (GMV) or gray matter concentration (GMC) to index differences in gray matter. Stereotactic data were extracted from 8 VBM studies of 149 narcoleptic patients and 162 control subjects. We applied activation likelihood estimation (ALE) technique and found significant regional gray matter reduction in the bilateral hypothalamus, thalamus, globus pallidus, extending to nucleus accumbens (NAcc) and anterior cingulate cortex (ACC), left mid orbital and rectal gyri (BAs 10 and 11), right inferior frontal gyrus (BA 47), and the right superior temporal gyrus (BA 41) in patients with narcolepsy. The significant gray matter deficits in narcoleptic patients occurred in the bilateral hypothalamus and frontotemporal regions, which may be related to the emotional processing abnormalities and orexin/hypocretin pathway common among populations of patients with narcolepsy. Copyright © 2015. Published by Elsevier Ltd.

Implementing informative priors for heterogeneity in meta-analysis using meta-regression and pseudo data.

PubMed

Rhodes, Kirsty M; Turner, Rebecca M; White, Ian R; Jackson, Dan; Spiegelhalter, David J; Higgins, Julian P T

2016-12-20

Many meta-analyses combine results from only a small number of studies, a situation in which the between-study variance is imprecisely estimated when standard methods are applied. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, providing the potential for more robust inference on the effect size of interest. We present a method for performing Bayesian meta-analysis using data augmentation, in which we represent an informative conjugate prior for between-study variance by pseudo data and use meta-regression for estimation. To assist in this, we derive predictive inverse-gamma distributions for the between-study variance expected in future meta-analyses. These may serve as priors for heterogeneity in new meta-analyses. In a simulation study, we compare approximate Bayesian methods using meta-regression and pseudo data against fully Bayesian approaches based on importance sampling techniques and Markov chain Monte Carlo (MCMC). We compare the frequentist properties of these Bayesian methods with those of the commonly used frequentist DerSimonian and Laird procedure. The method is implemented in standard statistical software and provides a less complex alternative to standard MCMC approaches. An importance sampling approach produces almost identical results to standard MCMC approaches, and results obtained through meta-regression and pseudo data are very similar. On average, data augmentation provides closer results to MCMC, if implemented using restricted maximum likelihood estimation rather than DerSimonian and Laird or maximum likelihood estimation. The methods are applied to real datasets, and an extension to network meta-analysis is described. The proposed method facilitates Bayesian meta-analysis in a way that is accessible to applied researchers. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd. © 2016 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Univariate and bivariate likelihood-based meta-analysis methods performed comparably when marginal sensitivity and specificity were the targets of inference.

PubMed

Dahabreh, Issa J; Trikalinos, Thomas A; Lau, Joseph; Schmid, Christopher H

2017-03-01

To compare statistical methods for meta-analysis of sensitivity and specificity of medical tests (e.g., diagnostic or screening tests). We constructed a database of PubMed-indexed meta-analyses of test performance from which 2 × 2 tables for each included study could be extracted. We reanalyzed the data using univariate and bivariate random effects models fit with inverse variance and maximum likelihood methods. Analyses were performed using both normal and binomial likelihoods to describe within-study variability. The bivariate model using the binomial likelihood was also fit using a fully Bayesian approach. We use two worked examples-thoracic computerized tomography to detect aortic injury and rapid prescreening of Papanicolaou smears to detect cytological abnormalities-to highlight that different meta-analysis approaches can produce different results. We also present results from reanalysis of 308 meta-analyses of sensitivity and specificity. Models using the normal approximation produced sensitivity and specificity estimates closer to 50% and smaller standard errors compared to models using the binomial likelihood; absolute differences of 5% or greater were observed in 12% and 5% of meta-analyses for sensitivity and specificity, respectively. Results from univariate and bivariate random effects models were similar, regardless of estimation method. Maximum likelihood and Bayesian methods produced almost identical summary estimates under the bivariate model; however, Bayesian analyses indicated greater uncertainty around those estimates. Bivariate models produced imprecise estimates of the between-study correlation of sensitivity and specificity. Differences between methods were larger with increasing proportion of studies that were small or required a continuity correction. The binomial likelihood should be used to model within-study variability. Univariate and bivariate models give similar estimates of the marginal distributions for sensitivity and specificity. Bayesian methods fully quantify uncertainty and their ability to incorporate external evidence may be useful for imprecisely estimated parameters. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors Affecting Medial Temporal Lobe Engagement for Past and Future Episodic Events: An ALE Meta-Analysis of Neuroimaging Studies

ERIC Educational Resources Information Center

Viard, Armelle; Desgranges, Beatrice; Eustache, Francis; Piolino, Pascale

2012-01-01

Remembering the past and envisioning the future are at the core of one's sense of identity. Neuroimaging studies investigating the neural substrates underlying past and future episodic events have been growing in number. However, the experimental paradigms used to select and elicit episodic events vary greatly, leading to disparate results,…

On the Multilevel Nature of Meta-Analysis: A Tutorial, Comparison of Software Programs, and Discussion of Analytic Choices.

PubMed

Pastor, Dena A; Lazowski, Rory A

2018-01-01

The term "multilevel meta-analysis" is encountered not only in applied research studies, but in multilevel resources comparing traditional meta-analysis to multilevel meta-analysis. In this tutorial, we argue that the term "multilevel meta-analysis" is redundant since all meta-analysis can be formulated as a special kind of multilevel model. To clarify the multilevel nature of meta-analysis the four standard meta-analytic models are presented using multilevel equations and fit to an example data set using four software programs: two specific to meta-analysis (metafor in R and SPSS macros) and two specific to multilevel modeling (PROC MIXED in SAS and HLM). The same parameter estimates are obtained across programs underscoring that all meta-analyses are multilevel in nature. Despite the equivalent results, not all software programs are alike and differences are noted in the output provided and estimators available. This tutorial also recasts distinctions made in the literature between traditional and multilevel meta-analysis as differences between meta-analytic choices, not between meta-analytic models, and provides guidance to inform choices in estimators, significance tests, moderator analyses, and modeling sequence. The extent to which the software programs allow flexibility with respect to these decisions is noted, with metafor emerging as the most favorable program reviewed.

Predicting the extent of heterogeneity in meta-analysis, using empirical data from the Cochrane Database of Systematic Reviews

PubMed Central

Turner, Rebecca M; Davey, Jonathan; Clarke, Mike J; Thompson, Simon G; Higgins, Julian PT

2012-01-01

Background Many meta-analyses contain only a small number of studies, which makes it difficult to estimate the extent of between-study heterogeneity. Bayesian meta-analysis allows incorporation of external evidence on heterogeneity, and offers advantages over conventional random-effects meta-analysis. To assist in this, we provide empirical evidence on the likely extent of heterogeneity in particular areas of health care. Methods Our analyses included 14 886 meta-analyses from the Cochrane Database of Systematic Reviews. We classified each meta-analysis according to the type of outcome, type of intervention comparison and medical specialty. By modelling the study data from all meta-analyses simultaneously, using the log odds ratio scale, we investigated the impact of meta-analysis characteristics on the underlying between-study heterogeneity variance. Predictive distributions were obtained for the heterogeneity expected in future meta-analyses. Results Between-study heterogeneity variances for meta-analyses in which the outcome was all-cause mortality were found to be on average 17% (95% CI 10–26) of variances for other outcomes. In meta-analyses comparing two active pharmacological interventions, heterogeneity was on average 75% (95% CI 58–95) of variances for non-pharmacological interventions. Meta-analysis size was found to have only a small effect on heterogeneity. Predictive distributions are presented for nine different settings, defined by type of outcome and type of intervention comparison. For example, for a planned meta-analysis comparing a pharmacological intervention against placebo or control with a subjectively measured outcome, the predictive distribution for heterogeneity is a log-normal (−2.13, 1.582) distribution, which has a median value of 0.12. In an example of meta-analysis of six studies, incorporating external evidence led to a smaller heterogeneity estimate and a narrower confidence interval for the combined intervention effect. Conclusions Meta-analysis characteristics were strongly associated with the degree of between-study heterogeneity, and predictive distributions for heterogeneity differed substantially across settings. The informative priors provided will be very beneficial in future meta-analyses including few studies. PMID:22461129

Investigation of 2-stage meta-analysis methods for joint longitudinal and time-to-event data through simulation and real data application.

PubMed

Sudell, Maria; Tudur Smith, Catrin; Gueyffier, François; Kolamunnage-Dona, Ruwanthi

2018-04-15

Joint modelling of longitudinal and time-to-event data is often preferred over separate longitudinal or time-to-event analyses as it can account for study dropout, error in longitudinally measured covariates, and correlation between longitudinal and time-to-event outcomes. The joint modelling literature focuses mainly on the analysis of single studies with no methods currently available for the meta-analysis of joint model estimates from multiple studies. We propose a 2-stage method for meta-analysis of joint model estimates. These methods are applied to the INDANA dataset to combine joint model estimates of systolic blood pressure with time to death, time to myocardial infarction, and time to stroke. Results are compared to meta-analyses of separate longitudinal or time-to-event models. A simulation study is conducted to contrast separate versus joint analyses over a range of scenarios. Using the real dataset, similar results were obtained by using the separate and joint analyses. However, the simulation study indicated a benefit of use of joint rather than separate methods in a meta-analytic setting where association exists between the longitudinal and time-to-event outcomes. Where evidence of association between longitudinal and time-to-event outcomes exists, results from joint models over standalone analyses should be pooled in 2-stage meta-analyses. © 2017 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Where Is the Semantic System? A Critical Review and Meta-Analysis of 120 Functional Neuroimaging Studies

PubMed Central

Desai, Rutvik H.; Graves, William W.; Conant, Lisa L.

2009-01-01

Semantic memory refers to knowledge about people, objects, actions, relations, self, and culture acquired through experience. The neural systems that store and retrieve this information have been studied for many years, but a consensus regarding their identity has not been reached. Using strict inclusion criteria, we analyzed 120 functional neuroimaging studies focusing on semantic processing. Reliable areas of activation in these studies were identified using the activation likelihood estimate (ALE) technique. These activations formed a distinct, left-lateralized network comprised of 7 regions: posterior inferior parietal lobe, middle temporal gyrus, fusiform and parahippocampal gyri, dorsomedial prefrontal cortex, inferior frontal gyrus, ventromedial prefrontal cortex, and posterior cingulate gyrus. Secondary analyses showed specific subregions of this network associated with knowledge of actions, manipulable artifacts, abstract concepts, and concrete concepts. The cortical regions involved in semantic processing can be grouped into 3 broad categories: posterior multimodal and heteromodal association cortex, heteromodal prefrontal cortex, and medial limbic regions. The expansion of these regions in the human relative to the nonhuman primate brain may explain uniquely human capacities to use language productively, plan, solve problems, and create cultural and technological artifacts, all of which depend on the fluid and efficient retrieval and manipulation of semantic knowledge. PMID:19329570

A Systematic Review and Meta-Analyses Show that Carbapenem Use and Medical Devices Are the Leading Risk Factors for Carbapenem-Resistant Pseudomonas aeruginosa

PubMed Central

Voor in ‘t holt, Anne F.; Severin, Juliëtte A.; Lesaffre, Emmanuel M. E. H.

2014-01-01

A systematic review and meta-analyses were performed to identify the risk factors associated with carbapenem-resistant Pseudomonas aeruginosa and to identify sources and reservoirs for the pathogen. A systematic search of PubMed and Embase databases from 1 January 1987 until 27 January 2012 identified 1,662 articles, 53 of which were included in a systematic review and 38 in a random-effects meta-analysis study. The use of carbapenem, use of fluoroquinolones, use of vancomycin, use of other antibiotics, having medical devices, intensive care unit (ICU) admission, having underlying diseases, patient characteristics, and length of hospital stay were significant risk factors in multivariate analyses. The meta-analyses showed that carbapenem use (odds ratio [OR] = 7.09; 95% confidence interval [CI] = 5.43 to 9.25) and medical devices (OR = 5.11; 95% CI = 3.55 to 7.37) generated the highest pooled estimates. Cumulative meta-analyses showed that the pooled estimate of carbapenem use was stable and that the pooled estimate of the risk factor “having medical devices” increased with time. We conclude that our results highlight the importance of antibiotic stewardship and the thoughtful use of medical devices in helping prevent outbreaks of carbapenem-resistant P. aeruginosa. PMID:24550343

Borrowing of strength and study weights in multivariate and network meta-analysis.

PubMed

Jackson, Dan; White, Ian R; Price, Malcolm; Copas, John; Riley, Richard D

2017-12-01

Multivariate and network meta-analysis have the potential for the estimated mean of one effect to borrow strength from the data on other effects of interest. The extent of this borrowing of strength is usually assessed informally. We present new mathematical definitions of 'borrowing of strength'. Our main proposal is based on a decomposition of the score statistic, which we show can be interpreted as comparing the precision of estimates from the multivariate and univariate models. Our definition of borrowing of strength therefore emulates the usual informal assessment. We also derive a method for calculating study weights, which we embed into the same framework as our borrowing of strength statistics, so that percentage study weights can accompany the results from multivariate and network meta-analyses as they do in conventional univariate meta-analyses. Our proposals are illustrated using three meta-analyses involving correlated effects for multiple outcomes, multiple risk factor associations and multiple treatments (network meta-analysis).

Borrowing of strength and study weights in multivariate and network meta-analysis

PubMed Central

Jackson, Dan; White, Ian R; Price, Malcolm; Copas, John; Riley, Richard D

2016-01-01

Multivariate and network meta-analysis have the potential for the estimated mean of one effect to borrow strength from the data on other effects of interest. The extent of this borrowing of strength is usually assessed informally. We present new mathematical definitions of ‘borrowing of strength’. Our main proposal is based on a decomposition of the score statistic, which we show can be interpreted as comparing the precision of estimates from the multivariate and univariate models. Our definition of borrowing of strength therefore emulates the usual informal assessment. We also derive a method for calculating study weights, which we embed into the same framework as our borrowing of strength statistics, so that percentage study weights can accompany the results from multivariate and network meta-analyses as they do in conventional univariate meta-analyses. Our proposals are illustrated using three meta-analyses involving correlated effects for multiple outcomes, multiple risk factor associations and multiple treatments (network meta-analysis). PMID:26546254

The nuclear hormone receptor E75A regulates vitellogenin gene (Al-Vg) expression in the mirid bug Apolygus lucorum.

PubMed

Tan, Y-A; Zhao, X-D; Sun, Y; Hao, D-J; Zhao, J; Jiang, Y-P; Bai, L-X; Xiao, L-B

2018-04-01

Apolygus lucorum is the predominant pest of Bacillus thuringiensis (Bt) cotton in China. 20-hydroxyecdysone (20E) plays a key role in the reproduction of this insect. To better understand the mechanism underlying 20E-regulated reproduction, the nuclear hormone receptor E75 isoform-A of Ap. lucorum (Al-E75A) was cloned and its expression analysed. A 2241-bp sequence of Al-E75A cDNA encoded an open reading frame of a polypeptide with a predicted molecular mass of 69.04 kDa. Al-E75A mRNA was detected in female adult stages of Ap. lucorum with peak expression in 7-day-old animals. Al-E75A was also expressed in several tissues, particularly in the fat body and ovary. A 3.2 kb Al-E75A mRNA was detected in all tissues by Northern blot. The fecundity and longevity were significantly decreased in female adults treated with Al-E75A small interfering RNA. The rates of egg incubation rates were considerably lower in the RNA interference-treated animals compared to the untreated controls. In order to investigate the molecular mechanism underlying the effects described above, vitellogenin (Al-Vg) was selected for further investigation. The expression pattern of Al-Vg was similar to that of Al-E75A and was up-regulated by 20E. After knockdown of Al-E75A, the expression profile of Al-Vg and the protein levels were down-regulated. These findings suggest that Al-E75A plays a crucial role in the regulation of Al-Vg expression in Ap. lucorum. © 2017 The Royal Entomological Society.

Contour plot assessment of existing meta-analyses confirms robust association of statin use and acute kidney injury risk.

PubMed

Chevance, Aurélie; Schuster, Tibor; Steele, Russell; Ternès, Nils; Platt, Robert W

2015-10-01

Robustness of an existing meta-analysis can justify decisions on whether to conduct an additional study addressing the same research question. We illustrate the graphical assessment of the potential impact of an additional study on an existing meta-analysis using published data on statin use and the risk of acute kidney injury. A previously proposed graphical augmentation approach is used to assess the sensitivity of the current test and heterogeneity statistics extracted from existing meta-analysis data. In addition, we extended the graphical augmentation approach to assess potential changes in the pooled effect estimate after updating a current meta-analysis and applied the three graphical contour definitions to data from meta-analyses on statin use and acute kidney injury risk. In the considered example data, the pooled effect estimates and heterogeneity indices demonstrated to be considerably robust to the addition of a future study. Supportingly, for some previously inconclusive meta-analyses, a study update might yield statistically significant kidney injury risk increase associated with higher statin exposure. The illustrated contour approach should become a standard tool for the assessment of the robustness of meta-analyses. It can guide decisions on whether to conduct additional studies addressing a relevant research question. Copyright © 2015 Elsevier Inc. All rights reserved.

Systematic overview and critical appraisal of meta-analyses of interventions in intensive care medicine.

PubMed

Koster, T M; Wetterslev, J; Gluud, C; Keus, F; van der Horst, I C C

2018-05-24

Meta-analysed intervention effect estimates are perceived to represent the highest level of evidence. However, such effects and the randomized clinical trials which are included in them need critical appraisal before the effects can be trusted. Critical appraisal of a predefined set of all meta-analyses on interventions in intensive care medicine to assess their quality and assessed the risks of bias in those meta-analyses having the best quality. We conducted a systematic search to select all meta-analyses of randomized clinical trials on interventions used in intensive care medicine. Selected meta-analyses were critically appraised for basic scientific criteria, (1) presence of an available protocol, (2) report of a full search strategy, and (3) use of any bias risk assessment of included trials. All meta-analyses which qualified these criteria were scrutinized by full "Risk of Bias in Systematic Reviews" ROBIS evaluation of 4 domains of risks of bias, and a "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" PRISMA evaluation. We identified 467 meta-analyses. A total of 56 meta-analyses complied with these basic scientific criteria. We scrutinized the risks of bias in the 56 meta-analyses by full ROBIS evaluation and a PRISMA evaluation. Only 4 meta-analyses scored low risk of bias in all the 4 ROBIS domains and 41 meta-analyses reported all 27 items of the PRISMA checklist. In contrast with what might be perceived as the highest level of evidence only 0.9% of all meta-analyses were judged to have overall low risk of bias. © 2018 The Acta Anaesthesiologica Scandinavica Foundation. Published by John Wiley & Sons Ltd.

An Empirical Comparison of Heterogeneity Variance Estimators in 12,894 Meta-Analyses

ERIC Educational Resources Information Center

Langan, Dean; Higgins, Julian P. T.; Simmonds, Mark

2015-01-01

Heterogeneity in meta-analysis is most commonly estimated using a moment-based approach described by DerSimonian and Laird. However, this method has been shown to produce biased estimates. Alternative methods to estimate heterogeneity include the restricted maximum likelihood approach and those proposed by Paule and Mandel, Sidik and Jonkman, and…

Evaluation of Coastal Sea Level from Jason-2 Altimetry Offshore Hong Kong

NASA Astrophysics Data System (ADS)

Birol, F.; Xu, X. Y., , Dr; Cazenave, A. A.

2017-12-01

In the recent years, several coastal altimetry products of Jason-2 mission have been distributed by different agencies, the most advance ones of which are XTRACK, PISTACH and ALES. Each product represents extraordinary endeavors on some aspects of retracking or advanced geophysical corrections, and each has its advantage. The motivation of this presentation is to evaluate these products in order to refine the sea level measurements at the coast. Three retrackers: MLE4, MLE3 and ALES are focused on. Within 20km coastward, neither GDR nor ALES readily provides sea level anomaly (SLA) measurements, so we recomputed the 20Hz GDR and ALES SLA from the raw data, adopting auxiliary information (such as waveform classification and wet tropospheric delay) from PISTACH. The region of interest is track #153 of the Jason-2 satellite (offshore Hong Kong, China), and the altimetry products are processed over seven years (2008-2015, cycles 1-252). The coastline offshore Hong Kong is rather complicated and we feel that it can be a good indicator of the performance of coastal altimetry under undesirable coast conditions. We computed the bias and noise level of ALES, MLE3 and MLE4 SLA over open ocean and in the coastal zone (within 10km or 5km coast-ward). The results showed that, after outlier-editing, ALES performs better than MLE4 and MLE3 both in terms of noise level and uncertainty in sea level trend estimation. We validated the coastal altimetry-based SLA by comparing with data from the Hong Kong tide gauge (located 10km across-track). An interesting , but still preliminary, result is that the computed sea level trend within 5 km from the coast is significantly larger than the trend estimated at larger distances from the coast. Keywords: Jason-2, Hong Kong coast, ALES, MLE3, MLE4

Neural correlates of social exclusion across ages: A coordinate-based meta-analysis of functional MRI studies.

PubMed

Vijayakumar, Nandita; Cheng, Theresa W; Pfeifer, Jennifer H

2017-06-01

Given the recent surge in functional neuroimaging studies on social exclusion, the current study employed activation likelihood estimation (ALE) based meta-analyses to identify brain regions that have consistently been implicated across different experimental paradigms used to investigate exclusion. We also examined the neural correlates underlying Cyberball, the most commonly used paradigm to study exclusion, as well as differences in exclusion-related activation between developing (7-18 years of age, from pre-adolescence up to late adolescence) and emerging adult (broadly defined as undergraduates, including late adolescence and young adulthood) samples. Results revealed involvement of the bilateral medial prefrontal and posterior cingulate cortices, right precuneus and left ventrolateral prefrontal cortex across the different paradigms used to examine social exclusion; similar activation patterns were identified when restricting the analysis to Cyberball studies. Investigations into age-related effects revealed that ventrolateral prefrontal activations identified in the full sample were driven by (i.e. present in) developmental samples, while medial prefrontal activations were driven by emerging adult samples. In addition, the right ventral striatum was implicated in exclusion, but only in developmental samples. Subtraction analysis revealed significantly greater activation likelihood in striatal and ventrolateral prefrontal clusters in the developmental samples as compared to emerging adults, though the opposite contrast failed to identify any significant regions. Findings integrate the knowledge accrued from functional neuroimaging studies on social exclusion to date, highlighting involvement of lateral prefrontal regions implicated in regulation and midline structures involved in social cognitive and self-evaluative processes across experimental paradigms and ages, as well as limbic structures in developing samples specifically. Copyright © 2017 Elsevier Inc. All rights reserved.

Centrality of prefrontal and motor preparation cortices to Tourette Syndrome revealed by meta-analysis of task-based neuroimaging studies.

PubMed

Polyanska, Liliana; Critchley, Hugo D; Rae, Charlotte L

2017-01-01

Tourette Syndrome (TS) is a neurodevelopmental condition characterized by chronic multiple tics, which are experienced as compulsive and 'unwilled'. Patients with TS can differ markedly in the frequency, severity, and bodily distribution of tics. Moreover, there are high comorbidity rates with attention deficit hyperactivity disorder (ADHD), obsessive compulsive disorder (OCD), anxiety disorders, and depression. This complex clinical profile may account for apparent variability of findings across neuroimaging studies that connect neural function to cognitive and motor behavior in TS. Here we crystalized information from neuroimaging regarding the functional circuitry of TS, and furthermore, tested specifically for neural determinants of tic severity, by applying activation likelihood estimation (ALE) meta-analyses to neuroimaging (activation) studies of TS. Fourteen task-based studies (13 fMRI and one H2O-PET) met rigorous inclusion criteria. These studies, encompassing 25 experiments and 651 participants, tested for differences between TS participants and healthy controls across cognitive, motor, perceptual and somatosensory domains. Relative to controls, TS participants showed distributed differences in the activation of prefrontal (inferior, middle, and superior frontal gyri), anterior cingulate, and motor preparation cortices (lateral premotor cortex and supplementary motor area; SMA). Differences also extended into sensory (somatosensory cortex and the lingual gyrus; V4); and temporo-parietal association cortices (posterior superior temporal sulcus, supramarginal gyrus, and retrosplenial cortex). Within TS participants, tic severity (reported using the Yale Global Tic Severity Scale; YGTSS) selectively correlated with engagement of SMA, precentral gyrus, and middle frontal gyrus across tasks. The dispersed involvement of multiple cortical regions with differences in functional reactivity may account for heterogeneity in the symptomatic expression of TS and its comorbidities. More specifically for tics and tic severity, the findings reinforce previously proposed contributions of premotor and lateral prefrontal cortices to tic expression.

Anti-inflammatory evaluation and characterization of leaf extract of Ananas comosus.

PubMed

Kargutkar, Samira; Brijesh, S

2018-04-01

Ananas comosus (L.) Merr (Pineapple) is a tropical plant with an edible fruit. In the present study, the potential anti-inflammatory activity of A. comosus leaf extract (ALE) was studied. ALE prepared using soxhlet apparatus was subjected to preliminary qualitative phytochemical analysis and quantitative estimations of flavonoids and tannins. The components present in ALE were identified using liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-mass spectrometry (GC-MS). Inhibitory effects of ALE on protein denaturation, and proteinase activity were assessed. Its effect on secretion of pro-inflammatory cytokines and inflammatory mediators by lipopolysaccharide-stimulated macrophages was also analyzed. Further, its anti-inflammatory activity in carrageenan-induced inflammatory rat model was examined. The preliminary qualitative phytochemical analysis revealed presence of flavonoids, phenols, tannins, carbohydrates, glycosides, and proteins in the extract. Total flavonoids and total tannins were 0.17 ± 0.006 mg equivalent of quercetin/g of ALE and 4.04 ± 0.56 mg equivalent of gallic acid/g of ALE. LC-MS analysis identified the presence of 4-hydroxy pelargonic acid, 3,4,5-trimethoxycinnamic and 4-methoxycinnamic acid, whereas GC-MS analysis identified the presence of campesterol and ethyl isoallocholate that have been previously reported for anti-inflammatory activity. ALE showed significant inhibition of protein denaturation and proteinase activity and also controlled secretion of tumour necrosis factor-α, interleukin-1β and prostaglandins, as well as the generation of reactive oxygen species by activated macrophages. ALE also significantly decreased carrageenan-induced acute paw edema. The study, therefore, identified the components present in ALE that may be responsible for its anti-inflammatory activity and thus demonstrated its potential use against acute inflammatory diseases.

A framework for the meta-analysis of Bland-Altman studies based on a limits of agreement approach.

PubMed

Tipton, Elizabeth; Shuster, Jonathan

2017-10-15

Bland-Altman method comparison studies are common in the medical sciences and are used to compare a new measure to a gold-standard (often costlier or more invasive) measure. The distribution of these differences is summarized by two statistics, the 'bias' and standard deviation, and these measures are combined to provide estimates of the limits of agreement (LoA). When these LoA are within the bounds of clinically insignificant differences, the new non-invasive measure is preferred. Very often, multiple Bland-Altman studies have been conducted comparing the same two measures, and random-effects meta-analysis provides a means to pool these estimates. We provide a framework for the meta-analysis of Bland-Altman studies, including methods for estimating the LoA and measures of uncertainty (i.e., confidence intervals). Importantly, these LoA are likely to be wider than those typically reported in Bland-Altman meta-analyses. Frequently, Bland-Altman studies report results based on repeated measures designs but do not properly adjust for this design in the analysis. Meta-analyses of Bland-Altman studies frequently exclude these studies for this reason. We provide a meta-analytic approach that allows inclusion of estimates from these studies. This includes adjustments to the estimate of the standard deviation and a method for pooling the estimates based upon robust variance estimation. An example is included based on a previously published meta-analysis. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Using beta coefficients to impute missing correlations in meta-analysis research: Reasons for caution.

PubMed

Roth, Philip L; Le, Huy; Oh, In-Sue; Van Iddekinge, Chad H; Bobko, Philip

2018-06-01

Meta-analysis has become a well-accepted method for synthesizing empirical research about a given phenomenon. Many meta-analyses focus on synthesizing correlations across primary studies, but some primary studies do not report correlations. Peterson and Brown (2005) suggested that researchers could use standardized regression weights (i.e., beta coefficients) to impute missing correlations. Indeed, their beta estimation procedures (BEPs) have been used in meta-analyses in a wide variety of fields. In this study, the authors evaluated the accuracy of BEPs in meta-analysis. We first examined how use of BEPs might affect results from a published meta-analysis. We then developed a series of Monte Carlo simulations that systematically compared the use of existing correlations (that were not missing) to data sets that incorporated BEPs (that impute missing correlations from corresponding beta coefficients). These simulations estimated ρ̄ (mean population correlation) and SDρ (true standard deviation) across a variety of meta-analytic conditions. Results from both the existing meta-analysis and the Monte Carlo simulations revealed that BEPs were associated with potentially large biases when estimating ρ̄ and even larger biases when estimating SDρ. Using only existing correlations often substantially outperformed use of BEPs and virtually never performed worse than BEPs. Overall, the authors urge a return to the standard practice of using only existing correlations in meta-analysis. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Alcohol intake and gastric cancer: Meta-analyses of published data versus individual participant data pooled analyses (StoP Project).

PubMed

Ferro, Ana; Morais, Samantha; Rota, Matteo; Pelucchi, Claudio; Bertuccio, Paola; Bonzi, Rossella; Galeone, Carlotta; Zhang, Zuo-Feng; Matsuo, Keitaro; Ito, Hidemi; Hu, Jinfu; Johnson, Kenneth C; Yu, Guo-Pei; Palli, Domenico; Ferraroni, Monica; Muscat, Joshua; Malekzadeh, Reza; Ye, Weimin; Song, Huan; Zaridze, David; Maximovitch, Dmitry; Fernández de Larrea, Nerea; Kogevinas, Manolis; Vioque, Jesus; Navarrete-Muñoz, Eva M; Pakseresht, Mohammadreza; Pourfarzi, Farhad; Wolk, Alicja; Orsini, Nicola; Bellavia, Andrea; Håkansson, Niclas; Mu, Lina; Pastorino, Roberta; Kurtz, Robert C; Derakhshan, Mohammad H; Lagiou, Areti; Lagiou, Pagona; Boffetta, Paolo; Boccia, Stefania; Negri, Eva; La Vecchia, Carlo; Peleteiro, Bárbara; Lunet, Nuno

2018-05-01

Individual participant data pooled analyses allow access to non-published data and statistical reanalyses based on more homogeneous criteria than meta-analyses based on systematic reviews. We quantified the impact of publication-related biases and heterogeneity in data analysis and presentation in summary estimates of the association between alcohol drinking and gastric cancer. We compared estimates obtained from conventional meta-analyses, using only data available in published reports from studies that take part in the Stomach Cancer Pooling (StoP) Project, with individual participant data pooled analyses including the same studies. A total of 22 studies from the StoP Project assessed the relation between alcohol intake and gastric cancer, 19 had specific data for levels of consumption and 18 according to cancer location; published reports addressing these associations were available from 18, 5 and 5 studies, respectively. The summary odds ratios [OR, (95%CI)] estimate obtained with published data for drinkers vs. non-drinkers was 10% higher than the one obtained with individual StoP data [18 vs. 22 studies: 1.21 (1.07-1.36) vs. 1.10 (0.99-1.23)] and more heterogeneous (I 2 : 63.6% vs 54.4%). In general, published data yielded less precise summary estimates (standard errors up to 2.6 times higher). Funnel plot analysis suggested publication bias. Meta-analyses of the association between alcohol drinking and gastric cancer tended to overestimate the magnitude of the effects, possibly due to publication bias. Additionally, individual participant data pooled analyses yielded more precise estimates for different levels of exposure or cancer subtypes. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Mass Production of Redundant, Misleading, and Conflicted Systematic Reviews and Meta-analyses.

PubMed

Ioannidis, John P A

2016-09-01

Currently, there is massive production of unnecessary, misleading, and conflicted systematic reviews and meta-analyses. Instead of promoting evidence-based medicine and health care, these instruments often serve mostly as easily produced publishable units or marketing tools. Suboptimal systematic reviews and meta-analyses can be harmful given the major prestige and influence these types of studies have acquired. The publication of systematic reviews and meta-analyses should be realigned to remove biases and vested interests and to integrate them better with the primary production of evidence. Currently, most systematic reviews and meta-analyses are done retrospectively with fragmented published information. This article aims to explore the growth of published systematic reviews and meta-analyses and to estimate how often they are redundant, misleading, or serving conflicted interests. Data included information from PubMed surveys and from empirical evaluations of meta-analyses. Publication of systematic reviews and meta-analyses has increased rapidly. In the period January 1, 1986, to December 4, 2015, PubMed tags 266,782 items as "systematic reviews" and 58,611 as "meta-analyses." Annual publications between 1991 and 2014 increased 2,728% for systematic reviews and 2,635% for meta-analyses versus only 153% for all PubMed-indexed items. Currently, probably more systematic reviews of trials than new randomized trials are published annually. Most topics addressed by meta-analyses of randomized trials have overlapping, redundant meta-analyses; same-topic meta-analyses may exceed 20 sometimes. Some fields produce massive numbers of meta-analyses; for example, 185 meta-analyses of antidepressants for depression were published between 2007 and 2014. These meta-analyses are often produced either by industry employees or by authors with industry ties and results are aligned with sponsor interests. China has rapidly become the most prolific producer of English-language, PubMed-indexed meta-analyses. The most massive presence of Chinese meta-analyses is on genetic associations (63% of global production in 2014), where almost all results are misleading since they combine fragmented information from mostly abandoned era of candidate genes. Furthermore, many contracting companies working on evidence synthesis receive industry contracts to produce meta-analyses, many of which probably remain unpublished. Many other meta-analyses have serious flaws. Of the remaining, most have weak or insufficient evidence to inform decision making. Few systematic reviews and meta-analyses are both non-misleading and useful. The production of systematic reviews and meta-analyses has reached epidemic proportions. Possibly, the large majority of produced systematic reviews and meta-analyses are unnecessary, misleading, and/or conflicted. © 2016 Milbank Memorial Fund.

Predictive distributions for between-study heterogeneity and simple methods for their application in Bayesian meta-analysis

PubMed Central

Turner, Rebecca M; Jackson, Dan; Wei, Yinghui; Thompson, Simon G; Higgins, Julian P T

2015-01-01

Numerous meta-analyses in healthcare research combine results from only a small number of studies, for which the variance representing between-study heterogeneity is estimated imprecisely. A Bayesian approach to estimation allows external evidence on the expected magnitude of heterogeneity to be incorporated. The aim of this paper is to provide tools that improve the accessibility of Bayesian meta-analysis. We present two methods for implementing Bayesian meta-analysis, using numerical integration and importance sampling techniques. Based on 14 886 binary outcome meta-analyses in the Cochrane Database of Systematic Reviews, we derive a novel set of predictive distributions for the degree of heterogeneity expected in 80 settings depending on the outcomes assessed and comparisons made. These can be used as prior distributions for heterogeneity in future meta-analyses. The two methods are implemented in R, for which code is provided. Both methods produce equivalent results to standard but more complex Markov chain Monte Carlo approaches. The priors are derived as log-normal distributions for the between-study variance, applicable to meta-analyses of binary outcomes on the log odds-ratio scale. The methods are applied to two example meta-analyses, incorporating the relevant predictive distributions as prior distributions for between-study heterogeneity. We have provided resources to facilitate Bayesian meta-analysis, in a form accessible to applied researchers, which allow relevant prior information on the degree of heterogeneity to be incorporated. © 2014 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. PMID:25475839

Mapping the “What” and “Where” Visual Cortices and Their Atrophy in Alzheimer's Disease: Combined Activation Likelihood Estimation with Voxel-Based Morphometry

PubMed Central

Deng, Yanjia; Shi, Lin; Lei, Yi; Liang, Peipeng; Li, Kuncheng; Chu, Winnie C. W.; Wang, Defeng

2016-01-01

The human cortical regions for processing high-level visual (HLV) functions of different categories remain ambiguous, especially in terms of their conjunctions and specifications. Moreover, the neurobiology of declined HLV functions in patients with Alzheimer's disease (AD) has not been fully investigated. This study provides a functionally sorted overview of HLV cortices for processing “what” and “where” visual perceptions and it investigates their atrophy in AD and MCI patients. Based upon activation likelihood estimation (ALE), brain regions responsible for processing five categories of visual perceptions included in “what” and “where” visions (i.e., object, face, word, motion, and spatial visions) were analyzed, and subsequent contrast analyses were performed to show regions with conjunctive and specific activations for processing these visual functions. Next, based on the resulting ALE maps, the atrophy of HLV cortices in AD and MCI patients was evaluated using voxel-based morphometry. Our ALE results showed brain regions for processing visual perception across the five categories, as well as areas of conjunction and specification. Our comparisons of gray matter (GM) volume demonstrated atrophy of three “where” visual cortices in late MCI group and extensive atrophy of HLV cortices (25 regions in both “what” and “where” visual cortices) in AD group. In addition, the GM volume of atrophied visual cortices in AD and MCI subjects was found to be correlated to the deterioration of overall cognitive status and to the cognitive performances related to memory, execution, and object recognition functions. In summary, these findings may add to our understanding of HLV network organization and of the evolution of visual perceptual dysfunction in AD as the disease progresses. PMID:27445770

Sex differences in emotional perception: Meta analysis of divergent activation.

PubMed

Filkowski, Megan M; Olsen, Rachel M; Duda, Bryant; Wanger, Timothy J; Sabatinelli, Dean

2017-02-15

Behavioral and physiological sex differences in emotional reactivity are well documented, yet comparatively few neural differences have been identified. Here we apply quantitative activation likelihood estimation (ALE) meta-analysis across functional brain imaging studies that each reported clusters of activity differentiating men and women as they participated in emotion-evoking tasks in the visual modality. This approach requires the experimental paradigm to be balanced across the sexes, and thus may provide greater clarity than previous efforts. Results across 56 emotion-eliciting studies (n=1907) reveal distinct activation in the medial prefrontal cortex, anterior cingulate cortex, frontal pole, and mediodorsal nucleus of the thalamus in men relative to women. Women show distinct activation in bilateral amygdala, hippocampus, and regions of the dorsal midbrain including the periaqueductal gray/superior colliculus and locus coeruleus. While some clusters are consistent with prevailing perspectives on the foundations of sex differences in emotional reactivity, thalamic and brainstem regions have not previously been highlighted as sexually divergent. These data strongly support the need to include sex as a factor in functional brain imaging studies of emotion, and to extend our investigative focus beyond the cortex. Copyright © 2016 Elsevier Inc. All rights reserved.

Oxytocin and brain activity in humans: A systematic review and coordinate-based meta-analysis of functional MRI studies.

PubMed

Grace, Sally A; Rossell, Susan L; Heinrichs, Markus; Kordsachia, Catarina; Labuschagne, Izelle

2018-05-24

Oxytocin (OXT) is a neuropeptide which has a critical role in human social behaviour and cognition. Research investigating the role of OXT on functional brain changes in humans has often used task paradigms that probe socioemotional processes. Preliminary evidence suggests a central role of the amygdala in the social cognitive effects of intranasal OXT (IN-OXT), however, inconsistencies in task-design and analysis methods have led to inconclusive findings regarding a cohesive model of the neural mechanisms underlying OXT's actions. The aim of this meta-analysis was to systematically investigate these findings. A systematic search of PubMed, PsycINFO, and Scopus databases was conducted for fMRI studies which compared IN-OXT to placebo in humans. First, we systematically reviewed functional magnetic resonance imaging (fMRI) studies of IN-OXT, including studies of healthy humans, those with clinical disorders, and studies examining resting-state fMRI (rsfMRI). Second, we employed a coordinate-based meta-analysis for task-based neuroimaging literature using activation likelihood estimation (ALE), whereby, coordinates were extracted from clusters with significant differences in IN-OXT versus placebo in healthy adults. Data were included for 39 fMRI studies that reported a total of 374 distinct foci. The meta-analysis identified task-related IN-OXT increases in activity within a cluster of the left superior temporal gyrus during tasks of emotion processing. These findings are important as they implicate regions beyond the amygdala in the neural effects of IN-OXT. The outcomes from this meta-analysis can guide a priori predictions for future OXT research, and provide an avenue for targeted treatment interventions. Copyright © 2018 Elsevier Ltd. All rights reserved.

Conducting Meta-Analyses Based on p Values

PubMed Central

van Aert, Robbie C. M.; Wicherts, Jelte M.; van Assen, Marcel A. L. M.

2016-01-01

Because of overwhelming evidence of publication bias in psychology, techniques to correct meta-analytic estimates for such bias are greatly needed. The methodology on which the p-uniform and p-curve methods are based has great promise for providing accurate meta-analytic estimates in the presence of publication bias. However, in this article, we show that in some situations, p-curve behaves erratically, whereas p-uniform may yield implausible estimates of negative effect size. Moreover, we show that (and explain why) p-curve and p-uniform result in overestimation of effect size under moderate-to-large heterogeneity and may yield unpredictable bias when researchers employ p-hacking. We offer hands-on recommendations on applying and interpreting results of meta-analyses in general and p-uniform and p-curve in particular. Both methods as well as traditional methods are applied to a meta-analysis on the effect of weight on judgments of importance. We offer guidance for applying p-uniform or p-curve using R and a user-friendly web application for applying p-uniform. PMID:27694466

Adaptive signal processing and higher order time- frequency analysis for acoustic and vibration signatures in condition monitoring

NASA Astrophysics Data System (ADS)

Lee, Sang-Kwon

This thesis is concerned with the development of a useful engineering technique to detect and analyse faults in rotating machinery. The methods developed are based on the advanced signal processing such as the adaptive signal processing and higher-order time frequency methods. The two-stage Adaptive Line Enhancer (ALE), using adaptive signal processing, has been developed for increasing the Signal to Noise Ratio of impulsive signals. The enhanced signal can then be analysed using time frequency methods to identify fault characteristics. However, if after pre-processing by the two stage ALE, the SNR of the signals is low, the residual noise often hinders clear identification of the fault characteristics in the time-frequency domain. In such cases, higher order time-frequency methods have been proposed and studied. As examples of rotating machinery, the internal combustion engine and an industrial gear box are considered in this thesis. The noise signal from an internal combustion engine and vibration signal measured on a gear box are studied in detail. Typically an impulsive signal manifests itself when the fault occurs in the machinery and is embedded in background noise, such as the fundamental frequency and its harmonic orders of the rotation speed and broadband noise. The two-stage ALE is developed for reducing this background noise. Conditions for the choice of adaptive filter parameters are studied and suitable adaptive algorithms given. The enhanced impulsive signal is analysed in the time- frequency domain using the Wigner higher order moment spectra (WHOMS) and the multi-time WHOMS (which is a dual form of the WHOMS). The WHOMS suffers from unwanted cross-terms, which increase dramatically as the order increases. Novel expressions for the cross-terms in WHOMS have been presented. The number of cross-terms can be reduced by taking the principal slice of the WHOMS. The residual cross-terms are smoothed by using a general class of kernel functions and the γ-method kernel function which is a novel development in this thesis. The WVD and the sliced WHOMS for synthesised signals and measured data from rotating machinery are analysed. The estimated ROC (Receive Operating Characteristic) curves for these methods are computed. These results lead to the conclusion that the detection performance when using the sliced WHOMS, for impulsive signals in embedded in broadband noise, is better than that of the Wigner-Ville distribution. Real data from a faulty car engine and faulty industrial gears are analysed. The car engine radiates an impulsive noise signal due to the loosening of a spark plug. The faulty industrial gear produces an impulsive vibration signal due to a spall on the tooth face in gear. The two- stage ALE and WHOMS are successfully applied to detection and analysis of these impulsive signals.

A general framework for the use of logistic regression models in meta-analysis.

PubMed

Simmonds, Mark C; Higgins, Julian Pt

2016-12-01

Where individual participant data are available for every randomised trial in a meta-analysis of dichotomous event outcomes, "one-stage" random-effects logistic regression models have been proposed as a way to analyse these data. Such models can also be used even when individual participant data are not available and we have only summary contingency table data. One benefit of this one-stage regression model over conventional meta-analysis methods is that it maximises the correct binomial likelihood for the data and so does not require the common assumption that effect estimates are normally distributed. A second benefit of using this model is that it may be applied, with only minor modification, in a range of meta-analytic scenarios, including meta-regression, network meta-analyses and meta-analyses of diagnostic test accuracy. This single model can potentially replace the variety of often complex methods used in these areas. This paper considers, with a range of meta-analysis examples, how random-effects logistic regression models may be used in a number of different types of meta-analyses. This one-stage approach is compared with widely used meta-analysis methods including Bayesian network meta-analysis and the bivariate and hierarchical summary receiver operating characteristic (ROC) models for meta-analyses of diagnostic test accuracy. © The Author(s) 2014.

Systematic review and meta-analysis in cardiac surgery: a primer.

PubMed

Yanagawa, Bobby; Tam, Derrick Y; Mazine, Amine; Tricco, Andrea C

2018-03-01

The purpose of this article is to review the strengths and weaknesses of systematic reviews and meta-analyses to inform our current understanding of cardiac surgery. A systematic review and meta-analysis of a focused topic can provide a quantitative estimate for the effect of a treatment intervention or exposure. In cardiac surgery, observational studies and small, single-center prospective trials provide most of the clinical outcomes that form the evidence base for patient management and guideline recommendations. As such, meta-analyses can be particularly valuable in synthesizing the literature for a particular focused surgical question. Since the year 2000, there are over 800 meta-analysis-related publications in our field. There are some limitations to this technique, including clinical, methodological and statistical heterogeneity, among other challenges. Despite these caveats, results of meta-analyses have been useful in forming treatment recommendations or in providing guidance in the design of future clinical trials. There is a growing number of meta-analyses in the field of cardiac surgery. Knowledge translation via meta-analyses will continue to guide and inform cardiac surgical practice and our practice guidelines.

Methods to Estimate the Between-Study Variance and Its Uncertainty in Meta-Analysis

ERIC Educational Resources Information Center

Veroniki, Areti Angeliki; Jackson, Dan; Viechtbauer, Wolfgang; Bender, Ralf; Bowden, Jack; Knapp, Guido; Kuss, Oliver; Higgins, Julian P. T.; Langan, Dean; Salanti, Georgia

2016-01-01

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,…

Network meta-analyses performed by contracting companies and commissioned by industry.

PubMed

Schuit, Ewoud; Ioannidis, John Pa

2016-11-25

Industry commissions contracting companies to perform network meta-analysis for health technology assessment (HTA) and reimbursement submissions. Our objective was to estimate the number of network meta-analyses performed by consulting companies contracted by industry, to assess whether they were published, and to explore reasons for non-publication. We searched MEDLINE for network meta-analyses of randomized trials. Papers were included if they had authors affiliated with any contracting company. All identified contracting companies as well as additional ones from the list of the exhibitors at the International Society for Pharmacoeconomics and Outcomes Research, an annual meeting that representatives from many contracting companies attend and exhibit at, were surveyed regarding conduct and publication of network meta-analyses. In 162 of 822 (20%) network meta-analysis papers, authors were affiliated to 66 contracting companies. Another 36 contracting companies were identified by the exhibitors list. Three companies had no contact information and six merged with others, therefore 93 companies were contacted. Thirty seven out of ninety three (40%) companies responded, and 19 indicated that they had performed a total of 476 network meta-analyses, but only 102 (21%) papers were published. Thirteen companies that disclosed to have conducted 174 network meta-analyses (45 published) provided reasons for non-publication. Of the 129 still unpublished meta-analyses, for 40 there were plans for future publication, for 37 the sponsor did not allow publication, for 16 the contracting companies did not plan to publish the meta-analysis, for another 23 plans were unclear, and the remaining 13 were used as HTA submission. The protocol of the network meta-analysis was publically available from 11/162 (6.8%) network meta-analyses published by authors affiliated with contracting companies. There is a prolific sector of professional contracting companies that perform network meta-analyses. Industry commissions many network meta-analyses, but most are not registered before or published after analyses in the scientific literature. Mechanisms to improve publication rates of network meta-analysis commissioned by industry are warranted.

The Cognitive Side of M1

PubMed Central

Tomasino, Barbara; Gremese, Michele

2016-01-01

The primary motor cortex (M1) is traditionally implicated in voluntary movement control. In order to test the hypothesis that there is a functional topography of M1 activation in studies where it has been implicated in higher cognitive tasks we performed activation-likelihood-estimation (ALE) meta-analyses of functional neuroimaging experiments reporting M1 activation in relation to six cognitive functional categories for which there was a sufficient number of studies to include, namely motor imagery, working memory, mental rotation, social/emotion/empathy, language, and auditory processing. The six categories activated different sub-sectors of M1, either bilaterally or lateralized to one hemisphere. Notably, the activations found in the M1 of the left or right hemisphere detected in our study were unlikely due to button presses. In fact, all contrasts were selected in order to eliminate M1 activation due to activity related to the finger button press. In addition, we identified the M1 sub-region of Area 4a commonly activated by 4/6 categories, namely motor imagery and working memory, emotion/empathy, and language. Overall, our findings lend support to the idea that there is a functional topography of M1 activation in studies where it has been found activated in higher cognitive tasks and that the left Area 4a can be involved in a number of cognitive processes, likely as a product of implicit mental simulation processing. PMID:27378891

An improved method for bivariate meta-analysis when within-study correlations are unknown.

PubMed

Hong, Chuan; D Riley, Richard; Chen, Yong

2018-03-01

Multivariate meta-analysis, which jointly analyzes multiple and possibly correlated outcomes in a single analysis, is becoming increasingly popular in recent years. An attractive feature of the multivariate meta-analysis is its ability to account for the dependence between multiple estimates from the same study. However, standard inference procedures for multivariate meta-analysis require the knowledge of within-study correlations, which are usually unavailable. This limits standard inference approaches in practice. Riley et al proposed a working model and an overall synthesis correlation parameter to account for the marginal correlation between outcomes, where the only data needed are those required for a separate univariate random-effects meta-analysis. As within-study correlations are not required, the Riley method is applicable to a wide variety of evidence synthesis situations. However, the standard variance estimator of the Riley method is not entirely correct under many important settings. As a consequence, the coverage of a function of pooled estimates may not reach the nominal level even when the number of studies in the multivariate meta-analysis is large. In this paper, we improve the Riley method by proposing a robust variance estimator, which is asymptotically correct even when the model is misspecified (ie, when the likelihood function is incorrect). Simulation studies of a bivariate meta-analysis, in a variety of settings, show a function of pooled estimates has improved performance when using the proposed robust variance estimator. In terms of individual pooled estimates themselves, the standard variance estimator and robust variance estimator give similar results to the original method, with appropriate coverage. The proposed robust variance estimator performs well when the number of studies is relatively large. Therefore, we recommend the use of the robust method for meta-analyses with a relatively large number of studies (eg, m≥50). When the sample size is relatively small, we recommend the use of the robust method under the working independence assumption. We illustrate the proposed method through 2 meta-analyses. Copyright © 2017 John Wiley & Sons, Ltd.

Stuttering, Induced Fluency, and Natural Fluency: A Hierarchical Series of Activation Likelihood Estimation Meta-Analyses

PubMed Central

Budde, Kristin S.; Barron, Daniel S.; Fox, Peter T.

2015-01-01

Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as “neural signatures of stuttering” (Brown 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: 1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and 2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). PMID:25463820

A Practical Guide to Conducting a Systematic Review and Meta-analysis of Health State Utility Values.

PubMed

Petrou, Stavros; Kwon, Joseph; Madan, Jason

2018-05-10

Economic analysts are increasingly likely to rely on systematic reviews and meta-analyses of health state utility values to inform the parameter inputs of decision-analytic modelling-based economic evaluations. Beyond the context of economic evaluation, evidence from systematic reviews and meta-analyses of health state utility values can be used to inform broader health policy decisions. This paper provides practical guidance on how to conduct a systematic review and meta-analysis of health state utility values. The paper outlines a number of stages in conducting a systematic review, including identifying the appropriate evidence, study selection, data extraction and presentation, and quality and relevance assessment. The paper outlines three broad approaches that can be used to synthesise multiple estimates of health utilities for a given health state or condition, namely fixed-effect meta-analysis, random-effects meta-analysis and mixed-effects meta-regression. Each approach is illustrated by a synthesis of utility values for a hypothetical decision problem, and software code is provided. The paper highlights a number of methodological issues pertinent to the conduct of meta-analysis or meta-regression. These include the importance of limiting synthesis to 'comparable' utility estimates, for example those derived using common utility measurement approaches and sources of valuation; the effects of reliance on limited or poorly reported published data from primary utility assessment studies; the use of aggregate outcomes within analyses; approaches to generating measures of uncertainty; handling of median utility values; challenges surrounding the disentanglement of utility estimates collected serially within the context of prospective observational studies or prospective randomised trials; challenges surrounding the disentanglement of intervention effects; and approaches to measuring model validity. Areas of methodological debate and avenues for future research are highlighted.

Diverging Conclusions from the Same Meta-Analysis in Drug Safety: Source of Data (Primary Versus Secondary) Takes a Toll.

PubMed

Prada-Ramallal, Guillermo; Takkouche, Bahi; Figueiras, Adolfo

2017-04-01

Meta-analyses of observational studies represent an important tool for assessing efficacy and safety in the pharmacoepidemiologic field. The data from the individual studies are either primary (i.e., collected through interviews or self-administered questionnaires) or secondary (i.e., collected from databases that were established for other purposes). So far, the origin of the data (primary vs. secondary) has not been systematically assessed as a source of heterogeneity in pharmacoepidemiologic meta-analyses. The aim was to assess the impact of considering the source of exposure data as a criterion in sensitivity and subgroup analysis on the conclusions of drug safety meta-analyses. We selected meta-analyses published between 2013 and 2015 in which the intake of frequently used over-the-counter medicines was either the main exposure or a concomitant treatment and the outcome had short latency and induction periods. We stratified the results by origin of data (primary vs. secondary) and compared the new results to those presented originally in the meta-analyses. We used four meta-analyses that fulfilled our criteria of inclusion. The results were selective serotonin reuptake inhibitors and upper gastrointestinal bleeding: original estimate odds ratio (OR) = 1.71 [95% confidence interval (CI) 1.44-2.04], OR primary data = 1.19 (95% CI 0.90-1.58), OR secondary data = 1.81 (95% CI 1.50-2.17); proton pump inhibitors and cardiac events: original estimate hazard ratio (HR) = 1.35 (95% CI 1.18-1.54), HR primary data = 1.05 (95% CI 0.87-1.26), HR secondary data = 1.43 (95% CI 1.23-1.66); non-aspirin non-steroidal anti-inflammatory drugs and myocardial infarction: original estimate risk ratio (RR) = 1.08 (95% CI 0.95-1.22), RR primary data = 0.57 (95% CI 0.34-0.96), RR secondary data = 1.15 (95% CI 1.03-1.28); paracetamol during pregnancy and childhood asthma: original estimate OR = 1.32 (95% CI 1.14-1.52), OR primary data = 1.23 (95% CI 1.06-1.42), OR secondary data = 1.53 (95% CI 1.33-1.75). The results after stratification are considerably modified. It is crucial to explore the origin of the data, either primary or secondary, as a source of heterogeneity in pharmacoepidemiologic meta-analyses to avoid misleading conclusions.

Measuring the statistical validity of summary meta-analysis and meta-regression results for use in clinical practice.

PubMed

Willis, Brian H; Riley, Richard D

2017-09-20

An important question for clinicians appraising a meta-analysis is: are the findings likely to be valid in their own practice-does the reported effect accurately represent the effect that would occur in their own clinical population? To this end we advance the concept of statistical validity-where the parameter being estimated equals the corresponding parameter for a new independent study. Using a simple ('leave-one-out') cross-validation technique, we demonstrate how we may test meta-analysis estimates for statistical validity using a new validation statistic, Vn, and derive its distribution. We compare this with the usual approach of investigating heterogeneity in meta-analyses and demonstrate the link between statistical validity and homogeneity. Using a simulation study, the properties of Vn and the Q statistic are compared for univariate random effects meta-analysis and a tailored meta-regression model, where information from the setting (included as model covariates) is used to calibrate the summary estimate to the setting of application. Their properties are found to be similar when there are 50 studies or more, but for fewer studies Vn has greater power but a higher type 1 error rate than Q. The power and type 1 error rate of Vn are also shown to depend on the within-study variance, between-study variance, study sample size, and the number of studies in the meta-analysis. Finally, we apply Vn to two published meta-analyses and conclude that it usefully augments standard methods when deciding upon the likely validity of summary meta-analysis estimates in clinical practice. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd. © 2017 The Authors. Statistics in Medicine published by John Wiley & Sons Ltd.

Adjusting for publication biases across similar interventions performed well when compared with gold standard data.

PubMed

Moreno, Santiago G; Sutton, Alex J; Ades, A E; Cooper, Nicola J; Abrams, Keith R

2011-11-01

To extend, apply, and evaluate a regression-based approach to adjusting meta-analysis for publication and related biases. The approach uses related meta-analyses to improve estimation by borrowing strength on the degree of bias. The proposed adjustment approach is described. Adjustments are applied both independently and by borrowing strength across journal-extracted data on the effectiveness of 12 antidepressant drugs from placebo-controlled trials. The methods are also applied to Food and Drug Administration (FDA) data obtained on the same 12 drugs. Results are compared, viewing the FDA observed data as gold standard. Estimates adjusted for publication biases made independently for each drug were very uncertain using both the journal and FDA data. Adjusted estimates were much more precise when borrowing strength across meta-analyses. Reassuringly, adjustments in this way made to the journal data agreed closely with the observed estimates from the FDA data, while the adjusted FDA results changed only minimally from those observed from the FDA data. The method worked well in the case study considered and therefore further evaluation is encouraged. It is suggested that this approach may be especially useful when adjusting several meta-analyses on similar interventions and outcomes, particularly when there are small numbers of studies. Copyright © 2011 Elsevier Inc. All rights reserved.

Systematic literature reviews and meta-analyses: part 6 of a series on evaluation of scientific publications.

PubMed

Ressing, Meike; Blettner, Maria; Klug, Stefanie J

2009-07-01

Because of the rising number of scientific publications, it is important to have a means of jointly summarizing and assessing different studies on a single topic. Systematic literature reviews, meta-analyses of published data, and meta-analyses of individual data (pooled reanalyses) are now being published with increasing frequency. We here describe the essential features of these methods and discuss their strengths and weaknesses. This article is based on a selective literature search. The different types of review and meta-analysis are described, the methods used in each are outlined so that they can be evaluated, and a checklist is given for the assessment of reviews and meta-analyses of scientific articles. Systematic literature reviews provide an overview of the state of research on a given topic and enable an assessment of the quality of individual studies. They also allow the results of different studies to be evaluated together when these are inconsistent. Meta-analyses additionally allow calculation of pooled estimates of an effect. The different types of review and meta-analysis are discussed with examples from the literature on one particular topic. Systematic literature reviews and meta-analyses enable the research findings and treatment effects obtained in different individual studies to be summed up and evaluated.

Can statistic adjustment of OR minimize the potential confounding bias for meta-analysis of case-control study? A secondary data analysis.

PubMed

Liu, Tianyi; Nie, Xiaolu; Wu, Zehao; Zhang, Ying; Feng, Guoshuang; Cai, Siyu; Lv, Yaqi; Peng, Xiaoxia

2017-12-29

Different confounder adjustment strategies were used to estimate odds ratios (ORs) in case-control study, i.e. how many confounders original studies adjusted and what the variables are. This secondary data analysis is aimed to detect whether there are potential biases caused by difference of confounding factor adjustment strategies in case-control study, and whether such bias would impact the summary effect size of meta-analysis. We included all meta-analyses that focused on the association between breast cancer and passive smoking among non-smoking women, as well as each original case-control studies included in these meta-analyses. The relative deviations (RDs) of each original study were calculated to detect how magnitude the adjustment would impact the estimation of ORs, compared with crude ORs. At the same time, a scatter diagram was sketched to describe the distribution of adjusted ORs with different number of adjusted confounders. Substantial inconsistency existed in meta-analysis of case-control studies, which would influence the precision of the summary effect size. First, mixed unadjusted and adjusted ORs were used to combine individual OR in majority of meta-analysis. Second, original studies with different adjustment strategies of confounders were combined, i.e. the number of adjusted confounders and different factors being adjusted in each original study. Third, adjustment did not make the effect size of original studies trend to constringency, which suggested that model fitting might have failed to correct the systematic error caused by confounding. The heterogeneity of confounder adjustment strategies in case-control studies may lead to further bias for summary effect size in meta-analyses, especially for weak or medium associations so that the direction of causal inference would be even reversed. Therefore, further methodological researches are needed, referring to the assessment of confounder adjustment strategies, as well as how to take this kind of bias into consideration when drawing conclusion based on summary estimation of meta-analyses.

Stuttering, induced fluency, and natural fluency: a hierarchical series of activation likelihood estimation meta-analyses.

PubMed

Budde, Kristin S; Barron, Daniel S; Fox, Peter T

2014-12-01

Developmental stuttering is a speech disorder most likely due to a heritable form of developmental dysmyelination impairing the function of the speech-motor system. Speech-induced brain-activation patterns in persons who stutter (PWS) are anomalous in various ways; the consistency of these aberrant patterns is a matter of ongoing debate. Here, we present a hierarchical series of coordinate-based meta-analyses addressing this issue. Two tiers of meta-analyses were performed on a 17-paper dataset (202 PWS; 167 fluent controls). Four large-scale (top-tier) meta-analyses were performed, two for each subject group (PWS and controls). These analyses robustly confirmed the regional effects previously postulated as "neural signatures of stuttering" (Brown, Ingham, Ingham, Laird, & Fox, 2005) and extended this designation to additional regions. Two smaller-scale (lower-tier) meta-analyses refined the interpretation of the large-scale analyses: (1) a between-group contrast targeting differences between PWS and controls (stuttering trait); and (2) a within-group contrast (PWS only) of stuttering with induced fluency (stuttering state). Copyright © 2014 Elsevier Inc. All rights reserved.

The Meditative Mind: A Comprehensive Meta-Analysis of MRI Studies

PubMed Central

2015-01-01

Over the past decade mind and body practices, such as yoga and meditation, have raised interest in different scientific fields; in particular, the physiological mechanisms underlying the beneficial effects observed in meditators have been investigated. Neuroimaging studies have studied the effects of meditation on brain structure and function and findings have helped clarify the biological underpinnings of the positive effects of meditation practice and the possible integration of this technique in standard therapy. The large amount of data collected thus far allows drawing some conclusions about the neural effects of meditation practice. In the present study we used activation likelihood estimation (ALE) analysis to make a coordinate-based meta-analysis of neuroimaging data on the effects of meditation on brain structure and function. Results indicate that meditation leads to activation in brain areas involved in processing self-relevant information, self-regulation, focused problem-solving, adaptive behavior, and interoception. Results also show that meditation practice induces functional and structural brain modifications in expert meditators, especially in areas involved in self-referential processes such as self-awareness and self-regulation. These results demonstrate that a biological substrate underlies the positive pervasive effect of meditation practice and suggest that meditation techniques could be adopted in clinical populations and to prevent disease. PMID:26146618

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies.

PubMed

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-05-17

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks.

Effects of cue focality on the neural mechanisms of prospective memory: A meta-analysis of neuroimaging studies

PubMed Central

Cona, Giorgia; Bisiacchi, Patrizia Silvia; Sartori, Giuseppe; Scarpazza, Cristina

2016-01-01

Remembering to execute pre-defined intentions at the appropriate time in the future is typically referred to as Prospective Memory (PM). Studies of PM showed that distinct cognitive processes underlie the execution of delayed intentions depending on whether the cue associated with such intentions is focal to ongoing activity processing or not (i.e., cue focality). The present activation likelihood estimation (ALE) meta-analysis revealed several differences in brain activity as a function of focality of the PM cue. The retrieval of intention is supported mainly by left anterior prefrontal cortex (Brodmann Area, BA 10) in nonfocal tasks, and by cerebellum and ventral parietal regions in focal tasks. Furthermore, the precuneus showed increased activation during the maintenance phase of intentions compared to the retrieval phase in nonfocal tasks, whereas the inferior parietal lobule showed increased activation during the retrieval of intention compared to maintenance phase in the focal tasks. Finally, the retrieval of intention relies more on the activity in anterior cingulate cortex for nonfocal tasks, and on posterior cingulate cortex for focal tasks. Such focality-related pattern of activations suggests that prospective remembering is mediated mainly by top-down and stimulus-independent processes in nonfocal tasks, whereas by more automatic, bottom-up, processes in focal tasks. PMID:27185531

Meta-analyses on intra-aortic balloon pump in cardiogenic shock complicating acute myocardial infarction may provide biased results.

PubMed

Acconcia, M C; Caretta, Q; Romeo, F; Borzi, M; Perrone, M A; Sergi, D; Chiarotti, F; Calabrese, C M; Sili Scavalli, A; Gaudio, C

2018-04-01

Intra-aortic balloon pump (IABP) is the device most commonly investigated in patients with cardiogenic shock (CS) complicating acute myocardial infarction (AMI). Recently meta-analyses on this topic showed opposite results: some complied with the actual guideline recommendations, while others did not, due to the presence of bias. We investigated the reasons for the discrepancy among meta-analyses and strategies employed to avoid the potential source of bias. Scientific databases were searched for meta-analyses of IABP support in AMI complicated by CS. The presence of clinical diversity, methodological diversity and statistical heterogeneity were analyzed. When we found clinical or methodological diversity, we reanalyzed the data by comparing the patients selected for homogeneous groups. When the fixed effect model was employed despite the presence of statistical heterogeneity, the meta-analysis was repeated adopting the random effect model, with the same estimator used in the original meta-analysis. Twelve meta-analysis were selected. Six meta-analyses of randomized controlled trials (RCTs) were inconclusive because underpowered to detect the IABP effect. Five included RCTs and observational studies (Obs) and one only Obs. Some meta-analyses on RCTs and Obs had biased results due to presence of clinical and/or methodological diversity. The reanalysis of data reallocated for homogeneous groups was no more in contrast with guidelines recommendations. Meta-analyses performed without controlling for clinical and/or methodological diversity, represent a confounding message against a good clinical practice. The reanalysis of data demonstrates the validity of the current guidelines recommendations in addressing clinical decision making in providing IABP support in AMI complicated by CS.

Exposure to traffic-related air pollution and risk of development of childhood asthma: A systematic review and meta-analysis.

PubMed

Khreis, Haneen; Kelly, Charlotte; Tate, James; Parslow, Roger; Lucas, Karen; Nieuwenhuijsen, Mark

2017-03-01

The question of whether children's exposure to traffic-related air pollution (TRAP) contributes to their development of asthma is unresolved. We conducted a systematic review and performed meta-analyses to analyze the association between TRAP and asthma development in childhood. We systematically reviewed epidemiological studies published until 8 September 2016 and available in the Embase, Ovid MEDLINE (R), and Transport databases. We included studies that examined the association between children's exposure to TRAP metrics and their risk of 'asthma' incidence or lifetime prevalence, from birth to age 18years old. We extracted key characteristics of each included study using a predefined data items template and these were tabulated. We used the Critical Appraisal Skills Programme checklists to assess the validity of each included study. Where four or more independent risk estimates were available for a continuous pollutant exposure, we conducted overall and age-specific meta-analyses, and four sensitivity analyses for each summary meta-analytic exposure-outcome association. Forty-one studies met our eligibility criteria. There was notable variability in asthma definitions, TRAP exposure assessment methods and confounder adjustment. The overall random-effects risk estimates (95% CI) were 1.08 (1.03, 1.14) per 0.5×10 -5 m -1 black carbon (BC), 1.05 (1.02, 1.07) per 4μg/m 3 nitrogen dioxide (NO 2 ), 1.48 (0.89, 2.45) per 30μg/m 3 nitrogen oxides (NO x ), 1.03 (1.01, 1.05) per 1μg/m 3 Particulate Matter <2.5μm in diameter (PM 2.5 ), and 1.05 (1.02, 1.08) per 2μg/m 3 Particulate Matter <10μm in diameter (PM 10 ). Sensitivity analyses supported these findings. Across the main analysis and age-specific analysis, the least heterogeneity was seen for the BC estimates, some heterogeneity for the PM 2.5 and PM 10 estimates and the most heterogeneity for the NO 2 and NO x estimates. The overall risk estimates from the meta-analyses showed statistically significant associations for BC, NO 2 , PM 2.5 , PM 10 exposures and risk of asthma development. Our findings support the hypothesis that childhood exposure to TRAP contributes to their development of asthma. Future meta-analyses would benefit from greater standardization of study methods including exposure assessment harmonization, outcome harmonization, confounders' harmonization and the inclusion of all important confounders in individual studies. PROSPERO 2014: CRD42014015448. Copyright © 2016 Elsevier Ltd. All rights reserved.

Consequences of Not Accounting for One-Group Clustering in Meta-Analysis

ERIC Educational Resources Information Center

Citkowicz, Martyna; Polanin, Joshua R.

2014-01-01

Meta-analyses are syntheses of effect-size estimates obtained from a collection of studies to summarize a particular field or topic (Hedges, 1992; Lipsey & Wilson, 2001). These reviews are used to integrate knowledge that can inform both scientific inquiry and public policy, therefore it is important to ensure that the estimates of the effect…

Comparative evidence on harms in pediatric randomized clinical trials from less developed versus more developed countries is limited.

PubMed

Tedesco, Dario; Farid-Kapadia, Mufiza; Offringa, Martin; Bhutta, Zulfiqar A; Maldonado, Yvonne; Ioannidis, John P A; Contopoulos-Ioannidis, Despina G

2018-03-01

Evaluate comparative harm rates from medical interventions in pediatric randomized clinical trials (RCTs) from more developed (MDCs) and less developed countries (LDCs). Meta-epidemiologic empirical evaluation of Cochrane Database of Systematic Reviews (June 2014) meta-analyses reporting clinically important harm-outcomes (severe adverse events [AEs], discontinuations due to AEs, any AE, and mortality) that included at least one pediatric RCT from MDCs and at least one from LDCs. We estimated relative odds ratios (RORs) for each harm, within each meta-analysis, between RCTs from MDCs and LDCs and calculated random-effects-summary-RORs (sRORs) for each harm across multiple meta-analyses. Only 1% (26/2,363) of meta-analyses with clinically important harm-outcomes in the entire Cochrane Database of Systematic Reviews included pediatric RCTs both from MDCs and LDCs. We analyzed 26 meta-analyses with 244 data sets from pediatric RCTs, 116 from MDCs and 128 from LDCs (64 and 66 unique RCTs respectively). The summary ROR was 0.92 (95% confidence intervals: 0.78-1.08) for severe AEs; 1.13 (0.54-2.34) for discontinuations due to AEs; 1.10 (0.77-1.59) for any AE; and 0.99 (0.61-1.61) for mortality and for the all-harms-combined-end point 0.96 (0.83-1.10). Differences of ROR-point-estimates ≥2-fold between MDCs and LDCs were identified in 35% of meta-analyses. We found no major systematic differences in harm rates in pediatric trials between MDCs and LDCs, but data on harms in children were overall very limited. Copyright © 2017 Elsevier Inc. All rights reserved.

Meta-analytic estimates predict the effectiveness of emotion regulation strategies in the "real world": reply to Augustine and Hemenover (2013).

PubMed

Miles, Eleanor; Sheeran, Paschal; Webb, Thomas L

2013-05-01

Augustine and Hemenover (2013) were right to state that meta-analyses should be accurate and generalizable. However, we disagree that our meta-analysis of emotion regulation strategies (Webb, Miles, & Sheeran, 2012) fell short in these respects. Augustine and Hemenover's concerns appear to have accrued from misunderstandings of our inclusion criteria or from disagreements with methodological decisions that are crucial to the validity of meta-analysis. This response clarifies the bases of these decisions and discusses implications for the accuracy and validity of meta-analyses. Furthermore, we show that our findings are consistent with theoretical predictions and previous reviews, and we present new evidence that the effect sizes that we obtained are generalizable. In particular, we demonstrate that our estimates of the effectiveness of emotion regulation strategies reveal how well these strategies predict important emotional outcomes over 1 year. PsycINFO Database Record (c) 2013 APA, all rights reserved.

The Paired Availability Design and Related Instrumental Variable Meta-analyses | Division of Cancer Prevention

Cancer.gov

Stuart G. Baker, 2017 Introduction This software computes meta-analysis and extrapolation estimates for an instrumental variable meta-analysis of randomized trial or before-and-after studies (the latter also known as the paired availability design). The software also checks on the assumptions if sufficient data are available. |

Night shift work and breast cancer risk: what do the meta-analyses tell us?

PubMed

Pahwa, Manisha; Labrèche, France; Demers, Paul A

2018-05-22

Objectives This paper aims to compare results, assess the quality, and discuss the implications of recently published meta-analyses of night shift work and breast cancer risk. Methods A comprehensive search was conducted for meta-analyses published from 2007-2017 that included at least one pooled effect size (ES) for breast cancer associated with any night shift work exposure metric and were accompanied by a systematic literature review. Pooled ES from each meta-analysis were ascertained with a focus on ever/never exposure associations. Assessments of heterogeneity and publication bias were also extracted. The AMSTAR 2 checklist was used to evaluate quality. Results Seven meta-analyses, published from 2013-2016, collectively included 30 cohort and case-control studies spanning 1996-2016. Five meta-analyses reported pooled ES for ever/never night shift work exposure; these ranged from 0.99 [95% confidence interval (CI) 0.95-1.03, N=10 cohort studies) to 1.40 (95% CI 1.13-1.73, N=9 high quality studies). Estimates for duration, frequency, and cumulative night shift work exposure were scant and mostly not statistically significant. Meta-analyses of cohort, Asian, and more fully-adjusted studies generally resulted in lower pooled ES than case-control, European, American, or minimally-adjusted studies. Most reported statistically significant between-study heterogeneity. Publication bias was not evident in any of the meta-analyses. Only one meta-analysis was strong in critical quality domains. Conclusions Fairly consistent elevated pooled ES were found for ever/never night shift work and breast cancer risk, but results for other shift work exposure metrics were inconclusive. Future evaluations of shift work should incorporate high quality meta-analyses that better appraise individual study quality.

Report on the EPA Work Group on VSL Meta-Analyses (2006)

EPA Pesticide Factsheets

The following report contains an analysis of the use of meta-analytic procedures to determine an estimate of VSL. Many detailed issues are covered in this report, but several general comments are also highlighted.

A Meta-Analysis of Randomized Controlled Trials and Prospective Cohort Studies of Eicosapentaenoic and Docosahexaenoic Long-Chain Omega-3 Fatty Acids and Coronary Heart Disease Risk.

PubMed

Alexander, Dominik D; Miller, Paige E; Van Elswyk, Mary E; Kuratko, Connye N; Bylsma, Lauren C

2017-01-01

To conduct meta-analyses of randomized controlled trials (RCTs) to estimate the effect of eicosapentaenoic and docosahexaenoic acid (EPA+DHA) on coronary heart disease (CHD), and to conduct meta-analyses of prospective cohort studies to estimate the association between EPA+DHA intake and CHD risk. A systematic literature search of Ovid/Medline, PubMed, Embase, and the Cochrane Library from January 1, 1947, to November 2, 2015, was conducted; 18 RCTs and 16 prospective cohort studies examining EPA+DHA from foods or supplements and CHD, including myocardial infarction, sudden cardiac death, coronary death, and angina, were identified. Random-effects meta-analysis models were used to generate summary relative risk estimates (SRREs) and 95% CIs. Heterogeneity was examined in subgroup and sensitivity analyses and by meta-regression. Dose-response was evaluated in stratified dose or intake analyses. Publication bias assessments were performed. Among RCTs, there was a nonstatistically significant reduction in CHD risk with EPA+DHA provision (SRRE=0.94; 95% CI, 0.85-1.05). Subgroup analyses of data from RCTs indicated a statistically significant CHD risk reduction with EPA+DHA provision among higher-risk populations, including participants with elevated triglyceride levels (SRRE=0.84; 95% CI, 0.72-0.98) and elevated low-density lipoprotein cholesterol (SRRE=0.86; 95% CI, 0.76-0.98). Meta-analysis of data from prospective cohort studies resulted in a statistically significant SRRE of 0.82 (95% CI, 0.74-0.92) for higher intakes of EPA+DHA and risk of any CHD event. Results indicate that EPA+DHA may be associated with reducing CHD risk, with a greater benefit observed among higher-risk populations in RCTs. Copyright © 2016 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

Individual participant data meta-analyses should not ignore clustering

PubMed Central

Abo-Zaid, Ghada; Guo, Boliang; Deeks, Jonathan J.; Debray, Thomas P.A.; Steyerberg, Ewout W.; Moons, Karel G.M.; Riley, Richard David

2013-01-01

Objectives Individual participant data (IPD) meta-analyses often analyze their IPD as if coming from a single study. We compare this approach with analyses that rather account for clustering of patients within studies. Study Design and Setting Comparison of effect estimates from logistic regression models in real and simulated examples. Results The estimated prognostic effect of age in patients with traumatic brain injury is similar, regardless of whether clustering is accounted for. However, a family history of thrombophilia is found to be a diagnostic marker of deep vein thrombosis [odds ratio, 1.30; 95% confidence interval (CI): 1.00, 1.70; P = 0.05] when clustering is accounted for but not when it is ignored (odds ratio, 1.06; 95% CI: 0.83, 1.37; P = 0.64). Similarly, the treatment effect of nicotine gum on smoking cessation is severely attenuated when clustering is ignored (odds ratio, 1.40; 95% CI: 1.02, 1.92) rather than accounted for (odds ratio, 1.80; 95% CI: 1.29, 2.52). Simulations show models accounting for clustering perform consistently well, but downwardly biased effect estimates and low coverage can occur when ignoring clustering. Conclusion Researchers must routinely account for clustering in IPD meta-analyses; otherwise, misleading effect estimates and conclusions may arise. PMID:23651765

The handyman's brain: a neuroimaging meta-analysis describing the similarities and differences between grip type and pattern in humans.

PubMed

King, M; Rauch, H G; Stein, D J; Brooks, S J

2014-11-15

Handgrip is a ubiquitous human movement that was critical in our evolution. However, the differences in brain activity between grip type (i.e. power or precision) and pattern (i.e. dynamic or static) are not fully understood. In order to address this, we performed Activation Likelihood Estimation (ALE) analysis between grip type and grip pattern using functional magnetic resonance imaging (fMRI) data. ALE provides a probabilistic summary of the BOLD response in hundreds of subjects, which is often beyond the scope of a single fMRI experiment. We collected data from 28 functional magnetic resonance data sets, which included a total of 398 male and female subjects. Using ALE, we analyzed the BOLD response during power, precision, static and dynamic grip in a range of forces and age in right handed healthy individuals without physical impairment, cardiovascular or neurological dysfunction using a variety of grip tools, feedback and experimental training. Power grip generates unique activation in the postcentral gyrus (areas 1 and 3b) and precision grip generates unique activation in the supplementary motor area (SMA, area 6) and precentral gyrus (area 4a). Dynamic handgrip generates unique activation in the precentral gyrus (area 4p) and SMA (area 6) and of particular interest, both dynamic and static grip share activation in the area 2 of the postcentral gyrus, an area implicated in the evolution of handgrip. According to effect size analysis, precision and dynamic grip generates stronger activity than power and static, respectively. Our study demonstrates specific differences between grip type and pattern. However, there was a large degree of overlap in the pre and postcentral gyrus, SMA and areas of the frontal-parietal-cerebellar network, which indicates that other mechanisms are potentially involved in regulating handgrip. Further, our study provides empirically based regions of interest, which can be downloaded here within, that can be used to more effectively study power grip in a range of populations and conditions. Copyright © 2014 Elsevier Inc. All rights reserved.

Conducting meta-analyses of HIV prevention literatures from a theory-testing perspective.

PubMed

Marsh, K L; Johnson, B T; Carey, M P

2001-09-01

Using illustrations from HIV prevention research, the current article advocates approaching meta-analysis as a theory-testing scientific method rather than as merely a set of rules for quantitative analysis. Like other scientific methods, meta-analysis has central concerns with internal, external, and construct validity. The focus of a meta-analysis should only rarely be merely describing the effects of health promotion, but rather should be on understanding and explaining phenomena and the processes underlying them. The methodological decisions meta-analysts make in conducting reviews should be guided by a consideration of the underlying goals of the review (e.g., simply effect size estimation or, preferably theory testing). From the advocated perspective that a health behavior meta-analyst should test theory, the authors present a number of issues to be considered during the conduct of meta-analyses.

Empirical evidence about inconsistency among studies in a pair-wise meta-analysis.

PubMed

Rhodes, Kirsty M; Turner, Rebecca M; Higgins, Julian P T

2016-12-01

This paper investigates how inconsistency (as measured by the I 2 statistic) among studies in a meta-analysis may differ, according to the type of outcome data and effect measure. We used hierarchical models to analyse data from 3873 binary, 5132 continuous and 880 mixed outcome meta-analyses within the Cochrane Database of Systematic Reviews. Predictive distributions for inconsistency expected in future meta-analyses were obtained, which can inform priors for between-study variance. Inconsistency estimates were highest on average for binary outcome meta-analyses of risk differences and continuous outcome meta-analyses. For a planned binary outcome meta-analysis in a general research setting, the predictive distribution for inconsistency among log odds ratios had median 22% and 95% CI: 12% to 39%. For a continuous outcome meta-analysis, the predictive distribution for inconsistency among standardized mean differences had median 40% and 95% CI: 15% to 73%. Levels of inconsistency were similar for binary data measured by log odds ratios and log relative risks. Fitted distributions for inconsistency expected in continuous outcome meta-analyses using mean differences were almost identical to those using standardized mean differences. The empirical evidence on inconsistency gives guidance on which outcome measures are most likely to be consistent in particular circumstances and facilitates Bayesian meta-analysis with an informative prior for heterogeneity. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd. © 2015 The Authors. Research Synthesis Methods published by John Wiley & Sons, Ltd.

The effect of oral rehydration solution and recommended home fluids on diarrhoea mortality

PubMed Central

Munos, Melinda K.; Walker, Christa L Fischer; Black, Robert E

2010-01-01

Background Most diarrhoeal deaths can be prevented through the prevention and treatment of dehydration. Oral rehydration solution (ORS) and recommended home fluids (RHFs) have been recommended since 1970s and 1980s to prevent and treat diarrhoeal dehydration. We sought to estimate the effects of these interventions on diarrhoea mortality in children aged <5 years. Methods We conducted a systematic review to identify studies evaluating the efficacy and effectiveness of ORS and RHFs and abstracted study characteristics and outcome measures into standardized tables. We categorized the evidence by intervention and outcome, conducted meta-analyses for all outcomes with two or more data points and graded the quality of the evidence supporting each outcome. The CHERG Rules for Evidence Review were used to estimate the effectiveness of ORS and RHFs against diarrhoea mortality. Results We identified 205 papers for abstraction, of which 157 were included in the meta-analyses of ORS outcomes and 12 were included in the meta-analyses of RHF outcomes. We estimated that ORS may prevent 93% of diarrhoea deaths. Conclusions ORS is effective against diarrhoea mortality in home, community and facility settings; however, there is insufficient evidence to estimate the effectiveness of RHFs against diarrhoea mortality. PMID:20348131

Subliminal versus supraliminal stimuli activate neural responses in anterior cingulate cortex, fusiform gyrus and insula: a meta-analysis of fMRI studies.

PubMed

Meneguzzo, Paolo; Tsakiris, Manos; Schioth, Helgi B; Stein, Dan J; Brooks, Samantha J

2014-01-01

Non-conscious neural activation may underlie various psychological functions in health and disorder. However, the neural substrates of non-conscious processing have not been entirely elucidated. Examining the differential effects of arousing stimuli that are consciously, versus unconsciously perceived will improve our knowledge of neural circuitry involved in non-conscious perception. Here we conduct preliminary analyses of neural activation in studies that have used both subliminal and supraliminal presentation of the same stimulus. We use Activation Likelihood Estimation (ALE) to examine functional Magnetic Resonance Imaging (fMRI) studies that uniquely present the same stimuli subliminally and supraliminally to healthy participants during functional magnetic resonance imaging (fMRI). We included a total of 193 foci from 9 studies representing subliminal stimulation and 315 foci from 10 studies representing supraliminal stimulation. The anterior cingulate cortex is significantly activated during both subliminal and supraliminal stimulus presentation. Subliminal stimuli are linked to significantly increased activation in the right fusiform gyrus and right insula. Supraliminal stimuli show significantly increased activation in the left rostral anterior cingulate. Non-conscious processing of arousing stimuli may involve primary visual areas and may also recruit the insula, a brain area involved in eventual interoceptive awareness. The anterior cingulate is perhaps a key brain region for the integration of conscious and non-conscious processing. These preliminary data provide candidate brain regions for further study in to the neural correlates of conscious experience.

Quantifying, displaying and accounting for heterogeneity in the meta-analysis of RCTs using standard and generalised Q statistics

PubMed Central

2011-01-01

Background Clinical researchers have often preferred to use a fixed effects model for the primary interpretation of a meta-analysis. Heterogeneity is usually assessed via the well known Q and I2 statistics, along with the random effects estimate they imply. In recent years, alternative methods for quantifying heterogeneity have been proposed, that are based on a 'generalised' Q statistic. Methods We review 18 IPD meta-analyses of RCTs into treatments for cancer, in order to quantify the amount of heterogeneity present and also to discuss practical methods for explaining heterogeneity. Results Differing results were obtained when the standard Q and I2 statistics were used to test for the presence of heterogeneity. The two meta-analyses with the largest amount of heterogeneity were investigated further, and on inspection the straightforward application of a random effects model was not deemed appropriate. Compared to the standard Q statistic, the generalised Q statistic provided a more accurate platform for estimating the amount of heterogeneity in the 18 meta-analyses. Conclusions Explaining heterogeneity via the pre-specification of trial subgroups, graphical diagnostic tools and sensitivity analyses produced a more desirable outcome than an automatic application of the random effects model. Generalised Q statistic methods for quantifying and adjusting for heterogeneity should be incorporated as standard into statistical software. Software is provided to help achieve this aim. PMID:21473747

The effect of English-language restriction on systematic review-based meta-analyses: a systematic review of empirical studies.

PubMed

Morrison, Andra; Polisena, Julie; Husereau, Don; Moulton, Kristen; Clark, Michelle; Fiander, Michelle; Mierzwinski-Urban, Monika; Clifford, Tammy; Hutton, Brian; Rabb, Danielle

2012-04-01

The English language is generally perceived to be the universal language of science. However, the exclusive reliance on English-language studies may not represent all of the evidence. Excluding languages other than English (LOE) may introduce a language bias and lead to erroneous conclusions. We conducted a comprehensive literature search using bibliographic databases and grey literature sources. Studies were eligible for inclusion if they measured the effect of excluding randomized controlled trials (RCTs) reported in LOE from systematic review-based meta-analyses (SR/MA) for one or more outcomes. None of the included studies found major differences between summary treatment effects in English-language restricted meta-analyses and LOE-inclusive meta-analyses. Findings differed about the methodological and reporting quality of trials reported in LOE. The precision of pooled estimates improved with the inclusion of LOE trials. Overall, we found no evidence of a systematic bias from the use of language restrictions in systematic review-based meta-analyses in conventional medicine. Further research is needed to determine the impact of language restriction on systematic reviews in particular fields of medicine.

Meta-analysis of randomized clinical trials in the era of individual patient data sharing.

PubMed

Kawahara, Takuya; Fukuda, Musashi; Oba, Koji; Sakamoto, Junichi; Buyse, Marc

2018-06-01

Individual patient data (IPD) meta-analysis is considered to be a gold standard when the results of several randomized trials are combined. Recent initiatives on sharing IPD from clinical trials offer unprecedented opportunities for using such data in IPD meta-analyses. First, we discuss the evidence generated and the benefits obtained by a long-established prospective IPD meta-analysis in early breast cancer. Next, we discuss a data-sharing system that has been adopted by several pharmaceutical sponsors. We review a number of retrospective IPD meta-analyses that have already been proposed using this data-sharing system. Finally, we discuss the role of data sharing in IPD meta-analysis in the future. Treatment effects can be more reliably estimated in both types of IPD meta-analyses than with summary statistics extracted from published papers. Specifically, with rich covariate information available on each patient, prognostic and predictive factors can be identified or confirmed. Also, when several endpoints are available, surrogate endpoints can be assessed statistically. Although there are difficulties in conducting, analyzing, and interpreting retrospective IPD meta-analysis utilizing the currently available data-sharing systems, data sharing will play an important role in IPD meta-analysis in the future.

A Critical Meta-Analysis of Lens Model Studies in Human Judgment and Decision-Making

PubMed Central

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W.

2013-01-01

Achieving accurate judgment (‘judgmental achievement’) is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping. PMID:24391781

A critical meta-analysis of lens model studies in human judgment and decision-making.

PubMed

Kaufmann, Esther; Reips, Ulf-Dietrich; Wittmann, Werner W

2013-01-01

Achieving accurate judgment ('judgmental achievement') is of utmost importance in daily life across multiple domains. The lens model and the lens model equation provide useful frameworks for modeling components of judgmental achievement and for creating tools to help decision makers (e.g., physicians, teachers) reach better judgments (e.g., a correct diagnosis, an accurate estimation of intelligence). Previous meta-analyses of judgment and decision-making studies have attempted to evaluate overall judgmental achievement and have provided the basis for evaluating the success of bootstrapping (i.e., replacing judges by linear models that guide decision making). However, previous meta-analyses have failed to appropriately correct for a number of study design artifacts (e.g., measurement error, dichotomization), which may have potentially biased estimations (e.g., of the variability between studies) and led to erroneous interpretations (e.g., with regards to moderator variables). In the current study we therefore conduct the first psychometric meta-analysis of judgmental achievement studies that corrects for a number of study design artifacts. We identified 31 lens model studies (N = 1,151, k = 49) that met our inclusion criteria. We evaluated overall judgmental achievement as well as whether judgmental achievement depended on decision domain (e.g., medicine, education) and/or the level of expertise (expert vs. novice). We also evaluated whether using corrected estimates affected conclusions with regards to the success of bootstrapping with psychometrically-corrected models. Further, we introduce a new psychometric trim-and-fill method to estimate the effect sizes of potentially missing studies correct psychometric meta-analyses for effects of publication bias. Comparison of the results of the psychometric meta-analysis with the results of a traditional meta-analysis (which only corrected for sampling error) indicated that artifact correction leads to a) an increase in values of the lens model components, b) reduced heterogeneity between studies, and c) increases the success of bootstrapping. We argue that psychometric meta-analysis is useful for accurately evaluating human judgment and show the success of bootstrapping.

Neural foundation of human moral reasoning: an ALE meta-analysis about the role of personal perspective.

PubMed

Boccia, M; Dacquino, C; Piccardi, L; Cordellieri, P; Guariglia, C; Ferlazzo, F; Ferracuti, S; Giannini, A M

2017-02-01

Moral sense is defined as a feeling of the rightness or wrongness of an action that knowingly causes harm to people other than the agent. The large amount of data collected over the past decade allows drawing some definite conclusions about the neurobiological foundations of moral reasoning as well as a systematic investigation of methodological variables during fMRI studies. Here, we verified the existence of converging and consistent evidence in the current literature by means of a meta-analysis of fMRI studies of moral reasoning, using activation likelihood estimation meta-analysis. We also tested for a possible neural segregation as function of the perspective used during moral reasoning i.e., first or third person perspectives. Results demonstrate the existence of a wide network of areas underpinning moral reasoning, including orbitofrontal cortex, insula, amygdala, anterior cingulate cortex as well as precuneus and posterior cingulate cortex. Within this network we found a neural segregation as a function of the personal perspective, with 1PP eliciting higher activation in the bilateral insula and superior temporal gyrus as well as in the anterior cingulate cortex, lingual and fusiform gyri, middle temporal gyrus and precentral gyrus in the left hemisphere, and 3PP eliciting higher activation in the bilateral amygdala, the posterior cingulate cortex, insula and supramarginal gyrus in the left hemisphere as well as the medial and ventromedial prefrontal cortex in the right hemisphere. These results shed some more light on the contribution of these areas to moral reasoning, strongly supporting a functional specialization as a function of the perspective used during moral reasoning.

Publication Bias Currently Makes an Accurate Estimate of the Benefits of Enrichment Programs Difficult: A Postmortem of Two Meta-Analyses Using Statistical Power Analysis

ERIC Educational Resources Information Center

Warne, Russell T.

2016-01-01

Recently Kim (2016) published a meta-analysis on the effects of enrichment programs for gifted students. She found that these programs produced substantial effects for academic achievement (g = 0.96) and socioemotional outcomes (g = 0.55). However, given current theory and empirical research these estimates of the benefits of enrichment programs…

Empirical evidence of the importance of comparative studies of diagnostic test accuracy.

PubMed

Takwoingi, Yemisi; Leeflang, Mariska M G; Deeks, Jonathan J

2013-04-02

Systematic reviews that "compare" the accuracy of 2 or more tests often include different sets of studies for each test. To investigate the availability of direct comparative studies of test accuracy and to assess whether summary estimates of accuracy differ between meta-analyses of noncomparative and comparative studies. Systematic reviews in any language from the Database of Abstracts of Reviews of Effects and the Cochrane Database of Systematic Reviews from 1994 to October 2012. 1 of 2 assessors selected reviews that evaluated at least 2 tests and identified meta-analyses that included both noncomparative studies and comparative studies. 1 of 3 assessors extracted data about review and study characteristics and test performance. 248 reviews compared test accuracy; of the 6915 studies, 2113 (31%) were comparative. Thirty-six reviews (with 52 meta-analyses) had adequate studies to compare results of noncomparative and comparative studies by using a hierarchical summary receiver-operating characteristic meta-regression model for each test comparison. In 10 meta-analyses, noncomparative studies ranked tests in the opposite order of comparative studies. A total of 25 meta-analyses showed more than a 2-fold discrepancy in the relative diagnostic odds ratio between noncomparative and comparative studies. Differences in accuracy estimates between noncomparative and comparative studies were greater than expected by chance (P < 0.001). A paucity of comparative studies limited exploration of direction in bias. Evidence derived from noncomparative studies often differs from that derived from comparative studies. Robustly designed studies in which all patients receive all tests or are randomly assigned to receive one or other of the tests should be more routinely undertaken and are preferred for evidence to guide test selection. National Institute for Health Research (United Kingdom).

Likelihood ratio meta-analysis: New motivation and approach for an old method.

PubMed

Dormuth, Colin R; Filion, Kristian B; Platt, Robert W

2016-03-01

A 95% confidence interval (CI) in an updated meta-analysis may not have the expected 95% coverage. If a meta-analysis is simply updated with additional data, then the resulting 95% CI will be wrong because it will not have accounted for the fact that the earlier meta-analysis failed or succeeded to exclude the null. This situation can be avoided by using the likelihood ratio (LR) as a measure of evidence that does not depend on type-1 error. We show how an LR-based approach, first advanced by Goodman, can be used in a meta-analysis to pool data from separate studies to quantitatively assess where the total evidence points. The method works by estimating the log-likelihood ratio (LogLR) function from each study. Those functions are then summed to obtain a combined function, which is then used to retrieve the total effect estimate, and a corresponding 'intrinsic' confidence interval. Using as illustrations the CAPRIE trial of clopidogrel versus aspirin in the prevention of ischemic events, and our own meta-analysis of higher potency statins and the risk of acute kidney injury, we show that the LR-based method yields the same point estimate as the traditional analysis, but with an intrinsic confidence interval that is appropriately wider than the traditional 95% CI. The LR-based method can be used to conduct both fixed effect and random effects meta-analyses, it can be applied to old and new meta-analyses alike, and results can be presented in a format that is familiar to a meta-analytic audience. Copyright © 2016 Elsevier Inc. All rights reserved.

Meta-Analytic Estimates Predict the Effectiveness of Emotion Regulation Strategies in the "Real World": Reply to Augustine and Hemenover (2013)

ERIC Educational Resources Information Center

Miles, Eleanor; Sheeran, Paschal; Webb, Thomas L.

2013-01-01

Augustine and Hemenover (2013) were right to state that meta-analyses should be accurate and generalizable. However, we disagree that our meta-analysis of emotion regulation strategies (Webb, Miles, & Sheeran, 2012) fell short in these respects. Augustine and Hemenover's concerns appear to have accrued from misunderstandings of our inclusion…

Using meta-analytic path analysis to test theoretical predictions in health behavior: An illustration based on meta-analyses of the theory of planned behavior.

PubMed

Hagger, Martin S; Chan, Derwin K C; Protogerou, Cleo; Chatzisarantis, Nikos L D

2016-08-01

Synthesizing research on social cognitive theories applied to health behavior is an important step in the development of an evidence base of psychological factors as targets for effective behavioral interventions. However, few meta-analyses of research on social cognitive theories in health contexts have conducted simultaneous tests of theoretically-stipulated pattern effects using path analysis. We argue that conducting path analyses of meta-analytic effects among constructs from social cognitive theories is important to test nomological validity, account for mediation effects, and evaluate unique effects of theory constructs independent of past behavior. We illustrate our points by conducting new analyses of two meta-analyses of a popular theory applied to health behaviors, the theory of planned behavior. We conducted meta-analytic path analyses of the theory in two behavioral contexts (alcohol and dietary behaviors) using data from the primary studies included in the original meta-analyses augmented to include intercorrelations among constructs and relations with past behavior missing from the original analysis. Findings supported the nomological validity of the theory and its hypotheses for both behaviors, confirmed important model processes through mediation analysis, demonstrated the attenuating effect of past behavior on theory relations, and provided estimates of the unique effects of theory constructs independent of past behavior. Our analysis illustrates the importance of conducting a simultaneous test of theory-stipulated effects in meta-analyses of social cognitive theories applied to health behavior. We recommend researchers adopt this analytic procedure when synthesizing evidence across primary tests of social cognitive theories in health. Copyright © 2016 Elsevier Inc. All rights reserved.

Validating new diagnostic imaging criteria for primary progressive aphasia via anatomical likelihood estimation meta-analyses.

PubMed

Bisenius, S; Neumann, J; Schroeter, M L

2016-04-01

Recently, diagnostic clinical and imaging criteria for primary progressive aphasia (PPA) have been revised by an international consortium (Gorno-Tempini et al. Neurology 2011;76:1006-14). The aim of this study was to validate the specificity of the new imaging criteria and investigate whether different imaging modalities [magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET)] require different diagnostic subtype-specific imaging criteria. Anatomical likelihood estimation meta-analyses were conducted for PPA subtypes across a large cohort of 396 patients: firstly, across MRI studies for each of the three PPA subtypes followed by conjunction and subtraction analyses to investigate the specificity, and, secondly, by comparing results across MRI vs. FDG-PET studies in semantic dementia and progressive nonfluent aphasia. Semantic dementia showed atrophy in temporal, fusiform, parahippocampal gyri, hippocampus, and amygdala, progressive nonfluent aphasia in left putamen, insula, middle/superior temporal, precentral, and frontal gyri, logopenic progressive aphasia in middle/superior temporal, supramarginal, and dorsal posterior cingulate gyri. Results of the disease-specific meta-analyses across MRI studies were disjunct. Similarly, atrophic and hypometabolic brain networks were regionally dissociated in both semantic dementia and progressive nonfluent aphasia. In conclusion, meta-analyses support the specificity of new diagnostic imaging criteria for PPA and suggest that they should be specified for each imaging modality separately. © 2016 EAN.

Estimation of the biserial correlation and its sampling variance for use in meta-analysis.

PubMed

Jacobs, Perke; Viechtbauer, Wolfgang

2017-06-01

Meta-analyses are often used to synthesize the findings of studies examining the correlational relationship between two continuous variables. When only dichotomous measurements are available for one of the two variables, the biserial correlation coefficient can be used to estimate the product-moment correlation between the two underlying continuous variables. Unlike the point-biserial correlation coefficient, biserial correlation coefficients can therefore be integrated with product-moment correlation coefficients in the same meta-analysis. The present article describes the estimation of the biserial correlation coefficient for meta-analytic purposes and reports simulation results comparing different methods for estimating the coefficient's sampling variance. The findings indicate that commonly employed methods yield inconsistent estimates of the sampling variance across a broad range of research situations. In contrast, consistent estimates can be obtained using two methods that appear to be unknown in the meta-analytic literature. A variance-stabilizing transformation for the biserial correlation coefficient is described that allows for the construction of confidence intervals for individual coefficients with close to nominal coverage probabilities in most of the examined conditions. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

The Success of Linear Bootstrapping Models: Decision Domain-, Expertise-, and Criterion-Specific Meta-Analysis

PubMed Central

Kaufmann, Esther; Wittmann, Werner W.

2016-01-01

The success of bootstrapping or replacing a human judge with a model (e.g., an equation) has been demonstrated in Paul Meehl’s (1954) seminal work and bolstered by the results of several meta-analyses. To date, however, analyses considering different types of meta-analyses as well as the potential dependence of bootstrapping success on the decision domain, the level of expertise of the human judge, and the criterion for what constitutes an accurate decision have been missing from the literature. In this study, we addressed these research gaps by conducting a meta-analysis of lens model studies. We compared the results of a traditional (bare-bones) meta-analysis with findings of a meta-analysis of the success of bootstrap models corrected for various methodological artifacts. In line with previous studies, we found that bootstrapping was more successful than human judgment. Furthermore, bootstrapping was more successful in studies with an objective decision criterion than in studies with subjective or test score criteria. We did not find clear evidence that the success of bootstrapping depended on the decision domain (e.g., education or medicine) or on the judge’s level of expertise (novice or expert). Correction of methodological artifacts increased the estimated success of bootstrapping, suggesting that previous analyses without artifact correction (i.e., traditional meta-analyses) may have underestimated the value of bootstrapping models. PMID:27327085

Ecological perspectives of land use history: The Arid Lands Ecology (ALE) Reserve

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hinds, N R; Rogers, L E

The objective of this study was to gather information on the land use history of the Arid Land Ecology (ALE) Reserve so that current ecological research could be placed within a historical perspective. The data were gathered in the early 1980s by interviewing former users of the land and from previously published research (where available). Interviews with former land users of the ALE Reserve in Benton County, Washington, revealed that major land uses from 1880 to 1940 were homesteading, grazing, oil/gas production, and road building. Land use practices associated with grazing and homesteading have left the greatest impact on themore » landscape. Disturbed sites where succession is characterized by non-native species, plots where sagebrush was railed away, and sheep trails are major indications today of past land uses. Recent estimates of annual bunchgrass production do ALE do not support the widespread belief that bunchgrass were more productive during the homesteading era, though the invasion of cheatgrass (Bromus tectorum), Jim Hill mustard (Sisymbrium altissium), and other European alien plant species has altered pre-settlement succession patterns. 15 refs., 6 figs., 1 tab.« less

The Evaluation of Bivariate Mixed Models in Meta-analyses of Diagnostic Accuracy Studies with SAS, Stata and R.

PubMed

Vogelgesang, Felicitas; Schlattmann, Peter; Dewey, Marc

2018-05-01

Meta-analyses require a thoroughly planned procedure to obtain unbiased overall estimates. From a statistical point of view not only model selection but also model implementation in the software affects the results. The present simulation study investigates the accuracy of different implementations of general and generalized bivariate mixed models in SAS (using proc mixed, proc glimmix and proc nlmixed), Stata (using gllamm, xtmelogit and midas) and R (using reitsma from package mada and glmer from package lme4). Both models incorporate the relationship between sensitivity and specificity - the two outcomes of interest in meta-analyses of diagnostic accuracy studies - utilizing random effects. Model performance is compared in nine meta-analytic scenarios reflecting the combination of three sizes for meta-analyses (89, 30 and 10 studies) with three pairs of sensitivity/specificity values (97%/87%; 85%/75%; 90%/93%). The evaluation of accuracy in terms of bias, standard error and mean squared error reveals that all implementations of the generalized bivariate model calculate sensitivity and specificity estimates with deviations less than two percentage points. proc mixed which together with reitsma implements the general bivariate mixed model proposed by Reitsma rather shows convergence problems. The random effect parameters are in general underestimated. This study shows that flexibility and simplicity of model specification together with convergence robustness should influence implementation recommendations, as the accuracy in terms of bias was acceptable in all implementations using the generalized approach. Schattauer GmbH.

Dealing with missing standard deviation and mean values in meta-analysis of continuous outcomes: a systematic review.

PubMed

Weir, Christopher J; Butcher, Isabella; Assi, Valentina; Lewis, Stephanie C; Murray, Gordon D; Langhorne, Peter; Brady, Marian C

2018-03-07

Rigorous, informative meta-analyses rely on availability of appropriate summary statistics or individual participant data. For continuous outcomes, especially those with naturally skewed distributions, summary information on the mean or variability often goes unreported. While full reporting of original trial data is the ideal, we sought to identify methods for handling unreported mean or variability summary statistics in meta-analysis. We undertook two systematic literature reviews to identify methodological approaches used to deal with missing mean or variability summary statistics. Five electronic databases were searched, in addition to the Cochrane Colloquium abstract books and the Cochrane Statistics Methods Group mailing list archive. We also conducted cited reference searching and emailed topic experts to identify recent methodological developments. Details recorded included the description of the method, the information required to implement the method, any underlying assumptions and whether the method could be readily applied in standard statistical software. We provided a summary description of the methods identified, illustrating selected methods in example meta-analysis scenarios. For missing standard deviations (SDs), following screening of 503 articles, fifteen methods were identified in addition to those reported in a previous review. These included Bayesian hierarchical modelling at the meta-analysis level; summary statistic level imputation based on observed SD values from other trials in the meta-analysis; a practical approximation based on the range; and algebraic estimation of the SD based on other summary statistics. Following screening of 1124 articles for methods estimating the mean, one approximate Bayesian computation approach and three papers based on alternative summary statistics were identified. Illustrative meta-analyses showed that when replacing a missing SD the approximation using the range minimised loss of precision and generally performed better than omitting trials. When estimating missing means, a formula using the median, lower quartile and upper quartile performed best in preserving the precision of the meta-analysis findings, although in some scenarios, omitting trials gave superior results. Methods based on summary statistics (minimum, maximum, lower quartile, upper quartile, median) reported in the literature facilitate more comprehensive inclusion of randomised controlled trials with missing mean or variability summary statistics within meta-analyses.

Cannabis Smoking and Diabetes Mellitus: Results from Meta-Analysis with Eight Independent Replication Samples

PubMed Central

Alshaarawy, Omayma; Anthony, James C.

2016-01-01

Background In preclinical animal studies, evidence links cannabis smoking (CS) with hyperphagia, obesity, and insulin resistance. Nonetheless, in humans, CS might protect against type 2 diabetes mellitus (DM). Here, we offer epidemiological estimates from eight independent replications from (1) the National Health and Nutrition Examination Surveys, and (2) the National Surveys on Drug Use and Health (2005-12). Methods For each national survey participant, computer-assisted self-interviews assess CS and physician-diagnosed DM; NHANES provides additional biomarker values and a composite DM diagnosis. Regression analyses produce estimates of CS-DM associations. Meta-analyses summarize the replication estimates. Results Recently active CS and DM are inversely associated. The meta-analytic summary odds ratio is 0.7 (95% CI = 0.6, 0.8). Conclusions Current evidence is too weak for causal inference, but there now is a more stable evidence base for new lines of clinical translational research on a possibly protective (or spurious) CS-DM association suggested in prior research. PMID:25978795

Diesel engine exhaust and lung cancer risks - evaluation of the meta-analysis by Vermeulen et al. 2014.

PubMed

Morfeld, Peter; Spallek, Michael

2015-01-01

Vermeulen et al. 2014 published a meta-regression analysis of three relevant epidemiological US studies (Steenland et al. 1998, Garshick et al. 2012, Silverman et al. 2012) that estimated the association between occupational diesel engine exhaust (DEE) exposure and lung cancer mortality. The DEE exposure was measured as cumulative exposure to estimated respirable elemental carbon in μg/m(3)-years. Vermeulen et al. 2014 found a statistically significant dose-response association and described elevated lung cancer risks even at very low exposures. We performed an extended re-analysis using different modelling approaches (fixed and random effects regression analyses, Greenland/Longnecker method) and explored the impact of varying input data (modified coefficients of Garshick et al. 2012, results from Crump et al. 2015 replacing Silverman et al. 2012, modified analysis of Moehner et al. 2013). We reproduced the individual and main meta-analytical results of Vermeulen et al. 2014. However, our analysis demonstrated a heterogeneity of the baseline relative risk levels between the three studies. This heterogeneity was reduced after the coefficients of Garshick et al. 2012 were modified while the dose coefficient dropped by an order of magnitude for this study and was far from being significant (P = 0.6). A (non-significant) threshold estimate for the cumulative DEE exposure was found at 150 μg/m(3)-years when extending the meta-analyses of the three studies by hockey-stick regression modelling (including the modified coefficients for Garshick et al. 2012). The data used by Vermeulen and colleagues led to the highest relative risk estimate across all sensitivity analyses performed. The lowest relative risk estimate was found after exclusion of the explorative study by Steenland et al. 1998 in a meta-regression analysis of Garshick et al. 2012 (modified), Silverman et al. 2012 (modified according to Crump et al. 2015) and Möhner et al. 2013. The meta-coefficient was estimated to be about 10-20 % of the main effect estimate in Vermeulen et al. 2014 in this analysis. The findings of Vermeulen et al. 2014 should not be used without reservations in any risk assessments. This is particularly true for the low end of the exposure scale.

Neutrophil/lymphocyte ratio and platelet/lymphocyte ratio in mood disorders: A meta-analysis.

PubMed

Mazza, Mario Gennaro; Lucchi, Sara; Tringali, Agnese Grazia Maria; Rossetti, Aurora; Botti, Eugenia Rossana; Clerici, Massimo

2018-06-08

The immune and inflammatory system is involved in the etiology of mood disorders. Neutrophil/lymphocyte ratio (NLR), platelet/lymphocyte ratio (PLR) and monocyte/lymphocyte ratio (MLR) are inexpensive and reproducible biomarkers of inflammation. This is the first meta-analysis exploring the role of NLR and PLR in mood disorder. We identified 11 studies according to our inclusion criteria from the main Electronic Databases. Meta-analyses were carried out generating pooled standardized mean differences (SMDs) between index and healthy controls (HC). Heterogeneity was estimated. Relevant sensitivity and meta-regression analyses were conducted. Subjects with bipolar disorder (BD) had higher NLR and PLR as compared with HC (respectively SMD = 0.672; p < 0.001; I 2  = 82.4% and SMD = 0.425; p = 0.048; I 2  = 86.53%). Heterogeneity-based sensitivity analyses confirmed these findings. Subgroup analysis evidenced an influence of bipolar phase on the overall estimate whit studies including subjects in manic and any bipolar phase showing a significantly higher NLR and PLR as compared with HC whereas the effect was not significant among studies including only euthymic bipolar subjects. Meta-regression showed that age and sex influenced the relationship between BD and NLR but not the relationship between BD and PLR. Meta-analysis was not carried out for MLR because our search identified only one study when comparing BD to HC, and only one study when comparing MDD to HC. Subjects with major depressive disorder (MDD) had higher NLR as compared with HC (SMD = 0.670; p = 0.028; I 2  = 89.931%). Heterogeneity-based sensitivity analyses and meta-regression confirmed these findings. Our meta-analysis supports the hypothesis that an inflammatory activation occurs in mood disorders and NLR and PLR may be useful to detect this activation. More researches including comparison of NLR, PLR and MLR between different bipolar phases and between BD and MDD are needed. Copyright © 2018 Elsevier Inc. All rights reserved.

Obesity and gynaecological and obstetric conditions: umbrella review of the literature.

PubMed

Kalliala, Ilkka; Markozannes, Georgios; Gunter, Marc J; Paraskevaidis, Evangelos; Gabra, Hani; Mitra, Anita; Terzidou, Vasso; Bennett, Phillip; Martin-Hirsch, Pierre; Tsilidis, Konstantinos K; Kyrgiou, Maria

2017-10-26

Objective  To study the strength and validity of associations between adiposity and risk of any type of obstetric or gynaecological conditions. Design  An umbrella review of meta-analyses. Data sources  PubMed, Cochrane database of systematic reviews, manual screening of references for systematic reviews or meta-analyses of observational and interventional studies evaluating the association between adiposity and risk of any obstetrical or gynaecological outcome. Main outcomes  Meta-analyses of cohort studies on associations between indices of adiposity and obstetric and gynaecological outcomes. Data synthesis  Evidence from observational studies was graded into strong, highly suggestive, suggestive, or weak based on the significance of the random effects summary estimate and the largest study in the included meta-analysis, the number of cases, heterogeneity between studies, 95% prediction intervals, small study effects, excess significance bias, and sensitivity analysis with credibility ceilings. Interventional meta-analyses were assessed separately. Results  156 meta-analyses of observational studies were included, investigating associations between adiposity and risk of 84 obstetric or gynaecological outcomes. Of the 144 meta-analyses that included cohort studies, only 11 (8%) had strong evidence for eight outcomes: adiposity was associated with a higher risk of endometrial cancer, ovarian cancer, antenatal depression, total and emergency caesarean section, pre-eclampsia, fetal macrosomia, and low Apgar score. The summary effect estimates ranged from 1.21 (95% confidence interval 1.13 to 1.29) for an association between a 0.1 unit increase in waist to hip ratio and risk endometrial cancer up to 4.14 (3.61 to 4.75) for risk of pre-eclampsia for BMI >35 compared with <25. Only three out of these eight outcomes were also assessed in meta-analyses of trials evaluating weight loss interventions. These interventions significantly reduced the risk of caesarean section and pre-eclampsia, whereas there was no evidence of association with fetal macrosomia. Conclusions  Although the associations between adiposity and obstetric and gynaecological outcomes have been extensively studied, only a minority were considered strong and without hints of bias. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Effect size calculation in meta-analyses of psychotherapy outcome research.

PubMed

Hoyt, William T; Del Re, A C

2018-05-01

Meta-analysis of psychotherapy intervention research normally examines differences between treatment groups and some form of comparison group (e.g., wait list control; alternative treatment group). The effect of treatment is normally quantified as a standardized mean difference (SMD). We describe procedures for computing unbiased estimates of the population SMD from sample data (e.g., group Ms and SDs), and provide guidance about a number of complications that may arise related to effect size computation. These complications include (a) incomplete data in research reports; (b) use of baseline data in computing SMDs and estimating the population standard deviation (σ); (c) combining effect size data from studies using different research designs; and (d) appropriate techniques for analysis of data from studies providing multiple estimates of the effect of interest (i.e., dependent effect sizes). Clinical or Methodological Significance of this article: Meta-analysis is a set of techniques for producing valid summaries of existing research. The initial computational step for meta-analyses of research on intervention outcomes involves computing an effect size quantifying the change attributable to the intervention. We discuss common issues in the computation of effect sizes and provide recommended procedures to address them.

Methodological Quality Assessment of Meta-analyses in Endodontics.

PubMed

Kattan, Sereen; Lee, Su-Min; Kohli, Meetu R; Setzer, Frank C; Karabucak, Bekir

2018-01-01

The objectives of this review were to assess the methodological quality of published meta-analyses related to endodontics using the assessment of multiple systematic reviews (AMSTAR) tool and to provide a follow-up to previously published reviews. Three electronic databases were searched for eligible studies according to the inclusion and exclusion criteria: Embase via Ovid, The Cochrane Library, and Scopus. The electronic search was amended by a hand search of 6 dental journals (International Endodontic Journal; Journal of Endodontics; Australian Endodontic Journal; Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology; Endodontics and Dental Traumatology; and Journal of Dental Research). The searches were conducted to include articles published after July 2009, and the deadline for inclusion of the meta-analyses was November 30, 2016. The AMSTAR assessment tool was used to evaluate the methodological quality of all included studies. A total of 36 reports of meta-analyses were included. The overall quality of the meta-analyses reports was found to be medium, with an estimated mean overall AMSTAR score of 7.25 (95% confidence interval, 6.59-7.90). The most poorly assessed areas were providing an a priori design, the assessment of the status of publication, and publication bias. In recent publications in the field of endodontics, the overall quality of the reported meta-analyses is medium according to AMSTAR. Copyright © 2017 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

The prevalence of pathological gambling among college students: a meta-analytic synthesis, 2005-2013.

PubMed

Nowak, Donald E; Aloe, Ariel M

2014-12-01

The problem of gambling addiction can be especially noteworthy among college and university students, many of whom have the resources, proximity, free time, and desire to become involved in the myriad options of gambling now available. Although limited attention has been paid specifically to college student gambling in the body of literature, there have been two published meta-analyses estimating the prevalence of probable pathological gambling among college students. This present study aims to be the third, presenting an up-to-date proportion of those students exhibiting gambling pathology, and is the first to include international studies from outside the United States and Canada. The purpose of this study was to use the most up-to-date meta-analytical procedures to synthesize the rates of probable pathological gambling for college and university students worldwide. A thorough literature review and coding procedure resulted in 19 independent data estimates retrieved from 18 studies conducted between 2005 and 2013. To synthesize the studies, a random effects model for meta-analysis was applied. The estimated proportion of probable pathological gamblers among the over 13,000 college students surveyed was computed at 10.23%, considerably higher than either of the two previously published meta-analyses, and more than double the rate reported in the first meta-analysis of this type published in 1999. Implications and recommendations for future practice in dealing with college students and gambling addiction are outlined and described for both administrators and mental health professionals.

The link between employee attitudes and employee effectiveness: Data matrix of meta-analytic estimates based on 1161 unique correlations.

PubMed

Mackay, Michael M

2016-09-01

This article offers a correlation matrix of meta-analytic estimates between various employee job attitudes (i.e., Employee engagement, job satisfaction, job involvement, and organizational commitment) and indicators of employee effectiveness (i.e., Focal performance, contextual performance, turnover intention, and absenteeism). The meta-analytic correlations in the matrix are based on over 1100 individual studies representing over 340,000 employees. Data was collected worldwide via employee self-report surveys. Structural path analyses based on the matrix, and the interpretation of the data, can be found in "Investigating the incremental validity of employee engagement in the prediction of employee effectiveness: a meta-analytic path analysis" (Mackay et al., 2016) [1].

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes.

PubMed

Achana, Felix A; Cooper, Nicola J; Bujkiewicz, Sylwia; Hubbard, Stephanie J; Kendrick, Denise; Jones, David R; Sutton, Alex J

2014-07-21

Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately.

Using aggregate data to estimate the standard error of a treatment-covariate interaction in an individual patient data meta-analysis.

PubMed

Kovalchik, Stephanie A; Cumberland, William G

2012-05-01

Subgroup analyses are important to medical research because they shed light on the heterogeneity of treatment effectts. A treatment-covariate interaction in an individual patient data (IPD) meta-analysis is the most reliable means to estimate how a subgroup factor modifies a treatment's effectiveness. However, owing to the challenges in collecting participant data, an approach based on aggregate data might be the only option. In these circumstances, it would be useful to assess the relative efficiency and power loss of a subgroup analysis without patient-level data. We present methods that use aggregate data to estimate the standard error of an IPD meta-analysis' treatment-covariate interaction for regression models of a continuous or dichotomous patient outcome. Numerical studies indicate that the estimators have good accuracy. An application to a previously published meta-regression illustrates the practical utility of the methodology. © 2012 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Personality and job performance: the Big Five revisited.

PubMed

Hurtz, G M; Donovan, J J

2000-12-01

Prior meta-analyses investigating the relation between the Big 5 personality dimensions and job performance have all contained a threat to construct validity, in that much of the data included within these analyses was not derived from actual Big 5 measures. In addition, these reviews did not address the relations between the Big 5 and contextual performance. Therefore, the present study sought to provide a meta-analytic estimate of the criterion-related validity of explicit Big 5 measures for predicting job performance and contextual performance. The results for job performance closely paralleled 2 of the previous meta-analyses, whereas analyses with contextual performance showed more complex relations among the Big 5 and performance. A more critical interpretation of the Big 5-performance relationship is presented, and suggestions for future research aimed at enhancing the validity of personality predictors are provided.

Alcohol consumption as a risk factor for tuberculosis: meta-analyses and burden of disease

PubMed Central

Shield, Kevin D.; Roerecke, Michael; Samokhvalov, Andriy V.; Lönnroth, Knut; Rehm, Jürgen

2017-01-01

Meta-analyses of alcohol use, alcohol dosage and alcohol-related problems as risk factors for tuberculosis incidence were undertaken. The global alcohol-attributable tuberculosis burden of disease was also re-estimated. Systematic searches were conducted, reference lists were reviewed and expert consultations were held to identify studies. Cohort and case-control studies were included if there were no temporal violations of exposure and outcome. Risk relations (RRs) were pooled by using categorical and dose-response meta-analyses. The alcohol-attributable tuberculosis burden of disease was estimated by using alcohol-attributable fractions. 36 of 1108 studies were included. RRs for alcohol use and alcohol-related problems were 1.35 (95% CI 1.09–1.68; I2: 83%) and 3.33 (95% CI 2.14–5.19; 87%), respectively. Concerning alcohol dosage, tuberculosis risk rose as ethanol intake increased, with evidence of a threshold effect. Alcohol consumption caused 22.02 incident cases (95% CI 19.70–40.77) and 2.35 deaths (95% CI 2.05–4.79) per 100 000 people from tuberculosis in 2014. Alcohol-attributable tuberculosis incidence increased between 2000 and 2014 in most high tuberculosis burden countries, whereas mortality decreased. Alcohol consumption was associated with an increased risk of tuberculosis in all meta-analyses. It was consequently a major contributor to the tuberculosis burden of disease. PMID:28705945

Environmental risk factors and Parkinson's disease: An umbrella review of meta-analyses.

PubMed

Bellou, Vanesa; Belbasis, Lazaros; Tzoulaki, Ioanna; Evangelou, Evangelos; Ioannidis, John P A

2016-02-01

Parkinson's disease is a neurological disorder with complex pathogenesis implicating both environmental and genetic factors. We aimed to summarise the environmental risk factors that have been studied for potential association with Parkinson's disease, assess the presence of diverse biases, and identify the risk factors with the strongest support. We searched PubMed from inception to September 18, 2015, to identify systematic reviews and meta-analyses of observational studies that examined associations between environmental factors and Parkinson's disease. For each meta-analysis we estimated the summary effect size by random-effects and fixed-effects models, the 95% confidence interval and the 95% prediction interval. We estimated the between-study heterogeneity expressed by I(2), evidence of small-study effects and evidence of excess significance bias. Overall, 75 unique meta-analyses on different risk factors for Parkinson's disease were examined, covering diverse biomarkers, dietary factors, drugs, medical history or comorbid diseases, exposure to toxic environmental agents and habits. 21 of 75 meta-analyses had results that were significant at p < 0.001 by random-effects. Evidence for an association was convincing (more than 1000 cases, p < 10(-6) by random-effects, not large heterogeneity, 95% prediction interval excluding the null value and absence of hints for small-study effects and excess significance bias) for constipation, and physical activity. Many environmental factors have substantial evidence of association with Parkinson's disease, but several, perhaps most, of them may reflect reverse causation, residual confounding, information bias, sponsor conflicts or other caveats. Copyright © 2016. Published by Elsevier Ltd.

Multi-site study of additive genetic effects on fractional anisotropy of cerebral white matter: Comparing meta and megaanalytical approaches for data pooling.

PubMed

Kochunov, Peter; Jahanshad, Neda; Sprooten, Emma; Nichols, Thomas E; Mandl, René C; Almasy, Laura; Booth, Tom; Brouwer, Rachel M; Curran, Joanne E; de Zubicaray, Greig I; Dimitrova, Rali; Duggirala, Ravi; Fox, Peter T; Hong, L Elliot; Landman, Bennett A; Lemaitre, Hervé; Lopez, Lorna M; Martin, Nicholas G; McMahon, Katie L; Mitchell, Braxton D; Olvera, Rene L; Peterson, Charles P; Starr, John M; Sussmann, Jessika E; Toga, Arthur W; Wardlaw, Joanna M; Wright, Margaret J; Wright, Susan N; Bastin, Mark E; McIntosh, Andrew M; Boomsma, Dorret I; Kahn, René S; den Braber, Anouk; de Geus, Eco J C; Deary, Ian J; Hulshoff Pol, Hilleke E; Williamson, Douglas E; Blangero, John; van 't Ent, Dennis; Thompson, Paul M; Glahn, David C

2014-07-15

Combining datasets across independent studies can boost statistical power by increasing the numbers of observations and can achieve more accurate estimates of effect sizes. This is especially important for genetic studies where a large number of observations are required to obtain sufficient power to detect and replicate genetic effects. There is a need to develop and evaluate methods for joint-analytical analyses of rich datasets collected in imaging genetics studies. The ENIGMA-DTI consortium is developing and evaluating approaches for obtaining pooled estimates of heritability through meta-and mega-genetic analytical approaches, to estimate the general additive genetic contributions to the intersubject variance in fractional anisotropy (FA) measured from diffusion tensor imaging (DTI). We used the ENIGMA-DTI data harmonization protocol for uniform processing of DTI data from multiple sites. We evaluated this protocol in five family-based cohorts providing data from a total of 2248 children and adults (ages: 9-85) collected with various imaging protocols. We used the imaging genetics analysis tool, SOLAR-Eclipse, to combine twin and family data from Dutch, Australian and Mexican-American cohorts into one large "mega-family". We showed that heritability estimates may vary from one cohort to another. We used two meta-analytical (the sample-size and standard-error weighted) approaches and a mega-genetic analysis to calculate heritability estimates across-population. We performed leave-one-out analysis of the joint estimates of heritability, removing a different cohort each time to understand the estimate variability. Overall, meta- and mega-genetic analyses of heritability produced robust estimates of heritability. Copyright © 2014 Elsevier Inc. All rights reserved.

Short-term Effect of Fine Particulate Matter on Children's Hospital Admissions and Emergency Department Visits for Asthma: A Systematic Review and Meta-analysis.

PubMed

Lim, Hyungryul; Kwon, Ho-Jang; Lim, Ji-Ae; Choi, Jong Hyuk; Ha, Mina; Hwang, Seung-Sik; Choi, Won-Jun

2016-07-01

No children-specified review and meta-analysis paper about the short-term effect of fine particulate matter (PM2.5) on hospital admissions and emergency department visits for asthma has been published. We calculated more precise pooled effect estimates on this topic and evaluated the variation in effect size according to the differences in study characteristics not considered in previous studies. Two authors each independently searched PubMed and EMBASE for relevant studies in March, 2016. We conducted random effect meta-analyses and mixed-effect meta-regression analyses using retrieved summary effect estimates and 95% confidence intervals (CIs) and some characteristics of selected studies. The Egger's test and funnel plot were used to check publication bias. All analyses were done using R version 3.1.3. We ultimately retrieved 26 time-series and case-crossover design studies about the short-term effect of PM2.5 on children's hospital admissions and emergency department visits for asthma. In the primary meta-analysis, children's hospital admissions and emergency department visits for asthma were positively associated with a short-term 10 μg/m3 increase in PM2.5 (relative risk, 1.048; 95% CI, 1.028 to 1.067; I2=95.7%). We also found different effect coefficients by region; the value in Asia was estimated to be lower than in North America or Europe. We strengthened the evidence on the short-term effect of PM2.5 on children's hospital admissions and emergency department visits for asthma. Further studies from other regions outside North America and Europe regions are needed for more generalizable evidence.

Utility-Based Instruments for People with Dementia: A Systematic Review and Meta-Regression Analysis.

PubMed

Li, Li; Nguyen, Kim-Huong; Comans, Tracy; Scuffham, Paul

2018-04-01

Several utility-based instruments have been applied in cost-utility analysis to assess health state values for people with dementia. Nevertheless, concerns and uncertainty regarding their performance for people with dementia have been raised. To assess the performance of available utility-based instruments for people with dementia by comparing their psychometric properties and to explore factors that cause variations in the reported health state values generated from those instruments by conducting meta-regression analyses. A literature search was conducted and psychometric properties were synthesized to demonstrate the overall performance of each instrument. When available, health state values and variables such as the type of instrument and cognitive impairment levels were extracted from each article. A meta-regression analysis was undertaken and available covariates were included in the models. A total of 64 studies providing preference-based values were identified and included. The EuroQol five-dimension questionnaire demonstrated the best combination of feasibility, reliability, and validity. Meta-regression analyses suggested that significant differences exist between instruments, type of respondents, and mode of administration and the variations in estimated utility values had influences on incremental quality-adjusted life-year calculation. This review finds that the EuroQol five-dimension questionnaire is the most valid utility-based instrument for people with dementia, but should be replaced by others under certain circumstances. Although no utility estimates were reported in the article, the meta-regression analyses that examined variations in utility estimates produced by different instruments impact on cost-utility analysis, potentially altering the decision-making process in some circumstances. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Gestational syphilis and stillbirth in the Americas: a systematic review and meta-analysis.

PubMed

Arnesen, Lauren; Serruya, Suzanne; Duran, Pablo

2015-06-01

To perform a systematic review and meta-analysis of reported estimates of the association between gestational syphilis (GS) and stillbirth in the Americas region. Cochrane Library, Embase, LILACS, MEDLINE/PubMed, PLOS, and ScienceDirect were searched for original research studies quantifying the relationship between GS and stillbirth in the region. A final sample of eight studies was selected. A cumulative meta-analysis plus four subgroup meta-analyses of study data on the association between maternal syphilis during pregnancy and stillbirth were conducted. The four meta-analyses were based on 1) definition of cases and the control; 2) syphilis treatment (presence or absence, effective or ineffective); 3) definition of stillbirth as "showing no signs of life at birth"; and 4) definition of stillbirth based on low birth weight and gestational age. Random-effects metaanalyses were used to calculate pooled estimates of stillbirth with exposure to GS, and each subgroup analysis was tested for heterogeneity. Women with GS had increased odds of stillbirth (pooled odds ratio (OR): 6.87; 95% confidence interval: 2.93, 16.08). There was considerable heterogeneity across the eight studies (percentage of variance (I²) = 95). The funnel plot was not statistically significant, pointing to a lack of publication bias. Increased odds of stillbirth among pregnant women with syphilis were also seen in all four subgroup meta-analyses. GS is a major contributing factor for stillbirths in the Americas. Interventions targeting GS are highly cost-effective and, along with high-quality point-of-care testing, should be implemented across the region to help reach the goal of eliminating congenital syphilis.

Estimating the Difference between Published and Unpublished Effect Sizes: A Meta-Review

ERIC Educational Resources Information Center

Polanin, Joshua R.; Tanner-Smith, Emily E.; Hennessy, Emily A.

2016-01-01

Practitioners and policymakers rely on meta-analyses to inform decision making around the allocation of resources to individuals and organizations. It is therefore paramount to consider the validity of these results. A well-documented threat to the validity of research synthesis results is the presence of publication bias, a phenomenon where…

Estimating the Difference between Published and Unpublished Effect Sizes: A Meta-Review

ERIC Educational Resources Information Center

Polanin, Joshua R.; Tanner-Smith, Emily E.; Hennessy, Emily A.

2016-01-01

Practitioners and policymakers rely on meta-analyses to inform decision-making around the allocation of resources to individuals and organizations. It is therefore paramount to consider the validity of these results. A well-documented threat to the validity of research synthesis results is the presence of publication bias, a phenomenon where…

The global distribution, host range and prevalence of Trypanosoma evansi causing surra: A systematic review and meta-analysis

USDA-ARS?s Scientific Manuscript database

In contrast with the tsetse transmitted animal trypanosomoses, surra is severely neglected. A systematic literature review and meta-analyses were used to determine the geographic distribution, to identify the naturally susceptible domestic and wild animals and to critically estimate the prevalence o...

Deriving percentage study weights in multi-parameter meta-analysis models: with application to meta-regression, network meta-analysis and one-stage individual participant data models.

PubMed

Riley, Richard D; Ensor, Joie; Jackson, Dan; Burke, Danielle L

2017-01-01

Many meta-analysis models contain multiple parameters, for example due to multiple outcomes, multiple treatments or multiple regression coefficients. In particular, meta-regression models may contain multiple study-level covariates, and one-stage individual participant data meta-analysis models may contain multiple patient-level covariates and interactions. Here, we propose how to derive percentage study weights for such situations, in order to reveal the (otherwise hidden) contribution of each study toward the parameter estimates of interest. We assume that studies are independent, and utilise a decomposition of Fisher's information matrix to decompose the total variance matrix of parameter estimates into study-specific contributions, from which percentage weights are derived. This approach generalises how percentage weights are calculated in a traditional, single parameter meta-analysis model. Application is made to one- and two-stage individual participant data meta-analyses, meta-regression and network (multivariate) meta-analysis of multiple treatments. These reveal percentage study weights toward clinically important estimates, such as summary treatment effects and treatment-covariate interactions, and are especially useful when some studies are potential outliers or at high risk of bias. We also derive percentage study weights toward methodologically interesting measures, such as the magnitude of ecological bias (difference between within-study and across-study associations) and the amount of inconsistency (difference between direct and indirect evidence in a network meta-analysis).

Efficient Exploration of the Space of Reconciled Gene Trees

PubMed Central

Szöllősi, Gergely J.; Rosikiewicz, Wojciech; Boussau, Bastien; Tannier, Eric; Daubin, Vincent

2013-01-01

Gene trees record the combination of gene-level events, such as duplication, transfer and loss (DTL), and species-level events, such as speciation and extinction. Gene tree–species tree reconciliation methods model these processes by drawing gene trees into the species tree using a series of gene and species-level events. The reconstruction of gene trees based on sequence alone almost always involves choosing between statistically equivalent or weakly distinguishable relationships that could be much better resolved based on a putative species tree. To exploit this potential for accurate reconstruction of gene trees, the space of reconciled gene trees must be explored according to a joint model of sequence evolution and gene tree–species tree reconciliation. Here we present amalgamated likelihood estimation (ALE), a probabilistic approach to exhaustively explore all reconciled gene trees that can be amalgamated as a combination of clades observed in a sample of gene trees. We implement the ALE approach in the context of a reconciliation model (Szöllősi et al. 2013), which allows for the DTL of genes. We use ALE to efficiently approximate the sum of the joint likelihood over amalgamations and to find the reconciled gene tree that maximizes the joint likelihood among all such trees. We demonstrate using simulations that gene trees reconstructed using the joint likelihood are substantially more accurate than those reconstructed using sequence alone. Using realistic gene tree topologies, branch lengths, and alignment sizes, we demonstrate that ALE produces more accurate gene trees even if the model of sequence evolution is greatly simplified. Finally, examining 1099 gene families from 36 cyanobacterial genomes we find that joint likelihood-based inference results in a striking reduction in apparent phylogenetic discord, with respectively. 24%, 59%, and 46% reductions in the mean numbers of duplications, transfers, and losses per gene family. The open source implementation of ALE is available from https://github.com/ssolo/ALE.git. [amalgamation; gene tree reconciliation; gene tree reconstruction; lateral gene transfer; phylogeny.] PMID:23925510

Living systematic reviews: 3. Statistical methods for updating meta-analyses.

PubMed

Simmonds, Mark; Salanti, Georgia; McKenzie, Joanne; Elliott, Julian

2017-11-01

A living systematic review (LSR) should keep the review current as new research evidence emerges. Any meta-analyses included in the review will also need updating as new material is identified. If the aim of the review is solely to present the best current evidence standard meta-analysis may be sufficient, provided reviewers are aware that results may change at later updates. If the review is used in a decision-making context, more caution may be needed. When using standard meta-analysis methods, the chance of incorrectly concluding that any updated meta-analysis is statistically significant when there is no effect (the type I error) increases rapidly as more updates are performed. Inaccurate estimation of any heterogeneity across studies may also lead to inappropriate conclusions. This paper considers four methods to avoid some of these statistical problems when updating meta-analyses: two methods, that is, law of the iterated logarithm and the Shuster method control primarily for inflation of type I error and two other methods, that is, trial sequential analysis and sequential meta-analysis control for type I and II errors (failing to detect a genuine effect) and take account of heterogeneity. This paper compares the methods and considers how they could be applied to LSRs. Copyright © 2017 Elsevier Inc. All rights reserved.

Efficacy of adjuvant chemotherapy after surgery when considered over all cancer types: a synthesis of meta-analyses.

PubMed

Bowater, Russell J; Abdelmalik, Sally M E; Lilford, Richard J

2012-10-01

Despite a large number of clinical trials having been conducted to assess the efficacy of adjuvant chemotherapy after surgery for various cancers, whether it is best to use this treatment remains a generally contentious issue for many common cancers. The purpose of this study was to ascertain whether any general conclusions can be drawn about the efficacy or inefficacy of this treatment within different cancer classifications. Meta-analyses of randomized, controlled trials (RCTs) of adjuvant chemotherapy after surgery were synthesized over as many types of cancer as possible. Data sources were Medline, Embase, and the Cochrane library. Eligible meta-analyses were meta-analyses of RCTs for any type of cancer that compared surgery followed by adjuvant chemotherapy with surgery followed by no adjuvant chemotherapy. The literature search found 25 meta-analyses for 15 cancer types that satisfied the criteria necessary for detailed analysis within this study. The estimates of relative risk for all cause mortality were reported as being less than one (indicating adjuvant chemotherapy is beneficial) by all meta-analyses apart from a meta-analysis for colorectal cancer metastasized to the liver. Moreover, 15 of these meta-analyses also reported that the 95% confidence interval for this relative risk is less than one (indicating statistical significance at the 5% level). The results for all cancer types included in this study except for cancer metastasized to the liver can be thought of as supporting each other through the idea of there being a common treatment effect or at least a common range of effect across all (or most) of these cancer types. For example, with regard to cancer types where the evidence in favor of adjuvant chemotherapy after surgery is only moderately strong, the results of this study may encourage more clinicians to regard the use of this treatment as standard practice.

Propagation of population pharmacokinetic information using a Bayesian approach: comparison with meta-analysis.

PubMed

Dokoumetzidis, Aristides; Aarons, Leon

2005-08-01

We investigated the propagation of population pharmacokinetic information across clinical studies by applying Bayesian techniques. The aim was to summarize the population pharmacokinetic estimates of a study in appropriate statistical distributions in order to use them as Bayesian priors in consequent population pharmacokinetic analyses. Various data sets of simulated and real clinical data were fitted with WinBUGS, with and without informative priors. The posterior estimates of fittings with non-informative priors were used to build parametric informative priors and the whole procedure was carried on in a consecutive manner. The posterior distributions of the fittings with informative priors where compared to those of the meta-analysis fittings of the respective combinations of data sets. Good agreement was found, for the simulated and experimental datasets when the populations were exchangeable, with the posterior distribution from the fittings with the prior to be nearly identical to the ones estimated with meta-analysis. However, when populations were not exchangeble an alternative parametric form for the prior, the natural conjugate prior, had to be used in order to have consistent results. In conclusion, the results of a population pharmacokinetic analysis may be summarized in Bayesian prior distributions that can be used consecutively with other analyses. The procedure is an alternative to meta-analysis and gives comparable results. It has the advantage that it is faster than the meta-analysis, due to the large datasets used with the latter and can be performed when the data included in the prior are not actually available.

An overview of meta-analysis for clinicians.

PubMed

Lee, Young Ho

2018-03-01

The number of medical studies being published is increasing exponentially, and clinicians must routinely process large amounts of new information. Moreover, the results of individual studies are often insufficient to provide confident answers, as their results are not consistently reproducible. A meta-analysis is a statistical method for combining the results of different studies on the same topic and it may resolve conflicts among studies. Meta-analysis is being used increasingly and plays an important role in medical research. This review introduces the basic concepts, steps, advantages, and caveats of meta-analysis, to help clinicians understand it in clinical practice and research. A major advantage of a meta-analysis is that it produces a precise estimate of the effect size, with considerably increased statistical power, which is important when the power of the primary study is limited because of a small sample size. A meta-analysis may yield conclusive results when individual studies are inconclusive. Furthermore, meta-analyses investigate the source of variation and different effects among subgroups. In summary, a meta-analysis is an objective, quantitative method that provides less biased estimates on a specific topic. Understanding how to conduct a meta-analysis aids clinicians in the process of making clinical decisions.

Assessing the dependence of sensitivity and specificity on prevalence in meta-analysis

PubMed Central

Li, Jialiang; Fine, Jason P.

2011-01-01

We consider modeling the dependence of sensitivity and specificity on the disease prevalence in diagnostic accuracy studies. Many meta-analyses compare test accuracy across studies and fail to incorporate the possible connection between the accuracy measures and the prevalence. We propose a Pearson type correlation coefficient and an estimating equation–based regression framework to help understand such a practical dependence. The results we derive may then be used to better interpret the results from meta-analyses. In the biomedical examples analyzed in this paper, the diagnostic accuracy of biomarkers are shown to be associated with prevalence, providing insights into the utility of these biomarkers in low- and high-prevalence populations. PMID:21525421

Genetic polymorphisms for estimating risk of atrial fibrillation: a literature-based meta-analysis

PubMed Central

Smith, J. Gustav; Almgren, Peter; Engström, Gunnar; Hedblad, Bo; Platonov, Pyotr G.; Newton-Cheh, Christopher; Melander, Olle

2013-01-01

Objectives Genome-wide association studies have recently identified genetic polymorphisms associated with common, etiologically complex diseases, for which direct-to-consumer genetic testing with provision of absolute genetic risk estimates is marketed by commercial companies. Polymorphisms associated with atrial fibrillation (AF) have shown relatively large risk estimates but the robustness of such estimates across populations and study designs has not been studied. Design A systematic literature review with meta-analysis and assessment of between-study heterogeneity was performed for single nucleotide polymorphisms (SNPs) in the six genetic regions associated with AF in genome-wide or candidate gene studies. Results Data from 18 samples of European ancestry (n=12,100 cases; 115,702 controls) were identified for the SNP on chromosome 4q25 (rs220733), 16 samples (n=12,694 cases; 132,602 controls) for the SNP on 16q22 (rs2106261) and 4 samples (n=5,272 cases; 59,725 controls) for the SNP in KCNH2 (rs1805123). Only the discovery studies were identified for SNPs on 1q21 and in GJA5 and IL6R, why no meta-analyses were performed for those SNPs. In overall random-effects meta-analyses, association with AF was observed for both SNPs from genome-wide studies on 4q25 (OR 1.67, 95% CI=1.50–1.86, p=2×10−21) and 16q22 (OR 1.21, 95% CI=1.13–1.29, p=1×10−8), but not the SNP in KCNH2 from candidate gene studies (p=0.15). There was substantial effect heterogeneity across case-control and cross-sectional studies for both polymorphisms (I2=0.50–0.78, p<0.05), but not across prospective cohort studies (I2=0.39, p=0.15). Both polymorphisms were robustly associated with AF for each study design individually (p<0.05). Conclusions In meta-analyses including up to 150,000 individuals, polymorphisms in two genetic regions were robustly associated with AF across all study designs but with substantial context-dependency of risk estimates. PMID:22690879

Structural basis of empathy and the domain general region in the anterior insular cortex

PubMed Central

Mutschler, Isabella; Reinbold, Céline; Wankerl, Johanna; Seifritz, Erich; Ball, Tonio

2013-01-01

Empathy is key for healthy social functioning and individual differences in empathy have strong implications for manifold domains of social behavior. Empathy comprises of emotional and cognitive components and may also be closely linked to sensorimotor processes, which go along with the motivation and behavior to respond compassionately to another person's feelings. There is growing evidence for local plastic change in the structure of the healthy adult human brain in response to environmental demands or intrinsic factors. Here we have investigated changes in brain structure resulting from or predisposing to empathy. Structural MRI data of 101 healthy adult females was analyzed. Empathy in fictitious as well as real-life situations was assessed using a validated self-evaluation measure. Furthermore, empathy-related structural effects were also put into the context of a functional map of the anterior insular cortex (AIC) determined by activation likelihood estimate (ALE) meta-analysis of previous functional imaging studies. We found that gray matter (GM) density in the left dorsal AIC correlates with empathy and that this area overlaps with the domain general region (DGR) of the anterior insula that is situated in-between functional systems involved in emotion–cognition, pain, and motor tasks as determined by our meta-analysis. Thus, we propose that this insular region where we find structural differences depending on individual empathy may play a crucial role in modulating the efficiency of neural integration underlying emotional, cognitive, and sensorimotor information which is essential for global empathy. PMID:23675334

Differentiating between self and others: an ALE meta-analysis of fMRI studies of self-recognition and theory of mind.

PubMed

van Veluw, Susanne J; Chance, Steven A

2014-03-01

The perception of self and others is a key aspect of social cognition. In order to investigate the neurobiological basis of this distinction we reviewed two classes of task that study self-awareness and awareness of others (theory of mind, ToM). A reliable task to measure self-awareness is the recognition of one's own face in contrast to the recognition of others' faces. False-belief tasks are widely used to identify neural correlates of ToM as a measure of awareness of others. We performed an activation likelihood estimation meta-analysis, using the fMRI literature on self-face recognition and false-belief tasks. The brain areas involved in performing false-belief tasks were the medial prefrontal cortex (MPFC), bilateral temporo-parietal junction, precuneus, and the bilateral middle temporal gyrus. Distinct self-face recognition regions were the right superior temporal gyrus, the right parahippocampal gyrus, the right inferior frontal gyrus/anterior cingulate cortex, and the left inferior parietal lobe. Overlapping brain areas were the superior temporal gyrus, and the more ventral parts of the MPFC. We confirmed that self-recognition in contrast to recognition of others' faces, and awareness of others involves a network that consists of separate, distinct neural pathways, but also includes overlapping regions of higher order prefrontal cortex where these processes may be combined. Insights derived from the neurobiology of disorders such as autism and schizophrenia are consistent with this notion.

Neural correlates of conversion disorder: overview and meta-analysis of neuroimaging studies on motor conversion disorder.

PubMed

Boeckle, Markus; Liegl, Gregor; Jank, Robert; Pieh, Christoph

2016-06-10

Conversion Disorders (CD) are prevalent functional disorders. Although the pathogenesis is still not completely understood, an interaction of genetic, neurobiological, and psychosocial factors is quite likely. The aim of this study is to provide a systematic overview on imaging studies on CDs and investigate neuronal areas involved in Motor Conversion Disorders (MCD). A systematic literature search was conducted on CD. Subsequently a meta-analysis of functional neuroimaging studies on MCD was implemented using an Activation Likelihood Estimation (ALE). We calculated differences between patients and healthy controls as well as between affected versus unaffected sides in addition to an overall analysis in order to identify neuronal areas related to MCD. Patients with MCD differ from healthy controls in the amygdala, superior temporal lobe, retrosplenial area, primary motor cortex, insula, red nucleus, thalamus, anterior as well as dorsolateral prefrontal and frontal cortex. When comparing affected versus unaffected sides, temporal cortex, dorsal anterior cingulate cortex, supramarginal gyrus, dorsal temporal lobe, anterior insula, primary somatosensory cortex, superior frontal gyrus and anterior prefrontal as well as frontal cortex show significant differences. Neuronal areas seem to be involved in the pathogenesis, maintenance or as a result of MCD. Areas that are important for motor-planning, motor-selection or autonomic response seem to be especially relevant. Our results support the emotional unawareness theory but also underline the need of more support by conduction imaging studies on both CD and MCD.

Neural network of cognitive emotion regulation — An ALE meta-analysis and MACM analysis

PubMed Central

Kohn, N.; Eickhoff, S.B.; Scheller, M.; Laird, A.R.; Fox, P.T.; Habel, U.

2016-01-01

Cognitive regulation of emotions is a fundamental prerequisite for intact social functioning which impacts on both well being and psychopathology. The neural underpinnings of this process have been studied intensively in recent years, without, however, a general consensus. We here quantitatively summarize the published literature on cognitive emotion regulation using activation likelihood estimation in fMRI and PET (23 studies/479 subjects). In addition, we assessed the particular functional contribution of identified regions and their interactions using quantitative functional inference and meta-analytic connectivity modeling, respectively. In doing so, we developed a model for the core brain network involved in emotion regulation of emotional reactivity. According to this, the superior temporal gyrus, angular gyrus and (pre) supplementary motor area should be involved in execution of regulation initiated by frontal areas. The dorsolateral prefrontal cortex may be related to regulation of cognitive processes such as attention, while the ventrolateral prefrontal cortex may not necessarily reflect the regulatory process per se, but signals salience and therefore the need to regulate. We also identified a cluster in the anterior middle cingulate cortex as a region, which is anatomically and functionally in an ideal position to influence behavior and subcortical structures related to affect generation. Hence this area may play a central, integrative role in emotion regulation. By focusing on regions commonly active across multiple studies, this proposed model should provide important a priori information for the assessment of dysregulated emotion regulation in psychiatric disorders. PMID:24220041

Publication Bias and Nonreporting Found in Majority of Systematic Reviews and Meta-analyses in Anesthesiology Journals.

PubMed

Hedin, Riley J; Umberham, Blake A; Detweiler, Byron N; Kollmorgen, Lauren; Vassar, Matt

2016-10-01

Systematic reviews and meta-analyses are used by clinicians to derive treatment guidelines and make resource allocation decisions in anesthesiology. One cause for concern with such reviews is the possibility that results from unpublished trials are not represented in the review findings or data synthesis. This problem, known as publication bias, results when studies reporting statistically nonsignificant findings are left unpublished and, therefore, not included in meta-analyses when estimating a pooled treatment effect. In turn, publication bias may lead to skewed results with overestimated effect sizes. The primary objective of this study is to determine the extent to which evaluations for publication bias are conducted by systematic reviewers in highly ranked anesthesiology journals and which practices reviewers use to mitigate publication bias. The secondary objective of this study is to conduct publication bias analyses on the meta-analyses that did not perform these assessments and examine the adjusted pooled effect estimates after accounting for publication bias. This study considered meta-analyses and systematic reviews from 5 peer-reviewed anesthesia journals from 2007 through 2015. A PubMed search was conducted, and full-text systematic reviews that fit inclusion criteria were downloaded and coded independently by 2 authors. Coding was then validated, and disagreements were settled by consensus. In total, 207 systematic reviews were included for analysis. In addition, publication bias evaluation was performed for 25 systematic reviews that did not do so originally. We used Egger regression, Duval and Tweedie trim and fill, and funnel plots for these analyses. Fifty-five percent (n = 114) of the reviews discussed publication bias, and 43% (n = 89) of the reviews evaluated publication bias. Funnel plots and Egger regression were the most common methods for evaluating publication bias. Publication bias was reported in 34 reviews (16%). Thirty-six of the 45 (80.0%) publication bias analyses indicated the presence of publication bias by trim and fill analysis, whereas Egger regression indicated publication bias in 23 of 45 (51.1%) analyses. The mean absolute percent difference between adjusted and observed point estimates was 15.5%, the median was 6.2%, and the range was 0% to 85.5%. Many of these reviews reported following published guidelines such as PRISMA or MOOSE, yet only half appropriately addressed publication bias in their reviews. Compared with previous research, our study found fewer reviews assessing publication bias and greater likelihood of publication bias among reviews not performing these evaluations.

Prevalence of scoliosis among primary and middle school students in Mainland China: a systematic review and meta-analysis.

PubMed

Zhang, Hongqi; Guo, Chaofeng; Tang, Mingxing; Liu, Shaohua; Li, Jinsong; Guo, Qiang; Chen, Lizhang; Zhu, Yong; Zhao, Shushan

2015-01-01

Systematic review and meta-analysis of published prevalence of scoliosis among primary and middle school students in Mainland China. To evaluate the prevalence of scoliosis among primary and middle school students in Mainland China. There is substantial uncertainty regarding the prevalence of scoliosis in Mainland China among the primary and middle school students. We conducted a systematic review aiming to describe the prevalence of scoliosis in Mainland China. We systematically reviewed the published epidemiological studies or reports on the prevalence of scoliosis in Chinese cities. Scopus, PubMed, WanFang Database, CNKI, China National Science and Technology Digital Library, and WeiPu Database were searched for studies reporting a prevalence estimate for scoliosis in primary and middle school students. Meta-analyses were performed to estimate the pooled prevalence of scoliosis by STATA 12.0. Subgroup analyses were conducted according to the sex, age, and geographical area. A total of 38 articles, including 697,043 patients, were eligible for inclusion in this review. Meta-analyses revealed the prevalence of scoliosis to be 1.02% (95% [confidence interval] CI, 0.85-1.18) among the primary and middle school students in Mainland China. The female to male ratio was 1.54 (95% CI, 1.35-1.74; P < 0.001). According to the subgroup analysis by different ages, the prevalence of scoliosis increased from 0.73% (95% CI, 0.55-0.90) to 1.14% (95% CI, 0.86-1.42). Meta-analyses showed that the prevalence of scoliosis in Mainland China was 1.02% among the primary and middle school students. The prevalence of scoliosis in females was higher than in males and the ratio was 1.54. As they grew older, the prevalence of scoliosis increased in the students.

Alcohol consumption and the intention to engage in unprotected sex: systematic review and meta-analysis of experimental studies.

PubMed

Rehm, Jürgen; Shield, Kevin D; Joharchi, Narges; Shuper, Paul A

2012-01-01

To review and analyse in experimentally controlled studies the impact of alcohol consumption on intentions to engage in unprotected sex. To draw conclusions with respect to the question of whether alcohol has an independent effect on the incidence of human immunodeficiency virus (HIV) and other sexually transmitted infections (STIs). A systematic review and meta-analysis of randomized controlled studies examined the association between blood alcohol content (BAC) and self-perceived likelihood of using a condom during intercourse. The systematic review and meta-analysis were conducted according to internationally standardized protocols (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: PRISMA). The meta-analysis included an estimate of the dose-response effect, tests for publication bias and sensitivity analyses. Of the 12 studies included in the quantitative synthesis, our pooled analysis indicated that an increase in BAC of 0.1 mg/ml resulted in an increase of 5.0% (95% CI: 2.8-7.1%) in the indicated likelihood (indicated by a Likert scale) of engaging in unprotected sex. After adjusting for potential publication bias, this estimate dropped to 2.9% (95% CI: 2.0-3.9%). Thus, the larger the alcohol intake and the subsequent level of BAC, the higher the intentions to engage in unsafe sex. The main results were homogeneous, persisted in sensitivity analyses and after correction for publication bias. Alcohol use is an independent risk factor for intentions to engage in unprotected sex, and as risky sex intentions have been shown to be linked to actual risk behavior, the role of alcohol consumption in the transmission of HIV and other STIs may be of public health importance. © 2011 The Authors, Addiction © 2011 Society for the Study of Addiction.

The Andrews’ Principles of Risk, Need, and Responsivity as Applied in Drug Abuse Treatment Programs: Meta-Analysis of Crime and Drug Use Outcomes

PubMed Central

Prendergast, Michael L.; Pearson, Frank S.; Podus, Deborah; Hamilton, Zachary K.; Greenwell, Lisa

2013-01-01

Objectives The purpose of the present meta-analysis was to answer the question: Can the Andrews principles of risk, needs, and responsivity, originally developed for programs that treat offenders, be extended to programs that treat drug abusers? Methods Drawing from a dataset that included 243 independent comparisons, we conducted random-effects meta-regression and ANOVA-analog meta-analyses to test the Andrews principles by averaging crime and drug use outcomes over a diverse set of programs for drug abuse problems. Results For crime outcomes, in the meta-regressions the point estimates for each of the principles were substantial, consistent with previous studies of the Andrews principles. There was also a substantial point estimate for programs exhibiting a greater number of the principles. However, almost all of the 95% confidence intervals included the zero point. For drug use outcomes, in the meta-regressions the point estimates for each of the principles was approximately zero; however, the point estimate for programs exhibiting a greater number of the principles was somewhat positive. All of the estimates for the drug use principles had confidence intervals that included the zero point. Conclusions This study supports previous findings from primary research studies targeting the Andrews principles that those principles are effective in reducing crime outcomes, here in meta-analytic research focused on drug treatment programs. By contrast, programs that follow the principles appear to have very little effect on drug use outcomes. Primary research studies that experimentally test the Andrews principles in drug treatment programs are recommended. PMID:24058325

Meta-analysis in evidence-based healthcare: a paradigm shift away from random effects is overdue.

PubMed

Doi, Suhail A R; Furuya-Kanamori, Luis; Thalib, Lukman; Barendregt, Jan J

2017-12-01

Each year up to 20 000 systematic reviews and meta-analyses are published whose results influence healthcare decisions, thus making the robustness and reliability of meta-analytic methods one of the world's top clinical and public health priorities. The evidence synthesis makes use of either fixed-effect or random-effects statistical methods. The fixed-effect method has largely been replaced by the random-effects method as heterogeneity of study effects led to poor error estimation. However, despite the widespread use and acceptance of the random-effects method to correct this, it too remains unsatisfactory and continues to suffer from defective error estimation, posing a serious threat to decision-making in evidence-based clinical and public health practice. We discuss here the problem with the random-effects approach and demonstrate that there exist better estimators under the fixed-effect model framework that can achieve optimal error estimation. We argue for an urgent return to the earlier framework with updates that address these problems and conclude that doing so can markedly improve the reliability of meta-analytical findings and thus decision-making in healthcare.

Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study.

PubMed

Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias; Salanti, Georgia

2018-02-28

To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) ("living" network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (P<0.10). Cumulative pairwise and network meta-analyses were performed for each selected comparison. Monitoring boundaries of statistical significance were constructed and the evidence against the null hypothesis was considered to be strong when the monitoring boundaries were crossed. A significance level was defined as α=5%, power of 90% (β=10%), and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78, 95% confidence interval 1.00 to 7.72, P=0.05). Studies directly comparing the treatments of interest continued to be published for eight comparisons after strong evidence had become evident in network meta-analysis. In comparative effectiveness research, prospectively planned living network meta-analyses produced strong evidence against the null hypothesis more often and earlier than conventional, pairwise meta-analyses. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Living network meta-analysis compared with pairwise meta-analysis in comparative effectiveness research: empirical study

PubMed Central

Nikolakopoulou, Adriani; Mavridis, Dimitris; Furukawa, Toshi A; Cipriani, Andrea; Tricco, Andrea C; Straus, Sharon E; Siontis, George C M; Egger, Matthias

2018-01-01

Abstract Objective To examine whether the continuous updating of networks of prospectively planned randomised controlled trials (RCTs) (“living” network meta-analysis) provides strong evidence against the null hypothesis in comparative effectiveness of medical interventions earlier than the updating of conventional, pairwise meta-analysis. Design Empirical study of the accumulating evidence about the comparative effectiveness of clinical interventions. Data sources Database of network meta-analyses of RCTs identified through searches of Medline, Embase, and the Cochrane Database of Systematic Reviews until 14 April 2015. Eligibility criteria for study selection Network meta-analyses published after January 2012 that compared at least five treatments and included at least 20 RCTs. Clinical experts were asked to identify in each network the treatment comparison of greatest clinical interest. Comparisons were excluded for which direct and indirect evidence disagreed, based on side, or node, splitting test (P<0.10). Outcomes and analysis Cumulative pairwise and network meta-analyses were performed for each selected comparison. Monitoring boundaries of statistical significance were constructed and the evidence against the null hypothesis was considered to be strong when the monitoring boundaries were crossed. A significance level was defined as α=5%, power of 90% (β=10%), and an anticipated treatment effect to detect equal to the final estimate from the network meta-analysis. The frequency and time to strong evidence was compared against the null hypothesis between pairwise and network meta-analyses. Results 49 comparisons of interest from 44 networks were included; most (n=39, 80%) were between active drugs, mainly from the specialties of cardiology, endocrinology, psychiatry, and rheumatology. 29 comparisons were informed by both direct and indirect evidence (59%), 13 by indirect evidence (27%), and 7 by direct evidence (14%). Both network and pairwise meta-analysis provided strong evidence against the null hypothesis for seven comparisons, but for an additional 10 comparisons only network meta-analysis provided strong evidence against the null hypothesis (P=0.002). The median time to strong evidence against the null hypothesis was 19 years with living network meta-analysis and 23 years with living pairwise meta-analysis (hazard ratio 2.78, 95% confidence interval 1.00 to 7.72, P=0.05). Studies directly comparing the treatments of interest continued to be published for eight comparisons after strong evidence had become evident in network meta-analysis. Conclusions In comparative effectiveness research, prospectively planned living network meta-analyses produced strong evidence against the null hypothesis more often and earlier than conventional, pairwise meta-analyses. PMID:29490922

Joint models for longitudinal and time-to-event data: a review of reporting quality with a view to meta-analysis.

PubMed

Sudell, Maria; Kolamunnage-Dona, Ruwanthi; Tudur-Smith, Catrin

2016-12-05

Joint models for longitudinal and time-to-event data are commonly used to simultaneously analyse correlated data in single study cases. Synthesis of evidence from multiple studies using meta-analysis is a natural next step but its feasibility depends heavily on the standard of reporting of joint models in the medical literature. During this review we aim to assess the current standard of reporting of joint models applied in the literature, and to determine whether current reporting standards would allow or hinder future aggregate data meta-analyses of model results. We undertook a literature review of non-methodological studies that involved joint modelling of longitudinal and time-to-event medical data. Study characteristics were extracted and an assessment of whether separate meta-analyses for longitudinal, time-to-event and association parameters were possible was made. The 65 studies identified used a wide range of joint modelling methods in a selection of software. Identified studies concerned a variety of disease areas. The majority of studies reported adequate information to conduct a meta-analysis (67.7% for longitudinal parameter aggregate data meta-analysis, 69.2% for time-to-event parameter aggregate data meta-analysis, 76.9% for association parameter aggregate data meta-analysis). In some cases model structure was difficult to ascertain from the published reports. Whilst extraction of sufficient information to permit meta-analyses was possible in a majority of cases, the standard of reporting of joint models should be maintained and improved. Recommendations for future practice include clear statement of model structure, of values of estimated parameters, of software used and of statistical methods applied.

Meta-Analysis With Complex Research Designs: Dealing With Dependence From Multiple Measures and Multiple Group Comparisons

PubMed Central

Scammacca, Nancy; Roberts, Greg; Stuebing, Karla K.

2013-01-01

Previous research has shown that treating dependent effect sizes as independent inflates the variance of the mean effect size and introduces bias by giving studies with more effect sizes more weight in the meta-analysis. This article summarizes the different approaches to handling dependence that have been advocated by methodologists, some of which are more feasible to implement with education research studies than others. A case study using effect sizes from a recent meta-analysis of reading interventions is presented to compare the results obtained from different approaches to dealing with dependence. Overall, mean effect sizes and variance estimates were found to be similar, but estimates of indexes of heterogeneity varied. Meta-analysts are advised to explore the effect of the method of handling dependence on the heterogeneity estimates before conducting moderator analyses and to choose the approach to dependence that is best suited to their research question and their data set. PMID:25309002

Estimating the prevalence of heterozygous familial hypercholesterolaemia: a systematic review and meta-analysis

PubMed Central

Akioyamen, Leo E; Genest, Jacques; Shan, Shubham D; Reel, Rachel L; Albaum, Jordan M; Chu, Anna; Tu, Jack V

2017-01-01

Objectives Heterozygous familial hypercholesterolaemia (FH) confers a significant risk for premature cardiovascular disease (CVD). However, the estimated prevalence of FH varies substantially among studies. We aimed to provide a summary estimate of FH prevalence in the general population and assess variations in frequency across different sociodemographic characteristics. Setting, participants and outcome measures We searched MEDLINE, EMBASE, Global Health, the Cochrane Library, PsycINFO and PubMed for peer-reviewed literature using validated strategies. Results were limited to studies published in English between January 1990 and January 2017. Studies were eligible if they determined FH prevalence using clinical criteria or DNA-based analyses. We determined a pooled point prevalence of FH in adults and children and assessed the variation of the pooled frequency by age, sex, geographical location, diagnostic method, study quality and year of publication. Estimates were pooled using random-effects meta-analysis. Differences by study-level characteristics were investigated through subgroups, meta-regression and sensitivity analyses. Results The pooled prevalence of FH from 19 studies including 2 458 456 unique individuals was 0.40% (95% CI 0.29% to 0.52%) which corresponds to a frequency of 1 in 250 individuals. FH prevalence was found to vary by age and geographical location but not by any other covariates. Results were consistent in sensitivity analyses. Conclusions Our systematic review suggests that FH is a common disorder, affecting 1 in 250 individuals. These findings underscore the need for early detection and management to decrease CVD risk. PMID:28864697

Network meta-analysis of multiple outcome measures accounting for borrowing of information across outcomes

PubMed Central

2014-01-01

Background Network meta-analysis (NMA) enables simultaneous comparison of multiple treatments while preserving randomisation. When summarising evidence to inform an economic evaluation, it is important that the analysis accurately reflects the dependency structure within the data, as correlations between outcomes may have implication for estimating the net benefit associated with treatment. A multivariate NMA offers a framework for evaluating multiple treatments across multiple outcome measures while accounting for the correlation structure between outcomes. Methods The standard NMA model is extended to multiple outcome settings in two stages. In the first stage, information is borrowed across outcomes as well across studies through modelling the within-study and between-study correlation structure. In the second stage, we make use of the additional assumption that intervention effects are exchangeable between outcomes to predict effect estimates for all outcomes, including effect estimates on outcomes where evidence is either sparse or the treatment had not been considered by any one of the studies included in the analysis. We apply the methods to binary outcome data from a systematic review evaluating the effectiveness of nine home safety interventions on uptake of three poisoning prevention practices (safe storage of medicines, safe storage of other household products, and possession of poison centre control telephone number) in households with children. Analyses are conducted in WinBUGS using Markov Chain Monte Carlo (MCMC) simulations. Results Univariate and the first stage multivariate models produced broadly similar point estimates of intervention effects but the uncertainty around the multivariate estimates varied depending on the prior distribution specified for the between-study covariance structure. The second stage multivariate analyses produced more precise effect estimates while enabling intervention effects to be predicted for all outcomes, including intervention effects on outcomes not directly considered by the studies included in the analysis. Conclusions Accounting for the dependency between outcomes in a multivariate meta-analysis may or may not improve the precision of effect estimates from a network meta-analysis compared to analysing each outcome separately. PMID:25047164

History of kidney stones and risk of chronic kidney disease: a meta-analysis.

PubMed

Shang, Weifeng; Li, Lixi; Ren, Yali; Ge, Qiangqiang; Ku, Ming; Ge, Shuwang; Xu, Gang

2017-01-01

Although the relationship between a history of kidney stones and chronic kidney disease (CKD) has been explored in many studies, it is still far from being well understood. Thus, we conducted a meta-analysis of studies comparing rates of CKD in patients with a history of kidney stones. PubMed, EMBASE, and the reference lists of relevant articles were searched to identify observational studies related to the topic. A random-effects model was used to combine the study-specific risk estimates. We explored the potential heterogeneity by subgroup analyses and meta-regression analyses. Seven studies were included in this meta-analysis. Pooled results suggested that a history of kidney stones was associated with an increased adjusted risk estimate for CKD [risk ratio (RR), 1.47 95% confidence interval (CI) [1.23-1.76])], with significant heterogeneity among these studies ( I 2  = 93.6%, P  < 0.001). The observed positive association was observed in most of the subgroup analyses, whereas the association was not significant among studies from Asian countries, the mean age ≥50 years and male patients. A history of kidney stones is associated with increased risk of CKD. Future investigations are encouraged to reveal the underlying mechanisms in the connection between kidney stones and CKD, which may point the way to more effective preventive and therapeutic measures.

Endotoxin exposure and lung cancer risk: a systematic review and meta-analysis of the published literature on agriculture and cotton textile workers.

PubMed

Lenters, Virissa; Basinas, Ioannis; Beane-Freeman, Laura; Boffetta, Paolo; Checkoway, Harvey; Coggon, David; Portengen, Lützen; Sim, Malcolm; Wouters, Inge M; Heederik, Dick; Vermeulen, Roel

2010-04-01

To examine the association between exposure to endotoxins and lung cancer risk by conducting a systematic review and meta-analysis of epidemiologic studies of workers in the cotton textile and agricultural industries; industries known for high exposure levels of endotoxins. Risk estimates were extracted from studies published before 2009 that met predefined quality criteria, including 8 cohort, 1 case-cohort, and 2 case-control studies of cotton textile industry workers, and 15 cohort and 2 case-control studies of agricultural workers. Summary risk estimates were calculated using random effects meta-analyses. Potential sources of heterogeneity were explored through subgroup analyses. The summary risk of lung cancer was 0.72 (95% CI, 0.57-0.90) for textile workers and 0.62 (0.52-0.75) for agricultural workers. The relative risk of lung cancer was below 1.0 for most subgroups defined according to sex, study design, outcome, smoking adjustment, and geographic area. Two studies provided quantitative estimates of endotoxin exposure and both studies tended to support a dose-dependent protective effect of endotoxins on lung cancer risk. Despite several limitations, this meta-analysis based on high-quality studies adds weight to the hypothesis that occupational exposure to endotoxin in cotton textile production and agriculture is protective against lung cancer.

Evaluating the Quality of Evidence from a Network Meta-Analysis

PubMed Central

Salanti, Georgia; Del Giovane, Cinzia; Chaimani, Anna; Caldwell, Deborah M.; Higgins, Julian P. T.

2014-01-01

Systematic reviews that collate data about the relative effects of multiple interventions via network meta-analysis are highly informative for decision-making purposes. A network meta-analysis provides two types of findings for a specific outcome: the relative treatment effect for all pairwise comparisons, and a ranking of the treatments. It is important to consider the confidence with which these two types of results can enable clinicians, policy makers and patients to make informed decisions. We propose an approach to determining confidence in the output of a network meta-analysis. Our proposed approach is based on methodology developed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group for pairwise meta-analyses. The suggested framework for evaluating a network meta-analysis acknowledges (i) the key role of indirect comparisons (ii) the contributions of each piece of direct evidence to the network meta-analysis estimates of effect size; (iii) the importance of the transitivity assumption to the validity of network meta-analysis; and (iv) the possibility of disagreement between direct evidence and indirect evidence. We apply our proposed strategy to a systematic review comparing topical antibiotics without steroids for chronically discharging ears with underlying eardrum perforations. The proposed framework can be used to determine confidence in the results from a network meta-analysis. Judgements about evidence from a network meta-analysis can be different from those made about evidence from pairwise meta-analyses. PMID:24992266

Measuring coral reef decline through meta-analyses

PubMed Central

Côté, I.M; Gill, J.A; Gardner, T.A; Watkinson, A.R

2005-01-01

Coral reef ecosystems are in decline worldwide, owing to a variety of anthropogenic and natural causes. One of the most obvious signals of reef degradation is a reduction in live coral cover. Past and current rates of loss of coral are known for many individual reefs; however, until recently, no large-scale estimate was available. In this paper, we show how meta-analysis can be used to integrate existing small-scale estimates of change in coral and macroalgal cover, derived from in situ surveys of reefs, to generate a robust assessment of long-term patterns of large-scale ecological change. Using a large dataset from Caribbean reefs, we examine the possible biases inherent in meta-analytical studies and the sensitivity of the method to patchiness in data availability. Despite the fact that our meta-analysis included studies that used a variety of sampling methods, the regional estimate of change in coral cover we obtained is similar to that generated by a standardized survey programme that was implemented in 1991 in the Caribbean. We argue that for habitat types that are regularly and reasonably well surveyed in the course of ecological or conservation research, meta-analysis offers a cost-effective and rapid method for generating robust estimates of past and current states. PMID:15814352

A critical appraisal of the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing interventions: a systematic review of reviews

PubMed Central

Jin, Ying-Hui; Wang, Guo-Hao; Sun, Yi-Rong; Li, Qi; Zhao, Chen; Li, Ge; Si, Jin-Hua; Li, Yan; Lu, Cui; Shang, Hong-Cai

2016-01-01

Objective To assess the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing (TCMN) interventions in Chinese journals. These interventions include acupressure, massage, Tai Chi, Qi Gong, electroacupuncture and use of Chinese herbal medicines—for example, in enemas, foot massage and compressing the umbilicus. Design A systematic literature search for systematic reviews and meta-analyses of TCMN interventions was performed. Review characteristics were extracted. The methodological quality and the quality of the evidence were evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approaches. Result We included 20 systematic reviews and meta-analyses, and a total of 11 TCMN interventions were assessed in the 20 reviews. The compliance with AMSTAR checklist items ranged from 4.5 to 8 and systematic reviews/meta-analyses were, on average, of medium methodological quality. The quality of the evidence we assessed ranged from very low to moderate; no high-quality evidence was found. The top two causes for downrating confidence in effect estimates among the 31 bodies of evidence assessed were the risk of bias and inconsistency. Conclusions There is room for improvement in the methodological quality of systematic reviews/meta-analyses of TCMN interventions published in Chinese journals. Greater efforts should be devoted to ensuring a more comprehensive search strategy, clearer specification of the interventions of interest in the eligibility criteria and identification of meaningful outcomes for clinicians and patients (consumers). The overall quality of evidence among reviews remains suboptimal, which raise concerns about their roles in influencing clinical practice. Thus, the conclusions in reviews we assessed must be treated with caution and their roles in influencing clinical practice should be limited. A critical appraisal of systematic reviews/meta-analyses of TCMN interventions is particularly important to provide sound guidance for TCMN. PMID:28186925

Meta-analysis of the association between short-term exposure to ambient ozone and respiratory hospital admissions

NASA Astrophysics Data System (ADS)

Ji, Meng; Cohan, Daniel S.; Bell, Michelle L.

2011-04-01

Ozone is associated with health impacts including respiratory outcomes; however, results differ across studies. Meta-analysis is an increasingly important approach to synthesizing evidence across studies. We conducted meta-analysis of short-term ozone exposure and respiratory hospitalizations to evaluate variation across studies and explore some of the challenges in meta-analysis. We identified 136 estimates from 96 studies and investigated how estimates differed by age, ozone metric, season, lag, region, disease category, and hospitalization type. Overall results indicate associations between ozone and various kinds of respiratory hospitalizations; however, study characteristics affected risk estimates. Estimates were similar, but higher, for the elderly compared to all ages and for previous day exposure compared to same day exposure. Comparison across studies was hindered by variation in definitions of disease categories, as some (e.g., asthma) were identified through >= 3 different sets of ICD codes. Although not all analyses exhibited evidence of publication bias, adjustment for publication bias generally lowered overall estimates. Emergency hospitalizations for total respiratory disease increased by 4.47% (95% interval: 2.48, 6.50%) per 10 ppb 24 h ozone among the elderly without adjustment for publication bias and 2.97% (1.05, 4.94%) with adjustment. Comparison of multi-city study results and meta-analysis based on single-city studies further suggested publication bias.

Introduction, comparison, and validation of Meta-Essentials: A free and simple tool for meta-analysis.

PubMed

Suurmond, Robert; van Rhee, Henk; Hak, Tony

2017-12-01

We present a new tool for meta-analysis, Meta-Essentials, which is free of charge and easy to use. In this paper, we introduce the tool and compare its features to other tools for meta-analysis. We also provide detailed information on the validation of the tool. Although free of charge and simple, Meta-Essentials automatically calculates effect sizes from a wide range of statistics and can be used for a wide range of meta-analysis applications, including subgroup analysis, moderator analysis, and publication bias analyses. The confidence interval of the overall effect is automatically based on the Knapp-Hartung adjustment of the DerSimonian-Laird estimator. However, more advanced meta-analysis methods such as meta-analytical structural equation modelling and meta-regression with multiple covariates are not available. In summary, Meta-Essentials may prove a valuable resource for meta-analysts, including researchers, teachers, and students. © 2017 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

Overlapping meta-analyses on the same topic: survey of published studies.

PubMed

Siontis, Konstantinos C; Hernandez-Boussard, Tina; Ioannidis, John P A

2013-07-19

To assess how common it is to have multiple overlapping meta-analyses of randomized trials published on the same topic. Survey of published meta-analyses. PubMed. Meta-analyses published in 2010 were identified, and 5% of them were randomly selected. We further selected those that included randomized trials and examined effectiveness of any medical intervention. For eligible meta-analyses, we searched for other meta-analyses on the same topic (covering the same comparisons, indications/settings, and outcomes or overlapping subsets of them) published until February 2013. Of 73 eligible meta-analyses published in 2010, 49 (67%) had at least one other overlapping meta-analysis (median two meta-analyses per topic, interquartile range 1-4, maximum 13). In 17 topics at least one author was involved in at least two of the overlapping meta-analyses. No characteristics of the index meta-analyses were associated with the potential for overlapping meta-analyses. Among pairs of overlapping meta-analyses in 20 randomly selected topics, 13 of the more recent meta-analyses did not include any additional outcomes. In three of the four topics with eight or more published meta-analyses, many meta-analyses examined only a subset of the eligible interventions or indications/settings covered by the index meta-analysis. Conversely, for statins in the prevention of atrial fibrillation after cardiac surgery, 11 meta-analyses were published with similar eligibility criteria for interventions and setting: there was still variability on which studies were included, but the results were always similar or even identical across meta-analyses. While some independent replication of meta-analyses by different teams is possibly useful, the overall picture suggests that there is a waste of efforts with many topics covered by multiple overlapping meta-analyses.

Overview of atomic layer etching in the semiconductor industry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanarik, Keren J., E-mail: keren.kanarik@lamresearch.com; Lill, Thorsten; Hudson, Eric A.

2015-03-15

Atomic layer etching (ALE) is a technique for removing thin layers of material using sequential reaction steps that are self-limiting. ALE has been studied in the laboratory for more than 25 years. Today, it is being driven by the semiconductor industry as an alternative to continuous etching and is viewed as an essential counterpart to atomic layer deposition. As we enter the era of atomic-scale dimensions, there is need to unify the ALE field through increased effectiveness of collaboration between academia and industry, and to help enable the transition from lab to fab. With this in mind, this article providesmore » defining criteria for ALE, along with clarification of some of the terminology and assumptions of this field. To increase understanding of the process, the mechanistic understanding is described for the silicon ALE case study, including the advantages of plasma-assisted processing. A historical overview spanning more than 25 years is provided for silicon, as well as ALE studies on oxides, III–V compounds, and other materials. Together, these processes encompass a variety of implementations, all following the same ALE principles. While the focus is on directional etching, isotropic ALE is also included. As part of this review, the authors also address the role of power pulsing as a predecessor to ALE and examine the outlook of ALE in the manufacturing of advanced semiconductor devices.« less

Study protocol for examining job strain as a risk factor for severe unipolar depression in an individual participant meta-analysis of 14 European cohorts.

PubMed

Madsen, Ida E H; Hannerz, Harald; Nyberg, Solja T; Magnusson Hanson, Linda L; Ahola, Kirsi; Alfredsson, Lars; Batty, G David; Bjorner, Jakob B; Borritz, Marianne; Burr, Hermann; Dragano, Nico; Ferrie, Jane E; Hamer, Mark; Jokela, Markus; Knutsson, Anders; Koskenvuo, Markku; Koskinen, Aki; Leineweber, Constanze; Nielsen, Martin L; Nordin, Maria; Oksanen, Tuula; Pejtersen, Jan H; Pentti, Jaana; Salo, Paula; Singh-Manoux, Archana; Suominen, Sakari; Theorell, Töres; Toppinen-Tanner, Salla; Vahtera, Jussi; Väänänen, Ari; Westerholm, Peter J M; Westerlund, Hugo; Fransson, Eleonor; Heikkilä, Katriina; Virtanen, Marianna; Rugulies, Reiner; Kivimäki, Mika

2013-01-01

Previous studies have shown that gainfully employed individuals with high work demands and low control at work (denoted "job strain") are at increased risk of common mental disorders, including depression. Most existing studies have, however, measured depression using self-rated symptom scales that do not necessarily correspond to clinically diagnosed depression. In addition, a meta-analysis from 2008 indicated publication bias in the field.   This study protocol describes the planned design and analyses of an individual participant data meta-analysis, to examine whether job strain is associated with an increased risk of clinically diagnosed unipolar depression based on hospital treatment registers.  The study will be based on data from approximately 120,000 individuals who participated in 14 studies on work environment and health in 4 European countries. The self-reported working conditions data will be merged with national registers on psychiatric hospital treatment, primarily hospital admissions. Study-specific risk estimates for the association between job strain and depression will be calculated using Cox regressions. The study-specific risk estimates will be pooled using random effects meta-analysis.   The planned analyses will help clarify whether job strain is associated with an increased risk of clinically diagnosed unipolar depression. As the analysis is based on pre-planned study protocols and an individual participant data meta-analysis, the pooled risk estimates will not be influenced by selective reporting and publication bias. However, the results of the planned study may only pertain to severe cases of unipolar depression, because of the outcome measure applied.

Health State Utility Value in Chronic Obstructive Pulmonary Disease (COPD); The Challenge of Heterogeneity: A Systematic Review and Meta-Analysis.

PubMed

Moayeri, Foruhar; Hsueh, Ya-Seng Arthur; Clarke, Philip; Hua, Xinyang; Dunt, David

2016-06-01

Chronic obstructive pulmonary disease (COPD) has a considerable impact on quality of life and well-being of patients. Health state utility value (HSUV) is a recognized measure for health economic appraisals and is extensively used as an indicator for decision-making studies. This study is a systematic review of literature aimed to estimate mean utility value in COPD using meta-analysis and explore degree of heterogeneity in the utility values across a variety of clinical and study characteristic. The literature review covers studies that used EQ-5D to estimate utility value for patient level research in COPD. Studies that reported utility values elicited by EQ-5D in COPD patients were selected for random-effect meta-analysis addressing inter-study heterogeneity and subgroup analyses. Thirty-two studies were included in the general utility meta-analysis. The estimated general utility value was 0.673 (95% CI 0.653 to 0.693). Meta-analyses of COPD stages utility values showed influence of airway obstruction on utility value. The utility values ranged from 0.820 (95% CI 0.767 to 0.872) for stage I to 0.624 (95% CI 0.571 to 0.677) for stage IV. There was substantial heterogeneity in utility values: I(2) = 97.7%. A more accurate measurement of utility values in COPD is needed to refine valid and generalizable scores of HSUV. Given the limited success of the factors studied to reduce heterogeneity, an approach needs to be developed how best to use mean utility values for COPD in health economic evaluation.

Meta-analyses including data from observational studies.

PubMed

O'Connor, Annette M; Sargeant, Jan M

2014-02-15

Observational studies represent a wide group of studies where the disease or condition of interest is naturally occurring and the investigator does not control allocation to interventions or exposures. Observational studies are used to test hypotheses about the efficacy of interventions or about exposure-disease relationships, to estimate incidence or prevalence of conditions, and to assess the sensitivity and specificity of diagnostic assays. Experimental-study designs and randomized controlled trials (RCTs) can also contribute to the body of evidence about such questions. Meta-analyses (either with or without systematic reviews) aim to combine information from primary research studies to better describe the entire body of work. The aim of meta-analyses may be to obtain a summary effect size, or to understand factors that affect effect sizes. In this paper, we discuss the role of observational studies in meta-analysis questions and some factors to consider when deciding whether a meta-analysis should include results from such studies. Our suggestion is that one should only include studies that are not at high risk of inherent bias when calculating a summary effect size. Study design however can be a meaningful variable in assessment of outcome heterogeneity. Copyright © 2013 Elsevier B.V. All rights reserved.

[Reevaluation of the methodological quality in meta-analyses of accelerated rehabilitation on recovery after surgery for colorectal cancer].

PubMed

Ding, S N; Pan, H Y; Zhang, J G

2017-03-14

Objective: To evaluate the methodological quality and impacts on outcomes for systematic reviews (SRs) of accelerated rehabilitation versus traditional control for colorectal surgery. Methods: We comprehensively searched six databases and additional websites to collect SRs, or meta-analysis from inception to July 2016. The Overview Quality Assessment Questionnaire (OQAQ) was applied for quality assessment of the included studies, the tools recommended by the Cochrane Collaboration was applied for quality assessment for RCT and CCT and the Newcastle-Ottawa Scale (NOS) was applied to assess observational study. The relative ratios (RRs) and 95% confidence intervals (CIs) were integrated using Review Manager 5.3 software. Results: Fourteen meta-analyses were included in total. The mean OQAQ score was 3.8 with 95% CI 3.2 to 4.3. Only three meta-analyses were assessed as good quality. Two studies misused statistical models. A total of 42 primary studies referenced by meta-analyses were included, of which, 25 RCTs were levelled grade B and 1 CCT was levelled grade C. An estimated mean NOS score of 16 observation studies was 6.75 (totally scored 9 with 95% CI 6.4 to 7.1), of which, 10 studies scored ≥7 were high quality, 6 studies scored 6 were moderate quality. Conclusions: Currently, the overall quality of meta-analyses about comparing the effects and safety between accelerated rehabilitation and traditional control for colorectal surgery is fairly poor and the evidence level is lower. Health providers should apply the evidence with caution in clinical practice.

Meta-Analyses of Diagnostic Accuracy in Imaging Journals: Analysis of Pooling Techniques and Their Effect on Summary Estimates of Diagnostic Accuracy.

PubMed

McGrath, Trevor A; McInnes, Matthew D F; Korevaar, Daniël A; Bossuyt, Patrick M M

2016-10-01

Purpose To determine whether authors of systematic reviews of diagnostic accuracy studies published in imaging journals used recommended methods for meta-analysis, and to evaluate the effect of traditional methods on summary estimates of sensitivity and specificity. Materials and Methods Medline was searched for published systematic reviews that included meta-analysis of test accuracy data limited to imaging journals published from January 2005 to May 2015. Two reviewers independently extracted study data and classified methods for meta-analysis as traditional (univariate fixed- or random-effects pooling or summary receiver operating characteristic curve) or recommended (bivariate model or hierarchic summary receiver operating characteristic curve). Use of methods was analyzed for variation with time, geographical location, subspecialty, and journal. Results from reviews in which study authors used traditional univariate pooling methods were recalculated with a bivariate model. Results Three hundred reviews met the inclusion criteria, and in 118 (39%) of those, authors used recommended meta-analysis methods. No change in the method used was observed with time (r = 0.54, P = .09); however, there was geographic (χ(2) = 15.7, P = .001), subspecialty (χ(2) = 46.7, P < .001), and journal (χ(2) = 27.6, P < .001) heterogeneity. Fifty-one univariate random-effects meta-analyses were reanalyzed with the bivariate model; the average change in the summary estimate was -1.4% (P < .001) for sensitivity and -2.5% (P < .001) for specificity. The average change in width of the confidence interval was 7.7% (P < .001) for sensitivity and 9.9% (P ≤ .001) for specificity. Conclusion Recommended methods for meta-analysis of diagnostic accuracy in imaging journals are used in a minority of reviews; this has not changed significantly with time. Traditional (univariate) methods allow overestimation of diagnostic accuracy and provide narrower confidence intervals than do recommended (bivariate) methods. (©) RSNA, 2016 Online supplemental material is available for this article.

A new Arctic 25-year Altimetric Sea-level Record (1992-2016) and Initial look at Arctic Sea Level Budget Closure

NASA Astrophysics Data System (ADS)

Andersen, O. B.; Passaro, M.; Benveniste, J.; Piccioni, G.

2016-12-01

A new initiative within the ESA Sea Level Climate Change initiative (SL-cci) framework to improve the Arctic sea level record has been initiated as a combined effort to reprocess and retrack past altimetry to create a 25-year combined sea level record for sea level research studies. One of the objectives is to retracked ERS-2 dataset for the high latitudes based on the ALES retracking algorithm through adapting the ALES retracker for retracking of specular surfaces (leads). Secondly a reprocessing using tailored editing to Arctic Conditions will be carried out also focusing on the merging of the multi-mission data. Finally an effort is to combine physical and empirical retracked sea surface height information to derive an experimental spatio-temporal enhanced sea level product for high latitude. The first results in analysing Arctic Sea level variations on annual inter-annual scales for the 1992-2015 from a preliminar version of this dataset is presented. By including the GRACE water storage estimates and NOAA halo- and thermo-steric sea level variatios since 2002 a preliminary attempt to close the Arctic Sea level budget is presented here. Closing the Arctic sea level budget is by no mean trivial as both steric data and satellite altimetry is both sparse temporally and limited geographically.

Ataxia Telangiectasia–Mutated Gene Polymorphisms and Acute Normal Tissue Injuries in Cancer Patients After Radiation Therapy: A Systematic Review and Meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Dong, Lihua; Cui, Jingkun; Tang, Fengjiao

Purpose: Studies of the association between ataxia telangiectasia–mutated (ATM) gene polymorphisms and acute radiation injuries are often small in sample size, and the results are inconsistent. We conducted the first meta-analysis to provide a systematic review of published findings. Methods and Materials: Publications were identified by searching PubMed up to April 25, 2014. Primary meta-analysis was performed for all acute radiation injuries, and subgroup meta-analyses were based on clinical endpoint. The influence of sample size and radiation injury incidence on genetic effects was estimated in sensitivity analyses. Power calculations were also conducted. Results: The meta-analysis was conducted on the ATMmore » polymorphism rs1801516, including 5 studies with 1588 participants. For all studies, the cut-off for differentiating cases from controls was grade 2 acute radiation injuries. The primary meta-analysis showed a significant association with overall acute radiation injuries (allelic model: odds ratio = 1.33, 95% confidence interval: 1.04-1.71). Subgroup analyses detected an association between the rs1801516 polymorphism and a significant increase in urinary and lower gastrointestinal injuries and an increase in skin injury that was not statistically significant. There was no between-study heterogeneity in any meta-analyses. In the sensitivity analyses, small studies did not show larger effects than large studies. In addition, studies with high incidence of acute radiation injuries showed larger effects than studies with low incidence. Power calculations revealed that the statistical power of the primary meta-analysis was borderline, whereas there was adequate power for the subgroup analysis of studies with high incidence of acute radiation injuries. Conclusions: Our meta-analysis showed a consistency of the results from the overall and subgroup analyses. We also showed that the genetic effect of the rs1801516 polymorphism on acute radiation injuries was dependent on the incidence of the injury. These support the evidence of an association between the rs1801516 polymorphism and acute radiation injuries, encouraging further research of this topic.« less

Chronic widespread pain prevalence in the general population: A systematic review.

PubMed

Andrews, P; Steultjens, M; Riskowski, J

2018-01-01

Chronic widespread pain (CWP) is a significant burden in communities. Understanding the impact of population-dependent (e.g., age, gender) and contextual-dependent (e.g. survey method, region, inequality level) factors have on CWP prevalence may provide a foundation for population-based strategies to address CWP. Therefore, the purpose of this study was to estimate the global prevalence of CWP and evaluate the population and contextual factors associated with CWP. A systematic review of CWP prevalence studies (1990-2017) in the general population was undertaken. Meta-analyses were conducted to determine CWP prevalence, and study population data and contextual factors were evaluated using a meta-regression. Thirty-nine manuscripts met the inclusion criteria. Study CWP prevalence ranged from 1.4% to 24.0%, with CWP prevalence in men ranging from 0.8% to 15.3% and 1.7% to 22.1% in women. Estimated overall CWP prevalence was 9.6% (8.0-11.2%). Meta-regression analyses showed gender, United Nations country development status, and human development index (HDI) influenced CWP prevalence, while survey method, region, methodological and reporting quality, and inequality showed no significant effect on the CWP estimate. Globally CWP affects one in ten individuals within the general population, with women more likely to experience CWP than men. HDI was noted to be the socioeconomic factor related to CWP prevalence, with those in more developed countries having a lower CWP prevalence than those in less developed countries. Most CWP estimates were from developed countries, and CWP estimates from countries with a lower socioeconomic position is needed to further refine the global estimate of CWP. This systematic review and meta-analysis updates the current global CWP prevalence by examining the population-level (e.g. age, gender) and contextual (e.g. country development status; survey style; reporting and methodologic quality) factors associated with CWP prevalence. This analyses provides evidence to support higher levels of CWP in countries with a lower socioeconomic position relative to countries with a higher socioeconomic position. © 2017 European Pain Federation - EFIC®.

Identifying Regional Variation in the Prevalence of Postpartum Haemorrhage: A Systematic Review and Meta-Analysis

PubMed Central

Calvert, Clara; Thomas, Sara L.; Ronsmans, Carine; Wagner, Karen S.; Adler, Alma J.; Filippi, Veronique

2012-01-01

Objective To provide regional estimates of the prevalence of maternal haemorrhage and explore the effect of methodological differences between studies on any observed regional variation. Methods We conducted a systematic review of the prevalence of maternal haemorrhage, defined as blood loss greater than or equal to 1) 500 ml or 2) 1000 ml in the antepartum, intrapartum or postpartum period. We obtained regional estimates of the prevalence of maternal and severe maternal haemorrhage by conducting meta-analyses and used meta-regression to explore potential sources of between-study heterogeneity. Findings No studies reported the prevalence of antepartum haemorrhage (APH) according to our definitions. The prevalence of postpartum haemorrhage (PPH) (blood loss ≥500 ml) ranged from 7.2% in Oceania to 25.7% in Africa. The prevalence of severe PPH (blood loss ≥1000 ml) was highest in Africa at 5.1% and lowest in Asia at 1.9%. There was strong evidence of between-study heterogeneity in the prevalence of PPH and severe PPH in most regions. Meta-regression analyses suggested that region and method of measurement of blood loss influenced prevalence estimates for both PPH and severe PPH. The regional patterns changed after adjusting for the other predictors of PPH indicating that, compared with European women, Asian women have a lower prevalence of PPH. Conclusions We found evidence that Asian women have a very low prevalence of PPH compared with women in Europe. However, more reliable estimates will only be obtained with the standardisation of the measurement of PPH so that the data from different regions are comparable. PMID:22844432

Prevalence of attention deficit hyperactivity disorder among children and adolescents in Spain: a systematic review and meta-analysis of epidemiological studies

PubMed Central

2012-01-01

Background Attention deficit hyperactivity disorder (ADHD) is a commonly diagnosed neuropsychiatric disorder in childhood, but the frequency of the condition is not well established in many countries. The aim of the present study was to quantify the overall prevalence of ADHD among children and adolescents in Spain by means of a systematic review and meta-analysis. Methods PubMed/MEDLINE, IME, IBECS and TESEO were comprehensively searched. Original reports were selected if they provided data on prevalence estimates of ADHD among people under 18 years old in Spain and were cross-sectional, observational epidemiological studies. Information from included studies was systematically extracted and evaluated. Overall pooled-prevalence estimates of ADHD were calculated using random-effects models. Sources of heterogeneity were explored by means sub-groups analyses and univariate meta-regressions. Results Fourteen epidemiological studies (13,026 subjects) were selected. The overall pooled-prevalence of ADHD was estimated at 6.8% [95% confidence interval (CI) 4.9 – 8.8%] representing 361,580 (95% CI 260,550 – 467,927) children and adolescents in the community. There was significant heterogeneity (P < 0.001), which was incompletely explained by subgroup analyses and meta-regressions. Conclusions Our findings suggest that the prevalence of ADHD among children and adolescents in Spain is consistent with previous studies conducted in other countries and regions. This study represents a first step in estimating the national burden of ADHD that will be essential to building evidence-based programs and services. PMID:23057832

Advanced glycoxidation and lipoxidation end products (AGEs and ALEs): an overview of their mechanisms of formation.

PubMed

Vistoli, G; De Maddis, D; Cipak, A; Zarkovic, N; Carini, M; Aldini, G

2013-08-01

Advanced lipoxidation end products (ALEs) and advanced glycation end products (AGEs) have a pathogenetic role in the development and progression of different oxidative-based diseases including diabetes, atherosclerosis, and neurological disorders. AGEs and ALEs represent a quite complex class of compounds that are formed by different mechanisms, by heterogeneous precursors and that can be formed either exogenously or endogenously. There is a wide interest in AGEs and ALEs involving different aspects of research which are essentially focused on set-up and application of analytical strategies (1) to identify, characterize, and quantify AGEs and ALEs in different pathophysiological conditions; (2) to elucidate the molecular basis of their biological effects; and (3) to discover compounds able to inhibit AGEs/ALEs damaging effects not only as biological tools aimed at validating AGEs/ALEs as drug target, but also as promising drugs. All the above-mentioned research stages require a clear picture of the chemical formation of AGEs/ALEs but this is not simple, due to the complex and heterogeneous pathways, involving different precursors and mechanisms. In view of this intricate scenario, the aim of the present review is to group the main AGEs and ALEs and to describe, for each of them, the precursors and mechanisms of formation.

Incorporating uncertainty regarding applicability of evidence from meta-analyses into clinical decision making.

PubMed

Kriston, Levente; Meister, Ramona

2014-03-01

Judging applicability (relevance) of meta-analytical findings to particular clinical decision-making situations remains challenging. We aimed to describe an evidence synthesis method that accounts for possible uncertainty regarding applicability of the evidence. We conceptualized uncertainty regarding applicability of the meta-analytical estimates to a decision-making situation as the result of uncertainty regarding applicability of the findings of the trials that were included in the meta-analysis. This trial-level applicability uncertainty can be directly assessed by the decision maker and allows for the definition of trial inclusion probabilities, which can be used to perform a probabilistic meta-analysis with unequal probability resampling of trials (adaptive meta-analysis). A case study with several fictitious decision-making scenarios was performed to demonstrate the method in practice. We present options to elicit trial inclusion probabilities and perform the calculations. The result of an adaptive meta-analysis is a frequency distribution of the estimated parameters from traditional meta-analysis that provides individually tailored information according to the specific needs and uncertainty of the decision maker. The proposed method offers a direct and formalized combination of research evidence with individual clinical expertise and may aid clinicians in specific decision-making situations. Copyright © 2014 Elsevier Inc. All rights reserved.

Low Reporting Quality of the Meta-Analyses in Diagnostic Pathology.

PubMed

Liu, Xulei; Kinzler, Michael; Yuan, Jiangfan; He, Guozhong; Zhang, Lanjing

2017-03-01

- Little is known regarding the reporting quality of meta-analyses in diagnostic pathology. - To compare reporting quality of meta-analyses in diagnostic pathology and medicine and to examine factors associated with reporting quality of diagnostic pathology meta-analyses. - Meta-analyses were identified in 12 major diagnostic pathology journals without specifying years and 4 major medicine journals in 2006 and 2011 using PubMed. Reporting quality of meta-analyses was evaluated using the 27-item checklist of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement published in 2009. A higher PRISMA score indicates higher reporting quality. - Forty-one diagnostic pathology meta-analyses and 118 medicine meta-analyses were included. Overall, reporting quality of meta-analyses in diagnostic pathology was lower than that in medicine (median [interquartile range] = 22 [15, 25] versus 27 [23, 28], P < .001). Compared with medicine meta-analyses, diagnostic pathology meta-analyses less likely reported 23 of the 27 items (85.2%) on the PRISMA checklist, but more likely reported the data items. Higher reporting quality of diagnostic pathology meta-analyses was associated with recent publication years (later than 2009 versus 2009 or earlier, P = .002) and non-North American first authors (versus North American, P = .001), but not journal publisher's location (P = .11). Interestingly, reporting quality was not associated with adjusted citation ratio for meta-analyses in either diagnostic pathology or medicine (P = .40 and P = .09, respectively). - Meta-analyses in diagnostic pathology had lower reporting quality than those in medicine. Reporting quality of diagnostic pathology meta-analyses is linked to publication year and first author's location, but not to journal publisher's location or article's adjusted citation ratios. More research and education on meta-analysis methodology may improve the reporting quality of diagnostic pathology meta-analyses.

Are Study and Journal Characteristics Reliable Indicators of "Truth" in Imaging Research?

PubMed

Frank, Robert A; McInnes, Matthew D F; Levine, Deborah; Kressel, Herbert Y; Jesurum, Julia S; Petrcich, William; McGrath, Trevor A; Bossuyt, Patrick M

2018-04-01

Purpose To evaluate whether journal-level variables (impact factor, cited half-life, and Standards for Reporting of Diagnostic Accuracy Studies [STARD] endorsement) and study-level variables (citation rate, timing of publication, and order of publication) are associated with the distance between primary study results and summary estimates from meta-analyses. Materials and Methods MEDLINE was searched for meta-analyses of imaging diagnostic accuracy studies, published from January 2005 to April 2016. Data on journal-level and primary-study variables were extracted for each meta-analysis. Primary studies were dichotomized by variable as first versus subsequent publication, publication before versus after STARD introduction, STARD endorsement, or by median split. The mean absolute deviation of primary study estimates from the corresponding summary estimates for sensitivity and specificity was compared between groups. Means and confidence intervals were obtained by using bootstrap resampling; P values were calculated by using a t test. Results Ninety-eight meta-analyses summarizing 1458 primary studies met the inclusion criteria. There was substantial variability, but no significant differences, in deviations from the summary estimate between paired groups (P > .0041 in all comparisons). The largest difference found was in mean deviation for sensitivity, which was observed for publication timing, where studies published first on a topic demonstrated a mean deviation that was 2.5 percentage points smaller than subsequently published studies (P = .005). For journal-level factors, the greatest difference found (1.8 percentage points; P = .088) was in mean deviation for sensitivity in journals with impact factors above the median compared with those below the median. Conclusion Journal- and study-level variables considered important when evaluating diagnostic accuracy information to guide clinical decisions are not systematically associated with distance from the truth; critical appraisal of individual articles is recommended. © RSNA, 2017 Online supplemental material is available for this article.

Trial Sequential Analysis in systematic reviews with meta-analysis.

PubMed

Wetterslev, Jørn; Jakobsen, Janus Christian; Gluud, Christian

2017-03-06

Most meta-analyses in systematic reviews, including Cochrane ones, do not have sufficient statistical power to detect or refute even large intervention effects. This is why a meta-analysis ought to be regarded as an interim analysis on its way towards a required information size. The results of the meta-analyses should relate the total number of randomised participants to the estimated required meta-analytic information size accounting for statistical diversity. When the number of participants and the corresponding number of trials in a meta-analysis are insufficient, the use of the traditional 95% confidence interval or the 5% statistical significance threshold will lead to too many false positive conclusions (type I errors) and too many false negative conclusions (type II errors). We developed a methodology for interpreting meta-analysis results, using generally accepted, valid evidence on how to adjust thresholds for significance in randomised clinical trials when the required sample size has not been reached. The Lan-DeMets trial sequential monitoring boundaries in Trial Sequential Analysis offer adjusted confidence intervals and restricted thresholds for statistical significance when the diversity-adjusted required information size and the corresponding number of required trials for the meta-analysis have not been reached. Trial Sequential Analysis provides a frequentistic approach to control both type I and type II errors. We define the required information size and the corresponding number of required trials in a meta-analysis and the diversity (D 2 ) measure of heterogeneity. We explain the reasons for using Trial Sequential Analysis of meta-analysis when the actual information size fails to reach the required information size. We present examples drawn from traditional meta-analyses using unadjusted naïve 95% confidence intervals and 5% thresholds for statistical significance. Spurious conclusions in systematic reviews with traditional meta-analyses can be reduced using Trial Sequential Analysis. Several empirical studies have demonstrated that the Trial Sequential Analysis provides better control of type I errors and of type II errors than the traditional naïve meta-analysis. Trial Sequential Analysis represents analysis of meta-analytic data, with transparent assumptions, and better control of type I and type II errors than the traditional meta-analysis using naïve unadjusted confidence intervals.

Neural Systems Underlying Emotional and Non-emotional Interference Processing: An ALE Meta-Analysis of Functional Neuroimaging Studies

PubMed Central

Xu, Min; Xu, Guiping; Yang, Yang

2016-01-01

Understanding how the nature of interference might influence the recruitments of the neural systems is considered as the key to understanding cognitive control. Although, interference processing in the emotional domain has recently attracted great interest, the question of whether there are separable neural patterns for emotional and non-emotional interference processing remains open. Here, we performed an activation likelihood estimation meta-analysis of 78 neuroimaging experiments, and examined common and distinct neural systems for emotional and non-emotional interference processing. We examined brain activation in three domains of interference processing: emotional verbal interference in the face-word conflict task, non-emotional verbal interference in the color-word Stroop task, and non-emotional spatial interference in the Simon, SRC and Flanker tasks. Our results show that the dorsal anterior cingulate cortex (ACC) was recruited for both emotional and non-emotional interference. In addition, the right anterior insula, presupplementary motor area (pre-SMA), and right inferior frontal gyrus (IFG) were activated by interference processing across both emotional and non-emotional domains. In light of these results, we propose that the anterior insular cortex may serve to integrate information from different dimensions and work together with the dorsal ACC to detect and monitor conflicts, whereas pre-SMA and right IFG may be recruited to inhibit inappropriate responses. In contrast, the dorsolateral prefrontal cortex (DLPFC) and posterior parietal cortex (PPC) showed different degrees of activation and distinct lateralization patterns for different processing domains, which suggests that these regions may implement cognitive control based on the specific task requirements. PMID:27895564

A meta-analysis of fMRI studies on Chinese orthographic, phonological, and semantic processing.

PubMed

Wu, Chiao-Yi; Ho, Moon-Ho Ringo; Chen, Shen-Hsing Annabel

2012-10-15

A growing body of neuroimaging evidence has shown that Chinese character processing recruits differential activation from alphabetic languages due to its unique linguistic features. As more investigations on Chinese character processing have recently become available, we applied a meta-analytic approach to summarize previous findings and examined the neural networks for orthographic, phonological, and semantic processing of Chinese characters independently. The activation likelihood estimation (ALE) method was used to analyze eight studies in the orthographic task category, eleven in the phonological and fifteen in the semantic task categories. Converging activation among three language-processing components was found in the left middle frontal gyrus, the left superior parietal lobule and the left mid-fusiform gyrus, suggesting a common sub-network underlying the character recognition process regardless of the task nature. With increasing task demands, the left inferior parietal lobule and the right superior temporal gyrus were specialized for phonological processing, while the left middle temporal gyrus was involved in semantic processing. Functional dissociation was identified in the left inferior frontal gyrus, with the posterior dorsal part for phonological processing and the anterior ventral part for semantic processing. Moreover, bilateral involvement of the ventral occipito-temporal regions was found for both phonological and semantic processing. The results provide better understanding of the neural networks underlying Chinese orthographic, phonological, and semantic processing, and consolidate the findings of additional recruitment of the left middle frontal gyrus and the right fusiform gyrus for Chinese character processing as compared with the universal language network that has been based on alphabetic languages. Copyright © 2012 Elsevier Inc. All rights reserved.

Predicting synergy in atomic layer etching

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kanarik, Keren J.; Tan, Samantha; Yang, Wenbing

2017-03-27

Atomic layer etching (ALE) is a multistep process used today in manufacturing for removing ultrathin layers of material. In this article, the authors report on ALE of Si, Ge, C, W, GaN, and SiO 2 using a directional (anisotropic) plasma-enhanced approach. The authors analyze these systems by defining an “ALE synergy” parameter which quantifies the degree to which a process approaches the ideal ALE regime. This parameter is inspired by the ion-neutral synergy concept introduced in the 1979 paper by Coburn and Winters. ALE synergy is related to the energetics of underlying surface interactions and is understood in terms ofmore » energy criteria for the energy barriers involved in the reactions. Synergistic behavior is observed for all of the systems studied, with each exhibiting behavior unique to the reactant–material combination. By systematically studying atomic layer etching of a group of materials, the authors show that ALE synergy scales with the surface binding energy of the bulk material. This insight explains why some materials are more or less amenable to the directional ALE approach. Furthermore, they conclude that ALE is both simpler to understand than conventional plasma etch processing and is applicable to metals, semiconductors, and dielectrics.« less

A systematic review and meta-analysis of the nutrient content of preterm and term breast milk.

PubMed

Gidrewicz, Dominica A; Fenton, Tanis R

2014-08-30

Breast milk nutrient content varies with prematurity and postnatal age. Our aims were to conduct a meta-analysis of preterm and term breast milk nutrient content (energy, protein, lactose, oligosaccharides, fat, calcium, and phosphorus); and to assess the influence of gestational and postnatal age. Additionally we assessed for differences by laboratory methods for: energy (measured vs. calculated estimates) and protein (true protein measurement vs. the total nitrogen estimates). Systematic review results were summarized graphically to illustrate the changes in composition over time for term and preterm milk. Since breast milk fat content varies within feeds and diurnally, to obtain accurate estimates we limited the meta-analyses for fat and energy to 24-hour breast milk collections. Forty-one studies met the inclusion criteria: 26 (843 mothers) preterm studies and 30 (2299 mothers) term studies of breast milk composition. Preterm milk was higher in true protein than term milk, with differences up to 35% (0.7 g/dL) in colostrum, however, after postnatal day 3, most of the differences in true protein between preterm and term milk were within 0.2 g/dL, and the week 10-12 estimates suggested that term milk may be the same as preterm milk by that age. Colostrum was higher than mature milk for protein, and lower than mature milk for energy, fat and lactose for both preterm and term milk. Breast milk composition was relatively stable between 2 and 12 weeks. With milk maturation, there was a narrowing of the protein variance. Energy estimates differed whether measured or calculated, from -9 to 13%; true protein measurement vs. the total nitrogen estimates differed by 1 to 37%. Although breast milk is highly variable between individuals, postnatal age and gestational stage (preterm versus term) were found to be important predictors of breast milk content. Energy content of breast milk calculated from the macronutrients provides poor estimates of measured energy, and protein estimated from the nitrogen over-estimates the protein milk content. When breast milk energy, macronutrient and mineral content cannot be directly measured the average values from these meta-analyses may provide useful estimates of mother's milk energy and nutrient content.

Risk assessment for juvenile justice: a meta-analysis.

PubMed

Schwalbe, Craig S

2007-10-01

Risk assessment instruments are increasingly employed by juvenile justice settings to estimate the likelihood of recidivism among delinquent juveniles. In concert with their increased use, validation studies documenting their predictive validity have increased in number. The purpose of this study was to assess the average predictive validity of juvenile justice risk assessment instruments and to identify risk assessment characteristics that are associated with higher predictive validity. A search of the published and grey literature yielded 28 studies that estimated the predictive validity of 28 risk assessment instruments. Findings of the meta-analysis were consistent with effect sizes obtained in larger meta-analyses of criminal justice risk assessment instruments and showed that brief risk assessment instruments had smaller effect sizes than other types of instruments. However, this finding is tentative owing to limitations of the literature.

Real Time System for Practical Acoustic Monitoring of Global Ocean Temperature. Volume 3

DTIC Science & Technology

1994-06-30

signal processing software to the SSAR. This software performs Doppler correction , circulating sums, matched filtering and pulse compression, estimation...Doppler correction , circulating sums, matched filtering and pulse compression, estimation of multipath arrival angle, and peak- picking. At the... geometrica , sound speed, and focuing region sAles to the acoustic wavelengths Our work on this problem is based on an oceanographic application. To

Estimated prevalence of halitosis: a systematic review and meta-regression analysis.

PubMed

Silva, Manuela F; Leite, Fábio R M; Ferreira, Larissa B; Pola, Natália M; Scannapieco, Frank A; Demarco, Flávio F; Nascimento, Gustavo G

2018-01-01

This study aims to conduct a systematic review to determine the prevalence of halitosis in adolescents and adults. Electronic searches were performed using four different databases without restrictions: PubMed, Scopus, Web of Science, and SciELO. Population-based observational studies that provided data about the prevalence of halitosis in adolescents and adults were included. Additionally, meta-analyses, meta-regression, and sensitivity analyses were conducted to synthesize the evidence. A total of 584 articles were initially found and considered for title and abstract evaluation. Thirteen articles met inclusion criteria. The combined prevalence of halitosis was found to be 31.8% (95% CI 24.6-39.0%). Methodological aspects such as the year of publication and the socioeconomic status of the country where the study was conducted seemed to influence the prevalence of halitosis. Our results demonstrated that the estimated prevalence of halitosis was 31.8%, with high heterogeneity between studies. The results suggest a worldwide trend towards a rise in halitosis prevalence. Given the high prevalence of halitosis and its complex etiology, dental professionals should be aware of their roles in halitosis prevention and treatment.

Proper joint analysis of summary association statistics requires the adjustment of heterogeneity in SNP coverage pattern.

PubMed

Zhang, Han; Wheeler, William; Song, Lei; Yu, Kai

2017-07-07

As meta-analysis results published by consortia of genome-wide association studies (GWASs) become increasingly available, many association summary statistics-based multi-locus tests have been developed to jointly evaluate multiple single-nucleotide polymorphisms (SNPs) to reveal novel genetic architectures of various complex traits. The validity of these approaches relies on the accurate estimate of z-score correlations at considered SNPs, which in turn requires knowledge on the set of SNPs assessed by each study participating in the meta-analysis. However, this exact SNP coverage information is usually unavailable from the meta-analysis results published by GWAS consortia. In the absence of the coverage information, researchers typically estimate the z-score correlations by making oversimplified coverage assumptions. We show through real studies that such a practice can generate highly inflated type I errors, and we demonstrate the proper way to incorporate correct coverage information into multi-locus analyses. We advocate that consortia should make SNP coverage information available when posting their meta-analysis results, and that investigators who develop analytic tools for joint analyses based on summary data should pay attention to the variation in SNP coverage and adjust for it appropriately. Published by Oxford University Press 2017. This work is written by US Government employees and is in the public domain in the US.

Effects of exercise on depressive symptoms in adults with arthritis and other rheumatic disease: a systematic review of meta-analyses

PubMed Central

2014-01-01

Background Depression is a major public health problem among adults with arthritis and other rheumatic disease. The purpose of this study was to conduct a systematic review of previous meta-analyses addressing the effects of exercise (aerobic, strength or both) on depressive symptoms in adults with osteoarthritis, rheumatoid arthritis, fibromyalgia and systemic lupus erythematous. Methods Previous meta-analyses of randomized controlled trials were included by searching nine electronic databases and cross-referencing. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. Random-effects models that included the standardized mean difference (SMD) and 95% confidence intervals (CIs) were reported. The alpha value for statistical significance was set at p ≤ 0.05. The U3 index, number needed to treat (NNT) and number of US people who could benefit were also calculated. Results Of the 95 citations initially identified, two aggregate data meta-analyses representing 6 and 19 effect sizes in as many as 870 fibromyalgia participants were included. Methodological quality was 91% and 82%, respectively. Exercise minus control group reductions in depressive symptoms were found for both meta-analyses (SMD, -0.61, 95% CI, -0.99 to -0.23, p = 0.002; SMD, -0.32, 95% CI, -0.53 to -0.12, p = 0.002). Percentile improvements (U3) were equivalent to 22.9 and 12.6. The number needed to treat was 6 and 9 with an estimated 0.83 and 0.56 million US people with fibromyalgia potentially benefitting. Conclusions Exercise improves depressive symptoms in adults with fibromyalgia. However, a need exists for additional meta-analytic work on this topic. PMID:24708605

The acute effects of grape polyphenols supplementation on endothelial function in adults: meta-analyses of controlled trials.

PubMed

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects.

The Acute Effects of Grape Polyphenols Supplementation on Endothelial Function in Adults: Meta-Analyses of Controlled Trials

PubMed Central

Li, Shao-Hua; Tian, Hong-Bo; Zhao, Hong-Jin; Chen, Liang-Hua; Cui, Lian-Qun

2013-01-01

Background The acute effects of grape polyphenols on endothelial function in adults are inconsistent. Here, we performed meta-analyses to determine these acute effects as measured by flow-mediated dilation (FMD). Methods Trials were searched in PubMed, Embase and the Cochrane Library database. Summary estimates of weighted mean differences (WMDs) and 95% CIs were obtained by using random-effects models. Meta-regression and subgroup analyses were performed to identify the source of heterogeneity. The protocol details of our meta-analysis have been submitted to the PROSPERO register and our registration number is CRD42013004157. Results Nine studies were included in the present meta-analyses. The results showed that the FMD level was significantly increased in the initial 120 min after intake of grape polyphenols as compared with controls. Meta-regression and subgroup analyses were performed and showed that a health status was the main effect modifier of the significant heterogeneity. Subgroups indicated that intake of grape polyphenols could significantly increase FMD in healthy subjects, and the increased FMD appeared to be more obviously in subjects with high cardiovascular risk factors. Moreover, the peak effect of grape polyphenols on FMD in healthy subjects was found 30 min after ingestion, which was different from the effect in subjects with high cardiovascular risk factors, in whom the peak effect was found 60 min after ingestion. Conclusions Endothelial function can be significantly improved in healthy adults in the initial 2 h after intake of grape polyphenols. The acute effect of grape polyphenols on endothelial function may be more significant but the peak effect is delayed in subjects with a smoking history or coronary heart disease as compared with the healthy subjects. PMID:23894543

Improved Dietary Guidelines for Vitamin D: Application of Individual Participant Data (IPD)-Level Meta-Regression Analyses

PubMed Central

Cashman, Kevin D.; Ritz, Christian; Kiely, Mairead

2017-01-01

Dietary Reference Values (DRVs) for vitamin D have a key role in the prevention of vitamin D deficiency. However, despite adopting similar risk assessment protocols, estimates from authoritative agencies over the last 6 years have been diverse. This may have arisen from diverse approaches to data analysis. Modelling strategies for pooling of individual subject data from cognate vitamin D randomized controlled trials (RCTs) are likely to provide the most appropriate DRV estimates. Thus, the objective of the present work was to undertake the first-ever individual participant data (IPD)-level meta-regression, which is increasingly recognized as best practice, from seven winter-based RCTs (with 882 participants ranging in age from 4 to 90 years) of the vitamin D intake–serum 25-hydroxyvitamin D (25(OH)D) dose-response. Our IPD-derived estimates of vitamin D intakes required to maintain 97.5% of 25(OH)D concentrations >25, 30, and 50 nmol/L across the population are 10, 13, and 26 µg/day, respectively. In contrast, standard meta-regression analyses with aggregate data (as used by several agencies in recent years) from the same RCTs estimated that a vitamin D intake requirement of 14 µg/day would maintain 97.5% of 25(OH)D >50 nmol/L. These first IPD-derived estimates offer improved dietary recommendations for vitamin D because the underpinning modeling captures the between-person variability in response of serum 25(OH)D to vitamin D intake. PMID:28481259

Drivers of wetland conversion: a global meta-analysis.

PubMed

van Asselen, Sanneke; Verburg, Peter H; Vermaat, Jan E; Janse, Jan H

2013-01-01

Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic conversions.

Drivers of Wetland Conversion: a Global Meta-Analysis

PubMed Central

van Asselen, Sanneke; Verburg, Peter H.; Vermaat, Jan E.; Janse, Jan H.

2013-01-01

Meta-analysis of case studies has become an important tool for synthesizing case study findings in land change. Meta-analyses of deforestation, urbanization, desertification and change in shifting cultivation systems have been published. This present study adds to this literature, with an analysis of the proximate causes and underlying forces of wetland conversion at a global scale using two complementary approaches of systematic review. Firstly, a meta-analysis of 105 case-study papers describing wetland conversion was performed, showing that different combinations of multiple-factor proximate causes, and underlying forces, drive wetland conversion. Agricultural development has been the main proximate cause of wetland conversion, and economic growth and population density are the most frequently identified underlying forces. Secondly, to add a more quantitative component to the study, a logistic meta-regression analysis was performed to estimate the likelihood of wetland conversion worldwide, using globally-consistent biophysical and socioeconomic location factor maps. Significant factors explaining wetland conversion, in order of importance, are market influence, total wetland area (lower conversion probability), mean annual temperature and cropland or built-up area. The regression analyses results support the outcomes of the meta-analysis of the processes of conversion mentioned in the individual case studies. In other meta-analyses of land change, similar factors (e.g., agricultural development, population growth, market/economic factors) are also identified as important causes of various types of land change (e.g., deforestation, desertification). Meta-analysis helps to identify commonalities across the various local case studies and identify which variables may lead to individual cases to behave differently. The meta-regression provides maps indicating the likelihood of wetland conversion worldwide based on the location factors that have determined historic conversions. PMID:24282580

Individual-based versus aggregate meta-analysis in multi-database studies of pregnancy outcomes: the Nordic example of selective serotonin reuptake inhibitors and venlafaxine in pregnancy.

PubMed

Selmer, Randi; Haglund, Bengt; Furu, Kari; Andersen, Morten; Nørgaard, Mette; Zoëga, Helga; Kieler, Helle

2016-10-01

Compare analyses of a pooled data set on the individual level with aggregate meta-analysis in a multi-database study. We reanalysed data on 2.3 million births in a Nordic register based cohort study. We compared estimated odds ratios (OR) for the effect of selective serotonin reuptake inhibitors (SSRI) and venlafaxine use in pregnancy on any cardiovascular birth defect and the rare outcome right ventricular outflow tract obstructions (RVOTO). Common covariates included maternal age, calendar year, birth order, maternal diabetes, and co-medication. Additional covariates were added in analyses with country-optimized adjustment. Country adjusted OR (95%CI) for any cardiovascular birth defect in the individual-based pooled analysis was 1.27 (1.17-1.39), 1.17 (1.07-1.27) adjusted for common covariates and 1.15 (1.05-1.26) adjusted for all covariates. In fixed effects meta-analyses pooled OR was 1.29 (1.19-1.41) based on crude country specific ORs, 1.19 (1.09-1.29) adjusted for common covariates, and 1.16 (1.06-1.27) for country-optimized adjustment. In a random effects model the adjusted OR was 1.07 (0.87-1.32). For RVOTO, OR was 1.48 (1.15-1.89) adjusted for all covariates in the pooled data set, and 1.53 (1.19-1.96) after country-optimized adjustment. Country-specific adjusted analyses at the substance level were not possible for RVOTO. Results of fixed effects meta-analysis and individual-based analyses of a pooled dataset were similar in this study on the association of SSRI/venlafaxine and cardiovascular birth defects. Country-optimized adjustment attenuated the estimates more than adjustment for common covariates only. When data are sparse pooled data on the individual level are needed for adjusted analyses. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Recent meta-analyses neglect previous systematic reviews and meta-analyses about the same topic: a systematic examination.

PubMed

Helfer, Bartosz; Prosser, Aaron; Samara, Myrto T; Geddes, John R; Cipriani, Andrea; Davis, John M; Mavridis, Dimitris; Salanti, Georgia; Leucht, Stefan

2015-04-14

As the number of systematic reviews is growing rapidly, we systematically investigate whether meta-analyses published in leading medical journals present an outline of available evidence by referring to previous meta-analyses and systematic reviews. We searched PubMed for recent meta-analyses of pharmacological treatments published in high impact factor journals. Previous systematic reviews and meta-analyses were identified with electronic searches of keywords and by searching reference sections. We analyzed the number of meta-analyses and systematic reviews that were cited, described and discussed in each recent meta-analysis. Moreover, we investigated publication characteristics that potentially influence the referencing practices. We identified 52 recent meta-analyses and 242 previous meta-analyses on the same topics. Of these, 66% of identified previous meta-analyses were cited, 36% described, and only 20% discussed by recent meta-analyses. The probability of citing a previous meta-analysis was positively associated with its publication in a journal with a higher impact factor (odds ratio, 1.49; 95% confidence interval, 1.06 to 2.10) and more recent publication year (odds ratio, 1.19; 95% confidence interval 1.03 to 1.37). Additionally, the probability of a previous study being described by the recent meta-analysis was inversely associated with the concordance of results (odds ratio, 0.38; 95% confidence interval, 0.17 to 0.88), and the probability of being discussed was increased for previous studies that employed meta-analytic methods (odds ratio, 32.36; 95% confidence interval, 2.00 to 522.85). Meta-analyses on pharmacological treatments do not consistently refer to and discuss findings of previous meta-analyses on the same topic. Such neglect can lead to research waste and be confusing for readers. Journals should make the discussion of related meta-analyses mandatory.

Assessing the effect of elevated carbon dioxide on soil carbon: a comparison of four meta-analyses.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Hungate, B. A.; van Groenigen, K.; Six, J.

2009-08-01

Soil is the largest reservoir of organic carbon (C) in the terrestrial biosphere and soil C has a relatively long mean residence time. Rising atmospheric carbon dioxide (CO{sub 2}) concentrations generally increase plant growth and C input to soil, suggesting that soil might help mitigate atmospheric CO{sub 2} rise and global warming. But to what extent mitigation will occur is unclear. The large size of the soil C pool not only makes it a potential buffer against rising atmospheric CO{sub 2}, but also makes it difficult to measure changes amid the existing background. Meta-analysis is one tool that can overcomemore » the limited power of single studies. Four recent meta-analyses addressed this issue but reached somewhat different conclusions about the effect of elevated CO{sub 2} on soil C accumulation, especially regarding the role of nitrogen (N) inputs. Here, we assess the extent of differences between these conclusions and propose a new analysis of the data. The four meta-analyses included different studies, derived different effect size estimates from common studies, used different weighting functions and metrics of effect size, and used different approaches to address nonindependence of effect sizes. Although all factors influenced the mean effect size estimates and subsequent inferences, the approach to independence had the largest influence. We recommend that meta-analysts critically assess and report choices about effect size metrics and weighting functions, and criteria for study selection and independence. Such decisions need to be justified carefully because they affect the basis for inference. Our new analysis, with a combined data set, confirms that the effect of elevated CO{sub 2} on net soil C accumulation increases with the addition of N fertilizers. Although the effect at low N inputs was not significant, statistical power to detect biogeochemically important effect sizes at low N is limited, even with meta-analysis, suggesting the continued need for long-term experiments.« less

Lipoprotein (a) as a risk factor for ischemic stroke: a meta-analysis.

PubMed

Nave, Alexander H; Lange, Kristin S; Leonards, Christopher O; Siegerink, Bob; Doehner, Wolfram; Landmesser, Ulf; Steinhagen-Thiessen, Elisabeth; Endres, Matthias; Ebinger, Martin

2015-10-01

Lipoprotein (a) [Lp(a)] harbors atherogenic potential but its role as a risk factor for ischemic stroke remains controversial. We conducted a meta-analysis to determine the relative strength of the association between Lp(a) and ischemic stroke and identify potential subgroup-specific risk differences. A systematic search using the MeSH terms "lipoproteins" OR "lipoprotein a" AND "stroke" was performed in PubMed and ScienceDirect for case-control studies from June 2006 and prospective cohort studies from April 2009 until December 20th 2014. Data from eligible papers published before these dates were reviewed and extracted from previous meta-analyses. Studies that assessed the relationship between Lp(a) levels and ischemic stroke and reported generic data-i.e. odds ratio [OR], hazard ratio, or risk ratio [RR]-were eligible for inclusion. Studies that not distinguish between ischemic and hemorrhagic stroke and transient ischemic attack were excluded. Random effects meta-analyses with mixed-effects meta-regression were performed by pooling adjusted OR or RR. A total of 20 articles comprising 90,904 subjects and 5029 stroke events were eligible for the meta-analysis. Comparing high with low Lp(a) levels, the pooled estimated OR was 1.41 (95% CI, 1.26-1.57) for case-control studies (n = 11) and the pooled estimated RR was 1.29 (95% CI, 1.06-1.58) for prospective studies (n = 9). Sex-specific differences in RR were inconsistent between case-control and prospective studies. Study populations with a mean age of ≤55 years had an increased RR compared to older study populations. Reported Lp(a) contrast levels and ischemic stroke subtype significantly contributed to the heterogeneity observed in the analyses. Elevated Lp(a) is an independent risk factor for ischemic stroke and may be especially relevant for young stroke patients. Sex-specific risk differences remain conflicting. Further studies in these subgroups may be warranted. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Not all risks are created equal: A twin study and meta-analyses of risk taking across seven domains.

PubMed

Wang, X T Xiao-Tian; Zheng, Rui; Xuan, Yan-Hua; Chen, Jie; Li, Shu

2016-11-01

Humans routinely deal with both traditional and novel risks. Different kinds of risks have been a driving force for both evolutionary adaptations and personal development. This study explored the genetic and environmental influences on human risk taking in different task domains. Our approach was threefold. First, we integrated several scales of domain-specific risk-taking propensity and developed a synthetic scale, including both evolutionarily typical and modern risks in the following 7 domains: cooperation/competition, safety, reproduction, natural/physical risk, moral risk, financial risk, and gambling. Second, we conducted a twin study using the scale to estimate the contributions of genes and environment to risk taking in each of these 7 domains. Third, we conducted a series of meta-analyses of extant twin studies across the 7 risk domains. The results showed that individual differences in risk-taking propensity and its consistency across domains were mainly regulated by additive genetic influences and individually unique environmental experiences. The heritability estimates from the meta-analyses ranged from 29% in financial risk taking to 55% in safety. Supporting the notion of risk-domain specificity, both the behavioral and genetic correlations among the 7 domains were generally low. Among the relatively few correlations between pairs of risk domains, our analysis revealed a common genetic factor that regulates moral, financial, and natural/physical risk taking. This is the first effort to separate genetic and environmental influences on risk taking across multiple domains in a single study and integrate the findings of extant twin studies via a series of meta-analyses conducted in different task domains. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

How to Make Nothing Out of Something: Analyses of the Impact of Study Sampling and Statistical Interpretation in Misleading Meta-Analytic Conclusions

PubMed Central

Cunningham, Michael R.; Baumeister, Roy F.

2016-01-01

The limited resource model states that self-control is governed by a relatively finite set of inner resources on which people draw when exerting willpower. Once self-control resources have been used up or depleted, they are less available for other self-control tasks, leading to a decrement in subsequent self-control success. The depletion effect has been studied for over 20 years, tested or extended in more than 600 studies, and supported in an independent meta-analysis (Hagger et al., 2010). Meta-analyses are supposed to reduce bias in literature reviews. Carter et al.’s (2015) meta-analysis, by contrast, included a series of questionable decisions involving sampling, methods, and data analysis. We provide quantitative analyses of key sampling issues: exclusion of many of the best depletion studies based on idiosyncratic criteria and the emphasis on mini meta-analyses with low statistical power as opposed to the overall depletion effect. We discuss two key methodological issues: failure to code for research quality, and the quantitative impact of weak studies by novice researchers. We discuss two key data analysis issues: questionable interpretation of the results of trim and fill and Funnel Plot Asymmetry test procedures, and the use and misinterpretation of the untested Precision Effect Test and Precision Effect Estimate with Standard Error (PEESE) procedures. Despite these serious problems, the Carter et al. (2015) meta-analysis results actually indicate that there is a real depletion effect – contrary to their title. PMID:27826272

Do polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) gene affect the risk of childhood acute lymphoblastic leukemia?

PubMed

Pereira, Tiago Veiga; Rudnicki, Martina; Pereira, Alexandre Costa; Pombo-de-Oliveira, Maria S; Franco, Rendrik França

2006-01-01

Meta-analysis has become an important statistical tool in genetic association studies, since it may provide more powerful and precise estimates. However, meta-analytic studies are prone to several potential biases not only because the preferential publication of "positive'' studies but also due to difficulties in obtaining all relevant information during the study selection process. In this letter, we point out major problems in meta-analysis that may lead to biased conclusions, illustrating an empirical example of two recent meta-analyses on the relation between MTHFR polymorphisms and risk of acute lymphoblastic leukemia that, despite the similarity in statistical methods and period of study selection, provided partially conflicting results.

Efficacy of electromyographic biofeedback compared with conventional physical therapy for upper-extremity function in patients following stroke: a research overview and meta-analysis.

PubMed

Moreland, J; Thomson, M A

1994-06-01

The purpose of this study was to examine the efficacy of electromyographic biofeedback compared with conventional physical therapy for improving upper-extremity function in patients following a stroke. A literature search was done for the years 1976 to 1992. The selection criteria included single-blinded randomized control trials. Study quality was assessed for nine criteria. For functional (disability index or stage of recovery) and impairment outcomes, meta-analyses were performed on odds ratios for improvement versus no improvement. Mann-Whitney U-Test probability values were combined across studies. Six studies were selected, and outcome data were obtained for five studies. The common odds ratio was 2.2 for function and 1.1 for impairments in favor of biofeedback. The estimate of the number needed to treat to prevent a nonresponder was 11 for function and 22 for impairments. None of the meta-analyses were statistically significant. The results do not conclusively indicate superiority of either form of therapy. Although there is a chance of Type II error, the estimated size of the effect is small. Given this estimate of little or no difference, therapists need to consider cost, ease of application, and patient preference when selecting these therapies.

Consequences of atomic layer etching on wafer scale uniformity in inductively coupled plasmas

NASA Astrophysics Data System (ADS)

Huard, Chad M.; Lanham, Steven J.; Kushner, Mark J.

2018-04-01

Atomic layer etching (ALE) typically divides the etching process into two self-limited reactions. One reaction passivates a single layer of material while the second preferentially removes the passivated layer. As such, under ideal conditions the wafer scale uniformity of ALE should be independent of the uniformity of the reactant fluxes onto the wafers, provided all surface reactions are saturated. The passivation and etch steps should individually asymptotically saturate after a characteristic fluence of reactants has been delivered to each site. In this paper, results from a computational investigation are discussed regarding the uniformity of ALE of Si in Cl2 containing inductively coupled plasmas when the reactant fluxes are both non-uniform and non-ideal. In the parameter space investigated for inductively coupled plasmas, the local etch rate for continuous processing was proportional to the ion flux. When operated with saturated conditions (that is, both ALE steps are allowed to self-terminate), the ALE process is less sensitive to non-uniformities in the incoming ion flux than continuous etching. Operating ALE in a sub-saturation regime resulted in less uniform etching. It was also found that ALE processing with saturated steps requires a larger total ion fluence than continuous etching to achieve the same etch depth. This condition may result in increased resist erosion and/or damage to stopping layers using ALE. While these results demonstrate that ALE provides increased etch depth uniformity, they do not show an improved critical dimension uniformity in all cases. These possible limitations to ALE processing, as well as increased processing time, will be part of the process optimization that includes the benefits of atomic resolution and improved uniformity.

Estimating the Global Incidence of Aneurysmal Subarachnoid Hemorrhage: A Systematic Review for Central Nervous System Vascular Lesions and Meta-Analysis of Ruptured Aneurysms.

PubMed

Hughes, Joshua D; Bond, Kamila M; Mekary, Rania A; Dewan, Michael C; Rattani, Abbas; Baticulon, Ronnie; Kato, Yoko; Azevedo-Filho, Hildo; Morcos, Jacques J; Park, Kee B

2018-04-09

There is increasing acknowledgement that surgical care is important in global health initiatives. In particular, neurosurgical care is as limited as 1 per 10 million people in parts of the world. We performed a systematic literature review to examine the worldwide incidence of central nervous system vascular lesions and a meta-analysis of aneurysmal subarachnoid hemorrhage (aSAH) to define the disease burden and inform neurosurgical global health efforts. A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines to estimate the global epidemiology of central nervous system vascular lesions, including unruptured and ruptured aneurysms, arteriovenous malformations, cavernous malformations, dural arteriovenous fistulas, developmental venous anomalies, and vein of Galen malformations. Results were organized by World Health Organization regions. After literature review, because of a lack of data from particular World Health Organization regions, we determined we could only provide an estimate of aSAH. Using data from studies with aSAH and 12 high-quality stroke studies from regions lacking data, we meta-analyzed the yearly crude incidence of aSAH per 100,000 persons. Estimates were generated via random-effects models. From an initial yield of 1492 studies, 46 manuscripts on aSAH incidence were included. The final meta-analysis included 58 studies from 31 different countries. We estimated the global crude incidence for aSAH to be 6.67 per 100,000 persons with a wide variation across WHO regions from 0.71 to 12.38 per 100,000 persons. Worldwide, almost 500,000 individuals will suffer from aSAH each year, with almost two-thirds in low- and middle-income countries. Copyright © 2018 Elsevier Inc. All rights reserved.

RAS mutation prevalence among patients with metastatic colorectal cancer: a meta-analysis of real-world data.

PubMed

Kafatos, George; Niepel, Daniela; Lowe, Kimberley; Jenkins-Anderson, Sophie; Westhead, Hal; Garawin, Tamer; Traugottová, Zuzana; Bilalis, Antonios; Molnar, Edit; Timar, Jozsef; Toth, Erika; Gouvas, Nikolaos; Papaxoinis, George; Murray, Samuel; Mokhtar, Nadia; Vosmikova, Hana; Fabian, Pavel; Skalova, Alena; Wójcik, Piotr; Tysarowski, Andrzej; Barugel, Mario; van Krieken, J Han; Trojan, Jörg

2017-07-27

A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

A critical appraisal of the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing interventions: a systematic review of reviews.

PubMed

Jin, Ying-Hui; Wang, Guo-Hao; Sun, Yi-Rong; Li, Qi; Zhao, Chen; Li, Ge; Si, Jin-Hua; Li, Yan; Lu, Cui; Shang, Hong-Cai

2016-11-14

To assess the methodology and quality of evidence of systematic reviews and meta-analyses of traditional Chinese medical nursing (TCMN) interventions in Chinese journals. These interventions include acupressure, massage, Tai Chi, Qi Gong, electroacupuncture and use of Chinese herbal medicines-for example, in enemas, foot massage and compressing the umbilicus. A systematic literature search for systematic reviews and meta-analyses of TCMN interventions was performed. Review characteristics were extracted. The methodological quality and the quality of the evidence were evaluated using the Assessment of Multiple Systematic Reviews (AMSTAR) and Grading of Recommendations Assessment, Development and Evaluation (GRADE) approaches. We included 20 systematic reviews and meta-analyses, and a total of 11 TCMN interventions were assessed in the 20 reviews. The compliance with AMSTAR checklist items ranged from 4.5 to 8 and systematic reviews/meta-analyses were, on average, of medium methodological quality. The quality of the evidence we assessed ranged from very low to moderate; no high-quality evidence was found. The top two causes for downrating confidence in effect estimates among the 31 bodies of evidence assessed were the risk of bias and inconsistency. There is room for improvement in the methodological quality of systematic reviews/meta-analyses of TCMN interventions published in Chinese journals. Greater efforts should be devoted to ensuring a more comprehensive search strategy, clearer specification of the interventions of interest in the eligibility criteria and identification of meaningful outcomes for clinicians and patients (consumers). The overall quality of evidence among reviews remains suboptimal, which raise concerns about their roles in influencing clinical practice. Thus, the conclusions in reviews we assessed must be treated with caution and their roles in influencing clinical practice should be limited. A critical appraisal of systematic reviews/meta-analyses of TCMN interventions is particularly important to provide sound guidance for TCMN. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Avoiding Boundary Estimates in Hierarchical Linear Models through Weakly Informative Priors

ERIC Educational Resources Information Center

Chung, Yeojin; Rabe-Hesketh, Sophia; Gelman, Andrew; Dorie, Vincent; Liu, Jinchen

2012-01-01

Hierarchical or multilevel linear models are widely used for longitudinal or cross-sectional data on students nested in classes and schools, and are particularly important for estimating treatment effects in cluster-randomized trials, multi-site trials, and meta-analyses. The models can allow for variation in treatment effects, as well as…

The Effect of Study Design Biases on the Diagnostic Accuracy of Magnetic Resonance Imaging to Detect Silicone Breast Implant Ruptures: A Meta-Analysis

PubMed Central

Song, Jae W.; Kim, Hyungjin Myra; Bellfi, Lillian T.; Chung, Kevin C.

2010-01-01

Background All silicone breast implant recipients are recommended by the US Food and Drug Administration to undergo serial screening to detect implant rupture with magnetic resonance imaging (MRI). We performed a systematic review of the literature to assess the quality of diagnostic accuracy studies utilizing MRI or ultrasound to detect silicone breast implant rupture and conducted a meta-analysis to examine the effect of study design biases on the estimation of MRI diagnostic accuracy measures. Method Studies investigating the diagnostic accuracy of MRI and ultrasound in evaluating ruptured silicone breast implants were identified using MEDLINE, EMBASE, ISI Web of Science, and Cochrane library databases. Two reviewers independently screened potential studies for inclusion and extracted data. Study design biases were assessed using the QUADAS tool and the STARDS checklist. Meta-analyses estimated the influence of biases on diagnostic odds ratios. Results Among 1175 identified articles, 21 met the inclusion criteria. Most studies using MRI (n= 10 of 16) and ultrasound (n=10 of 13) examined symptomatic subjects. Meta-analyses revealed that MRI studies evaluating symptomatic subjects had 14-fold higher diagnostic accuracy estimates compared to studies using an asymptomatic sample (RDOR 13.8; 95% CI 1.83–104.6) and 2-fold higher diagnostic accuracy estimates compared to studies using a screening sample (RDOR 1.89; 95% CI 0.05–75.7). Conclusion Many of the published studies utilizing MRI or ultrasound to detect silicone breast implant rupture are flawed with methodological biases. These methodological shortcomings may result in overestimated MRI diagnostic accuracy measures and should be interpreted with caution when applying the data to a screening population. PMID:21364405

Analysis of categorical moderators in mixed-effects meta-analysis: Consequences of using pooled versus separate estimates of the residual between-studies variances.

PubMed

Rubio-Aparicio, María; Sánchez-Meca, Julio; López-López, José Antonio; Botella, Juan; Marín-Martínez, Fulgencio

2017-11-01

Subgroup analyses allow us to examine the influence of a categorical moderator on the effect size in meta-analysis. We conducted a simulation study using a dichotomous moderator, and compared the impact of pooled versus separate estimates of the residual between-studies variance on the statistical performance of the Q B (P) and Q B (S) tests for subgroup analyses assuming a mixed-effects model. Our results suggested that similar performance can be expected as long as there are at least 20 studies and these are approximately balanced across categories. Conversely, when subgroups were unbalanced, the practical consequences of having heterogeneous residual between-studies variances were more evident, with both tests leading to the wrong statistical conclusion more often than in the conditions with balanced subgroups. A pooled estimate should be preferred for most scenarios, unless the residual between-studies variances are clearly different and there are enough studies in each category to obtain precise separate estimates. © 2017 The British Psychological Society.

Publication Bias in Meta-Analysis: Confidence Intervals for Rosenthal's Fail-Safe Number.

PubMed

Fragkos, Konstantinos C; Tsagris, Michail; Frangos, Christos C

2014-01-01

The purpose of the present paper is to assess the efficacy of confidence intervals for Rosenthal's fail-safe number. Although Rosenthal's estimator is highly used by researchers, its statistical properties are largely unexplored. First of all, we developed statistical theory which allowed us to produce confidence intervals for Rosenthal's fail-safe number. This was produced by discerning whether the number of studies analysed in a meta-analysis is fixed or random. Each case produces different variance estimators. For a given number of studies and a given distribution, we provided five variance estimators. Confidence intervals are examined with a normal approximation and a nonparametric bootstrap. The accuracy of the different confidence interval estimates was then tested by methods of simulation under different distributional assumptions. The half normal distribution variance estimator has the best probability coverage. Finally, we provide a table of lower confidence intervals for Rosenthal's estimator.

Publication Bias in Meta-Analysis: Confidence Intervals for Rosenthal's Fail-Safe Number

PubMed Central

Fragkos, Konstantinos C.; Tsagris, Michail; Frangos, Christos C.

2014-01-01

The purpose of the present paper is to assess the efficacy of confidence intervals for Rosenthal's fail-safe number. Although Rosenthal's estimator is highly used by researchers, its statistical properties are largely unexplored. First of all, we developed statistical theory which allowed us to produce confidence intervals for Rosenthal's fail-safe number. This was produced by discerning whether the number of studies analysed in a meta-analysis is fixed or random. Each case produces different variance estimators. For a given number of studies and a given distribution, we provided five variance estimators. Confidence intervals are examined with a normal approximation and a nonparametric bootstrap. The accuracy of the different confidence interval estimates was then tested by methods of simulation under different distributional assumptions. The half normal distribution variance estimator has the best probability coverage. Finally, we provide a table of lower confidence intervals for Rosenthal's estimator. PMID:27437470

Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study

PubMed Central

Neupane, Binod; Beyene, Joseph

2015-01-01

In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously) than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE) of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when the missing data in the endpoint are imputed with null effects and quite large variance. PMID:26196398

Multivariate Meta-Analysis of Genetic Association Studies: A Simulation Study.

PubMed

Neupane, Binod; Beyene, Joseph

2015-01-01

In a meta-analysis with multiple end points of interests that are correlated between or within studies, multivariate approach to meta-analysis has a potential to produce more precise estimates of effects by exploiting the correlation structure between end points. However, under random-effects assumption the multivariate estimation is more complex (as it involves estimation of more parameters simultaneously) than univariate estimation, and sometimes can produce unrealistic parameter estimates. Usefulness of multivariate approach to meta-analysis of the effects of a genetic variant on two or more correlated traits is not well understood in the area of genetic association studies. In such studies, genetic variants are expected to roughly maintain Hardy-Weinberg equilibrium within studies, and also their effects on complex traits are generally very small to modest and could be heterogeneous across studies for genuine reasons. We carried out extensive simulation to explore the comparative performance of multivariate approach with most commonly used univariate inverse-variance weighted approach under random-effects assumption in various realistic meta-analytic scenarios of genetic association studies of correlated end points. We evaluated the performance with respect to relative mean bias percentage, and root mean square error (RMSE) of the estimate and coverage probability of corresponding 95% confidence interval of the effect for each end point. Our simulation results suggest that multivariate approach performs similarly or better than univariate method when correlations between end points within or between studies are at least moderate and between-study variation is similar or larger than average within-study variation for meta-analyses of 10 or more genetic studies. Multivariate approach produces estimates with smaller bias and RMSE especially for the end point that has randomly or informatively missing summary data in some individual studies, when the missing data in the endpoint are imputed with null effects and quite large variance.

Threatening communication: a critical re-analysis and a revised meta-analytic test of fear appeal theory.

PubMed

Peters, Gjalt-Jorn Ygram; Ruiter, Robert A C; Kok, Gerjo

2013-05-01

Despite decades of research, consensus regarding the dynamics of fear appeals remains elusive. A meta-analysis was conducted that was designed to resolve this controversy. Publications that were included in previous meta-analyses were re-analysed, and a number of additional publications were located. The inclusion criteria were full factorial orthogonal manipulations of threat and efficacy, and measurement of behaviour as an outcome. Fixed and random effects models were used to compute mean effect size estimates. Meta-analysis of the six studies that satisfied the inclusion criteria clearly showed a significant interaction between threat and efficacy, such that threat only had an effect under high efficacy (d = 0.31), and efficacy only had an effect under high threat (d = 0.71). Inconsistency in results regarding the effectiveness of threatening communication can likely be attributed to flawed methodology. Proper tests of fear appeal theory yielded the theoretically hypothesised interaction effect. Threatening communication should exclusively be used when pilot studies indicate that an intervention successfully enhances efficacy.

Threatening communication: a critical re-analysis and a revised meta-analytic test of fear appeal theory

PubMed Central

Peters, Gjalt-Jorn Ygram; Ruiter, Robert A.C.; Kok, Gerjo

2013-01-01

Despite decades of research, consensus regarding the dynamics of fear appeals remains elusive. A meta-analysis was conducted that was designed to resolve this controversy. Publications that were included in previous meta-analyses were re-analysed, and a number of additional publications were located. The inclusion criteria were full factorial orthogonal manipulations of threat and efficacy, and measurement of behaviour as an outcome. Fixed and random effects models were used to compute mean effect size estimates. Meta-analysis of the six studies that satisfied the inclusion criteria clearly showed a significant interaction between threat and efficacy, such that threat only had an effect under high efficacy (d = 0.31), and efficacy only had an effect under high threat (d = 0.71). Inconsistency in results regarding the effectiveness of threatening communication can likely be attributed to flawed methodology. Proper tests of fear appeal theory yielded the theoretically hypothesised interaction effect. Threatening communication should exclusively be used when pilot studies indicate that an intervention successfully enhances efficacy. PMID:23772231

Childhood adverse life events, disordered eating, and body mass index in US Military service members.

PubMed

Bakalar, Jennifer L; Barmine, Marissa; Druskin, Lindsay; Olsen, Cara H; Quinlan, Jeffrey; Sbrocco, Tracy; Tanofsky-Kraff, Marian

2018-03-02

US service members appear to be at high-risk for disordered eating. Further, the military is experiencing unprecedented prevalence of overweight and obesity. US service members also report a high prevalence of childhood adverse life event (ALE) exposure. Despite consistent links between early adversity with eating disorders and obesity, there is a dearth of research examining the association between ALE exposure and disordered eating and weight in military personnel. An online survey study was conducted in active duty personnel to examine childhood ALE history using the Life Stressor Checklist - Revised, disordered eating using the Eating Disorder Examination - Questionnaire total score, and self-reported body mass index (BMI, kg/m 2 ). Among 179 respondents, multiple indices of childhood ALE were positively associated with disordered eating. Traumatic childhood ALE and subjective impact of childhood ALE were associated with higher BMI and these associations were mediated by disordered eating. Findings support evaluating childhood ALE exposure among service members with disordered eating and weight concerns. Moreover, findings support the need for prospective research to elucidate these relationships. © 2018 Wiley Periodicals, Inc.

Reporting completeness and transparency of meta-analyses of depression screening tool accuracy: A comparison of meta-analyses published before and after the PRISMA statement.

PubMed

Rice, Danielle B; Kloda, Lorie A; Shrier, Ian; Thombs, Brett D

2016-08-01

Meta-analyses that are conducted rigorously and reported completely and transparently can provide accurate evidence to inform the best possible healthcare decisions. Guideline makers have raised concerns about the utility of existing evidence on the diagnostic accuracy of depression screening tools. The objective of our study was to evaluate the transparency and completeness of reporting in meta-analyses of the diagnostic accuracy of depression screening tools using the PRISMA tool adapted for diagnostic test accuracy meta-analyses. We searched MEDLINE and PsycINFO from January 1, 2005 through March 13, 2016 for recent meta-analyses in any language on the diagnostic accuracy of depression screening tools. Two reviewers independently assessed the transparency in reporting using the PRISMA tool with appropriate adaptations made for studies of diagnostic test accuracy. We identified 21 eligible meta-analyses. Twelve of 21 meta-analyses complied with at least 50% of adapted PRISMA items. Of 30 adapted PRISMA items, 11 were fulfilled by ≥80% of included meta-analyses, 3 by 50-79% of meta-analyses, 7 by 25-45% of meta-analyses, and 9 by <25%. On average, post-PRISMA meta-analyses complied with 17 of 30 items compared to 13 of 30 items pre-PRISMA. Deficiencies in the transparency of reporting in meta-analyses of the diagnostic test accuracy of depression screening tools of meta-analyses were identified. Authors, reviewers, and editors should adhere to the PRISMA statement to improve the reporting of meta-analyses of the diagnostic accuracy of depression screening tools. Copyright © 2016 Elsevier Inc. All rights reserved.

Comparison of ALE and SPH Methods for Simulating Mine Blast Effects on Structures

DTIC Science & Technology

2010-12-01

Comparison of ALE and SPH methods for simulating mine blast effects on struc- tures Geneviève Toussaint Amal Bouamoul DRDC Valcartier Defence R&D...Canada – Valcartier Technical Report DRDC Valcartier TR 2010-326 December 2010 Comparison of ALE and SPH methods for simulating mine blast...Valcartier TR 2010-326 iii Executive summary Comparison of ALE and SPH methods for simulating mine blast effects on structures

A coupled ALE-AMR method for shock hydrodynamics

DOE PAGES

Waltz, J.; Bakosi, J.

2018-03-05

We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less

A coupled ALE-AMR method for shock hydrodynamics

DOE Office of Scientific and Technical Information (OSTI.GOV)

Waltz, J.; Bakosi, J.

We present a numerical method combining adaptive mesh refinement (AMR) with arbitrary Lagrangian-Eulerian (ALE) mesh motion for the simulation of shock hydrodynamics on unstructured grids. The primary goal of the coupled method is to use AMR to reduce numerical error in ALE simulations at reduced computational expense relative to uniform fine mesh calculations, in the same manner that AMR has been used in Eulerian simulations. We also identify deficiencies with ALE methods that AMR is able to mitigate, and discuss the unique coupling challenges. The coupled method is demonstrated using three-dimensional unstructured meshes of up to O(10 7) tetrahedral cells.more » Convergence of ALE-AMR solutions towards both uniform fine mesh ALE results and analytic solutions is demonstrated. Speed-ups of 5-10× for a given level of error are observed relative to uniform fine mesh calculations.« less

Conceptualizing neuropsychiatric diseases with multimodal data-driven meta-analyses – The case of behavioral variant frontotemporal dementia

PubMed Central

Schroeter, Matthias L.; Laird, Angela R.; Chwiesko, Caroline; Deuschl, Christine; Schneider, Else; Bzdok, Danilo; Eickhoff, Simon B.; Neumann, Jane

2014-01-01

Introduction Uniform coordinate systems in neuroimaging research have enabled comprehensive systematic and quantitative meta-analyses. Such approaches are particularly relevant for neuropsychiatric diseases, the understanding of their symptoms, prediction and treatment. Behavioral variant frontotemporal dementia (bvFTD), a common neurodegenerative syndrome, is characterized by deep alterations in behavior and personality. Investigating this ‘nexopathy’ elucidates the healthy social and emotional brain. Methods Here, we combine three multimodal meta-analyses approaches – anatomical & activation likelihood estimates and behavioral domain profiles – to identify neural correlates of bvFTD in 417 patients and 406 control subjects and to extract mental functions associated with this disease by meta-analyzing functional activation studies in the comprehensive probabilistic functional brain atlas of the BrainMap database. Results The analyses identify the frontomedian cortex, basal ganglia, anterior insulae and thalamus as most relevant hubs, with a regional dissociation between atrophy and hypometabolism. Neural networks affected by bvFTD were associated with emotion and reward processing, empathy and executive functions (mainly inhibition), suggesting these functions as core domains affected by the disease and finally leading to its clinical symptoms. In contrast, changes in theory of mind or mentalizing abilities seem to be secondary phenomena of executive dysfunctions. Conclusions The study creates a novel conceptual framework to understand neuropsychiatric diseases by powerful data-driven meta-analytic approaches that shall be extended to the whole neuropsychiatric spectrum in the future. PMID:24763126

Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis

PubMed Central

Ryti, Niilo R.I.; Guo, Yuming; Jaakkola, Jouni J.K.

2015-01-01

Background There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. Objective We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Data sources and extraction Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. “Cold spell” was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Data synthesis Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0–64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Conclusions Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Citation Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta-analysis. Environ Health Perspect 124:12–22; http://dx.doi.org/10.1289/ehp.1408104 PMID:25978526

Opium and bladder cancer: A systematic review and meta-analysis of the odds ratios for opium use and the risk of bladder cancer

PubMed Central

Afshari, Mahdi; Janbabaei, Ghasem; Bahrami, Mohammad Amin

2017-01-01

Objective The association between opium use and bladder cancer has been investigated in many studies, with varying reporting results reported. This study aims to estimate the total odds ratio for the association between bladder cancer and opium consumption using meta-analysis. Methods The study was designed according to PRISMA guidelines. Two independent researchers searched for the relevant studies using PubMed, Web of Science, Scopus, OVID, Embase, and Google Scholar. After systematic screening of the studies identified during the first step, Cochrane risk of bias tool was determined for the selected studies. The case-control and the cohort studies were investigated to assess risk of bladder cancer due to opium use. In addition, the cross-sectional studies were analysed separately to assess frequency of opium consumption. These estimates were combined using the inverse variance method. Fixed or random effect models were applied to combine the point odds ratios. The heterogeneity between the primary results was assessed using the Cochran test and I-square index. The suspected factors for heterogeneity were investigated using meta-regression models. An Egger test was conducted to identify any probable publication bias. Forest plots illustrated the point and pooled estimates. All analyses were performed using Stata version 14 software and RevMan version 5.3. Results We included 17 primary studies (11 case-control, one cohort and five cross-sectional) in the final meta-analysis. The total odds ratios (95% confidence intervals) for developing bladder cancer by opium use alone, and concurrent use of opium and cigarettes were estimated as 3.85 (3.05–4.87) and 5.7 (1.9–16.3) respectively. The odds ratio (95% confidence interval) for opium use with or without cigarette smoking was estimated as 5.3 (3.6–7.7). Conclusion This meta-analysis showed that opium use similar to cigarette smoking and maybe with similar mechanisms can be a risk factor for bladder cancer. It is therefore expected to be a risk factor for other cancers. PMID:28586371

Global Association of Cold Spells and Adverse Health Effects: A Systematic Review and Meta-Analysis.

PubMed

Ryti, Niilo R I; Guo, Yuming; Jaakkola, Jouni J K

2016-01-01

There is substantial evidence that mortality increases in low temperatures. Less is known about the role of prolonged cold periods denoted as cold spells. We conducted the first systematic review and meta-analysis to summarize the evidence on the adverse health effects of cold spells in varying climates. Four databases (Ovid Medline, PubMed, Scopus, Web of Science) were searched for all years and languages available. "Cold spell" was defined as an event below a temperature threshold lasting for a minimum duration of 2 days. Of 1,527 identified articles, 26 satisfied our eligibility criteria for the systematic review, and 9 were eligible for meta-analyses. The articles were grouped by the three main study questions into Overall-effect Group, Added-effect Group, and Temperature-change-effect Group. Based on random-effects models in the meta-analyses, cold spells were associated with increased mortality from all or all nonaccidental causes (summary rate ratio = 1.10; 95% CI: 1.04, 1.17 based on 9 estimates from five studies), cardiovascular diseases (1.11; 95% CI: 1.03, 1.19; 12 estimates from eight studies), and respiratory diseases (1.21; 95% CI: 0.97, 1.51; 8 estimates from four studies). Estimated associations were stronger for people ≥ 65 years of age (1.06; 95% CI: 1.00, 1.12) than for people 0-64 years of age (1.01; 95% CI: 1.00, 1.03). Study-specific effect estimates from a limited number of studies suggested an increased morbidity related to cold spells, but it was not possible to quantitatively summarize the evidence. Cold spells are associated with increased mortality rates in populations around the world. The body of evidence suggests that cold spells also have other adverse health effects. There was substantial heterogeneity among the studies, which should be taken into account in the interpretation of the results. Ryti NR, Guo Y, Jaakkola JJ. 2016. Global association of cold spells and adverse health effects: a systematic review and meta-analysis. Environ Health Perspect 124:12-22; http://dx.doi.org/10.1289/ehp.1408104.

A Meta-Analysis of the Relative Risk of Mortality for Type 1 Diabetes Patients Compared to the General Population: Exploring Temporal Changes in Relative Mortality

PubMed Central

Lung, Tom W. C.; Hayes, Alison J.; Herman, William H.; Si, Lei; Palmer, Andrew J.; Clarke, Philip M.

2014-01-01

Aims Type 1 diabetes has been associated with an elevated relative risk (RR) of mortality compared to the general population. To review published studies on the RR of mortality of Type 1 diabetes patients compared to the general population, we conducted a meta-analysis and examined the temporal changes in the RR of mortality over time. Methods Systematic review of studies reporting RR of mortality for Type 1 diabetes compared to the general population. We conducted meta-analyses using a DerSimonian and Laird random effects model to obtain the average effect and the distribution of RR estimates. Sub-group meta-analyses and multivariate meta-regression analysis was performed to examine heterogeneity. Summary RR with 95% CIs was calculated using a random-effects model. Results 26 studies with a total of 88 subpopulations were included in the meta-analysis and overall RR of mortality was 3.82 (95% CI 3.41, 3.4.29) compared to the general population. Observations using data prior to 1971 had a much larger estimated RR (5.80 (95% CI 4.20, 8.01)) when compared to: data between; 1971 and 1980 (5.06 (95% CI 3.44, 7.45)); 1981–90 (3.59 (95% CI 3.15, 4.09)); and those after 1990 (3.11 (95% CI 2.47, 3.91)); suggesting mortality of Type 1 diabetes patients when compared to the general population have been improving over time. Similarly, females (4.54 (95% CI 3.79–5.45)) had a larger RR estimate when compared to males (3.25 (95% CI 2.82–3.73) and the meta-regression found evidence for temporal trends and sex (p<0.01) accounting for heterogeneity between studies. Conclusions Type 1 diabetes patients’ mortality has declined at a faster rate than the general population. However, the largest relative improvements have occurred prior to 1990. Emphasis on intensive blood glucose control alongside blood pressure control and statin therapy may translate into further reductions in mortality in coming years. PMID:25426948

Gender-specific Differences in Recurrence of Non-muscle-invasive Bladder Cancer: A Systematic Review and Meta-analysis.

PubMed

Uhlig, Annemarie; Strauss, Arne; Seif Amir Hosseini, Ali; Lotz, Joachim; Trojan, Lutz; Schmid, Marianne; Uhlig, Johannes

2017-09-06

The incidence of urothelial carcinoma of the bladder (UCB) is lower in women; however, women tend to present with more advanced disease. To date, there is no quantitative synthesis of studies reporting gender-specific outcomes in non-muscle-invasive UCB. To conduct a meta-analysis evaluating gender-specific differences in recurrence of non-muscle-invasive urinary bladder cancer (NMIBC). An unrestricted systematic literature search of the MEDLINE, EMBASE, and Cochrane libraries was conducted. Studies evaluating the impact of gender on disease recurrence after local treatment of NMIBC using multivariable Cox proportional hazard models were included. Random effect meta-analysis, subgroup analyses, meta-influence, and cumulative meta-analyses were conducted. Publication bias was assessed via a funnel plot and Eggeŕs test. Of 609 studies screened, 27 comprising 23 754 patients were included. Random effect meta-analyses indicated women at increased risk for UCB recurrence compared with men (hazard ratio [HR]=1.11, 95% confidence interval [CI]: 1.01-1.23, p=0.03). Subgroup analyses yielded estimates between HR=0.99 and HR=1.68. Gender-specific differences in UCB recurrence were most pronounced in studies administering exclusively bacillus Calmette-Guerin (BCG; HR=1.64, 95% CI: 1.13-2.39, p=0.01), especially in a long-term treatment regimen (HR=1.68, 95% CI: 1.32-2.15, p<0.001). Sensitivity analyses confirmed female patients at increased risk for UCB recurrence. Women are at increased risk for disease recurrence after local treatment of NMIBC compared with male patients. Reduced effectiveness of BCG treatment might underlie this observation. Gender-specific differences were evident across various subgroups and proved robust upon sensitivity analyses. In this report, we combined several studies on gender-specific differences in relapse of superficial bladder cancer. Women were more likely to experience cancer relapse than men. Copyright © 2017 European Association of Urology. Published by Elsevier B.V. All rights reserved.

The prevalence of compulsive buying: a meta-analysis.

PubMed

Maraz, Aniko; Griffiths, Mark D; Demetrovics, Zsolt

2016-03-01

To estimate the pooled prevalence of compulsive buying behaviour (CBB) in different populations and to determine the effect of age, gender, location and screening instrument on the reported heterogeneity in estimates of CBB and whether publication bias could be identified. Three databases were searched (Medline, PsychInfo, Web of Science) using the terms 'compulsive buying', 'pathological buying' and 'compulsive shopping' to estimate the pooled prevalence of CBB in different populations. Forty studies reporting 49 prevalence estimates from 16 countries were located (n = 32,000). To conduct the meta-analysis, data from non-clinical studies regarding mean age and gender proportion, geographical study location and screening instrument used to assess CBB were extracted by multiple independent observers and evaluated using a random-effects model. Four a priori subgroups were analysed using pooled estimation (Cohen's Q) and covariate testing (moderator and meta-regression analysis). The CBB pooled prevalence of adult representative studies was 4.9% (3.4-6.9%, eight estimates, 10,102 participants), although estimates were higher among university students: 8.3% (5.9-11.5%, 19 estimates, 14,947 participants) in adult non-representative samples: 12.3% (7.6-19.1%, 11 estimates, 3929 participants) and in shopping-specific samples: 16.2% (8.8-27.8%, 11 estimates, 4686 participants). Being young and female were associated with increased tendency, but not location (United States versus non-United States). Meta-regression revealed large heterogeneity within subgroups, due mainly to diverse measures and time-frames (current versus life-time) used to assess CBB. A pooled estimate of compulsive buying behaviour in the populations studied is approximately 5%, but there is large variation between samples accounted for largely by use of different time-frames and measures. © 2016 Society for the Study of Addiction.

Bias due to selective inclusion and reporting of outcomes and analyses in systematic reviews of randomised trials of healthcare interventions.

PubMed

Page, Matthew J; McKenzie, Joanne E; Kirkham, Jamie; Dwan, Kerry; Kramer, Sharon; Green, Sally; Forbes, Andrew

2014-10-01

Systematic reviews may be compromised by selective inclusion and reporting of outcomes and analyses. Selective inclusion occurs when there are multiple effect estimates in a trial report that could be included in a particular meta-analysis (e.g. from multiple measurement scales and time points) and the choice of effect estimate to include in the meta-analysis is based on the results (e.g. statistical significance, magnitude or direction of effect). Selective reporting occurs when the reporting of a subset of outcomes and analyses in the systematic review is based on the results (e.g. a protocol-defined outcome is omitted from the published systematic review). To summarise the characteristics and synthesise the results of empirical studies that have investigated the prevalence of selective inclusion or reporting in systematic reviews of randomised controlled trials (RCTs), investigated the factors (e.g. statistical significance or direction of effect) associated with the prevalence and quantified the bias. We searched the Cochrane Methodology Register (to July 2012), Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO and ISI Web of Science (each up to May 2013), and the US Agency for Healthcare Research and Quality (AHRQ) Effective Healthcare Program's Scientific Resource Center (SRC) Methods Library (to June 2013). We also searched the abstract books of the 2011 and 2012 Cochrane Colloquia and the article alerts for methodological work in research synthesis published from 2009 to 2011 and compiled in Research Synthesis Methods. We included both published and unpublished empirical studies that investigated the prevalence and factors associated with selective inclusion or reporting, or both, in systematic reviews of RCTs of healthcare interventions. We included empirical studies assessing any type of selective inclusion or reporting, such as investigations of how frequently RCT outcome data is selectively included in systematic reviews based on the results, outcomes and analyses are discrepant between protocol and published review or non-significant outcomes are partially reported in the full text or summary within systematic reviews. Two review authors independently selected empirical studies for inclusion, extracted the data and performed a risk of bias assessment. A third review author resolved any disagreements about inclusion or exclusion of empirical studies, data extraction and risk of bias. We contacted authors of included studies for additional unpublished data. Primary outcomes included overall prevalence of selective inclusion or reporting, association between selective inclusion or reporting and the statistical significance of the effect estimate, and association between selective inclusion or reporting and the direction of the effect estimate. We combined prevalence estimates and risk ratios (RRs) using a random-effects meta-analysis model. Seven studies met the inclusion criteria. No studies had investigated selective inclusion of results in systematic reviews, or discrepancies in outcomes and analyses between systematic review registry entries and published systematic reviews. Based on a meta-analysis of four studies (including 485 Cochrane Reviews), 38% (95% confidence interval (CI) 23% to 54%) of systematic reviews added, omitted, upgraded or downgraded at least one outcome between the protocol and published systematic review. The association between statistical significance and discrepant outcome reporting between protocol and published systematic review was uncertain. The meta-analytic estimate suggested an increased risk of adding or upgrading (i.e. changing a secondary outcome to primary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.43, 95% CI 0.71 to 2.85; two studies, n = 552 meta-analyses). Also, the meta-analytic estimate suggested an increased risk of downgrading (i.e. changing a primary outcome to secondary) when the outcome was statistically significant, although the 95% CI included no association and a decreased risk as plausible estimates (RR 1.26, 95% CI 0.60 to 2.62; two studies, n = 484 meta-analyses). None of the included studies had investigated whether the association between statistical significance and adding, upgrading or downgrading of outcomes was modified by the type of comparison, direction of effect or type of outcome; or whether there is an association between direction of the effect estimate and discrepant outcome reporting.Several secondary outcomes were reported in the included studies. Two studies found that reasons for discrepant outcome reporting were infrequently reported in published systematic reviews (6% in one study and 22% in the other). One study (including 62 Cochrane Reviews) found that 32% (95% CI 21% to 45%) of systematic reviews did not report all primary outcomes in the abstract. Another study (including 64 Cochrane and 118 non-Cochrane reviews) found that statistically significant primary outcomes were more likely to be completely reported in the systematic review abstract than non-significant primary outcomes (RR 2.66, 95% CI 1.81 to 3.90). None of the studies included systematic reviews published after 2009 when reporting standards for systematic reviews (Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) Statement, and Methodological Expectations of Cochrane Intervention Reviews (MECIR)) were disseminated, so the results might not be generalisable to more recent systematic reviews. Discrepant outcome reporting between the protocol and published systematic review is fairly common, although the association between statistical significance and discrepant outcome reporting is uncertain. Complete reporting of outcomes in systematic review abstracts is associated with statistical significance of the results for those outcomes. Systematic review outcomes and analysis plans should be specified prior to seeing the results of included studies to minimise post-hoc decisions that may be based on the observed results. Modifications that occur once the review has commenced, along with their justification, should be clearly reported. Effect estimates and CIs should be reported for all systematic review outcomes regardless of the results. The lack of research on selective inclusion of results in systematic reviews needs to be addressed and studies that avoid the methodological weaknesses of existing research are also needed.

Altered Brain Activity in Unipolar Depression Revisited: Meta-analyses of Neuroimaging Studies.

PubMed

Müller, Veronika I; Cieslik, Edna C; Serbanescu, Ilinca; Laird, Angela R; Fox, Peter T; Eickhoff, Simon B

2017-01-01

During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases. In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results. Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches.

Altered Brain Activity in Unipolar Depression Revisited Meta-analyses of Neuroimaging Studies

PubMed Central

Müller, Veronika I.; Cieslik, Edna C.; Serbanescu, Ilinca; Laird, Angela R.; Fox, Peter T.; Eickhoff, Simon B.

2017-01-01

IMPORTANCE During the past 20 years, numerous neuroimaging experiments have investigated aberrant brain activation during cognitive and emotional processing in patients with unipolar depression (UD). The results of those investigations, however, vary considerably; moreover, previous meta-analyses also yielded inconsistent findings. OBJECTIVE To readdress aberrant brain activation in UD as evidenced by neuroimaging experiments on cognitive and/or emotional processing. DATA SOURCES Neuroimaging experiments published from January 1, 1997, to October 1, 2015, were identified by a literature search of PubMed, Web of Science, and Google Scholar using different combinations of the terms fMRI (functional magnetic resonance imaging), PET (positron emission tomography), neural, major depression, depression, major depressive disorder, unipolar depression, dysthymia, emotion, emotional, affective, cognitive, task, memory, working memory, inhibition, control, n-back, and Stroop. STUDY SELECTION Neuroimaging experiments (using fMRI or PET) reporting whole-brain results of group comparisons between adults with UD and healthy control individuals as coordinates in a standard anatomic reference space and using an emotional or/and cognitive challenging task were selected. DATA EXTRACTION AND SYNTHESIS Coordinates reported to show significant activation differences between UD and healthy controls during emotional or cognitive processing were extracted. By using the revised activation likelihood estimation algorithm, different meta-analyses were calculated. MAIN OUTCOMES AND MEASURES Meta-analyses tested for brain regions consistently found to show aberrant brain activation in UD compared with controls. Analyses were calculated across all emotional processing experiments, all cognitive processing experiments, positive emotion processing, negative emotion processing, experiments using emotional face stimuli, experiments with a sex discrimination task, and memory processing. All meta-analyses were calculated across experiments independent of reporting an increase or decrease of activity in major depressive disorder. For meta-analyses with a minimum of 17 experiments available, separate analyses were performed for increases and decreases. RESULTS In total, 57 studies with 99 individual neuroimaging experiments comprising in total 1058 patients were included; 34 of them tested cognitive and 65 emotional processing. Overall analyses across cognitive processing experiments (P > .29) and across emotional processing experiments (P > .47) revealed no significant results. Similarly, no convergence was found in analyses investigating positive (all P > .15), negative (all P > .76), or memory (all P > .48) processes. Analyses that restricted inclusion of confounds (eg, medication, comorbidity, age) did not change the results. CONCLUSIONS AND RELEVANCE Inconsistencies exist across individual experiments investigating aberrant brain activity in UD and replication problems across previous neuroimaging meta-analyses. For individual experiments, these inconsistencies may relate to use of uncorrected inference procedures, differences in experimental design and contrasts, or heterogeneous clinical populations; meta-analytically, differences may be attributable to varying inclusion and exclusion criteria or rather liberal statistical inference approaches. PMID:27829086

Aqueous extracts from Uncaria tomentosa (Willd. ex Schult.) DC. reduce bronchial hyperresponsiveness and inflammation in a murine model of asthma.

PubMed

Azevedo, Bruna Cestari; Morel, Lucas Junqueira Freitas; Carmona, Fábio; Cunha, Thiago Mattar; Contini, Silvia Helena Taleb; Delprete, Piero Giuseppe; Ramalho, Fernando Silva; Crevelin, Eduardo; Bertoni, Bianca Waléria; França, Suzelei Castro; Borges, Marcos Carvalho; Pereira, Ana Maria Soares

2018-05-23

Uncaria tomentosa (Willd. Ex Schult) DC is used by indigenous tribes in the Amazonian region of Central and South America to treat inflammation, allergies and asthma. The therapeutic properties of U. tomentosa have been attributed to the presence of tetracyclic and pentacyclic oxindole alkaloids and to phenolic acids. To characterize aqueous bark extracts (ABE) and aqueous leaf extracts (ALE) of U. tomentosa and to compare their anti-inflammatory effects. Constituents of the extracts were identified by ultra performance liquid chromatography-mass spectrometry. Anti-inflammatory activities were assessed in vitro by exposing lipopolysaccharide-stimulated macrophage cells (RAW264.7-Luc) to ABE, ALE and standard mitraphylline. In vivo assays were performed using a murine model of ovalbumin (OVA)-induced asthma. OVA-sensitized animals were treated with ABE or ALE while controls received dexamethasone or saline solution. Bronchial hyperresponsiveness, production of Th1 and Th2 cytokines, total and differential counts of inflammatory cells in the bronchoalveolar lavage (BAL) and lung tissue were determined. Mitraphylline, isomitraphylline, chlorogenic acid and quinic acid were detected in both extracts, while isorhyncophylline and rutin were detected only in ALE. ABE, ALE and mitraphylline inhibited the transcription of nuclear factor kappa-B in cell cultures, ALE and mitraphylline reduced the production of interleukin (IL)-6, and mitraphylline reduced production of tumor necrosis factor-alpha. Treatment with ABE and ALE at 50 and 200 mg kg -1 , respectively, reduced respiratory elastance and tissue damping and elastance. ABE and ALE reduced the number of eosinophils in BAL, while ALE at 200 mg kg -1 reduced the levels of IL-4 and IL-5 in the lung homogenate. Peribronchial inflammation was significantly reduced by treatment with ABE and ALE at 50 and 100 mg kg -1 respectively. The results clarify for the first time the anti-inflammatory activity of U. tomentosa in a murine model of asthma. Although ABE and ALE exhibited distinct chemical compositions, both extracts inhibited the production of pro-inflammatory cytokines in vitro. In vivo assays revealed that ABE was more effective in treating asthmatic inflammation while ALE was more successful in controlling respiratory mechanics. Both extracts may have promising applications in the phytotherapy of allergic asthma. Copyright © 2018 Elsevier B.V. All rights reserved.

Grey literature in meta-analyses of randomized trials of health care interventions.

PubMed

Hopewell, S; McDonald, S; Clarke, M; Egger, M

2007-04-18

The inclusion of grey literature (i.e. literature that has not been formally published) in systematic reviews may help to overcome some of the problems of publication bias, which can arise due to the selective availability of data. To review systematically research studies, which have investigated the impact of grey literature in meta-analyses of randomized trials of health care interventions. We searched the Cochrane Methodology Register (The Cochrane Library Issue 3, 2005), MEDLINE (1966 to 20 May 2005), the Science Citation Index (June 2005) and contacted researchers who may have carried out relevant studies. A study was considered eligible for this review if it compared the effect of the inclusion and exclusion of grey literature on the results of a cohort of meta-analyses of randomized trials. Data were extracted from each report independently by two reviewers. The main outcome measure was an estimate of the impact of trials from the grey literature on the pooled effect estimates of the meta-analyses. Information was also collected on the area of health care, the number of meta-analyses, the number of trials, the number of trial participants, the year of publication of the trials, the language and country of publication of the trials, the number and type of grey and published literature, and methodological quality. Five studies met the inclusion criteria. All five studies showed that published trials showed an overall greater treatment effect than grey trials. This difference was statistically significant in one of the five studies. Data could be combined for three of the five studies. This showed that, on average, published trials showed a 9% greater treatment effect than grey trials (ratio of odds ratios for grey versus published trials 1.09; 95% CI 1.03-1.16). Overall there were more published trials included in the meta-analyses than grey trials (median 224 (IQR 108-365) versus 45(IQR 40-102)). Published trials had more participants on average. The most common types of grey literature were abstracts (55%) and unpublished data (30%). There is limited evidence to show whether grey trials are of poorer methodological quality than published trials. This review shows that published trials tend to be larger and show an overall greater treatment effect than grey trials. This has important implications for reviewers who need to ensure they identify grey trials, in order to minimise the risk of introducing bias into their review.

Guidance for deriving and presenting percentage study weights in meta-analysis of test accuracy studies.

PubMed

Burke, Danielle L; Ensor, Joie; Snell, Kym I E; van der Windt, Danielle; Riley, Richard D

2018-06-01

Percentage study weights in meta-analysis reveal the contribution of each study toward the overall summary results and are especially important when some studies are considered outliers or at high risk of bias. In meta-analyses of test accuracy reviews, such as a bivariate meta-analysis of sensitivity and specificity, the percentage study weights are not currently derived. Rather, the focus is on representing the precision of study estimates on receiver operating characteristic plots by scaling the points relative to the study sample size or to their standard error. In this article, we recommend that researchers should also provide the percentage study weights directly, and we propose a method to derive them based on a decomposition of Fisher information matrix. This method also generalises to a bivariate meta-regression so that percentage study weights can also be derived for estimates of study-level modifiers of test accuracy. Application is made to two meta-analyses examining test accuracy: one of ear temperature for diagnosis of fever in children and the other of positron emission tomography for diagnosis of Alzheimer's disease. These highlight that the percentage study weights provide important information that is otherwise hidden if the presentation only focuses on precision based on sample size or standard errors. Software code is provided for Stata, and we suggest that our proposed percentage weights should be routinely added on forest and receiver operating characteristic plots for sensitivity and specificity, to provide transparency of the contribution of each study toward the results. This has implications for the PRISMA-diagnostic test accuracy guidelines that are currently being produced. Copyright © 2017 John Wiley & Sons, Ltd.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses.

PubMed

Khankari, Nikhil K; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I; Easton, Douglas; Eeles, Rosalind A; Gruber, Stephen B; Haiman, Christopher A; Hunter, David J; Chanock, Stephen J; Pierce, Brandon L; Zheng, Wei

2016-09-01

Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers.

Meta-analysis of two studies in the presence of heterogeneity with applications in rare diseases.

PubMed

Friede, Tim; Röver, Christian; Wandel, Simon; Neuenschwander, Beat

2017-07-01

Random-effects meta-analyses are used to combine evidence of treatment effects from multiple studies. Since treatment effects may vary across trials due to differences in study characteristics, heterogeneity in treatment effects between studies must be accounted for to achieve valid inference. The standard model for random-effects meta-analysis assumes approximately normal effect estimates and a normal random-effects model. However, standard methods based on this model ignore the uncertainty in estimating the between-trial heterogeneity. In the special setting of only two studies and in the presence of heterogeneity, we investigate here alternatives such as the Hartung-Knapp-Sidik-Jonkman method (HKSJ), the modified Knapp-Hartung method (mKH, a variation of the HKSJ method) and Bayesian random-effects meta-analyses with priors covering plausible heterogeneity values; R code to reproduce the examples is presented in an appendix. The properties of these methods are assessed by applying them to five examples from various rare diseases and by a simulation study. Whereas the standard method based on normal quantiles has poor coverage, the HKSJ and mKH generally lead to very long, and therefore inconclusive, confidence intervals. The Bayesian intervals on the whole show satisfying properties and offer a reasonable compromise between these two extremes. © 2016 The Authors. Biometrical Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

An AMR capable finite element diffusion solver for ALE hydrocodes [An AMR capable diffusion solver for ALE-AMR

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisher, A. C.; Bailey, D. S.; Kaiser, T. B.

2015-02-01

Here, we present a novel method for the solution of the diffusion equation on a composite AMR mesh. This approach is suitable for including diffusion based physics modules to hydrocodes that support ALE and AMR capabilities. To illustrate, we proffer our implementations of diffusion based radiation transport and heat conduction in a hydrocode called ALE-AMR. Numerical experiments conducted with the diffusion solver and associated physics packages yield 2nd order convergence in the L 2 norm.

ALE3D: An Arbitrary Lagrangian-Eulerian Multi-Physics Code

DOE Office of Scientific and Technical Information (OSTI.GOV)

Noble, Charles R.; Anderson, Andrew T.; Barton, Nathan R.

ALE3D is a multi-physics numerical simulation software tool utilizing arbitrary-Lagrangian- Eulerian (ALE) techniques. The code is written to address both two-dimensional (2D plane and axisymmetric) and three-dimensional (3D) physics and engineering problems using a hybrid finite element and finite volume formulation to model fluid and elastic-plastic response of materials on an unstructured grid. As shown in Figure 1, ALE3D is a single code that integrates many physical phenomena.

Characterization and functional analysis of the MAL and MPH Loci for maltose utilization in some ale and lager yeast strains.

PubMed

Vidgren, Virve; Ruohonen, Laura; Londesborough, John

2005-12-01

Maltose and maltotriose are the major sugars in brewer's wort. Brewer's yeasts contain multiple genes for maltose transporters. It is not known which of these express functional transporters. We correlated maltose transport kinetics with the genotypes of some ale and lager yeasts. Maltose transport by two ale strains was strongly inhibited by other alpha-glucosides, suggesting the use of broad substrate specificity transporters, such as Agt1p. Maltose transport by three lager strains was weakly inhibited by other alpha-glucosides, suggesting the use of narrow substrate specificity transporters. Hybridization studies showed that all five strains contained complete MAL1, MAL2, MAL3, and MAL4 loci, except for one ale strain, which lacked a MAL2 locus. All five strains also contained both AGT1 (coding a broad specificity alpha-glucoside transporter) and MAL11 alleles. MPH genes (maltose permease homologues) were present in the lager but not in the ale strains. During growth on maltose, the lager strains expressed AGT1 at low levels and MALx1 genes at high levels, whereas the ale strains expressed AGT1 at high levels and MALx1 genes at low levels. MPHx expression was negligible in all strains. The AGT1 sequences from the ale strains encoded full-length (616 amino acid) polypeptides, but those from both sequenced lager strains encoded truncated (394 amino acid) polypeptides that are unlikely to be functional transporters. Thus, despite the apparently similar genotypes of these ale and lager strains revealed by hybridization, maltose is predominantly carried by AGT1-encoded transporters in the ale strains and by MALx1-encoded transporters in the lager strains.

Association of Hypertensive Disorders of Pregnancy With Risk of Neurodevelopmental Disorders in Offspring: A Systematic Review and Meta-analysis.

PubMed

Maher, Gillian M; O'Keeffe, Gerard W; Kearney, Patricia M; Kenny, Louise C; Dinan, Timothy G; Mattsson, Molly; Khashan, Ali S

2018-06-06

Although research suggests an association between hypertensive disorders of pregnancy (HDP) and autism spectrum disorder (ASD), attention-deficit/hyperactivity disorder (ADHD), and other neurodevelopmental disorders in offspring, consensus is lacking. Given the increasing prevalence of hypertension in pregnancy, it is important to examine the association of HDP with neurodevelopmental outcome. To synthesize the published literature on the association between HDP and risk of neurodevelopmental disorders in offspring in a systematic review and meta-analysis. On the basis of a preprepared protocol, a systematic search of PubMed, CINAHL, Embase, PsycINFO, and Web of Science was performed from inception through June 7, 2017, supplemented by hand searching of reference lists. Two investigators independently reviewed titles, abstracts, and full-text articles. English-language cohort and case-control studies were included in which HDP and neurodevelopmental disorders were reported. Data extraction and quality appraisal were performed independently by 2 reviewers. Meta-analysis of Observational Studies in Epidemiology (MOOSE) guidelines were followed throughout. Random-effects meta-analyses of estimated pooled odds ratios (ORs) for HDP and ASD and for HDP and ADHD. Stand-alone estimates were reported for all other neurodevelopmental disorders. Of 1166 studies identified, 61 unique articles met inclusion criteria. Twenty studies reported estimates for ASD. Eleven of these (including 777 518 participants) reported adjusted estimates, with a pooled adjusted OR of 1.35 (95% CI, 1.11-1.64). Ten studies reported estimates for ADHD. Six of these (including 1 395 605 participants) reported adjusted estimates, with a pooled adjusted OR of 1.29 (95% CI, 1.22-1.36). Subgroup analyses according to type of exposure (ie, preeclampsia or other HDP) showed no statistically significant differences for ASD or ADHD. Thirty-one studies met inclusion criteria for all other neurodevelopmental disorders. Individual estimates reported for these were largely inconsistent, with few patterns of association observed. Exposure to HDP may be associated with an increase in the risk of ASD and ADHD. These findings highlight the need for greater pediatric surveillance of infants exposed to HDP to allow early intervention that may improve neurodevelopmental outcome.

Attachment, Development, and Mental Health in Abused and Neglected Preschool Children in Foster Care: A Meta-Analysis.

PubMed

Vasileva, Mira; Petermann, Franz

2016-09-22

A proper preparation for foster parents to care for abused and neglected children includes effective training and initial diagnostics in order to plan individual treatment. Hence, a basic knowledge about the main psychosocial and developmental problems associated with abuse and neglect and their prevalence in foster children is needed. For this purpose, a systematical literature review and a series of meta-analyses were conducted. A total of 25 studies reporting data on development (n = 4,033), mental health (n = 726), and attachment (n = 255) of foster children in preschool age met the inclusion criteria. The meta-analyses indicated prevalence rates of approximately 40% for developmental, mental health problems, and insecure attachment. Rates of disorganized attachment were estimated to 22%. These findings outline the necessity of an initial trauma-oriented diagnostics and trainings for foster parents that address foster children's development, mental health, and disorganized attachment. © The Author(s) 2016.

Method of and apparatus for modeling interactions

DOEpatents

Budge, Kent G.

2004-01-13

A method and apparatus for modeling interactions can accurately model tribological and other properties and accommodate topological disruptions. Two portions of a problem space are represented, a first with a Lagrangian mesh and a second with an ALE mesh. The ALE and Lagrangian meshes are constructed so that each node on the surface of the Lagrangian mesh is in a known correspondence with adjacent nodes in the ALE mesh. The interaction can be predicted for a time interval. Material flow within the ALE mesh can accurately model complex interactions such as bifurcation. After prediction, nodes in the ALE mesh in correspondence with nodes on the surface of the Lagrangian mesh can be mapped so that they are once again adjacent to their corresponding Lagrangian mesh nodes. The ALE mesh can then be smoothed to reduce mesh distortion that might reduce the accuracy or efficiency of subsequent prediction steps. The process, from prediction through mapping and smoothing, can be repeated until a terminal condition is reached.

The value of urban open space: meta-analyses of contingent valuation and hedonic pricing results.

PubMed

Brander, Luke M; Koetse, Mark J

2011-10-01

Urban open space provides a number of valuable services to urban populations, including recreational opportunities, aesthetic enjoyment, environmental functions, and may also be associated with existence values. In separate meta-analyses of the contingent valuation (CV) and hedonic pricing (HP) literature we examine which physical, socio-economic, and study characteristics determine the value of open space. The dependent variable in the CV meta-regression is defined as the value of open space per hectare per year in 2003 US$, and in the HP model as the percentage change in house price for a 10 m decrease in distance to open space. Using a multi-level modelling approach we find in both the CV and HP analyses that there is a positive and significant relationship between the value of urban open space and population density, indicating that scarcity and crowdedness matter, and that the value of open space does not vary significantly with income. Further, urban parks are more highly valued than other types of urban open space (forests, agricultural and undeveloped land) and methodological differences in study design have a large influence on estimated values from both CV and HP. We also find important regional differences in preferences for urban open space, which suggests that the potential for transferring estimated values between regions is likely to be limited. Copyright © 2011 Elsevier Ltd. All rights reserved.

Evaluation of the United States Department Of Agriculture Northeast Area-wide Tick Control Project by meta-analysis.

PubMed

Brei, Brandon; Brownstein, John S; George, John E; Pound, J Mathews; Miller, J Allen; Daniels, Thomas J; Falco, Richard C; Stafford, Kirby C; Schulze, Terry L; Mather, Thomas N; Carroll, John F; Fish, Durland

2009-08-01

As part of the Northeast Area-wide Tick Control Project (NEATCP), meta-analyses were performed using pooled data on the extent of tick-vector control achieved through seven concurrent studies, conducted within five states, using U.S. Department of Agriculture "4-Poster" devices to deliver targeted-acaricide to white-tailed deer. Although reductions in the abundance of all life-stages of Ixodes scapularis were the measured outcomes, this study focused on metrics associated with I. scapularis nymphal tick densities as this measure has consistently proven to directly correlate with human risk of acquiring Lyme disease. Since independent tick sampling schemes were undertaken at each of the five environmentally distinct study locations, a meta-analytic approach permitted estimation of a single true control-effect size for each treatment year of the NEATCP. The control-effect is expressed as the annual percent I. scapularis nymphal control most consistent with meta-analysis data for each treatment year. Our meta-analyses indicate that by the sixth treatment year, the NEATCP effectively reduced the relative density of I. scapularis nymphs by 71% on the 5.14 km(2) treatment sites, corresponding to a 71% lower relative entomologic risk index for acquiring Lyme disease.

Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews.

PubMed

Lugo, Alessandra; Bosetti, Cristina; Peveri, Giulia; Rota, Matteo; Bagnardi, Vincenzo; Gallus, Silvano

2017-11-01

Only a limited number of meta-analyses providing risk curve functions of dose-response relationships between various smoking-related variables and cancer-specific risk are available. To identify all relevant original publications on the issue, we will conduct a series of comprehensive systematic reviews based on three subsequent literature searches: (1) an umbrella review, to identify meta-analyses, pooled analyses and systematic reviews published before 28 April 2017 on the association between cigarette smoking and the risk of 28 (namely all) malignant neoplasms; (2) for each cancer site, an updated review of original publications on the association between cigarette smoking and cancer risk, starting from the last available comprehensive review identified through the umbrella review; and (3) a review of all original articles on the association between cigarette smoking and site-specific cancer risk included in the publications identified through the umbrella review and the updated reviews. The primary outcomes of interest will be (1) the excess incidence/mortality of various cancers for smokers compared with never smokers; and (2) the dose-response curves describing the association between smoking intensity, duration and time since stopping and incidence/mortality for various cancers. For each cancer site, we will perform a meta-analysis by pooling study-specific estimates for smoking status. We will also estimate the dose-response curves for other smoking-related variables through random-effects meta-regression models based on a non-linear dose-response relationship framework. Ethics approval is not required for this study. Main results will be published in peer-reviewed journals and will also be included in a publicly available website. We will provide therefore the most complete and updated estimates on the association between various measures of cigarette smoking and site-specific cancer risk. This will allow us to obtain precise estimates on the cancer burden attributable to cigarette smoking. This protocol was registered in the International Prospective Register of Systematic Reviews (CRD42017063991). © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Household physical activity and cancer risk: a systematic review and dose-response meta-analysis of epidemiological studies

PubMed Central

Shi, Yun; Li, Tingting; Wang, Ying; Zhou, Lingling; Qin, Qin; Yin, Jieyun; Wei, Sheng; Liu, Li; Nie, Shaofa

2015-01-01

Controversial results of the association between household physical activity and cancer risk were reported among previous epidemiological studies. We conducted a meta-analysis to investigate the relationship of household physical activity and cancer risk quantitatively, especially in dose-response manner. PubMed, Embase, Web of science and the Cochrane Library were searched for cohort or case-control studies that examined the association between household physical activity and cancer risks. Random–effect models were conducted to estimate the summary relative risks (RRs), nonlinear or linear dose–response meta-analyses were performed to estimate the trend from the correlated log RR estimates across levels of household physical activity quantitatively. Totally, 30 studies including 41 comparisons met the inclusion criteria. Total cancer risks were reduced 16% among the people with highest household physical activity compared to those with lowest household physical activity (RR = 0.84, 95% CI = 0.76–0.93). The dose-response analyses indicated an inverse linear association between household physical activity and cancer risk. The relative risk was 0.98 (95% CI = 0.97–1.00) for per additional 10 MET-hours/week and it was 0.99 (95% CI = 0.98–0.99) for per 1 hour/week increase. These findings provide quantitative data supporting household physical activity is associated with decreased cancer risk in dose-response effect. PMID:26443426

Acanthus ilicifolius plant extract prevents DNA alterations in a transplantable Ehrlich ascites carcinoma-bearing murine model.

PubMed

Chakraborty, Tridib; Bhuniya, Dipak; Chatterjee, Mary; Rahaman, Mosiur; Singha, Dipak; Chatterjee, Baidya Nath; Datta, Subrata; Rana, Ajay; Samanta, Kartick; Srivastawa, Sunil; Maitra, Sankar K; Chatterjee, Malay

2007-12-28

To investigate the chemopreventive efficacy of the Indian medicinal plant Acanthus ilicifolius L Acanthaceae in a transplantable Ehrlich ascites carcinoma (EAC)-bearing murine model. Male Swiss albino mice were divided into four groups: Group A was the untreated normal control; Group B was the EAC control mice group that received serial, intraperitoneal (ip) inoculations of rapidly proliferating 2 x 10(5) viable EAC cells in 0.2 mL of sterile phosphate buffered saline; Group C was the plant extract-treated group that received the aqueous leaf extract (ALE) of the plant at a dose of 2.5 mg/kg body weight by single ip injections, once daily for 10, 20 and 30 consecutive days following tumour inoculation (ALE control); and Group D was the EAC + ALE-treatment group. The chemopreventive potential of the ALE was evaluated in a murine model by studying various biological parameters and genotoxic markers, such as tumour cell count, mean survival of the animals, haematological indices, hepatocellular histology, immunohistochemical expression of liver metallothionein (MT) protein, sister-chromatid exchanges (SCEs), and DNA alterations. Treatment of the EAC-bearing mice with the ALE significantly (P < 0.001) reduced viable tumour cell count by 68.34% (228.7 x 10(6) +/- 0.53) when compared to EAC control mice (72.4 x 10(6) +/- 0.49), and restored body and organ weights almost to the normal values. ALE administration also increased (P < 0.001) mean survival of the hosts from 35 +/- 3.46 d in EAC control mice to 83 +/- 2.69 d in EAC + ALE-treated mice. Haematological indices also showed marked improvement with administration of ALE in EAC-bearing animals. There was a significant increase in RBC count (P < 0.001), hemoglobin percent (P < 0.001), and haematocrit value (P < 0.001) from 4.3 +/- 0.12, 6.4 +/- 0.93, and 17.63 +/- 0.72 respectively in EAC control mice to 7.1 +/- 0.13, 12.1 +/- 0.77, and 30.23 +/- 0.57 respectively in EAC + ALE-treated group, along with concurrent decrement (P < 0.001) in WBC count from 18.8 +/- 0.54 in EAC control to 8.4 +/- 0.71 in EAC + ALE. Furthermore, treatment with ALE substantially improved hepatocellular architecture and no noticeable neoplastic lesions or foci of cellular alteration were observed. Daily administration of the ALE was found to limit liver MT expression, an important marker of cell proliferation with concomitant reduction in MT immunoreactivity (62.25 +/- 2.58 vs 86.24 +/- 5.69, P < 0.01). ALE was also potentially effective in reducing (P < 0.001) the frequency of SCEs from 14.94 +/- 2.14 in EAC control to 5.12 +/- 1.16 in EAC + ALE-treated group. Finally, in comparison to the EAC control, ALE was able to suppress in vivo DNA damage by abating the generations of 'tailed' DNA by 53.59% (98.65 +/- 2.31 vs 45.06 +/- 1.14, P < 0.001), and DNA single-strand breaks (SSBs) by 38.53% (3.14 +/- 0.31 vs 1.93 +/- 0.23, P < 0.01) in EAC-bearing murine liver. Our data indicate that, ALE is beneficial in restoring haematological and hepatic histological profiles and in lengthening the survival of the animals against the proliferation of ascites tumour in vivo. Finally, the chemopreventive efficacy of the ALE is manifested in limiting MT expression and in preventing DNA alterations in murine liver. The promising results of this study suggest further investigation into the chemopreventive mechanisms of the medicinal plant A. ilicifolius in vivo and in vitro.

Effects of Exercise in the Treatment of Overweight and Obese Children and Adolescents: A Systematic Review of Meta-Analyses

PubMed Central

Kelley, George A.; Kelley, Kristi S.

2013-01-01

Purpose. Conduct a systematic review of previous meta-analyses addressing the effects of exercise in the treatment of overweight and obese children and adolescents. Methods. Previous meta-analyses of randomized controlled exercise trials that assessed adiposity in overweight and obese children and adolescents were included by searching nine electronic databases and cross-referencing from retrieved studies. Methodological quality was assessed using the Assessment of Multiple Systematic Reviews (AMSTAR) Instrument. The alpha level for statistical significance was set at P ≤ 0.05. Results. Of the 308 studies reviewed, two aggregate data meta-analyses representing 14 and 17 studies and 481 and 701 boys and girls met all eligibility criteria. Methodological quality was 64% and 73%. For both studies, statistically significant reductions in percent body fat were observed (P = 0.006 and P < 0.00001). The number-needed-to treat (NNT) was 4 and 3 with an estimated 24.5 and 31.5 million overweight and obese children in the world potentially benefitting, 2.8 and 3.6 million in the US. No other measures of adiposity (BMI-related measures, body weight, and central obesity) were statistically significant. Conclusions. Exercise is efficacious for reducing percent body fat in overweight and obese children and adolescents. Insufficient evidence exists to suggest that exercise reduces other measures of adiposity. PMID:24455215

Active Learning in Engineering Education: A (Re)Introduction

ERIC Educational Resources Information Center

Lima, Rui M.; Andersson, Pernille Hammar; Saalman, Elisabeth

2017-01-01

The informal network "Active Learning in Engineering Education" (ALE) has been promoting Active Learning since 2001. ALE creates opportunity for practitioners and researchers of engineering education to collaboratively learn how to foster learning of engineering students. The activities in ALE are centred on the vision that learners…

The role of the salience network in processing lexical and nonlexical stimuli in cochlear implant users: an ALE meta-analysis of PET studies.

PubMed

Song, Jae-Jin; Vanneste, Sven; Lazard, Diane S; Van de Heyning, Paul; Park, Joo Hyun; Oh, Seung Ha; De Ridder, Dirk

2015-05-01

Previous positron emission tomography (PET) studies have shown that various cortical areas are activated to process speech signal in cochlear implant (CI) users. Nonetheless, differences in task dimension among studies and low statistical power preclude from understanding sound processing mechanism in CI users. Hence, we performed activation likelihood estimation meta-analysis of PET studies in CI users and normal hearing (NH) controls to compare the two groups. Eight studies (58 CI subjects/92 peak coordinates; 45 NH subjects/40 peak coordinates) were included and analyzed, retrieving areas significantly activated by lexical and nonlexical stimuli. For lexical and nonlexical stimuli, both groups showed activations in the components of the dual-stream model such as bilateral superior temporal gyrus/sulcus, middle temporal gyrus, left posterior inferior frontal gyrus, and left insula. However, CI users displayed additional unique activation patterns by lexical and nonlexical stimuli. That is, for the lexical stimuli, significant activations were observed in areas comprising salience network (SN), also known as the intrinsic alertness network, such as the left dorsal anterior cingulate cortex (dACC), left insula, and right supplementary motor area in the CI user group. Also, for the nonlexical stimuli, CI users activated areas comprising SN such as the right insula and left dACC. Previous episodic observations on lexical stimuli processing using the dual auditory stream in CI users were reconfirmed in this study. However, this study also suggests that dual-stream auditory processing in CI users may need supports from the SN. In other words, CI users need to pay extra attention to cope with degraded auditory signal provided by the implant. © 2015 Wiley Periodicals, Inc.

Formalizing the definition of meta-analysis in Molecular Ecology.

PubMed

ArchMiller, Althea A; Bauer, Eric F; Koch, Rebecca E; Wijayawardena, Bhagya K; Anil, Ammu; Kottwitz, Jack J; Munsterman, Amelia S; Wilson, Alan E

2015-08-01

Meta-analysis, the statistical synthesis of pertinent literature to develop evidence-based conclusions, is relatively new to the field of molecular ecology, with the first meta-analysis published in the journal Molecular Ecology in 2003 (Slate & Phua 2003). The goal of this article is to formalize the definition of meta-analysis for the authors, editors, reviewers and readers of Molecular Ecology by completing a review of the meta-analyses previously published in this journal. We also provide a brief overview of the many components required for meta-analysis with a more specific discussion of the issues related to the field of molecular ecology, including the use and statistical considerations of Wright's FST and its related analogues as effect sizes in meta-analysis. We performed a literature review to identify articles published as 'meta-analyses' in Molecular Ecology, which were then evaluated by at least two reviewers. We specifically targeted Molecular Ecology publications because as a flagship journal in this field, meta-analyses published in Molecular Ecology have the potential to set the standard for meta-analyses in other journals. We found that while many of these reviewed articles were strong meta-analyses, others failed to follow standard meta-analytical techniques. One of these unsatisfactory meta-analyses was in fact a secondary analysis. Other studies attempted meta-analyses but lacked the fundamental statistics that are considered necessary for an effective and powerful meta-analysis. By drawing attention to the inconsistency of studies labelled as meta-analyses, we emphasize the importance of understanding the components of traditional meta-analyses to fully embrace the strengths of quantitative data synthesis in the field of molecular ecology. © 2015 John Wiley & Sons Ltd.

Validity of Meta-analysis in Diabetes: We Need to Be Aware of Its Limitations

PubMed Central

Home, Philip D.

2013-01-01

To deliver high-quality clinical care to patients with diabetes and other chronic conditions, clinicians must understand the evidence available from studies that have been performed to address important clinical management questions. In an evidence-based approach to clinical care, the evidence from clinical research should be integrated with clinical expertise, pathophysiological knowledge, and an understanding of patient values. As such, in an effort to provide information from many studies, the publication of diabetes meta-analyses has increased markedly in the recent past, using either observational or clinical trial data. In this regard, guidelines have been developed to direct the performance of meta-analysis to provide consistency among contributions. Thus, when done appropriately, meta-analysis can provide estimates from clinically and statistically homogeneous but underpowered studies and is useful in supporting clinical decisions, guidelines, and cost-effectiveness analysis. However, often these conditions are not met, the data considered are unreliable, and the results should not be assumed to be any more valid than the data underlying the included studies. To provide an understanding of both sides of the argument, we provide a discussion of this topic as part of this two-part point-counterpoint narrative. In the point narrative as presented below, Dr. Home provides his opinion and review of the data to date showing that we need to carefully evaluate meta-analyses and to learn what results are reliable. In the counterpoint narrative following Dr. Home’s contribution, Drs. Golden and Bass emphasize that an effective system exists to guide meta-analysis and that rigorously conducted, high-quality systematic reviews and meta-analyses are an indispensable tool in evidence synthesis despite their limitations. —William T. Cefalu, MD Editor in Chief, Diabetes Care PMID:24065844

Alcohol Consumption and the Physical Availability of Take-Away Alcohol: Systematic Reviews and Meta-Analyses of the Days and Hours of Sale and Outlet Density.

PubMed

Sherk, Adam; Stockwell, Tim; Chikritzhs, Tanya; Andréasson, Sven; Angus, Colin; Gripenberg, Johanna; Holder, Harold; Holmes, John; Mäkelä, Pia; Mills, Megan; Norström, Thor; Ramstedt, Mats; Woods, Jonathan

2018-01-01

Systematic reviews and meta-analyses were completed studying the effect of changes in the physical availability of take-away alcohol on per capita alcohol consumption. Previous reviews examining this topic have not focused on off-premise outlets where take-away alcohol is sold and have not completed meta-analyses. Systematic reviews were conducted separately for policies affecting the temporal availability (days and hours of sale) and spatial availability (outlet density) of take-away alcohol. Studies were included up to December 2015. Quality criteria were used to select articles that studied the effect of changes in these policies on alcohol consumption with a focus on natural experiments. Random-effects meta-analyses were applied to produce the estimated effect of an additional day of sale on total and beverage-specific consumption. Separate systematic reviews identified seven studies regarding days and hours of sale and four studies regarding density. The majority of articles included in these systematic reviews, for days/hours of sale (7/7) and outlet density (3/4), concluded that restricting the physical availability of take-away alcohol reduces per capita alcohol consumption. Meta-analyses studying the effect of adding one additional day of sale found that this was associated with per capita consumption increases of 3.4% (95% CI [2.7, 4.1]) for total alcohol, 5.3% (95% CI [3.2, 7.4]) for beer, 2.6% (95% CI [1.8, 3.5]) for wine, and 2.6% (95% CI [2.1, 3.2]) for spirits. The small number of included studies regarding hours of sale and density precluded meta-analysis. The results of this study suggest that decreasing the physical availability of take-away alcohol will decrease per capita consumption. As decreasing per capita consumption has been shown to reduce alcohol-related harm, restricting the physical availability of take-away alcohol would be expected to result in improvements to public health.

Assessment of the quality of reporting in abstracts of systematic reviews with meta-analyses in periodontology and implant dentistry.

PubMed

Faggion, C M; Liu, J; Huda, F; Atieh, M

2014-04-01

Proper scientific reporting is necessary to ensure the correct interpretation of study results by readers. The main objective of this study was to assess the quality of reporting in abstracts of systematic reviews (SRs) with meta-analyses in periodontology and implant dentistry. Differences in reporting of abstracts in Cochrane and paper-based reviews were also assessed. The PubMed electronic database and the Cochrane database for SRs were searched on November 11, 2012, independently and in duplicate, for SRs with meta-analyses related to interventions in periodontology and implant dentistry. Assessment of the quality of reporting was performed independently and in duplicate, taking into account items related to the effect direction, numerical estimates of effect size, measures of precision, probability and consistency. We initially screened 433 papers and included 146 (127 paper-based and 19 Cochrane reviews, respectively). The direction of evidence was reported in two-thirds of the abstracts while strength of evidence and measure of precision (i.e., confidence interval) were reported in less than half the selected abstracts. Measures of consistency such as I(2) statistics were reported in only 5% of the selected sample of abstracts. Cochrane abstracts reported the limitations of evidence and precision better than paper-based ones. Two items ("meta-analysis" in title and abstract, respectively), were nevertheless better reported in paper-based abstracts. Abstracts of SRs with meta-analyses in periodontology and implant dentistry currently have no uniform standard of reporting, which may hinder readers' understanding of study outcomes. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

The Validity of Conscientiousness Is Overestimated in the Prediction of Job Performance.

PubMed

Kepes, Sven; McDaniel, Michael A

2015-01-01

Sensitivity analyses refer to investigations of the degree to which the results of a meta-analysis remain stable when conditions of the data or the analysis change. To the extent that results remain stable, one can refer to them as robust. Sensitivity analyses are rarely conducted in the organizational science literature. Despite conscientiousness being a valued predictor in employment selection, sensitivity analyses have not been conducted with respect to meta-analytic estimates of the correlation (i.e., validity) between conscientiousness and job performance. To address this deficiency, we reanalyzed the largest collection of conscientiousness validity data in the personnel selection literature and conducted a variety of sensitivity analyses. Publication bias analyses demonstrated that the validity of conscientiousness is moderately overestimated (by around 30%; a correlation difference of about .06). The misestimation of the validity appears to be due primarily to suppression of small effects sizes in the journal literature. These inflated validity estimates result in an overestimate of the dollar utility of personnel selection by millions of dollars and should be of considerable concern for organizations. The fields of management and applied psychology seldom conduct sensitivity analyses. Through the use of sensitivity analyses, this paper documents that the existing literature overestimates the validity of conscientiousness in the prediction of job performance. Our data show that effect sizes from journal articles are largely responsible for this overestimation.

The Validity of Conscientiousness Is Overestimated in the Prediction of Job Performance

PubMed Central

2015-01-01

Introduction Sensitivity analyses refer to investigations of the degree to which the results of a meta-analysis remain stable when conditions of the data or the analysis change. To the extent that results remain stable, one can refer to them as robust. Sensitivity analyses are rarely conducted in the organizational science literature. Despite conscientiousness being a valued predictor in employment selection, sensitivity analyses have not been conducted with respect to meta-analytic estimates of the correlation (i.e., validity) between conscientiousness and job performance. Methods To address this deficiency, we reanalyzed the largest collection of conscientiousness validity data in the personnel selection literature and conducted a variety of sensitivity analyses. Results Publication bias analyses demonstrated that the validity of conscientiousness is moderately overestimated (by around 30%; a correlation difference of about .06). The misestimation of the validity appears to be due primarily to suppression of small effects sizes in the journal literature. These inflated validity estimates result in an overestimate of the dollar utility of personnel selection by millions of dollars and should be of considerable concern for organizations. Conclusion The fields of management and applied psychology seldom conduct sensitivity analyses. Through the use of sensitivity analyses, this paper documents that the existing literature overestimates the validity of conscientiousness in the prediction of job performance. Our data show that effect sizes from journal articles are largely responsible for this overestimation. PMID:26517553

ALES: An Innovative Argument-Learning Environment

ERIC Educational Resources Information Center

Abbas, Safia; Sawamura, Hajime

2010-01-01

This paper presents the development of an Argument-Learning System (ALES). The idea is based on the AIF (argumentation interchange format) ontology using "Walton theory". ALES uses different mining techniques to manage a highly structured arguments repository. This repository was designed, developed and implemented by the authors. The aim is to…

Application of the ALE and MBE Methods to the Growth of Layered Hg sub x Cd sub 1-x Te Films.

DTIC Science & Technology

1986-09-26

films / We have studied the applicability of the Atomic Layer Epitaxy (ALE, vee Ref. -1pand Molecular Beam Epitaxy (MBE) ito growth of Hg2 Cdi- ,Te...thin- films throughout the composition range 0 x $ 0.8. The progress of the Contract has been reported periodically in five interim reports. This final...I separate sources) yielded films with high x values. On the grounds of these observations we do not find ALE suitable for growth of HgCdTe. 2) ALE

Estimating chronic hepatitis C prognosis using transient elastography-based liver stiffness: A systematic review and meta-analysis.

PubMed

Erman, A; Sathya, A; Nam, A; Bielecki, J M; Feld, J J; Thein, H-H; Wong, W W L; Grootendorst, P; Krahn, M D

2018-05-01

Chronic hepatitis C (CHC) is a leading cause of hepatic fibrosis and cirrhosis. The level of fibrosis is traditionally established by histology, and prognosis is estimated using fibrosis progression rates (FPRs; annual probability of progressing across histological stages). However, newer noninvasive alternatives are quickly replacing biopsy. One alternative, transient elastography (TE), quantifies fibrosis by measuring liver stiffness (LSM). Given these developments, the purpose of this study was (i) to estimate prognosis in treatment-naïve CHC patients using TE-based liver stiffness progression rates (LSPR) as an alternative to FPRs and (ii) to compare consistency between LSPRs and FPRs. A systematic literature search was performed using multiple databases (January 1990 to February 2016). LSPRs were calculated using either a direct method (given the difference in serial LSMs and time elapsed) or an indirect method given a single LSM and the estimated duration of infection and pooled using random-effects meta-analyses. For validation purposes, FPRs were also estimated. Heterogeneity was explored by random-effects meta-regression. Twenty-seven studies reporting on 39 groups of patients (N = 5874) were identified with 35 groups allowing for indirect and 8 for direct estimation of LSPR. The majority (~58%) of patients were HIV/HCV-coinfected. The estimated time-to-cirrhosis based on TE vs biopsy was 39 and 38 years, respectively. In univariate meta-regressions, male sex and HIV were positively and age at assessment, negatively associated with LSPRs. Noninvasive prognosis of HCV is consistent with FPRs in predicting time-to-cirrhosis, but more longitudinal studies of liver stiffness are needed to obtain refined estimates. © 2017 John Wiley & Sons Ltd.

[Basic concepts for network meta-analysis].

PubMed

Catalá-López, Ferrán; Tobías, Aurelio; Roqué, Marta

2014-12-01

Systematic reviews and meta-analyses have long been fundamental tools for evidence-based clinical practice. Initially, meta-analyses were proposed as a technique that could improve the accuracy and the statistical power of previous research from individual studies with small sample size. However, one of its main limitations has been the fact of being able to compare no more than two treatments in an analysis, even when the clinical research question necessitates that we compare multiple interventions. Network meta-analysis (NMA) uses novel statistical methods that incorporate information from both direct and indirect treatment comparisons in a network of studies examining the effects of various competing treatments, estimating comparisons between many treatments in a single analysis. Despite its potential limitations, NMA applications in clinical epidemiology can be of great value in situations where there are several treatments that have been compared against a common comparator. Also, NMA can be relevant to a research or clinical question when many treatments must be considered or when there is a mix of both direct and indirect information in the body of evidence. Copyright © 2013 Elsevier España, S.L.U. All rights reserved.

Adjusting for partial verification or workup bias in meta-analyses of diagnostic accuracy studies.

PubMed

de Groot, Joris A H; Dendukuri, Nandini; Janssen, Kristel J M; Reitsma, Johannes B; Brophy, James; Joseph, Lawrence; Bossuyt, Patrick M M; Moons, Karel G M

2012-04-15

A key requirement in the design of diagnostic accuracy studies is that all study participants receive both the test under evaluation and the reference standard test. For a variety of practical and ethical reasons, sometimes only a proportion of patients receive the reference standard, which can bias the accuracy estimates. Numerous methods have been described for correcting this partial verification bias or workup bias in individual studies. In this article, the authors describe a Bayesian method for obtaining adjusted results from a diagnostic meta-analysis when partial verification or workup bias is present in a subset of the primary studies. The method corrects for verification bias without having to exclude primary studies with verification bias, thus preserving the main advantages of a meta-analysis: increased precision and better generalizability. The results of this method are compared with the existing methods for dealing with verification bias in diagnostic meta-analyses. For illustration, the authors use empirical data from a systematic review of studies of the accuracy of the immunohistochemistry test for diagnosis of human epidermal growth factor receptor 2 status in breast cancer patients.

Characteristics and Methodological Quality of Meta-Analyses on Hypertension Treatments-A Cross-Sectional Study.

PubMed

Wu, Xin Yin; Du, Xin Jian; Ho, Robin S T; Lee, Clarence C Y; Yip, Benjamin H K; Wong, Martin C S; Wong, Samuel Y S; Chung, Vincent C H

2017-02-01

Methodological quality of meta-analyses on hypertension treatments can affect treatment decision-making. The authors conducted a cross-sectional study to investigate the methodological quality of meta-analyses on hypertension treatments. One hundred and fifty-eight meta-analyses were identified. Overall, methodological quality was unsatisfactory in the following aspects: comprehensive reporting of financial support (1.9%), provision of included and excluded lists of studies (22.8%), inclusion of grey literature (27.2%), and inclusion of protocols (32.9%). The 126 non-Cochrane meta-analyses had poor performance on almost all the methodological items. Non-Cochrane meta-analyses focused on nonpharmacologic treatments were more likely to consider scientific quality of included studies when making conclusions. The 32 Cochrane meta-analyses generally had good methodological quality except for comprehensive reporting of the sources of support. These results highlight the need for cautious interpretation of these meta-analyses, especially among physicians and policy makers when guidelines are formulated. Future meta-analyses should pay attention to improving these methodological aspects. ©2016 Wiley Periodicals, Inc.

Prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults: systematic review and meta-analysis.

PubMed

Nascimento, C; Di Lorenzo Alho, A T; Bazan Conceição Amaral, C; Leite, R E P; Nitrini, R; Jacob-Filho, W; Pasqualucci, C A; Hokkanen, S R K; Hunter, S; Keage, H; Kovacs, G G; Grinberg, L T; Suemoto, C K

2018-04-01

To perform a systematic review and meta-analysis on the prevalence of transactive response DNA-binding protein 43 (TDP-43) proteinopathy in cognitively normal older adults. We systematically reviewed and performed a meta-analysis on the prevalence of TDP-43 proteinopathy in older adults with normal cognition, evaluated by the Mini-Mental State Examination or the Clinical Dementia Rating. We estimated the overall prevalence of TDP-43 using random-effect models, and stratified by age, sex, sample size, study quality, antibody used to assess TDP-43 aggregates, analysed brain regions, Braak stage, Consortium to Establish a Registry for Alzheimer's Disease score, hippocampal sclerosis and geographic location. A total of 505 articles were identified in the systematic review, and 7 were included in the meta-analysis with 1196 cognitively normal older adults. We found an overall prevalence of TDP-43 proteinopathy of 24%. Prevalence of TDP-43 proteinopathy varied widely across geographic location (North America: 37%, Asia: 29%, Europe: 14%, and Latin America: 11%). Estimated prevalence of TDP-43 proteinopathy also varied according to study quality (quality score >7: 22% vs. quality score <7: 42%), antibody used to assess TDP-43 proteinopathy (native: 18% vs. hyperphosphorylated: 24%) and presence of hippocampal sclerosis (without 24% vs. with hippocampal sclerosis: 48%). Other stratified analyses by age, sex, analysed brain regions, sample size and severity of AD neuropathology showed similar pooled TDP-43 prevalence. Different methodology to access TDP-43, and also differences in lifestyle and genetic factors across different populations could explain our results. Standardization of TDP-43 measurement, and future studies about the impact of genetic and lifestyle characteristics on the development of neurodegenerative diseases are needed. © 2017 British Neuropathological Society.

Effects of intranasal oxytocin on symptoms of schizophrenia: A multivariate Bayesian meta-analysis.

PubMed

Williams, Donald R; Bürkner, Paul-Christian

2017-01-01

Schizophrenia is a heterogeneous disorder in which psychiatric symptoms are classified into two general subgroups-positive and negative symptoms. Current antipsychotic drugs are effective for treating positive symptoms, whereas negative symptoms are less responsive. Since the neuropeptide oxytocin (OT) has been shown to mediate social behavior in animals and humans, it has been used as an experimental therapeutic for treating schizophrenia and in particular negative symptoms which includes social deficits. Through eight randomized controlled trials (RCTs) and three meta-analyses, evidence for an effect of intranasal OT (IN-OT) has been inconsistent. We therefore conducted an updated meta-analysis that offers several advantages when compared to those done previously: (1) We used a multivariate analysis which allows for comparisons between symptoms and accounts for correlations between symptoms; (2) We controlled for baseline scores; (3) We used a fully Bayesian framework that allows for assessment of evidence in favor of the null hypothesis using Bayes factors; and (4) We addressed inconsistencies in the primary studies and previous meta-analyses. Eight RCTs (n=238) were included in the present study and we found that oxytocin did not improve any aspect of symptomology in schizophrenic patients and there was moderate evidence in favor of the null (no effect of oxytocin) for negative symptoms. Multivariate comparisons between symptom types revealed that oxytocin was not especially beneficial for treating negative symptoms. The effect size estimates were not moderated, publication bias was absent, and our estimates were robust to sensitivity analyses. These results suggest that IN-OT is not an effective therapeutic for schizophrenia. Copyright © 2016 Elsevier Ltd. All rights reserved.

Effect of low-magnitude whole-body vibration combined with alendronate in ovariectomized rats: a random controlled osteoporosis prevention study.

PubMed

Chen, Guo-Xian; Zheng, Shuai; Qin, Shuai; Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting

2014-01-01

Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45-55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture.

Effect of Low-Magnitude Whole-Body Vibration Combined with Alendronate in Ovariectomized Rats: A Random Controlled Osteoporosis Prevention Study

PubMed Central

Zhong, Zhao-Ming; Wu, Xiu-Hua; Huang, Zhi-Ping; Li, Wei; Ding, Ruo-Ting; Yu, Hui; Chen, Jian-Ting

2014-01-01

Background Alendronate (ALE) is a conventional drug used to treat osteoporosis. Low-magnitude whole-body vibration (WBV) exercise has been developed as a potential treatment for osteoporosis. The aim of this study was to investigate whether low-magnitude WBV could enhance the protective effect of ALE on bone properties in ovariectomized rats. Methods A total of 128 Sprague-Dawley rats were randomly divided into five groups (SHAM, OVX+VEH, OVX+WBV, OVX + ALE, OVX+WBV+ALE). The level of WBV applied was 0.3 g at 45–55 Hz for 20 min/day, 5 day/week and for 3 months. ALE was administered in dose of 1 mg/Kg once a week. Every four weeks eight rats from each group were sacrificed and their blood and both tibiae were harvested. The expression of osteocalcin and CTX in serum was measured by enzyme-linked immunosorbent assay (ELISA) and the tibiae were subjected to metaphyseal three-point bending and μCT analysis. Results Osteocalcin rose after ovariectomy and was not appreciably changed by either alendronate or WBV alone or in combination. Alendronate treatment significantly prevented an increase in CTX. WBV alone treatment did not alter this effect. Compared with the OVX+WBV group, nearly all tested indices such as the BV/TV, TV apparent, Tb.N, Tb.Th, and Conn.D were higher in the OVX+ALE group at week 12.Compared with the OVX+WBV group, certain tested indices such as BV/TV, TV apparent, Tb.N, and Con.D, were higher in the OVX+WBV+ALE group at week 12. At week 12, tibiae treated with WBV+ALE exhibited a significantly higher Fmax compared to the OVX+VEH group, and a significant difference was also found in energy absorption between the OVX+WBV+ALE and OVX+VEH groups. Conclusions Compared with the WBV, ALE was more effective at preventing bone loss and improved the trabecular architecture. However, WBV enhanced the effect of alendronate in ovariectomized rats by inducing further improvements in trabecular architecture. PMID:24796785

Meta-Analysis of Effect Sizes Reported at Multiple Time Points Using General Linear Mixed Model.

PubMed

Musekiwa, Alfred; Manda, Samuel O M; Mwambi, Henry G; Chen, Ding-Geng

2016-01-01

Meta-analysis of longitudinal studies combines effect sizes measured at pre-determined time points. The most common approach involves performing separate univariate meta-analyses at individual time points. This simplistic approach ignores dependence between longitudinal effect sizes, which might result in less precise parameter estimates. In this paper, we show how to conduct a meta-analysis of longitudinal effect sizes where we contrast different covariance structures for dependence between effect sizes, both within and between studies. We propose new combinations of covariance structures for the dependence between effect size and utilize a practical example involving meta-analysis of 17 trials comparing postoperative treatments for a type of cancer, where survival is measured at 6, 12, 18 and 24 months post randomization. Although the results from this particular data set show the benefit of accounting for within-study serial correlation between effect sizes, simulations are required to confirm these results.

Analysis and meta-analysis of single-case designs with a standardized mean difference statistic: a primer and applications.

PubMed

Shadish, William R; Hedges, Larry V; Pustejovsky, James E

2014-04-01

This article presents a d-statistic for single-case designs that is in the same metric as the d-statistic used in between-subjects designs such as randomized experiments and offers some reasons why such a statistic would be useful in SCD research. The d has a formal statistical development, is accompanied by appropriate power analyses, and can be estimated using user-friendly SPSS macros. We discuss both advantages and disadvantages of d compared to other approaches such as previous d-statistics, overlap statistics, and multilevel modeling. It requires at least three cases for computation and assumes normally distributed outcomes and stationarity, assumptions that are discussed in some detail. We also show how to test these assumptions. The core of the article then demonstrates in depth how to compute d for one study, including estimation of the autocorrelation and the ratio of between case variance to total variance (between case plus within case variance), how to compute power using a macro, and how to use the d to conduct a meta-analysis of studies using single-case designs in the free program R, including syntax in an appendix. This syntax includes how to read data, compute fixed and random effect average effect sizes, prepare a forest plot and a cumulative meta-analysis, estimate various influence statistics to identify studies contributing to heterogeneity and effect size, and do various kinds of publication bias analyses. This d may prove useful for both the analysis and meta-analysis of data from SCDs. Copyright © 2013 Society for the Study of School Psychology. Published by Elsevier Ltd. All rights reserved.

Outdoor Air Pollution and COPD-Related Emergency Department Visits, Hospital Admissions, and Mortality: A Meta-Analysis.

PubMed

DeVries, Rebecca; Kriebel, David; Sama, Susan

2017-02-01

A systematic literature review was performed to identify all peer-reviewed literature quantifying the association between short-term exposures of particulate matter <2.5 microns (PM 2.5 ), nitrogen dioxide (NO 2 ), and sulfur dioxide (SO 2 ) and COPD-related emergency department (ED) visits, hospital admissions (HA), and mortality. These results were then pooled for each pollutant through meta-analyses with a random effects model. Subgroup meta-analyses were explored to study the effects of selected lag/averaging times and health outcomes. A total of 37 studies satisfied our inclusion criteria, contributing to a total of approximately 1,115,000 COPD-related acute events (950,000 HAs, 80,000 EDs, and 130,000 deaths) to our meta-estimates. An increase in PM 2.5 of 10 ug/m 3 was associated with a 2.5% (95% CI: 1.6-3.4%) increased risk of COPD-related ED and HA, an increase of 10 ug/m 3 in NO 2 was associated with a 4.2% (2.5-6.0%) increase, and an increase of 10 ug/m 3 in SO 2 was associated with a 2.1% (0.7-3.5%) increase. The strength of these pooled effect estimates, however, varied depending on the selected lag/averaging time between exposure and outcome. Similar pooled effects were estimated for each pollutant and COPD-related mortality. These results suggest an ongoing threat to the health of COPD patients from both outdoor particulates and gaseous pollutants. Ambient outdoor concentrations of PM 2.5 , NO 2 , and SO 2 were significantly and positively associated with both COPD-related morbidity and mortality.

Traumatic brain injury and adverse life events: Group differences in young adults injured as children.

PubMed

Taylor, Olivia; Barrett, Robert D; McLellan, Tracey; McKinlay, Audrey

2015-01-01

To investigate whether individuals with a history of traumatic brain injury (TBI) experience a greater number of adverse life events (ALE) compared to controls, to identify significant predictors of experiencing ALE and whether the severity of childhood TBI negatively influences adult life outcomes. A total of 167 individuals, injured prior to age 18, 5 or more years post-injury and 18 or more years of age, were recruited in the Canterbury region of New Zealand, with 124 having sustained childhood TBI (62 mild, 62 moderate/severe) and 43 orthopaedic injury controls. Participants were asked about ALE they had experienced and other adult life outcomes. Individuals with a history of TBI experienced more ALE compared to controls. The number of ALE experienced by an individual was associated with more visits to the doctor, lower education level and lower satisfaction with material standard of living. Childhood TBI is associated with an increased number of ALE and adult negative life outcomes. Understanding factors that contribute to negative outcomes following childhood TBI will provide an avenue for rehabilitation and support to reduce any problems in adulthood.

The influence of emotional interference on cognitive control: A meta-analysis of neuroimaging studies using the emotional Stroop task.

PubMed

Song, Sensen; Zilverstand, Anna; Song, Hongwen; d'Oleire Uquillas, Federico; Wang, Yongming; Xie, Chao; Cheng, Li; Zou, Zhiling

2017-05-18

The neural correlates underlying the influence of emotional interference on cognitive control remain a topic of discussion. Here, we assessed 16 neuroimaging studies that used an emotional Stroop task and that reported a significant interaction effect between emotion (stimulus type) and cognitive conflict. There were a total of 330 participants, equaling 132 foci for an activation likelihood estimation (ALE) analysis. Results revealed consistent brain activation patterns related to emotionally-salient stimuli (as compared to emotionally-neutral trials) during cognitive conflict trials [incongruent trials (with task-irrelevant information interfering), versus congruent/baseline trials (less disturbance from task-irrelevant information)], that span the lateral prefrontal cortex (dorsolateral prefrontal cortex and inferior frontal gyrus), the medial prefrontal cortex, and the dorsal anterior cingulate cortex. Comparing mild emotional interference trials (without semantic conflict) versus intense emotional interference trials (with semantic conflict), revealed that while concurrent activation in similar brain regions as mentioned above was found for intense emotional interference trials, activation for mild emotional interference trials was only found in the precentral/postcentral gyrus. These data provide evidence for the potential neural mechanisms underlying emotional interference on cognitive control, and further elucidate an important distinction in brain activation patterns for different levels of emotional conflict across emotional Stroop tasks.

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description

PubMed Central

McGonigle, John; Murphy, Anna; Paterson, Louise M; Reed, Laurence J; Nestor, Liam; Nash, Jonathan; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy SA; Newbould, Rexford; Orban, Csaba; Smith, Dana G; Taylor, Eleanor M; Waldman, Adam D; Robbins, Trevor W; Deakin, JF William; Nutt, David J; Lingford-Hughes, Anne R; Suckling, John

2016-01-01

Objectives: We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction – reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. Experimental design: Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. Conclusions: In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres. PMID:27703042

The ICCAM platform study: An experimental medicine platform for evaluating new drugs for relapse prevention in addiction. Part B: fMRI description.

PubMed

McGonigle, John; Murphy, Anna; Paterson, Louise M; Reed, Laurence J; Nestor, Liam; Nash, Jonathan; Elliott, Rebecca; Ersche, Karen D; Flechais, Remy Sa; Newbould, Rexford; Orban, Csaba; Smith, Dana G; Taylor, Eleanor M; Waldman, Adam D; Robbins, Trevor W; Deakin, Jf William; Nutt, David J; Lingford-Hughes, Anne R; Suckling, John

2017-01-01

We aimed to set up a robust multi-centre clinical fMRI and neuropsychological platform to investigate the neuropharmacology of brain processes relevant to addiction - reward, impulsivity and emotional reactivity. Here we provide an overview of the fMRI battery, carried out across three centres, characterizing neuronal response to the tasks, along with exploring inter-centre differences in healthy participants. Three fMRI tasks were used: monetary incentive delay to probe reward sensitivity, go/no-go to probe impulsivity and an evocative images task to probe emotional reactivity. A coordinate-based activation likelihood estimation (ALE) meta-analysis was carried out for the reward and impulsivity tasks to help establish region of interest (ROI) placement. A group of healthy participants was recruited from across three centres (total n=43) to investigate inter-centre differences. Principle observations: The pattern of response observed for each of the three tasks was consistent with previous studies using similar paradigms. At the whole brain level, significant differences were not observed between centres for any task. In developing this platform we successfully integrated neuroimaging data from three centres, adapted validated tasks and applied whole brain and ROI approaches to explore and demonstrate their consistency across centres.

Serum uric acid and cancer mortality and incidence: a systematic review and meta-analysis.

PubMed

Dovell, Frances; Boffetta, Paolo

2018-07-01

Elevated serum uric acid (SUA) is a marker of chronic inflammation and has been suggested to be associated with increased risk of cancer, but its antioxidant capacity would justify an anticancer effect. Previous meta-analyses did not include all available results. We conducted a systematic review of prospective studies on SUA level and risk of all cancers and specific cancers, a conducted a meta-analysis based on random-effects models for high versus low SUA level as well as for an increase in 1 mg/dl SUA. The relative risk of all cancers for high versus low SUA level was 1.11 (95% confidence interval: 0.94-1.27; 11 risk estimates); that for a mg/dl increase in SUA level was 1.03 (95% confidence interval: 0.99-1.07). Similar results were obtained for lung cancer (six risk estimates) and colon cancer (four risk estimates). Results for other cancers were sparse. Elevated SUA levels appear to be associated with a modest increase in overall cancer risk, although the combined risk estimate did not reach the formal level of statistical significance. Results for specific cancers were limited and mainly negative.

Spent Fuel Ratio Estimates from Numerical Models in ALE3D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Margraf, J. D.; Dunn, T. A.

Potential threat of intentional sabotage of spent nuclear fuel storage facilities is of significant importance to national security. Paramount is the study of focused energy attacks on these materials and the potential release of aerosolized hazardous particulates into the environment. Depleted uranium oxide (DUO 2) is often chosen as a surrogate material for testing due to the unreasonable cost and safety demands for conducting full-scale tests with real spent nuclear fuel. To account for differences in mechanical response resulting in changes to particle distribution it is necessary to scale the DUO 2 results to get a proper measure for spentmore » fuel. This is accomplished with the spent fuel ratio (SFR), the ratio of respirable aerosol mass released due to identical damage conditions between a spent fuel and a surrogate material like depleted uranium oxide (DUO 2). A very limited number of full-scale experiments have been carried out to capture this data, and the oft-questioned validity of the results typically leads to overly-conservative risk estimates. In the present work, the ALE3D hydrocode is used to simulate DUO 2 and spent nuclear fuel pellets impacted by metal jets. The results demonstrate an alternative approach to estimate the respirable release fraction of fragmented nuclear fuel.« less

Untreated maternal syphilis and adverse outcomes of pregnancy: a systematic review and meta-analysis

PubMed Central

Kamb, Mary L; Newman, Lori M; Mark, Jennifer; Broutet, Nathalie; Hawkes, Sarah J

2013-01-01

Abstract Objective To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among untreated women with syphilis and women without syphilis. Methods PubMed, EMBASE and Cochrane Libraries were searched for literature assessing adverse pregnancy outcomes among untreated women with seroreactivity for Treponema pallidum infection and non-seroreactive women. Adverse pregnancy outcomes were fetal loss or stillbirth, neonatal death, prematurity or low birth weight, clinical evidence of syphilis and infant death. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Findings Of the 3258 citations identified, only six, all case-control studies, were included in the analysis. Pooled estimates showed that among untreated pregnant women with syphilis, fetal loss and stillbirth were 21% more frequent, neonatal deaths were 9.3% more frequent and prematurity or low birth weight were 5.8% more frequent than among women without syphilis. Of the infants of mothers with untreated syphilis, 15% had clinical evidence of congenital syphilis. The single study that estimated infant death showed a 10% higher frequency among infants of mothers with syphilis. Substantial heterogeneity was found across studies in the estimates of all adverse outcomes for both women with syphilis (66.5% [95% confidence interval, CI: 58.0–74.1]; I2 = 91.8%; P < 0.001) and women without syphilis (14.3% [95% CI: 11.8–17.2]; I2 = 95.9%; P < 0.001). Conclusion Untreated maternal syphilis is associated with adverse pregnancy outcomes. These findings can inform policy decisions on resource allocation for the detection of syphilis and its timely treatment in pregnant women. PMID:23476094

Prevalence of neuropathic pain in knee or hip osteoarthritis: A systematic review and meta-analysis.

PubMed

French, Helen P; Smart, Keith M; Doyle, Frank

2017-08-01

Discordance between radiographic and pain severity in osteoarthritis (OA) has led researchers to investigate other pain mechanisms, including neuropathic pain. Accurate identification of any neuropathic pain in hip or knee OA is important for appropriate management, but neuropathic pain prevalence is unknown. We aimed to obtain an overall prevalence estimate by systematically reviewing and meta-analysing the prevalence of neuropathic pain in people with hip or knee OA. Observational studies which measured neuropathic pain in people aged 18 years and older with hip or knee OA were considered for inclusion. Electronic databases were searched up to February 2016. Two reviewers independently identified eligible studies and assessed methodological quality. Prevalence estimates and 95% confidence intervals were calculated using random effects meta-analytic techniques. Nine studies met the inclusion criteria. Study samples were from general population, hospital and community settings and all used self-report questionnaires to determine neuropathic pain. The overall prevalence estimate was 23% (95% CI: 10-39%), with considerable heterogeneity (I 2 = 97.9%, p < 0.001). This estimate was largely unchanged with subgroup analyses based on index joint, questionnaire type, setting and consideration of other potential causes of neuropathic pain. However, the estimate for two studies that excluded other potential causes of neuropathic pain was substantially higher (32%, 95% CI: 29-35%). Neuropathic pain prevalence in people with knee or hip OA is considerable at 23%, and may be higher after other potential causes of neuropathic pain are excluded. Concerns regarding the validity of neuropathic pain questionnaires, selection bias, methodological quality and study heterogeneity suggest caution with interpretation of these findings. Prevalence studies using standardised criteria for neuropathic pain are required. Copyright © 2017 Elsevier Inc. All rights reserved.

Tuberculose péritonéale pseudo tumorale mimant un cancer ovarien: un diagnostic différentiel important à considérer

PubMed Central

Moukit, Mounir; Fadel, Fatimazahra Ait El; Kouach, Jaouad; Babahabib, Abdellah; Dehayni, Mohammed; Rahali, Driss Moussaoui

2016-01-01

La tuberculose est une maladie infectieuse curable qui peut simuler dans sa localisation péritonéale un cancer ovarien avancé conduisant ainsi à une chirurgie étendue et inutile souvent chez des femmes en âge de reproduction. Nous rapportons un nouveau cas de tuberculose péritonéale pseudo tumorale chez une patiente âgée de 43 ans chez qui le diagnostic d’un cancer ovarien avec carcinose péritonéale avait été suspecté. La laparotomie exploratrice avec examen histologique extemporané ont permis de confirmer le diagnostic de tuberculose péritonéale. La patiente a bien répondu au traitement antituberculeux selon le protocole 2ERHZ/4RH. PMID:28292155

The Influence of Judgment Calls on Meta-Analytic Findings.

PubMed

Tarrahi, Farid; Eisend, Martin

2016-01-01

Previous research has suggested that judgment calls (i.e., methodological choices made in the process of conducting a meta-analysis) have a strong influence on meta-analytic findings and question their robustness. However, prior research applies case study comparison or reanalysis of a few meta-analyses with a focus on a few selected judgment calls. These studies neglect the fact that different judgment calls are related to each other and simultaneously influence the outcomes of a meta-analysis, and that meta-analytic findings can vary due to non-judgment call differences between meta-analyses (e.g., variations of effects over time). The current study analyzes the influence of 13 judgment calls in 176 meta-analyses in marketing research by applying a multivariate, multilevel meta-meta-analysis. The analysis considers simultaneous influences from different judgment calls on meta-analytic effect sizes and controls for alternative explanations based on non-judgment call differences between meta-analyses. The findings suggest that judgment calls have only a minor influence on meta-analytic findings, whereas non-judgment call differences between meta-analyses are more likely to explain differences in meta-analytic findings. The findings support the robustness of meta-analytic results and conclusions.

Sensitivity subgroup analysis based on single-center vs. multi-center trial status when interpreting meta-analyses pooled estimates: the logical way forward.

PubMed

Alexander, Paul E; Bonner, Ashley J; Agarwal, Arnav; Li, Shelly-Anne; Hariharan, Abishek; Izhar, Zain; Bhatnagar, Neera; Alba, Carolina; Akl, Elie A; Fei, Yutong; Guyatt, Gordon H; Beyene, Joseph

2016-06-01

Prior studies regarding whether single-center trial estimates are larger than multi-center are equivocal. We examined the extent to which single-center trials yield systematically larger effects than multi-center trials. We searched the 119 core clinical journals and the Cochrane Database of Systematic Reviews for meta-analyses (MAs) of randomized controlled trials (RCTs) published during 2012. In this meta-epidemiologic study, for binary variables, we computed the pooled ratio of ORs (RORs), and for continuous outcomes mean difference in standardized mean differences (SMDs), we conducted weighted random-effects meta-regression and random-effects MA modeling. Our primary analyses were restricted to MAs that included at least five RCTs and in which at least 25% of the studies used each of single trial center (SC) and more trial center (MC) designs. We identified 81 MAs for the odds ratio (OR) and 43 for the SMD outcome measures. Based on our analytic plan, our primary analysis (core) is based on 25 MAs/241 RCTs (binary outcome) and 18 MAs/173 RCTs (continuous outcome). Based on the core analysis, we found no difference in magnitude of effect between SC and MC for binary outcomes [RORs: 1.02; 95% confidence interval (CI): 0.83, 1.24; I(2) 20.2%]. Effect sizes were systematically larger for SC than MC for the continuous outcome measure (mean difference in SMDs: -0.13; 95% CI: -0.21, -0.05; I(2) 0%). Our results do not support prior findings of larger effects in SC than MC trials addressing binary outcomes but show a very similar small increase in effect in SC than MC trials addressing continuous outcomes. Authors of systematic reviews would be wise to include all trials irrespective of SC vs. MC design and address SC vs. MC status as a possible explanation of heterogeneity (and consider sensitivity analyses). Copyright © 2015 Elsevier Inc. All rights reserved.

Twenty years of meta-analyses in orthopaedic surgery: has quality kept up with quantity?

PubMed

Dijkman, Bernadette G; Abouali, Jihad A K; Kooistra, Bauke W; Conter, Henry J; Poolman, Rudolf W; Kulkarni, Abhaya V; Tornetta, Paul; Bhandari, Mohit

2010-01-01

As the number of studies in the literature is increasing, orthopaedic surgeons highly depend on meta-analyses as their primary source of scientific evidence. The objectives of this review were to assess the scientific quality and number of published meta-analyses on orthopaedics-related topics over time. We conducted, in duplicate and independently, a systematic review of published meta-analyses in orthopaedics in the years 2005 and 2008 and compared them with a previous systematic review of meta-analyses from 1969 to 1999. A search of electronic databases (MEDLINE, EMBASE, and the Cochrane Database of Systematic Reviews) was performed to identify meta-analyses published in 2005 and 2008. We searched bibliographies and contacted content experts to identify additional relevant studies. Two investigators independently assessed the quality of the studies, using the Oxman and Guyatt index, and abstracted relevant data. We included forty-five and forty-four meta-analyses from 2005 and 2008, respectively. While the number of meta-analyses increased fivefold from 1999 to 2008, the mean quality score did not change significantly over time (p = 0.067). In the later years, a significantly lower proportion of meta-analyses had methodological flaws (56% in 2005 and 68% in 2008) compared with meta-analyses published prior to 2000 (88%) (p = 0.006). In 2005 and 2008, respectively, 18% and 30% of the meta-analyses had major to extensive flaws in their methodology. Studies from 2008 with positive conclusions used and described appropriate criteria for the validity assessment less often than did those with negative results. The use of random-effects and fixed-effects models as pooling methods became more popular toward 2008. Although the methodological quality of orthopaedic meta-analyses has increased in the past twenty years, a substantial proportion continues to show major to extensive flaws. As the number of published meta-analyses is increasing, a routine checklist for scientific quality should be used in the peer-review process to ensure methodological standards for publication.

Interrater reliability of schizoaffective disorder compared with schizophrenia, bipolar disorder, and unipolar depression - A systematic review and meta-analysis.

PubMed

Santelmann, Hanno; Franklin, Jeremy; Bußhoff, Jana; Baethge, Christopher

2016-10-01

Schizoaffective disorder is a common diagnosis in clinical practice but its nosological status has been subject to debate ever since it was conceptualized. Although it is key that diagnostic reliability is sufficient, schizoaffective disorder has been reported to have low interrater reliability. Evidence based on systematic review and meta-analysis methods, however, is lacking. Using a highly sensitive literature search in Medline, Embase, and PsycInfo we identified studies measuring the interrater reliability of schizoaffective disorder in comparison to schizophrenia, bipolar disorder, and unipolar disorder. Out of 4126 records screened we included 25 studies reporting on 7912 patients diagnosed by different raters. The interrater reliability of schizoaffective disorder was moderate (meta-analytic estimate of Cohen's kappa 0.57 [95% CI: 0.41-0.73]), and substantially lower than that of its main differential diagnoses (difference in kappa between 0.22 and 0.19). Although there was considerable heterogeneity, analyses revealed that the interrater reliability of schizoaffective disorder was consistently lower in the overwhelming majority of studies. The results remained robust in subgroup and sensitivity analyses (e.g., diagnostic manual used) as well as in meta-regressions (e.g., publication year) and analyses of publication bias. Clinically, the results highlight the particular importance of diagnostic re-evaluation in patients diagnosed with schizoaffective disorder. They also quantify a widely held clinical impression of lower interrater reliability and agree with earlier meta-analysis reporting low test-retest reliability. Copyright © 2016. Published by Elsevier B.V.

Gender and telomere length: Systematic review and meta-analysis☆

PubMed Central

Gardner, Michael; Bann, David; Wiley, Laura; Cooper, Rachel; Hardy, Rebecca; Nitsch, Dorothea; Martin-Ruiz, Carmen; Shiels, Paul; Sayer, Avan Aihie; Barbieri, Michelangela; Bekaert, Sofie; Bischoff, Claus; Brooks-Wilson, Angela; Chen, Wei; Cooper, Cyrus; Christensen, Kaare; De Meyer, Tim; Deary, Ian; Der, Geoff; Roux, Ana Diez; Fitzpatrick, Annette; Hajat, Anjum; Halaschek-Wiener, Julius; Harris, Sarah; Hunt, Steven C.; Jagger, Carol; Jeon, Hyo-Sung; Kaplan, Robert; Kimura, Masayuki; Lansdorp, Peter; Li, Changyong; Maeda, Toyoki; Mangino, Massimo; Nawrot, Tim S.; Nilsson, Peter; Nordfjall, Katarina; Paolisso, Giuseppe; Ren, Fu; Riabowol, Karl; Robertson, Tony; Roos, Goran; Staessen, Jan A.; Spector, Tim; Tang, Nelson; Unryn, Brad; van der Harst, Pim; Woo, Jean; Xing, Chao; Yadegarfar, Mohammad E.; Park, Jae Yong; Young, Neal; Kuh, Diana; von Zglinicki, Thomas; Ben-Shlomo, Yoav

2015-01-01

Background It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. Methods We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Results Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p = 1.00) or cell type (p = 0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Conclusions Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. PMID:24365661

Gender and telomere length: systematic review and meta-analysis.

PubMed

Gardner, Michael; Bann, David; Wiley, Laura; Cooper, Rachel; Hardy, Rebecca; Nitsch, Dorothea; Martin-Ruiz, Carmen; Shiels, Paul; Sayer, Avan Aihie; Barbieri, Michelangela; Bekaert, Sofie; Bischoff, Claus; Brooks-Wilson, Angela; Chen, Wei; Cooper, Cyrus; Christensen, Kaare; De Meyer, Tim; Deary, Ian; Der, Geoff; Diez Roux, Ana; Fitzpatrick, Annette; Hajat, Anjum; Halaschek-Wiener, Julius; Harris, Sarah; Hunt, Steven C; Jagger, Carol; Jeon, Hyo-Sung; Kaplan, Robert; Kimura, Masayuki; Lansdorp, Peter; Li, Changyong; Maeda, Toyoki; Mangino, Massimo; Nawrot, Tim S; Nilsson, Peter; Nordfjall, Katarina; Paolisso, Giuseppe; Ren, Fu; Riabowol, Karl; Robertson, Tony; Roos, Goran; Staessen, Jan A; Spector, Tim; Tang, Nelson; Unryn, Brad; van der Harst, Pim; Woo, Jean; Xing, Chao; Yadegarfar, Mohammad E; Park, Jae Yong; Young, Neal; Kuh, Diana; von Zglinicki, Thomas; Ben-Shlomo, Yoav

2014-03-01

It is widely believed that females have longer telomeres than males, although results from studies have been contradictory. We carried out a systematic review and meta-analyses to test the hypothesis that in humans, females have longer telomeres than males and that this association becomes stronger with increasing age. Searches were conducted in EMBASE and MEDLINE (by November 2009) and additional datasets were obtained from study investigators. Eligible observational studies measured telomeres for both females and males of any age, had a minimum sample size of 100 and included participants not part of a diseased group. We calculated summary estimates using random-effects meta-analyses. Heterogeneity between studies was investigated using sub-group analysis and meta-regression. Meta-analyses from 36 cohorts (36,230 participants) showed that on average females had longer telomeres than males (standardised difference in telomere length between females and males 0.090, 95% CI 0.015, 0.166; age-adjusted). There was little evidence that these associations varied by age group (p=1.00) or cell type (p=0.29). However, the size of this difference did vary by measurement methods, with only Southern blot but neither real-time PCR nor Flow-FISH showing a significant difference. This difference was not associated with random measurement error. Telomere length is longer in females than males, although this difference was not universally found in studies that did not use Southern blot methods. Further research on explanations for the methodological differences is required. Copyright © 2013. Published by Elsevier Inc.

Meta-analysis of diagnostic accuracy studies in mental health

PubMed Central

Takwoingi, Yemisi; Riley, Richard D; Deeks, Jonathan J

2015-01-01

Objectives To explain methods for data synthesis of evidence from diagnostic test accuracy (DTA) studies, and to illustrate different types of analyses that may be performed in a DTA systematic review. Methods We described properties of meta-analytic methods for quantitative synthesis of evidence. We used a DTA review comparing the accuracy of three screening questionnaires for bipolar disorder to illustrate application of the methods for each type of analysis. Results The discriminatory ability of a test is commonly expressed in terms of sensitivity (proportion of those with the condition who test positive) and specificity (proportion of those without the condition who test negative). There is a trade-off between sensitivity and specificity, as an increasing threshold for defining test positivity will decrease sensitivity and increase specificity. Methods recommended for meta-analysis of DTA studies --such as the bivariate or hierarchical summary receiver operating characteristic (HSROC) model --jointly summarise sensitivity and specificity while taking into account this threshold effect, as well as allowing for between study differences in test performance beyond what would be expected by chance. The bivariate model focuses on estimation of a summary sensitivity and specificity at a common threshold while the HSROC model focuses on the estimation of a summary curve from studies that have used different thresholds. Conclusions Meta-analyses of diagnostic accuracy studies can provide answers to important clinical questions. We hope this article will provide clinicians with sufficient understanding of the terminology and methods to aid interpretation of systematic reviews and facilitate better patient care. PMID:26446042

Meta-analyses with industry involvement are massively published and report no caveats for antidepressants.

PubMed

Ebrahim, Shanil; Bance, Sheena; Athale, Abha; Malachowski, Cindy; Ioannidis, John P A

2016-02-01

To identify the impact of industry involvement in the publication and interpretation of meta-analyses of antidepressant trials in depression. Using MEDLINE, we identified all meta-analyses evaluating antidepressants for depression published in January 2007-March 2014. We extracted data pertaining to author affiliations, conflicts of interest, and whether the conclusion of the abstract included negative statements on whether the antidepressant(s) were effective or safe. We identified 185 eligible meta-analyses. Fifty-four meta-analyses (29%) had authors who were employees of the assessed drug manufacturer, and 147 (79%) had some industry link (sponsorship or authors who were industry employees and/or had conflicts of interest). Only 58 meta-analyses (31%) had negative statements in the concluding statement of the abstract. Meta-analyses including an author who were employees of the manufacturer of the assessed drug were 22-fold less likely to have negative statements about the drug than other meta-analyses [1/54 (2%) vs. 57/131 (44%); P < 0.001]. There is a massive production of meta-analyses of antidepressants for depression authored by or linked to the industry, and they almost never report any caveats about antidepressants in their abstracts. Our findings add a note of caution for meta-analyses with ties to the manufacturers of the assessed products. Copyright © 2016 Elsevier Inc. All rights reserved.

A Genome-Wide Association Meta-Analysis of Attention-Deficit/Hyperactivity Disorder Symptoms in Population-Based Paediatric Cohorts

PubMed Central

Groen-Blokhuis, Maria M.; Pourcain, Beate St.; Greven, Corina U.; Pappa, Irene; Tiesler, Carla M.T.; Ang, Wei; Nolte, Ilja M.; Vilor-Tejedor, Natalia; Bacelis, Jonas; Ebejer, Jane L.; Zhao, Huiying; Davies, Gareth E.; Ehli, Erik A.; Evans, David M.; Fedko, Iryna O.; Guxens, Mònica; Hottenga, Jouke-Jan; Hudziak, James J.; Jugessur, Astanand; Kemp, John P.; Krapohl, Eva; Martin, Nicholas G.; Murcia, Mario; Myhre, Ronny; Ormel, Johan; Ring, Susan M.; Standl, Marie; Stergiakouli, Evie; Stoltenberg, Camilla; Thiering, Elisabeth; Timpson, Nicholas J.; Trzaskowski, Maciej; van der Most, Peter J.; Wang, Carol; Nyholt, Dale R.; Medland, Sarah E.; Neale, Benjamin; Jacobsson, Bo; Sunyer, Jordi; Hartman, Catharina A.; Whitehouse, Andrew J.O.; Pennell, Craig E.; Heinrich, Joachim; Plomin, Robert; Smith, George Davey; Tiemeier, Henning; Posthuma, Danielle; Boomsma, Dorret I.

2016-01-01

Objective To elucidate the influence of common genetic variants on childhood attention-deficit/hyperactivity disorder (ADHD) symptoms, to identify genetic variants that explain its high heritability, and to investigate the genetic overlap of ADHD symptom scores with ADHD diagnosis. Method Within the EArly Genetics and Lifecourse Epidemiology (EAGLE) consortium, genome-wide single nucleotide polymorphisms (SNPs) and ADHD symptom scores were available for 17,666 children (< 13 years) from nine population-based cohorts. SNP-based heritability was estimated in data from the three largest cohorts. Meta-analysis based on genome-wide association (GWA) analyses with SNPs was followed by gene-based association tests, and the overlap in results with a meta-analysis in the Psychiatric Genomics Consortium (PGC) case-control ADHD study was investigated. Results SNP-based heritability ranged from 5% to 34%, indicating that variation in common genetic variants influences ADHD symptom scores. The meta-analysis did not detect genome-wide significant SNPs, but three genes, lying close to each other with SNPs in high linkage disequilibrium (LD), showed a gene-wide significant association (p values between 1.46×10-6 and 2.66×10-6). One gene, WASL, is involved in neuronal development. Both SNP- and gene-based analyses indicated overlap with the PGC meta-analysis results with the genetic correlation estimated at 0.96. Conclusion The SNP-based heritability for ADHD symptom scores indicates a polygenic architecture and genes involved in neurite outgrowth are possibly involved. Continuous and dichotomous measures of ADHD appear to assess a genetically common phenotype. A next step is to combine data from population-based and case-control cohorts in genetic association studies to increase sample size and improve statistical power for identifying genetic variants. PMID:27663945

Meta-analysis to determine the effects of plant disease management measures: review and case studies on soybean and apple.

PubMed

Ngugi, Henry K; Esker, Paul D; Scherm, Harald

2011-01-01

The continuing exponential increase in scientific knowledge, the growing availability of large databases containing raw or partially annotated information, and the increased need to document impacts of large-scale research and funding programs provide a great incentive for integrating and adding value to previously published (or unpublished) research through quantitative synthesis. Meta-analysis has become the standard for quantitative evidence synthesis in many disciplines, offering a broadly accepted and statistically powerful framework for estimating the magnitude, consistency, and homogeneity of the effect of interest across studies. Here, we review previous and current uses of meta-analysis in plant pathology with a focus on applications in epidemiology and disease management. About a dozen formal meta-analyses have been published in the plant pathological literature in the past decade, and several more are currently in progress. Three broad research questions have been addressed, the most common being the comparative efficacy of chemical treatments for managing disease and reducing yield loss across environments. The second most common application has been the quantification of relationships between disease intensity and yield, or between different measures of disease, across studies. Lastly, meta-analysis has been applied to assess factors affecting pathogen-biocontrol agent interactions or the effectiveness of biological control of plant disease or weeds. In recent years, fixed-effects meta-analysis has been largely replaced by random- (or mixed-) effects analysis owing to the statistical benefits associated with the latter and the wider availability of computer software to conduct these analyses. Another recent trend has been the more common use of multivariate meta-analysis or meta-regression to analyze the impacts of study-level independent variables (moderator variables) on the response of interest. The application of meta-analysis to practical problems in epidemiology and disease management is illustrated with case studies from our work on Phakopsora pachyrhizi on soybean and Erwinia amylovora on apple. We show that although meta-analyses are often used to corroborate and validate general conclusions drawn from more traditional, qualitative reviews, they can also reveal new patterns and interpretations not obvious from individual studies.

Differences in effectiveness of the active living every day program for older adults with arthritis.

PubMed

Sperber, Nina R; Allen, Kelli D; Devellis, Brenda M; Devellis, Robert F; Lewis, Megan A; Callahan, Leigh F

2013-10-01

The authors explored whether demographic and psychosocial variables predicted differences in physical activity for participants with arthritis in a trial of Active Living Every Day (ALED). Participants (N = 280) from 17 community sites were randomized into ALED or usual care. The authors assessed participant demographic characteristics, self-efficacy, outcome expectations, pain, fatigue, and depressive symptoms at baseline and physical activity frequency at 20-wk follow-up. They conducted linear regression with interaction terms (Baseline Characteristic × Randomization Group). Being female (p ≤ .05), less depressed (p ≤ .05), or younger (p ≤ .10) was associated with more frequent posttest physical activity for ALED participants than for those with usual care. Higher education was associated with more physical activity for both ALED and usual-care groups. ALED was particularly effective for female, younger, and less depressed participants. Further research should determine whether modifications could produce better outcomes in other subgroups.

The use of meta-analysis or research synthesis to combine driving simulation or naturalistic study results on driver distraction.

PubMed

Caird, Jeff K; Johnston, Katherine A; Willness, Chelsea R; Asbridge, Mark

2014-06-01

Three important and inter-related topics are addressed in this paper. First, the importance of meta-analysis and research synthesis methods to combine studies on traffic safety, in general, and on driver distraction, in particular, is briefly reviewed. Second, naturalistic, epidemiologic, and driving simulation studies on driver distraction are used to illustrate convergent and divergent results that have accumulated thus far in this domain of research. In particular, mobile phone conversation, passenger presence, and text messaging naturalistic studies use meta-analyses and research syntheses to illustrate important patterns of results that are in need of more in-depth study. Third, a number of driver distraction study limitations such as poorly defined dependent variables, lack of methodological detail, and omission of statistical information prevent the integration of many studies into meta-analyses. In addition, the overall quality of road safety studies suffers from these same limitations and suggestions for improvement are made to guide researchers and reviewers. Practical Applications. The use of research synthesis and meta-analysis provide comprehensive estimates of the impact of distractions on driving performance, which can be used to guide public policy and future research. Copyright © 2014 National Safety Council and Elsevier Ltd. All rights reserved.

Does personality predict health and well-being? A metasynthesis.

PubMed

Strickhouser, Jason E; Zell, Ethan; Krizan, Zlatan

2017-08-01

To derive a robust and comprehensive estimate of the overall relation between Big Five personality traits and health variables using metasynthesis (i.e., second-order meta-analysis). Thirty-six meta-analyses, which collectively provided 150 meta-analytic effects from over 500,000 participants, met criteria for inclusion in the metasynthesis. Information on methodological quality as well as the type of health outcome, unreliability adjustment, population sampled, health outcome source, personality source, and research design was extracted from each meta-analysis. An unweighted model was used to aggregate data across meta-analyses. When entered simultaneously, the Big Five traits were moderately associated with overall health (multiple R = .35). Personality-health relations were larger when examining mental health outcomes than physical health outcomes or health-related behaviors and when researchers adjusted for measurement unreliability, used self-report as opposed to other-report Big Five scales, or focused on clinical as opposed to nonclinical samples. Further, effects were larger among agreeableness, conscientiousness, and neuroticism than extraversion or openness to experience. This metasynthesis provides among the most compelling evidence to date that personality predicts overall health and well-being. In addition, it may inform research on the mechanisms by which personality impacts health as well as research on the structure of personality. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Evaluation of the United States Department of Agriculture Northeast Area-Wide Tick Control Project by Meta-Analysis

PubMed Central

Brei, Brandon; George, John E.; Pound, J. Mathews; Miller, J. Allen; Daniels, Thomas J.; Falco, Richard C.; Stafford, Kirby C.; Schulze, Terry L.; Mather, Thomas N.; Carroll, John F.; Fish, Durland

2009-01-01

Abstract As part of the Northeast Area-wide Tick Control Project (NEATCP), meta-analyses were performed using pooled data on the extent of tick-vector control achieved through seven concurrent studies, conducted within five states, using U.S. Department of Agriculture “4-Poster” devices to deliver targeted-acaricide to white-tailed deer. Although reductions in the abundance of all life-stages of Ixodes scapularis were the measured outcomes, this study focused on metrics associated with I. scapularis nymphal tick densities as this measure has consistently proven to directly correlate with human risk of acquiring Lyme disease. Since independent tick sampling schemes were undertaken at each of the five environmentally distinct study locations, a meta-analytic approach permitted estimation of a single true control-effect size for each treatment year of the NEATCP. The control-effect is expressed as the annual percent I. scapularis nymphal control most consistent with meta-analysis data for each treatment year. Our meta-analyses indicate that by the sixth treatment year, the NEATCP effectively reduced the relative density of I. scapularis nymphs by 71% on the 5.14 km2 treatment sites, corresponding to a 71% lower relative entomologic risk index for acquiring Lyme disease. PMID:19650737

Gender differences in depression in representative national samples: Meta-analyses of diagnoses and symptoms.

PubMed

Salk, Rachel H; Hyde, Janet S; Abramson, Lyn Y

2017-08-01

In 2 meta-analyses on gender differences in depression in nationally representative samples, we advance previous work by including studies of depression diagnoses and symptoms to (a) estimate the magnitude of the gender difference in depression across a wide array of nations and ages; (b) use a developmental perspective to elucidate patterns of gender differences across the life span; and (c) incorporate additional theory-driven moderators (e.g., gender equity). For major depression diagnoses and depression symptoms, respectively, we meta-analyzed data from 65 and 95 articles and their corresponding national data sets, representing data from 1,716,195 and 1,922,064 people in over 90 different nations. Overall, odds ratio (OR) = 1.95, 95% confidence interval (CI) [1.88, 2.03], and d = 0.27 [0.26, 0.29]. Age was the strongest predictor of effect size. The gender difference for diagnoses emerged earlier than previously thought, with OR = 2.37 at age 12. For both meta-analyses, the gender difference peaked in adolescence (OR = 3.02 for ages 13-15, and d = 0.47 for age 16) but then declined and remained stable in adulthood. Cross-national analyses indicated that larger gender differences were found in nations with greater gender equity, for major depression, but not depression symptoms. The gender difference in depression represents a health disparity, especially in adolescence, yet the magnitude of the difference indicates that depression in men should not be overlooked. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Trends in published meta-analyses in cancer research, 2008-2013.

PubMed

Qadir, Ximena V; Clyne, Mindy; Lam, Tram Kim; Khoury, Muin J; Schully, Sheri D

2017-01-01

In order to capture trends in the contribution of epidemiology to cancer research, we describe an online meta-analysis database resource for cancer clinical and population research and illustrate trends and descriptive detail of cancer meta-analyses from 2008 through 2013. A total of 4,686 cancer meta-analyses met our inclusion criteria. During this 6-year period, a fivefold increase was observed in the yearly number of meta-analyses. Fifty-six percent of meta-analyses concerned observational studies, mostly of cancer risk, more than half of which were genetic studies. The major cancer sites were breast, colorectal, and digestive. This online database for Cancer Genomics and Epidemiology Navigator will be continuously updated to allow investigators to quickly navigate the meta-analyses emerging from cancer epidemiology studies and cancer clinical trials.

Phosphates behaviours in conversion of FP chlorides

NASA Astrophysics Data System (ADS)

Amamoto, I.; Kofuji, H.; Myochin, M.; Takasaki, Y.; Terai, T.

2009-06-01

The spent electrolyte of the pyroprocessing by metal electrorefining method should be considered for recycling after removal of fission products (FP) such as, alkali metals (AL), alkaline earth metals (ALE), and/or rare earth elements (REE), to reduce the volume of high-level radioactive waste. Among the various methods suggested for this purpose is precipitation by converting FP from chlorides to phosphates. Authors have been carrying out the theoretical analysis and experiment showing the behaviours of phosphate precipitates so as to estimate the feasibility of this method. From acquired results, it was found that AL except lithium and ALE are unlikely to form phosphate precipitates. However their conversion behaviours including REE were compatible with the theoretical analysis; in the case of LaPO 4 as one of the REE precipitates, submicron-size particles could be observed while that of Li 3PO 4 was larger; the precipitates were apt to grow larger at higher temperature; etc.

Meta-analysis: prevalence of HIV infection and syphilis among MSM in China.

PubMed

Gao, L; Zhang, L; Jin, Q

2009-09-01

The prevalence of HIV/AIDS and other sexually transmitted diseases is rapidly rising among men who have sex with men (MSM) in China. The aim is to systematically review the published studies and summarise the estimates of HIV prevalence among MSM in China. Published articles, both in English and in Chinese, on HIV prevalence among MSM in China until 15 September 2008 were systematically reviewed. Meta-analysis was used to quantitatively summarise the estimates, and the prevalence of syphilis presented in the included studies was also analysed. Twenty-six eligible studies, published during 2001-2008, were included in this review. Their results were frequently heterogeneous. The meta-analyses showed that MSM form a high-risk population for HIV infection in China with a summary prevalence of 2.5% (95% CI 0.9% to 3.3%). A much higher prevalence of syphilis (9.1%) may indicate a potential of more severe HIV epidemic in the future because of their common high-risk behaviours. MSM are a high-risk population for HIV infection in China. An effective strategy for prevention and control is required for this specific population. Differences between sampling methods, sample sizes and study locations may explain some of the inconsistencies found in the included studies.

Predicted effect size of lisdexamfetamine treatment of attention deficit/hyperactivity disorder (ADHD) in European adults: Estimates based on indirect analysis using a systematic review and meta-regression analysis.

PubMed

Fridman, M; Hodgkins, P S; Kahle, J S; Erder, M H

2015-06-01

There are few approved therapies for adults with attention-deficit/hyperactivity disorder (ADHD) in Europe. Lisdexamfetamine (LDX) is an effective treatment for ADHD; however, no clinical trials examining the efficacy of LDX specifically in European adults have been conducted. Therefore, to estimate the efficacy of LDX in European adults we performed a meta-regression of existing clinical data. A systematic review identified US- and Europe-based randomized efficacy trials of LDX, atomoxetine (ATX), or osmotic-release oral system methylphenidate (OROS-MPH) in children/adolescents and adults. A meta-regression model was then fitted to the published/calculated effect sizes (Cohen's d) using medication, geographical location, and age group as predictors. The LDX effect size in European adults was extrapolated from the fitted model. Sensitivity analyses performed included using adult-only studies and adding studies with placebo designs other than a standard pill-placebo design. Twenty-two of 2832 identified articles met inclusion criteria. The model-estimated effect size of LDX for European adults was 1.070 (95% confidence interval: 0.738, 1.401), larger than the 0.8 threshold for large effect sizes. The overall model fit was adequate (80%) and stable in the sensitivity analyses. This model predicts that LDX may have a large treatment effect size in European adults with ADHD. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

Over two hundred million injuries to anterior teeth attributable to large overjet: a meta-analysis.

PubMed

Petti, Stefano

2015-02-01

The association between large overjet and traumatic dental injuries (TDIs) to anterior teeth is documented. However, observational studies are discrepant and generalizability (i.e. external validity) of meta-analyses is limited. Therefore, this meta-analysis sought to reconcile such discrepancies seeking to provide reliable risk estimates which could be generalizable at global level. Literature search (years 1990-2014) was performed (Scopus, GOOGLE Scholar, Medline). Selected primary studies were divided into subsets: 'primary teeth, overjet threshold 3-4 mm' (Primary3); 'permanent teeth, overjet threshold 3-4 mm' (Permanent3); 'permanent teeth, overjet threshold 6 ± 1 mm' (Permanent6). The adjusted odds ratios (ORs) were extracted. To obtain the highest level of reliability (i.e. internal validity), the pooled OR estimates were assessed accounting for between-study heterogeneity, publication bias and confounding. Result robustness was investigated with sensitivity and subgroup analyses. Fifty-four primary studies from Africa, America, Asia and Europe were included. The sampled individuals were children, adolescents and adults. Overall, there were >10 000 patients with TDI. The pooled OR estimates resulted 2.31 (95% confidence interval - 95CI, 1.01-5.27), 2.01 (95CI, 1.39-2.91) and 2.24 (95CI, 1.56-3.21) for Primary3, Permanent3 and Permant6, respectively. Sensitivity and subgroup analyses corroborated these estimates. Reliability and generalizability of pooled ORs were high enough and made it possible to assess that the fraction of global TDIs attributable to large overjet is 21.8% (95CI, 9.7-34.5%) and that large overjet is co-responsible for 235 008 000 global TDI cases (95CI, 104,760,000-372,168,000). This high global burden of TDI suggests that preventive measures must be implemented in patients with large overjet. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Association between Adult Height and Risk of Colorectal, Lung, and Prostate Cancer: Results from Meta-analyses of Prospective Studies and Mendelian Randomization Analyses

PubMed Central

Khankari, Nikhil K.; Shu, Xiao-Ou; Wen, Wanqing; Kraft, Peter; Lindström, Sara; Peters, Ulrike; Schildkraut, Joellen; Schumacher, Fredrick; Bofetta, Paolo; Risch, Angela; Bickeböller, Heike; Amos, Christopher I.; Easton, Douglas; Gruber, Stephen B.; Haiman, Christopher A.; Hunter, David J.; Chanock, Stephen J.; Pierce, Brandon L.; Zheng, Wei

2016-01-01

Background Observational studies examining associations between adult height and risk of colorectal, prostate, and lung cancers have generated mixed results. We conducted meta-analyses using data from prospective cohort studies and further carried out Mendelian randomization analyses, using height-associated genetic variants identified in a genome-wide association study (GWAS), to evaluate the association of adult height with these cancers. Methods and Findings A systematic review of prospective studies was conducted using the PubMed, Embase, and Web of Science databases. Using meta-analyses, results obtained from 62 studies were summarized for the association of a 10-cm increase in height with cancer risk. Mendelian randomization analyses were conducted using summary statistics obtained for 423 genetic variants identified from a recent GWAS of adult height and from a cancer genetics consortium study of multiple cancers that included 47,800 cases and 81,353 controls. For a 10-cm increase in height, the summary relative risks derived from the meta-analyses of prospective studies were 1.12 (95% CI 1.10, 1.15), 1.07 (95% CI 1.05, 1.10), and 1.06 (95% CI 1.02, 1.11) for colorectal, prostate, and lung cancers, respectively. Mendelian randomization analyses showed increased risks of colorectal (odds ratio [OR] = 1.58, 95% CI 1.14, 2.18) and lung cancer (OR = 1.10, 95% CI 1.00, 1.22) associated with each 10-cm increase in genetically predicted height. No association was observed for prostate cancer (OR = 1.03, 95% CI 0.92, 1.15). Our meta-analysis was limited to published studies. The sample size for the Mendelian randomization analysis of colorectal cancer was relatively small, thus affecting the precision of the point estimate. Conclusions Our study provides evidence for a potential causal association of adult height with the risk of colorectal and lung cancers and suggests that certain genetic factors and biological pathways affecting adult height may also affect the risk of these cancers. PMID:27598322

Systematic Review and Meta-Analysis of Antimicrobial Treatment Effect Estimation in Complicated Urinary Tract Infection

PubMed Central

Li, Gang; Mitrani-Gold, Fanny S.; Kurtinecz, Milena; Wetherington, Jeffrey; Tomayko, John F.; Mundy, Linda M.

2013-01-01

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations. PMID:23939900

Income and child mortality in developing countries: a systematic review and meta-analysis.

PubMed

O'Hare, Bernadette; Makuta, Innocent; Chiwaula, Levison; Bar-Zeev, Naor

2013-10-01

We aimed to quantify the relationship between national income and infant and under-five mortality in developing countries. We conducted a systematic literature search of studies that examined the relationship between income and child mortality (infant and/or under-five mortality) and meta-analysed their results. Developing countries. Child mortality (infant and /or under-five mortality). The systematic literature search identified 24 studies, which produced 38 estimates that examined the impact of income on the mortality rates. Using meta-analysis, we produced pooled estimates of the relationship between income and mortality. The pooled estimate of the relationship between income and infant mortality before adjusting for covariates is -0.95 (95% CI -1.34 to -0.57) and that for under-five mortality is -0.45 (95% CI -0.79 to -0.11). After adjusting for covariates, pooled estimate of the relationship between income and infant mortality is -0.33 (-0.39 to -0.26) while the estimate for under-five mortality is -0.28 (-0.37 to -0.19). If a country has an infant mortality of 50 per 1000 live births and the gross domestic product per capita purchasing power parity increases by 10%, the infant mortality will decrease to 45 per 1000 live births. Income is an important determinant of child survival and this work provides a pooled estimate for the relationship.

Quantifying the impact of between-study heterogeneity in multivariate meta-analyses

PubMed Central

Jackson, Dan; White, Ian R; Riley, Richard D

2012-01-01

Measures that quantify the impact of heterogeneity in univariate meta-analysis, including the very popular I2 statistic, are now well established. Multivariate meta-analysis, where studies provide multiple outcomes that are pooled in a single analysis, is also becoming more commonly used. The question of how to quantify heterogeneity in the multivariate setting is therefore raised. It is the univariate R2 statistic, the ratio of the variance of the estimated treatment effect under the random and fixed effects models, that generalises most naturally, so this statistic provides our basis. This statistic is then used to derive a multivariate analogue of I2, which we call . We also provide a multivariate H2 statistic, the ratio of a generalisation of Cochran's heterogeneity statistic and its associated degrees of freedom, with an accompanying generalisation of the usual I2 statistic, . Our proposed heterogeneity statistics can be used alongside all the usual estimates and inferential procedures used in multivariate meta-analysis. We apply our methods to some real datasets and show how our statistics are equally appropriate in the context of multivariate meta-regression, where study level covariate effects are included in the model. Our heterogeneity statistics may be used when applying any procedure for fitting the multivariate random effects model. Copyright © 2012 John Wiley & Sons, Ltd. PMID:22763950

Do you see what I see? Optical morphology and visual capability of ‘disco’ clams (Ctenoides ales)

PubMed Central

Dubielzig, Richard R.; Schobert, Charles S.; Teixeira, Leandro B.; Li, Jingchun

2017-01-01

ABSTRACT The ‘disco’ clam Ctenoides ales (Finlay, 1927) is a marine bivalve that has a unique, vivid flashing display that is a result of light scattering by silica nanospheres and rapid mantle movement. The eyes of C. ales were examined to determine their visual capabilities and whether the clams can see the flashing of conspecifics. Similar to the congener C. scaber, C. ales exhibits an off-response (shadow reflex) and an on-response (light reflex). In field observations, a shadow caused a significant increase in flash rate from a mean of 3.9 Hz to 4.7 Hz (P=0.0016). In laboratory trials, a looming stimulus, which increased light intensity, caused a significant increase in flash rate from a median of 1.8 Hz to 2.2 Hz (P=0.0001). Morphological analysis of the eyes of C. ales revealed coarsely-packed photoreceptors lacking sophisticated structure, resulting in visual resolution that is likely too low to detect the flashing of conspecifics. As the eyes of C. ales are incapable of perceiving conspecific flashing, it is likely that their vision is instead used to detect predators. PMID:28396488

Variation in the Gender Gap in Inactive and Active Life Expectancy by the Definition of Inactivity Among Older Adults.

PubMed

Malhotra, Rahul; Chan, Angelique; Ajay, Shweta; Ma, Stefan; Saito, Yasuhiko

2016-10-01

To assess variation in gender gap (female-male) in inactive life expectancy (IALE) and active life expectancy (ALE) by definition of inactivity. Inactivity, among older Singaporeans, was defined as follows: Scenario 1-health-related difficulty in activities of daily living (ADLs); Scenario 2-health-related difficulty in ADLs/instrumental ADLs (IADLs); Scenario 3-health-related difficulty in ADLs/IADLs or non-health-related non-performance of IADLs. Multistate life tables computed IALE and ALE at age 60, testing three hypotheses: In all scenarios, life expectancy, absolute and relative IALE, and absolute ALE are higher for females (Hypothesis 1 [H1]); gender gap in absolute and relative IALE expands, and in absolute ALE, it contracts in Scenario 2 versus 1 (Hypothesis 2 [H2]); gender gap in absolute and relative IALE decreases, and in absolute ALE, it increases in Scenario 3 versus 2 (Hypothesis 3 [H3]). H1 was supported in Scenarios 1 and 3 but not Scenario 2. Both H2 and H3 were supported. Definition of inactivity influences gender gap in IALE and ALE. © The Author(s) 2016.

Financial ties and concordance between results and conclusions in meta-analyses: retrospective cohort study.

PubMed

Yank, Veronica; Rennie, Drummond; Bero, Lisa A

2007-12-08

To determine whether financial ties to one drug company are associated with favourable results or conclusions in meta-analyses on antihypertensive drugs. Retrospective cohort study. Meta-analyses published up to December 2004 that were not duplicates and evaluated the effects of antihypertensive drugs compared with any comparator on clinical end points in adults. Financial ties were categorised as one drug company compared with all others. The main outcomes were the results and conclusions of meta-analyses, with both outcomes separately categorised as being favourable or not favourable towards the study drug. We also collected data on characteristics of meta-analyses that the literature suggested might be associated with favourable results or conclusions. 124 meta-analyses were included in the study, 49 (40%) of which had financial ties to one drug company. On univariate logistic regression analyses, meta-analyses of better methodological quality were more likely to have favourable results (odds ratio 1.16, 95% confidence interval 1.07 to 1.27). Although financial ties to one drug company were not associated with favourable results, such ties constituted the only characteristic significantly associated with favourable conclusions (4.09, 1.30 to 12.83). When controlling for other characteristics of meta-analyses in multiple logistic regression analyses, meta-analyses that had financial ties to one drug company remained more likely to report favourable conclusions (5.11, 1.54 to 16.92). Meta-analyses on antihypertensive drugs and with financial ties to one drug company are not associated with favourable results but are associated with favourable conclusions.

Russia-specific relative risks and their effects on the estimated alcohol-attributable burden of disease.

PubMed

Shield, Kevin D; Rehm, Jürgen

2015-05-10

Alcohol consumption is a major risk factor for the burden of disease globally. This burden is estimated using Relative Risk (RR) functions for alcohol from meta-analyses that use data from all countries; however, for Russia and surrounding countries, country-specific risk data may need to be used. The objective of this paper is to compare the estimated burden of alcohol consumption calculated using Russia-specific alcohol RRs with the estimated burden of alcohol consumption calculated using alcohol RRs from meta-analyses. Data for 2012 on drinking indicators were calculated based on the Global Information System on Alcohol and Health. Data for 2012 on mortality, Years of Life Lost, Years Lived with Disability, and Disability-Adjusted Life Years (DALYs) lost by cause were obtained by country from the World Health Organization. Alcohol Population-Attributable Fractions (PAFs) were calculated based on a risk modelling methodology from Russia. These PAFs were compared to PAFs calculated using methods applied for all other countries. The 95% Uncertainty Intervals (UIs) for the alcohol PAFs were calculated using a Monte Carlo-like method. Using Russia-specific alcohol RR functions, in Russia in 2012 alcohol caused an estimated 231,900 deaths (95% UI: 185,600 to 278,200) (70,800 deaths among women and 161,100 deaths among men) and 13,295,000 DALYs lost (95% UI: 11,242,000 to 15,348,000) (3,670,000 DALYs lost among women and 9,625,000 DALYs lost among men) among people 0 to 64 years of age. This compares to an estimated 165,600 deaths (95% UI: 97,200 to 228,100) (29,700 deaths among women and 135,900 deaths among men) and 10,623,000 DALYs lost (95% UI: 7,265,000 to 13,754,000) (1,783,000 DALYs lost among women and 8,840,000 DALYs lost among men) among people 0 to 64 years of age caused by alcohol when non-Russia-specific alcohol RRs were used. Results indicate that if the Russia-specific RRs are used when estimating the health burden attributable to alcohol consumption in Russia, then the total estimated burden will be more than if RRs from meta-analyses are used. Furthermore, additional research is needed to understand which aspects of the Russian style of drinking cause the most harm.

Daily potassium intake and sodium-to-potassium ratio in the reduction of blood pressure: a meta-analysis of randomized controlled trials.

PubMed

Binia, Aristea; Jaeger, Jonathan; Hu, Youyou; Singh, Anurag; Zimmermann, Diane

2015-08-01

To evaluate the efficacy of daily potassium intake on decreasing blood pressure in non-medicated normotensive or hypertensive patients, and to determine the relationship between potassium intake, sodium-to-potassium ratio and reduction in blood pressure. Mixed-effect meta-analyses and meta-regression models. Medline and the references of previous meta-analyses. Randomized controlled trials with potassium supplementation, with blood pressure as the primary outcome, in non-medicated patients. Fifteen randomized controlled trials of potassium supplementation in patients without antihypertensive medication were selected for the meta-analyses (917 patients). Potassium supplementation resulted in reduction of SBP by 4.7 mmHg [95% confidence interval (CI) 2.4-7.0] and DBP by 3.5 mmHg (95% CI 1.3-5.7) in all patients. The effect was found to be greater in hypertensive patients, with a reduction of SBP by 6.8 mmHg (95% CI 4.3-9.3) and DBP by 4.6 mmHg (95% CI 1.8-7.5). Meta-regression analysis showed that both increased daily potassium excretion and decreased sodium-to-potassium ratio were associated with blood pressure reduction (P < 0.05). Increased total daily potassium urinary excretion from 60 to 100 mmol/day and decrease of sodium-to-potassium ratio were shown to be necessary to explain the estimated effect. Potassium supplementation is associated with reduction of blood pressure in patients who are not on antihypertensive medication, and the effect is significant in hypertensive patients. The reduction in blood pressure significantly correlates with decreased daily urinary sodium-to-potassium ratio and increased urinary potassium. Patients with elevated blood pressure may benefit from increased potassium intake along with controlled or decreased sodium intake.

Nalmefene for the management of alcohol dependence: review on its pharmacology, mechanism of action and meta-analysis on its clinical efficacy.

PubMed

Mann, Karl; Torup, Lars; Sørensen, Per; Gual, Antoni; Swift, Robert; Walker, Brendan; van den Brink, Wim

2016-12-01

Nalmefene, a mu- and delta-opioid receptor (MOR, DOR) antagonist and a partial kappa-opioid receptor (KOR) agonist, is approved in the European Union and other countries for the reduction of alcohol consumption in alcohol dependent patients with a high drinking risk level according to WHO ("target population"). This review presents an overview of nalmefene׳s pharmacology, its mechanisms of action and a meta-analysis on its efficacy in reducing alcohol consumption. The review was based on a systematic search of the literature. Random effects meta-analyses were performed on published and unpublished trials directed at drinking reduction using the changes in heavy drinking days (HDDs) and daily total alcohol consumption (TAC) from baseline to the primary endpoint. For each included study and each dose, Hedges' g was used as an unbiased estimator of the standardised mean differences between nalmefene and placebo. Preclinical data suggests that nalmefene counters alcohol-induced dysregulations of the MOR/endorphine and the KOR/dynorphin system. Evidence further suggests that reduced alcohol consumption is an effective treatment strategy that appeals to patients not ready for abstinence. Finally, meta-analyses confirmed the efficacy of 20mg nalmefene for reducing HDDs in the ITT population (Hedge׳s g=-0.20; 95% CI -0.30 to -0.09) and the target population (Hedge׳s g=-0.33; 95% CI -0.48 to -0.18). Similar results were seen for TAC. Several meta-analyses, including this new meta-analysis, support nalmefene׳s efficacy in reducing alcohol consumption. In conclusion, because it does not require abstinence, this treatment has the potential to motivate more patients for treatment and thus helps to address a major public health concern. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

A note on variance estimation in random effects meta-regression.

PubMed

Sidik, Kurex; Jonkman, Jeffrey N

2005-01-01

For random effects meta-regression inference, variance estimation for the parameter estimates is discussed. Because estimated weights are used for meta-regression analysis in practice, the assumed or estimated covariance matrix used in meta-regression is not strictly correct, due to possible errors in estimating the weights. Therefore, this note investigates the use of a robust variance estimation approach for obtaining variances of the parameter estimates in random effects meta-regression inference. This method treats the assumed covariance matrix of the effect measure variables as a working covariance matrix. Using an example of meta-analysis data from clinical trials of a vaccine, the robust variance estimation approach is illustrated in comparison with two other methods of variance estimation. A simulation study is presented, comparing the three methods of variance estimation in terms of bias and coverage probability. We find that, despite the seeming suitability of the robust estimator for random effects meta-regression, the improved variance estimator of Knapp and Hartung (2003) yields the best performance among the three estimators, and thus may provide the best protection against errors in the estimated weights.

Reporting of meta-analyses of randomized controlled trials with a focus on drug safety: an empirical assessment.

PubMed

Hammad, Tarek A; Neyarapally, George A; Pinheiro, Simone P; Iyasu, Solomon; Rochester, George; Dal Pan, Gerald

2013-01-01

Due to the sparse nature of serious drug-related adverse events (AEs), meta-analyses combining data from several randomized controlled trials (RCTs) to evaluate drug safety issues are increasingly being conducted and published, influencing clinical and regulatory decision making. Evaluation of meta-analyses involves the assessment of both the individual constituent trials and the approaches used to combine them. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting framework is designed to enhance the reporting of systematic reviews and meta-analyses. However, PRISMA may not cover all critical elements useful in the evaluation of meta-analyses with a focus on drug safety particularly in the regulatory-public health setting. This work was conducted to (1) evaluate the adherence of a sample of published drug safety-focused meta-analyses to the PRISMA reporting framework, (2) identify gaps in this framework based on key aspects pertinent to drug safety, and (3) stimulate the development and validation of a more comprehensive reporting tool that incorporates elements unique to drug safety evaluation. We selected a sample of meta-analyses of RCTs based on review of abstracts from high-impact journals as well as top medical specialty journals between 2009 and 2011. We developed a preliminary reporting framework based on PRISMA with specific additional reporting elements critical for the evaluation of drug safety meta-analyses of RCTs. The reporting of pertinent elements in each meta-analysis was reviewed independently by two authors; discrepancies in the independent evaluations were resolved through discussions between the two authors. A total of 27 meta-analyses, 12 from highest impact journals, 13 from specialty medical journals, and 2 from Cochrane reviews, were identified and evaluated. The great majority (>85%) of PRISMA elements were addressed in more than half of the meta-analyses reviewed. However, the majority of meta-analyses (>60%) did not address most (>80%) of the additional reporting elements critical for the evaluation of drug safety. Some of these elements were not addressed in any of the reviewed meta-analyses. This review included a sample of meta-analyses, with a focus on drug safety, recently published in high-impact journals; therefore, we may have underestimated the extent of the reporting problem across all meta-analyses of drug safety. Furthermore, temporal trends in reporting could not be evaluated in this review because of the short time interval selected. While the majority of PRISMA elements were addressed by most studies reviewed, the majority of studies did not address most of the additional safety-related elements. These findings highlight the need for the development and validation of a drug safety reporting framework and the importance of the current initiative by the Council for International Organizations of Medical Sciences (CIOMS) to create a guidance document for drug safety information synthesis/meta-analysis, which may improve reporting, conduct, and evaluation of meta-analyses of drug safety and inform clinical and regulatory decision making.

Prevalence of placenta previa among deliveries in Mainland China: A PRISMA-compliant systematic review and meta-analysis.

PubMed

Fan, Dazhi; Wu, Song; Wang, Wen; Xin, Lihong; Tian, Guo; Liu, Li; Feng, Jinping; Guo, Xiaoling; Liu, Zhengping

2016-10-01

Placenta previa is characterized by the abnormal placenta overlying the endocervical os, and it is known as one of the most feared adverse maternal and fetal-neonatal complications in obstetrics. We aimed to obtain overall and regional estimates of placenta previa prevalence among deliveries in Mainland China. The research was performed a systematic review, following the Meta-analysis of observational studies in epidemiology (MOOSE) guidelines for systematic reviews of observational studies, and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement for reporting systematic reviews and meta-analysis. Electronic databases were searched and included hospital-based studies that reported placenta previa prevalence in Mainland China. Random-effects meta-analyses were used to pool prevalence estimates of placenta previa. Meta-regression analyses were performed to explore sources of heterogeneity across the included studies. For exploring the geographical distributions of placenta previa, the ArcGIS software (Esri) was used to construct the map of prevalence. A total of 80 articles and 86 datasets (including 1,298,548 subjects and 14,199 placenta previa cases) from 1965 through 2015 were included. The pooled overall prevalence of placenta previa among deliveries was 1.24% (95% confidence interval [CI], 1.12-1.36) in Mainland China during 1965 to 2015. And, the trend in the prevalence of placenta previa was steady. The occurrence rate of placenta previa in the region groups Northeast, North, Northwest, Central China, East, South, and Southwest was 1.20%, 1.01%, 1.10%, 1.15%, 0.93%, 1.42%, and 2.01%, respectively. The prevalence map based on a geographic information system showed an unequal geographic distribution. The results showed that placenta previa is currently a high-burden disease in Mainland China. This review would be useful for the design of placenta previa planning and implementation adequate health care systems and treatment programs in Mainland China.

Exploring changes over time and characteristics associated with data retrieval across individual participant data meta-analyses: systematic review

PubMed Central

Marson, Anthony G; Davie, Becky; Reynolds, Sally; Williams, Lisa; Smith, Catrin Tudur

2017-01-01

Abstract Objective To investigate whether the success rate of retrieving individual participant data (IPD) for use in IPD meta-analyses has increased over time, and to explore the characteristics associated with IPD retrieval. Design Systematic review of published IPD meta-analyses, supplemented by a reflection of the Cochrane Epilepsy Group’s 20 years’ experience of requesting IPD. Data sources Medline, CENTRAL, Scopus, Web of Science, CINAHL Plus, and PsycINFO. Eligibility criteria for study selection IPD meta-analyses of studies of all designs and all clinical areas published in English. Results 760 IPD meta-analyses which identified studies by systematic methods that had been published between 1987 and 2015 were included. Only 188 (25%) of these IPD meta-analyses retrieved 100% of the eligible IPD for analysis, with 324 (43%) of these IPD meta-analyses retrieving 80% or more of relevant IPD. There is insufficient evidence to suggest that IPD retrieval rates have improved over time. IPD meta-analyses that included only randomised trials, had an authorship policy, included fewer eligible participants, and were conducted outside of the Cochrane Database of Systematic Reviews were associated with a high or complete IPD retrieval rate. There was no association between the source of funding of the IPD meta-analyses and IPD retrieval rate. The IPD retrieval rate of the Cochrane Epilepsy Group has declined from 83% (up to 2005) to 65% (between 2012 and 2015) and the reported reasons for lack of data availability have changed in recent years. Conclusions IPD meta-analyses are considered to be the “gold standard” for the synthesis of data from clinical research studies; however, only 25% of published IPD meta-analyses have had access to all IPD. PMID:28381561

Reappraisal of previously reported meta-analyses on antibiotic prophylaxis for low-risk laparoscopic cholecystectomy: an overview of systematic reviews

PubMed Central

Matsui, Yoichi; Satoi, Sohei; Hirooka, Satoshi; Kosaka, Hisashi; Kawaura, Takayuki; Kitawaki, Tomoki

2018-01-01

Introduction Many researchers have addressed overdosage and inappropriate use of antibiotics. Many meta-analyses have investigated antibiotic prophylaxis for low-risk laparoscopic cholecystectomy with the aim of reducing unnecessary antibiotic use. Most of these meta-analyses have concluded that prophylactic antibiotics are not required for low-risk laparoscopic cholecystectomies. This study aimed to assess the validity of this conclusion by systematically reviewing these meta-analyses. Methods A systematic review was undertaken. Searches were limited to meta-analyses and systematic reviews. PubMed and Cochrane Library electronic databases were searched from inception until March 2016 using the following keyword combinations: ‘antibiotic prophylaxis’, ‘laparoscopic cholecystectomy’ and ‘systematic review or meta-analysis’. Two independent reviewers selected meta-analyses or systematic reviews evaluating prophylactic antibiotics for laparoscopic cholecystectomy. All of the randomised controlled trials (RCTs) analysed in these meta-analyses were also reviewed. Results Seven meta-analyses regarding prophylactic antibiotics for low-risk laparoscopic cholecystectomy that had examined a total of 28 RCTs were included. Review of these meta-analyses revealed 48 miscounts of the number of outcomes. Six RCTs were inappropriate for the meta-analyses; one targeted patients with acute cholecystitis, another measured inappropriate outcomes, the original source of a third was not found and the study protocols of the remaining three were not appropriate for the meta-analyses. After correcting the above miscounts and excluding the six inappropriate RCTs, pooled risk ratios (RRs) were recalculated. These showed that, contrary to what had previously been concluded, antibiotics significantly reduced the risk of postoperative infections. The rates of surgical site, distant and overall infections were all significantly reduced by antibiotic administration (RR (95% CI); 0.71 (0.51 to 0.99), 0.37 (0.19 to 0.73), 0.50 (0.34 to 0.75), respectively). Conclusions Prophylactic antibiotics reduce the incidence of postoperative infections after elective laparoscopic cholecystectomy. PMID:29549197

Alcohol and the risk of sleep apnoea: a systematic review and meta-analysis.

PubMed

Simou, Evangelia; Britton, John; Leonardi-Bee, Jo

2018-02-01

A systematic review and meta-analysis of the association between alcohol consumption and risk of sleep apnoea in adults. We searched Medline, EMBASE and Web of Science databases from 1985 to 2015 for comparative epidemiological studies assessing the relation between alcohol consumption and sleep apnoea. Two authors independently screened and extracted data. Random effects meta-analysis was used to estimate pooled effect sizes with 95% confidence intervals (CI). Heterogeneity was quantified using I 2 and explored using subgroup analyses based on study exposure and outcome measures, quality, design, adjustment for confounders and geographical location. Publication bias was assessed using a funnel plot and Egger's test. We identified 21 studies from which estimates of relative risk could be obtained. Meta-analysis of these estimates demonstrated that higher levels of alcohol consumption increased the risk of sleep apnoea by 25% (RR 1.25, 95%CI 1.13-1.38, I 2  = 82%, p < 0.0001). This estimate's differences were robust in alcohol consumption and sleep apnoea definitions, study design, and quality but was greater in Low and Middle Income Country locations. We detected evidence of publication bias (p = 0.001). A further eight included studies reported average alcohol consumption in people with and without sleep apnoea. Meta-analysis revealed that mean alcohol intake was two units/week higher in those with sleep apnoea, but this difference was not statistically significant (p = 0.41). These findings suggest that alcohol consumption is associated with a higher risk of sleep apnoea, further supporting evidence that reducing alcohol intake is of potential therapeutic and preventive value in this condition. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses--an overview and application of NetMetaXL.

PubMed

Brown, Stephen; Hutton, Brian; Clifford, Tammy; Coyle, Doug; Grima, Daniel; Wells, George; Cameron, Chris

2014-09-29

The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL's interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based.

Annual research review: A meta-analysis of the worldwide prevalence of mental disorders in children and adolescents.

PubMed

Polanczyk, Guilherme V; Salum, Giovanni A; Sugaya, Luisa S; Caye, Arthur; Rohde, Luis A

2015-03-01

The literature on the prevalence of mental disorders affecting children and adolescents has expanded significantly over the last three decades around the world. Despite the field having matured significantly, there has been no meta-analysis to calculate a worldwide-pooled prevalence and to empirically assess the sources of heterogeneity of estimates. We conducted a systematic review of the literature searching in PubMed, PsycINFO, and EMBASE for prevalence studies of mental disorders investigating probabilistic community samples of children and adolescents with standardized assessments methods that derive diagnoses according to the DSM or ICD. Meta-analytical techniques were used to estimate the prevalence rates of any mental disorder and individual diagnostic groups. A meta-regression analysis was performed to estimate the effect of population and sample characteristics, study methods, assessment procedures, and case definition in determining the heterogeneity of estimates. We included 41 studies conducted in 27 countries from every world region. The worldwide-pooled prevalence of mental disorders was 13.4% (CI 95% 11.3-15.9). The worldwide prevalence of any anxiety disorder was 6.5% (CI 95% 4.7-9.1), any depressive disorder was 2.6% (CI 95% 1.7-3.9), attention-deficit hyperactivity disorder was 3.4% (CI 95% 2.6-4.5), and any disruptive disorder was 5.7% (CI 95% 4.0-8.1). Significant heterogeneity was detected for all pooled estimates. The multivariate metaregression analyses indicated that sample representativeness, sample frame, and diagnostic interview were significant moderators of prevalence estimates. Estimates did not vary as a function of geographic location of studies and year of data collection. The multivariate model explained 88.89% of prevalence heterogeneity, but residual heterogeneity was still significant. Additional meta-analysis detected significant pooled difference in prevalence rates according to requirement of funcional impairment for the diagnosis of mental disorders. Our findings suggest that mental disorders affect a significant number of children and adolescents worldwide. The pooled prevalence estimates and the identification of sources of heterogeneity have important implications to service, training, and research planning around the world. © 2015 Association for Child and Adolescent Mental Health.

Methodological Quality of Meta-Analyses: Matched-Pairs Comparison over Time and between Industry-Sponsored and Academic-Sponsored Reports

ERIC Educational Resources Information Center

Lane, Peter W.; Higgins, Julian P. T.; Anagnostelis, Betsy; Anzures-Cabrera, Judith; Baker, Nigel F.; Cappelleri, Joseph C.; Haughie, Scott; Hollis, Sally; Lewis, Steff C.; Moneuse, Patrick; Whitehead, Anne

2013-01-01

Context: Meta-analyses are regularly used to inform healthcare decisions. Concerns have been expressed about the quality of meta-analyses and, in particular, about those supported by the pharmaceutical industry. Objective: The objective of this study is to compare the quality of pharmaceutical-industry-supported meta-analyses with academic…

Less Is Less: A Systematic Review of Graph Use in Meta-Analyses

ERIC Educational Resources Information Center

Schild, Anne H. E.; Voracek, Martin

2013-01-01

Graphs are an essential part of scientific communication. Complex datasets, of which meta-analyses are textbook examples, benefit the most from visualization. Although a number of graph options for meta-analyses exist, the extent to which these are used was hitherto unclear. A systematic review on graph use in meta-analyses in three disciplines…

Early Versus Delayed Motion After Rotator Cuff Repair: A Systematic Review of Overlapping Meta-analyses.

PubMed

Houck, Darby A; Kraeutler, Matthew J; Schuette, Hayden B; McCarty, Eric C; Bravman, Jonathan T

2017-10-01

Previous meta-analyses have been conducted to compare outcomes of early versus delayed motion after rotator cuff repair. To conduct a systematic review of overlapping meta-analyses comparing early versus delayed motion rehabilitation protocols after rotator cuff repair to determine which meta-analyses provide the best available evidence. Systematic review. A systematic review was performed by searching PubMed and Cochrane Library databases. Search terms included "rotator cuff repair," "early passive motion," "immobilization," "rehabilitation protocol," and "meta-analysis." Results were reviewed to determine study eligibility. Patient outcomes and structural healing were extracted from these meta-analyses. Meta-analysis quality was assessed using the Oxman-Guyatt and Quality of Reporting of Meta-analyses (QUOROM) systems. The Jadad decision algorithm was then used to determine which meta-analyses provided the best level of evidence. Seven meta-analyses containing a total of 5896 patients met the eligibility criteria (1 Level I evidence, 4 Level II evidence, 2 Level III evidence). None of these meta-analyses found immobilization to be superior to early motion; however, most studies suggested that early motion would increase range of motion (ROM), thereby reducing time of recovery. Three of these studies suggested that tear size contributed to the choice of rehabilitation to ensure proper healing of the shoulder. A study by Chan et al in 2014 received the highest QUOROM and Oxman-Guyatt scores, and therefore this meta-analysis appeared to have the highest level of evidence. Additionally, a study by Riboh and Garrigues in 2014 was selected as the highest quality study in this systematic review according to the Jadad decision algorithm. The current, best available evidence suggests that early motion improves ROM after rotator cuff repair but increases the risk of rotator cuff retear. Lower quality meta-analyses indicate that tear size may provide a better strategy in determining the correct rehabilitation protocol.

Using structural equation modeling for network meta-analysis.

PubMed

Tu, Yu-Kang; Wu, Yun-Chun

2017-07-14

Network meta-analysis overcomes the limitations of traditional pair-wise meta-analysis by incorporating all available evidence into a general statistical framework for simultaneous comparisons of several treatments. Currently, network meta-analyses are undertaken either within the Bayesian hierarchical linear models or frequentist generalized linear mixed models. Structural equation modeling (SEM) is a statistical method originally developed for modeling causal relations among observed and latent variables. As random effect is explicitly modeled as a latent variable in SEM, it is very flexible for analysts to specify complex random effect structure and to make linear and nonlinear constraints on parameters. The aim of this article is to show how to undertake a network meta-analysis within the statistical framework of SEM. We used an example dataset to demonstrate the standard fixed and random effect network meta-analysis models can be easily implemented in SEM. It contains results of 26 studies that directly compared three treatment groups A, B and C for prevention of first bleeding in patients with liver cirrhosis. We also showed that a new approach to network meta-analysis based on the technique of unrestricted weighted least squares (UWLS) method can also be undertaken using SEM. For both the fixed and random effect network meta-analysis, SEM yielded similar coefficients and confidence intervals to those reported in the previous literature. The point estimates of two UWLS models were identical to those in the fixed effect model but the confidence intervals were greater. This is consistent with results from the traditional pairwise meta-analyses. Comparing to UWLS model with common variance adjusted factor, UWLS model with unique variance adjusted factor has greater confidence intervals when the heterogeneity was larger in the pairwise comparison. The UWLS model with unique variance adjusted factor reflects the difference in heterogeneity within each comparison. SEM provides a very flexible framework for univariate and multivariate meta-analysis, and its potential as a powerful tool for advanced meta-analysis is still to be explored.

The effects of 'ecstasy' (MDMA) on visuospatial memory performance: findings from a systematic review with meta-analyses.

PubMed

Murphy, Philip N; Bruno, Raimondo; Ryland, Ida; Wareing, Michele; Fisk, John E; Montgomery, Catharine; Hilton, Joanne

2012-03-01

To review, with meta-analyses where appropriate, performance differences between ecstasy (3,4-methylenedioxymethamphetamine) users and non-users on a wider range of visuospatial tasks than previously reviewed. Such tasks have been shown to draw upon working memory executive resources. Abstract databases were searched using the United Kingdom National Health Service Evidence Health Information Resource. Inclusion criteria were publication in English language peer-reviewed journals and the reporting of new findings regarding human ecstasy-users' performance on visuospatial tasks. Data extracted included specific task requirements to provide a basis for meta-analyses for categories of tasks with similar requirements. Fifty-two studies were identified for review, although not all were suitable for meta-analysis. Significant weighted mean effect sizes indicating poorer performance by ecstasy users compared with matched controls were found for tasks requiring recall of spatial stimulus elements, recognition of figures and production/reproduction of figures. There was no evidence of a linear relationship between estimated ecstasy consumption and effect sizes. Given the networked nature of processing for spatial and non-spatial visual information, future scanning and imaging studies should focus on brain activation differences between ecstasy users and non-users in the context of specific tasks to facilitate identification of loci of potentially compromised activity in users. Copyright © 2012 John Wiley & Sons, Ltd.

Evaluating gender similarities and differences using metasynthesis.

PubMed

Zell, Ethan; Krizan, Zlatan; Teeter, Sabrina R

2015-01-01

Despite the common lay assumption that males and females are profoundly different, Hyde (2005) used data from 46 meta-analyses to demonstrate that males and females are highly similar. Nonetheless, the gender similarities hypothesis has remained controversial. Since Hyde's provocative report, there has been an explosion of meta-analytic interest in psychological gender differences. We utilized this enormous collection of 106 meta-analyses and 386 individual meta-analytic effects to reevaluate the gender similarities hypothesis. Furthermore, we employed a novel data-analytic approach called metasynthesis (Zell & Krizan, 2014) to estimate the average difference between males and females and to explore moderators of gender differences. The average, absolute difference between males and females across domains was relatively small (d = 0.21, SD = 0.14), with the majority of effects being either small (46%) or very small (39%). Magnitude of differences fluctuated somewhat as a function of the psychological domain (e.g., cognitive variables, social and personality variables, well-being), but remained largely constant across age, culture, and generations. These findings provide compelling support for the gender similarities hypothesis, but also underscore conditions under which gender differences are most pronounced. PsycINFO Database Record (c) 2015 APA, all rights reserved.

Weighing Evidence "Steampunk" Style via the Meta-Analyser.

PubMed

Bowden, Jack; Jackson, Chris

2016-10-01

The funnel plot is a graphical visualization of summary data estimates from a meta-analysis, and is a useful tool for detecting departures from the standard modeling assumptions. Although perhaps not widely appreciated, a simple extension of the funnel plot can help to facilitate an intuitive interpretation of the mathematics underlying a meta-analysis at a more fundamental level, by equating it to determining the center of mass of a physical system. We used this analogy to explain the concepts of weighing evidence and of biased evidence to a young audience at the Cambridge Science Festival, without recourse to precise definitions or statistical formulas and with a little help from Sherlock Holmes! Following on from the science fair, we have developed an interactive web-application (named the Meta-Analyser) to bring these ideas to a wider audience. We envisage that our application will be a useful tool for researchers when interpreting their data. First, to facilitate a simple understanding of fixed and random effects modeling approaches; second, to assess the importance of outliers; and third, to show the impact of adjusting for small study bias. This final aim is realized by introducing a novel graphical interpretation of the well-known method of Egger regression.

Early Response to treatment in Eating Disorders: A Systematic Review and a Diagnostic Test Accuracy Meta-Analysis.

PubMed

Nazar, Bruno Palazzo; Gregor, Louise Kathrine; Albano, Gaia; Marchica, Angelo; Coco, Gianluca Lo; Cardi, Valentina; Treasure, Janet

2017-03-01

Early response to eating disorders treatment is thought to predict a later favourable outcome. A systematic review of the literature and meta-analyses examined the robustness of this concept. The criteria used across studies to define early response were summarised following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Diagnostic Test Accuracy methodology was used to estimate the size of the effect. Findings from 24 studies were synthesized and data from 14 studies were included in the meta-analysis. In Anorexia Nervosa, the odds ratio of early response predicting remission was 4.85(95%CI: 2.94-8.01) and the summary Area Under the Curve (AUC) = .77. In Bulimia Nervosa, the odds ratio was 2.75(95%CI:1.24-6.09) and AUC = .67. For Binge Eating Disorder, the odds ratio was 5.01(95%CI: 3.38-7.42) and AUC = .71. Early behaviour change accurately predicts later symptom remission for Anorexia Nervosa and Binge Eating Disorder but there is less predictive accuracy for Bulimia Nervosa. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association. Copyright © 2016 John Wiley & Sons, Ltd and Eating Disorders Association.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis.

PubMed

Tierney, Jayne F; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L; Burdett, Sarah

2015-11-01

To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. Crown Copyright © 2015. Published by Elsevier Inc. All rights reserved.

How individual participant data meta-analyses have influenced trial design, conduct, and analysis

PubMed Central

Tierney, Jayne F.; Pignon, Jean-Pierre; Gueffyier, Francois; Clarke, Mike; Askie, Lisa; Vale, Claire L.; Burdett, Sarah; Alderson, P.; Askie, L.; Bennett, D.; Burdett, S.; Clarke, M.; Dias, S.; Emberson, J.; Gueyffier, F.; Iorio, A.; Macleod, M.; Mol, B.W.; Moons, C.; Parmar, M.; Perera, R.; Phillips, R.; Pignon, J.P.; Rees, J.; Reitsma, H.; Riley, R.; Rovers, M.; Rydzewska, L.; Schmid, C.; Shepperd, S.; Stenning, S.; Stewart, L.; Tierney, J.; Tudur Smith, C.; Vale, C.; Welge, J.; White, I.; Whiteley, W.

2015-01-01

Objectives To demonstrate how individual participant data (IPD) meta-analyses have impacted directly on the design and conduct of trials and highlight other advantages IPD might offer. Study Design and Setting Potential examples of the impact of IPD meta-analyses on trials were identified at an international workshop, attended by individuals with experience in the conduct of IPD meta-analyses and knowledge of trials in their respective clinical areas. Experts in the field who did not attend were asked to provide any further examples. We then examined relevant trial protocols, publications, and Web sites to verify the impacts of the IPD meta-analyses. A subgroup of workshop attendees sought further examples and identified other aspects of trial design and conduct that may inform IPD meta-analyses. Results We identified 52 examples of IPD meta-analyses thought to have had a direct impact on the design or conduct of trials. After screening relevant trial protocols and publications, we identified 28 instances where IPD meta-analyses had clearly impacted on trials. They have influenced the selection of comparators and participants, sample size calculations, analysis and interpretation of subsequent trials, and the conduct and analysis of ongoing trials, sometimes in ways that would not possible with systematic reviews of aggregate data. We identified additional potential ways that IPD meta-analyses could be used to influence trials. Conclusions IPD meta-analysis could be better used to inform the design, conduct, analysis, and interpretation of trials. PMID:26186982

Ain't necessarily so: review and critique of recent meta-analyses of behavioral medicine interventions in health psychology.

PubMed

Coyne, James C; Thombs, Brett D; Hagedoorn, Mariet

2010-03-01

We examined four meta-analyses of behavioral interventions for adults (Dixon, Keefe, Scipio, Perri, & Abernethy, 2007; Hoffman, Papas, Chatkoff, & Kerns, 2007; Irwin, Cole, & Nicassio, 2006; and Jacobsen, Donovan, Vadaparampil, & Small, 2007) that have appeared in the Evidence Based Treatment Reviews section of Health Psychology. Narrative review. We applied the following criteria to each meta-analysis: (1) whether each meta-analysis was described accurately, adequately, and transparently in the article; (2) whether there was an adequate attempt to deal with methodological quality of the original trials; (3) the extent to which the meta-analysis depended on small, underpowered studies; and (4) the extent to which the meta-analysis provided valid and useful evidence-based recommendations. Across the four meta-analyses, we identified substantial problems with the transparency and completeness with which these meta-analyses were reported, as well as a dependence on small, underpowered trials of generally poor quality. Results of our exercise raise questions about the clinical validity and utility of the conclusions of these meta-analyses. Results should serve as a wake up call to prospective authors, reviewers, and end-users of meta-analyses now appearing in the literature. Copyright 2010 APA, all rights reserved.

Simulating Small-Scale Experiments of In-Tunnel Airblast Using STUN and ALE3D

DOE Office of Scientific and Technical Information (OSTI.GOV)

Neuscamman, Stephanie; Glenn, Lewis; Schebler, Gregory

2011-09-12

This report details continuing validation efforts for the Sphere and Tunnel (STUN) and ALE3D codes. STUN has been validated previously for blast propagation through tunnels using several sets of experimental data with varying charge sizes and tunnel configurations, including the MARVEL nuclear driven shock tube experiment (Glenn, 2001). The DHS-funded STUNTool version is compared to experimental data and the LLNL ALE3D hydrocode. In this particular study, we compare the performance of the STUN and ALE3D codes in modeling an in-tunnel airblast to experimental results obtained by Lunderman and Ohrt in a series of small-scale high explosive experiments (1997).

Worldwide prevalence of adverse pregnancy outcomes associated with in vitro fertilization/intracytoplasmic sperm injection among multiple births: a systematic review and meta-analysis based on cohort studies.

PubMed

Qin, Jia-Bi; Sheng, Xiao-Qi; Wang, Hua; Chen, Guo-Chong; Yang, Jing; Yu, Hong; Yang, Tu-Bao

2017-03-01

To perform a systematic review and meta-analysis of reported estimates of adverse pregnancy outcomes among multiple births conceived with in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI). PubMed, Google Scholar, Cochrane Libraries and Chinese databases were searched through May 2016 for cohort studies assessing adverse pregnancy outcomes associated with IVF/ICSI multiple births. Random-effects meta-analyses were used to calculate pooled estimates of adverse pregnancy outcomes and, where appropriate, heterogeneity was explored in group-specific analyses. Sixty-four studies, with 60,210 IVF/ICSI multiple births and 146,737 spontaneously conceived multiple births, were selected for analysis. Among IVF/ICSI multiple births, the pooled estimates were 51.5% [95% confidence interval (CI): 48.7-54.3] for preterm birth, 12.1% (95% CI: 10.4-14.1) for very preterm birth, 49.8% (95% CI: 47.6-52.0) for low birth weight, 8.4% (95% CI: 7.1-9.9) for very low birth weight, 16.2% (95% CI: 12.9-20.1) for small for gestational age, 3.0% (95% CI: 2.5-3.7) for perinatal mortality and 4.7% (95% CI: 4.0-5.6) for congenital malformations. When the data were restricted to twins, the pooled estimates also showed a high prevalence of adverse outcomes. There was a similar prevalence of poor outcomes among multiple births conceived with IVF/ICSI and naturally (all P ≥ 0.0792). Significant differences in different continents, countries, and income groups were found. The IVF/ICSI multiple pregnancies have a high prevalence of adverse pregnancy outcomes. However, population-wide prospective adverse outcomes registries covering the entire world population for IVF/ICSI pregnancies are needed to determine the exact perinatal prevalence.

Research Review: Test-retest reliability of standardized diagnostic interviews to assess child and adolescent psychiatric disorders: a systematic review and meta-analysis.

PubMed

Duncan, Laura; Comeau, Jinette; Wang, Li; Vitoroulis, Irene; Boyle, Michael H; Bennett, Kathryn

2018-02-19

A better understanding of factors contributing to the observed variability in estimates of test-retest reliability in published studies on standardized diagnostic interviews (SDI) is needed. The objectives of this systematic review and meta-analysis were to estimate the pooled test-retest reliability for parent and youth assessments of seven common disorders, and to examine sources of between-study heterogeneity in reliability. Following a systematic review of the literature, multilevel random effects meta-analyses were used to analyse 202 reliability estimates (Cohen's kappa = ҡ) from 31 eligible studies and 5,369 assessments of 3,344 children and youth. Pooled reliability was moderate at ҡ = .58 (CI 95% 0.53-0.63) and between-study heterogeneity was substantial (Q = 2,063 (df = 201), p < .001 and I 2  = 79%). In subgroup analysis, reliability varied across informants for specific types of psychiatric disorder (ҡ = .53-.69 for parent vs. ҡ = .39-.68 for youth) with estimates significantly higher for parents on attention deficit hyperactivity disorder, oppositional defiant disorder and the broad groupings of externalizing and any disorder. Reliability was also significantly higher in studies with indicators of poor or fair study methodology quality (sample size <50, retest interval <7 days). Our findings raise important questions about the meaningfulness of published evidence on the test-retest reliability of SDIs and the usefulness of these tools in both clinical and research contexts. Potential remedies include the introduction of standardized study and reporting requirements for reliability studies, and exploration of other approaches to assessing and classifying child and adolescent psychiatric disorder. © 2018 Association for Child and Adolescent Mental Health.

Network meta-analysis in health psychology and behavioural medicine: a primer.

PubMed

Molloy, G J; Noone, C; Caldwell, D; Welton, N J; Newell, J

2018-04-05

Progress in the science and practice of health psychology depends on the systematic synthesis of quantitative psychological evidence. Meta-analyses of experimental studies have led to important advances in understanding health-related behaviour change interventions. Fundamental questions regarding such interventions have been systematically investigated through synthesising relevant experimental evidence using standard pairwise meta-analytic procedures that provide reliable estimates of the magnitude, homogeneity and potential biases in effects observed. However, these syntheses only provide information about whether particular types of interventions work better than a control condition or specific alternative approaches. To increase the impact of health psychology on health-related policy-making, evidence regarding the comparative efficacy of all relevant intervention approaches - which may include biomedical approaches - is necessary. With the development of network meta-analysis (NMA), such evidence can be synthesised, even when direct head-to-head trials do not exist. However, care must be taken in its application to ensure reliable estimates of the effect sizes between interventions are revealed. This review paper describes the potential importance of NMA to health psychology, how the technique works and important considerations for its appropriate application within health psychology.

Composition differences between organic and conventional meat: a systematic literature review and meta-analysis.

PubMed

Średnicka-Tober, Dominika; Barański, Marcin; Seal, Chris; Sanderson, Roy; Benbrook, Charles; Steinshamn, Håvard; Gromadzka-Ostrowska, Joanna; Rembiałkowska, Ewa; Skwarło-Sońta, Krystyna; Eyre, Mick; Cozzi, Giulio; Krogh Larsen, Mette; Jordon, Teresa; Niggli, Urs; Sakowski, Tomasz; Calder, Philip C; Burdge, Graham C; Sotiraki, Smaragda; Stefanakis, Alexandros; Yolcu, Halil; Stergiadis, Sokratis; Chatzidimitriou, Eleni; Butler, Gillian; Stewart, Gavin; Leifert, Carlo

2016-03-28

Demand for organic meat is partially driven by consumer perceptions that organic foods are more nutritious than non-organic foods. However, there have been no systematic reviews comparing specifically the nutrient content of organic and conventionally produced meat. In this study, we report results of a meta-analysis based on sixty-seven published studies comparing the composition of organic and non-organic meat products. For many nutritionally relevant compounds (e.g. minerals, antioxidants and most individual fatty acids (FA)), the evidence base was too weak for meaningful meta-analyses. However, significant differences in FA profiles were detected when data from all livestock species were pooled. Concentrations of SFA and MUFA were similar or slightly lower, respectively, in organic compared with conventional meat. Larger differences were detected for total PUFA and n-3 PUFA, which were an estimated 23 (95 % CI 11, 35) % and 47 (95 % CI 10, 84) % higher in organic meat, respectively. However, for these and many other composition parameters, for which meta-analyses found significant differences, heterogeneity was high, and this could be explained by differences between animal species/meat types. Evidence from controlled experimental studies indicates that the high grazing/forage-based diets prescribed under organic farming standards may be the main reason for differences in FA profiles. Further studies are required to enable meta-analyses for a wider range of parameters (e.g. antioxidant, vitamin and mineral concentrations) and to improve both precision and consistency of results for FA profiles for all species. Potential impacts of composition differences on human health are discussed.

The RTEL1 rs6010620 polymorphism and glioma risk: a meta-analysis based on 12 case-control studies.

PubMed

Du, Shu-Li; Geng, Ting-Ting; Feng, Tian; Chen, Cui-Ping; Jin, Tian-Bo; Chen, Chao

2014-01-01

The association between the RTEL1 rs6010620 single nucleotide polymorphism (SNP) and glioma risk has been extensively studied. However, the results remain inconclusive. To further examine this association, we performed a meta-analysis. A computerized search of the PubMed and Embase databases for publications regarding the RTEL1 rs6010620 polymorphism and glioma cancer risk was performed. Genotype data were analyzed in a meta-analysis. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association. Sensitivity analyses, tests of heterogeneity, cumulative meta-analyses, and assessments of bias were performed in our meta-analysis. Our meta-analysis confirmed that risk with allele A is lower than with allele G for glioma. The A allele of rs6010620 in RTEL1 decreased the risk of developing glioma in the 12 case-control studies for all genetic models: the allele model (OR=0.752, 95%CI: 0.715-0.792), the dominant model (OR=0.729, 95%CI: 0.685-0.776), the recessive model (OR=0.647, 95%CI: 0.569-0.734), the homozygote comparison (OR=0.528, 95%CI: 0.456-0.612), and the heterozygote comparison (OR=0.761, 95%CI: 0.713-0.812). In all genetic models, the association between the RTEL1 rs6010620 polymorphism and glioma risk was significant. This meta-analysis suggests that the RTEL1 rs6010620 polymorphism may be a risk factor for glioma. Further functional studies evaluating this polymorphism and glioma risk are warranted.

Investigation of the in vivo antioxidative activity of Cynara scolymus (artichoke) leaf extract in the streptozotocin-induced diabetic rat.

PubMed

Magielse, Joanna; Verlaet, Annelies; Breynaert, Annelies; Keenoy, Begoña Manuel Y; Apers, Sandra; Pieters, Luc; Hermans, Nina

2014-01-01

The in vivo antioxidant activity of a quantified leaf extract of Cynara scolymus (artichoke) was studied. The aqueous artichoke leaf extract (ALE), containing 1.5% caffeoylquinic acid with chlorogenic acid being most abundant (0.30%), and luteolin-7-O-glucoside as major flavonoid (0.15%), was investigated by evaluating the effect on different oxidative stress biomarkers, after 3 wk oral supplementation in the streptozotocin-induced diabetic rat model. Apart from two test groups (0.2 g ALE/kg BW/day and 1 g ALE/kg BW/day, where BW is body weight), a healthy control group, untreated oxidative stress group, and vitamin E treated group (positive control) were included. A 0.2 g/kg BW/day of ALE decreased oxidative stress: malondialdehyde and 8-hydroxydeoxyguanosine levels significantly diminished, whereas erythrocyte glutathione levels significantly increased. A 1.0 g/kg BW/day ALE did not show higher antioxidant activity. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Allowing for uncertainty due to missing continuous outcome data in pairwise and network meta-analysis.

PubMed

Mavridis, Dimitris; White, Ian R; Higgins, Julian P T; Cipriani, Andrea; Salanti, Georgia

2015-02-28

Missing outcome data are commonly encountered in randomized controlled trials and hence may need to be addressed in a meta-analysis of multiple trials. A common and simple approach to deal with missing data is to restrict analysis to individuals for whom the outcome was obtained (complete case analysis). However, estimated treatment effects from complete case analyses are potentially biased if informative missing data are ignored. We develop methods for estimating meta-analytic summary treatment effects for continuous outcomes in the presence of missing data for some of the individuals within the trials. We build on a method previously developed for binary outcomes, which quantifies the degree of departure from a missing at random assumption via the informative missingness odds ratio. Our new model quantifies the degree of departure from missing at random using either an informative missingness difference of means or an informative missingness ratio of means, both of which relate the mean value of the missing outcome data to that of the observed data. We propose estimating the treatment effects, adjusted for informative missingness, and their standard errors by a Taylor series approximation and by a Monte Carlo method. We apply the methodology to examples of both pairwise and network meta-analysis with multi-arm trials. © 2014 The Authors. Statistics in Medicine Published by John Wiley & Sons Ltd.

Power considerations for λ inflation factor in meta-analyses of genome-wide association studies.

PubMed

Georgiopoulos, Georgios; Evangelou, Evangelos

2016-05-19

The genomic control (GC) approach is extensively used to effectively control false positive signals due to population stratification in genome-wide association studies (GWAS). However, GC affects the statistical power of GWAS. The loss of power depends on the magnitude of the inflation factor (λ) that is used for GC. We simulated meta-analyses of different GWAS. Minor allele frequency (MAF) ranged from 0·001 to 0·5 and λ was sampled from two scenarios: (i) random scenario (empirically-derived distribution of real λ values) and (ii) selected scenario from simulation parameter modification. Adjustment for λ was considered under single correction (within study corrected standard errors) and double correction (additional λ corrected summary estimate). MAF was a pivotal determinant of observed power. In random λ scenario, double correction induced a symmetric power reduction in comparison to single correction. For MAF 1·2 and MAF >5%. Our results provide a quick but detailed index for power considerations of future meta-analyses of GWAS that enables a more flexible design from early steps based on the number of studies accumulated in different groups and the λ values observed in the single studies.

Non-Hodgkin Lymphoma and Occupational Exposure to Agricultural Pesticide Chemical Groups and Active Ingredients: A Systematic Review and Meta-Analysis

PubMed Central

Schinasi, Leah; Leon, Maria E.

2014-01-01

This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world’s agriculture, were missing in the literature that were reviewed. PMID:24762670

Non-Hodgkin lymphoma and occupational exposure to agricultural pesticide chemical groups and active ingredients: a systematic review and meta-analysis.

PubMed

Schinasi, Leah; Leon, Maria E

2014-04-23

This paper describes results from a systematic review and a series of meta-analyses of nearly three decades worth of epidemiologic research on the relationship between non-Hodgkin lymphoma (NHL) and occupational exposure to agricultural pesticide active ingredients and chemical groups. Estimates of associations of NHL with 21 pesticide chemical groups and 80 active ingredients were extracted from 44 papers, all of which reported results from analyses of studies conducted in high-income countries. Random effects meta-analyses showed that phenoxy herbicides, carbamate insecticides, organophosphorus insecticides and the active ingredient lindane, an organochlorine insecticide, were positively associated with NHL. In a handful of papers, associations between pesticides and NHL subtypes were reported; B cell lymphoma was positively associated with phenoxy herbicides and the organophosphorus herbicide glyphosate. Diffuse large B-cell lymphoma was positively associated with phenoxy herbicide exposure. Despite compelling evidence that NHL is associated with certain chemicals, this review indicates the need for investigations of a larger variety of pesticides in more geographic areas, especially in low- and middle-income countries, which, despite producing a large portion of the world's agriculture, were missing in the literature that were reviewed.

Impact of searching clinical trial registries in systematic reviews of pharmaceutical treatments: methodological systematic review and reanalysis of meta-analyses.

PubMed

Baudard, Marie; Yavchitz, Amélie; Ravaud, Philippe; Perrodeau, Elodie; Boutron, Isabelle

2017-02-17

Objective  To evaluate the impact of searching clinical trial registries in systematic reviews. Design  Methodological systematic review and reanalyses of meta-analyses. Data sources  Medline was searched to identify systematic reviews of randomised controlled trials (RCTs) assessing pharmaceutical treatments published between June 2014 and January 2015. For all systematic reviews that did not report a trial registry search but reported the information to perform it, the World Health Organization International Trials Registry Platform (WHO ICTRP search portal) was searched for completed or terminated RCTs not originally included in the systematic review. Data extraction  For each systematic review, two researchers independently extracted the outcomes analysed, the number of patients included, and the treatment effect estimated. For each RCT identified, two researchers independently determined whether the results were available (ie, posted, published, or available on the sponsor website) and extracted the data. When additional data were retrieved, we reanalysed meta-analyses and calculated the weight of the additional RCTs and the change in summary statistics by comparison with the original meta-analysis. Results  Among 223 selected systematic reviews, 116 (52%) did not report a search of trial registries; 21 of these did not report the information to perform the search (key words, search date). A search was performed for 95 systematic reviews; for 54 (57%), no additional RCTs were found and for 41 (43%) 122 additional RCTs were identified. The search allowed for increasing the number of patients by more than 10% in 19 systematic reviews, 20% in 10, 30% in seven, and 50% in four. Moreover, 63 RCTs had results available; the results for 45 could be included in a meta-analysis. 14 systematic reviews including 45 RCTs were reanalysed. The weight of the additional RCTs in the recalculated meta-analyses ranged from 0% to 58% and was greater than 10% in five of 14 systematic reviews, 20% in three, and 50% in one. The change in summary statistics ranged from 0% to 29% and was greater than 10% for five of 14 systematic reviews and greater than 20% for two. However, none of the changes to summary effect estimates led to a qualitative change in the interpretation of the results once the new trials were added. Conclusions  Trial registries are an important source for identifying additional RCTs. The additional number of RCTs and patients included if a search were performed varied across systematic reviews. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

An unstructured mesh arbitrary Lagrangian-Eulerian unsteady incompressible flow solver and its application to insect flight aerodynamics

NASA Astrophysics Data System (ADS)

Su, Xiaohui; Cao, Yuanwei; Zhao, Yong

2016-06-01

In this paper, an unstructured mesh Arbitrary Lagrangian-Eulerian (ALE) incompressible flow solver is developed to investigate the aerodynamics of insect hovering flight. The proposed finite-volume ALE Navier-Stokes solver is based on the artificial compressibility method (ACM) with a high-resolution method of characteristics-based scheme on unstructured grids. The present ALE model is validated and assessed through flow passing over an oscillating cylinder. Good agreements with experimental results and other numerical solutions are obtained, which demonstrates the accuracy and the capability of the present model. The lift generation mechanisms of 2D wing in hovering motion, including wake capture, delayed stall, rapid pitch, as well as clap and fling are then studied and illustrated using the current ALE model. Moreover, the optimized angular amplitude in symmetry model, 45°, is firstly reported in details using averaged lift and the energy power method. Besides, the lift generation of complete cyclic clap and fling motion, which is simulated by few researchers using the ALE method due to large deformation, is studied and clarified for the first time. The present ALE model is found to be a useful tool to investigate lift force generation mechanism for insect wing flight.

Non-occupational exposure to asbestos and risk of pleural mesothelioma: review and meta-analysis.

PubMed

Marsh, Gary M; Riordan, Alexander S; Keeton, Kara A; Benson, Stacey M

2017-11-01

To conduct an updated literature review and meta-analysis of studies of pleural malignant mesothelioma (PMM) risk among persons exposed to asbestos non-occupationally (household and neighbourhood). We performed a literature search for articles available in the National Center for Biotechnology Information's PubMed database published between 1967 and 2016. Meta-analyses were conducted to calculate pooled PMM risk estimates, stratifying for household or neighbourhood exposure to asbestos and/or predominant asbestos fibre type (chrysotile, amphibole or mixed). Eighteen studies in 12 countries comprising 665 cases met the meta-analysis inclusion criteria. We identified 13 estimates of PMM risk from neighbourhood exposures, 10 from household and one from mixed exposure, and combined the estimates using random-effects models. The overall meta-relative risk (meta-RR) was 5.9 (95% CI 4.4 to 8.7). The meta-RRs for household and neighbourhood exposures were 5.4 (95% CI 2.6 to 11.2) and 6.9 (95% CI 4.2 to 11.4), respectively. We observed trends in risk in relation to fibre type for both household and neighbourhood studies. For chrysotile, mixed and amphibole fibres, respectively, meta-RRs for neighbourhood studies were 3.8 (95% CI 0.4 to 38.4), 8.4 (95% CI 4.7 to 14.9) and 21.1 (95% CI 5.3 to 84.5) and meta-RRs for household studies were 4.0 (95% CI 0.8 to 18.8), 5.3 (95% CI 1.9 to 15.0) and 21.1 (95% CI 2.8 to 156.0). PMM risks from non-occupational asbestos exposure are consistent with the fibre-type potency response observed in occupational settings. By relating our findings to knowledge of exposure-response relationships in occupational settings, we can better evaluate PMM risks in communities with ambient asbestos exposures from industrial or other sources. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

False-positive findings in Cochrane meta-analyses with and without application of trial sequential analysis: an empirical review.

PubMed

Imberger, Georgina; Thorlund, Kristian; Gluud, Christian; Wetterslev, Jørn

2016-08-12

Many published meta-analyses are underpowered. We explored the role of trial sequential analysis (TSA) in assessing the reliability of conclusions in underpowered meta-analyses. We screened The Cochrane Database of Systematic Reviews and selected 100 meta-analyses with a binary outcome, a negative result and sufficient power. We defined a negative result as one where the 95% CI for the effect included 1.00, a positive result as one where the 95% CI did not include 1.00, and sufficient power as the required information size for 80% power, 5% type 1 error, relative risk reduction of 10% or number needed to treat of 100, and control event proportion and heterogeneity taken from the included studies. We re-conducted the meta-analyses, using conventional cumulative techniques, to measure how many false positives would have occurred if these meta-analyses had been updated after each new trial. For each false positive, we performed TSA, using three different approaches. We screened 4736 systematic reviews to find 100 meta-analyses that fulfilled our inclusion criteria. Using conventional cumulative meta-analysis, false positives were present in seven of the meta-analyses (7%, 95% CI 3% to 14%), occurring more than once in three. The total number of false positives was 14 and TSA prevented 13 of these (93%, 95% CI 68% to 98%). In a post hoc analysis, we found that Cochrane meta-analyses that are negative are 1.67 times more likely to be updated (95% CI 0.92 to 2.68) than those that are positive. We found false positives in 7% (95% CI 3% to 14%) of the included meta-analyses. Owing to limitations of external validity and to the decreased likelihood of updating positive meta-analyses, the true proportion of false positives in meta-analysis is probably higher. TSA prevented 93% of the false positives (95% CI 68% to 98%). Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Characteristics of meta-analyses and their component studies in the Cochrane Database of Systematic Reviews: a cross-sectional, descriptive analysis

PubMed Central

2011-01-01

Background Cochrane systematic reviews collate and summarise studies of the effects of healthcare interventions. The characteristics of these reviews and the meta-analyses and individual studies they contain provide insights into the nature of healthcare research and important context for the development of relevant statistical and other methods. Methods We classified every meta-analysis with at least two studies in every review in the January 2008 issue of the Cochrane Database of Systematic Reviews (CDSR) according to the medical specialty, the types of interventions being compared and the type of outcome. We provide descriptive statistics for numbers of meta-analyses, numbers of component studies and sample sizes of component studies, broken down by these categories. Results We included 2321 reviews containing 22,453 meta-analyses, which themselves consist of data from 112,600 individual studies (which may appear in more than one meta-analysis). Meta-analyses in the areas of gynaecology, pregnancy and childbirth (21%), mental health (13%) and respiratory diseases (13%) are well represented in the CDSR. Most meta-analyses address drugs, either with a control or placebo group (37%) or in a comparison with another drug (25%). The median number of meta-analyses per review is six (inter-quartile range 3 to 12). The median number of studies included in the meta-analyses with at least two studies is three (inter-quartile range 2 to 6). Sample sizes of individual studies range from 2 to 1,242,071, with a median of 91 participants. Discussion It is clear that the numbers of studies eligible for meta-analyses are typically very small for all medical areas, outcomes and interventions covered by Cochrane reviews. This highlights the particular importance of suitable methods for the meta-analysis of small data sets. There was little variation in number of studies per meta-analysis across medical areas, across outcome data types or across types of interventions being compared. PMID:22114982

The Yale-Brown Obsessive Compulsive Scale: A Reliability Generalization Meta-Analysis.

PubMed

López-Pina, José Antonio; Sánchez-Meca, Julio; López-López, José Antonio; Marín-Martínez, Fulgencio; Núñez-Núñez, Rosa Maria; Rosa-Alcázar, Ana I; Gómez-Conesa, Antonia; Ferrer-Requena, Josefa

2015-10-01

The Yale-Brown Obsessive Compulsive Scale (Y-BOCS) is the most frequently applied test to assess obsessive compulsive symptoms. We conducted a reliability generalization meta-analysis on the Y-BOCS to estimate the average reliability, examine the variability among the reliability estimates, search for moderators, and propose a predictive model that researchers and clinicians can use to estimate the expected reliability of the Y-BOCS. We included studies where the Y-BOCS was applied to a sample of adults and reliability estimate was reported. Out of the 11,490 references located, 144 studies met the selection criteria. For the total scale, the mean reliability was 0.866 for coefficients alpha, 0.848 for test-retest correlations, and 0.922 for intraclass correlations. The moderator analyses led to a predictive model where the standard deviation of the total test and the target population (clinical vs. nonclinical) explained 38.6% of the total variability among coefficients alpha. Finally, clinical implications of the results are discussed. © The Author(s) 2014.

Overview of Meta-Analyses of the Prevention of Mental Health, Substance Use and Conduct Problems

PubMed Central

Sandler, Irwin; Wolchik, Sharlene A.; Cruden, Gracelyn; Mahrer, Nicole E.; Ahn, Soyeon; Brincks, Ahnalee; Brown, C. Hendricks

2014-01-01

This paper presents findings from an overview of meta-analyses of the effects of prevention and promotion programs to prevent mental health, substance use and conduct problems. The review of 48 meta-analyses found small but significant effects to reduce depression, anxiety, anti-social behavior and substance use. Further, the effects are sustained over time. Meta-analyses often found that the effects were heterogeneous. A conceptual model is proposed to guide the study of moderators of program effects in future meta-analyses and methodological issues in synthesizing findings across preventive interventions are discussed. PMID:24471372

WO3 and W Thermal Atomic Layer Etching Using "Conversion-Fluorination" and "Oxidation-Conversion-Fluorination" Mechanisms.

PubMed

Johnson, Nicholas R; George, Steven M

2017-10-04

The thermal atomic layer etching (ALE) of WO 3 and W was demonstrated with new "conversion-fluorination" and "oxidation-conversion-fluorination" etching mechanisms. Both of these mechanisms are based on sequential, self-limiting reactions. WO 3 ALE was achieved by a "conversion-fluorination" mechanism using an AB exposure sequence with boron trichloride (BCl 3 ) and hydrogen fluoride (HF). BCl 3 converts the WO 3 surface to a B 2 O 3 layer while forming volatile WO x Cl y products. Subsequently, HF spontaneously etches the B 2 O 3 layer producing volatile BF 3 and H 2 O products. In situ spectroscopic ellipsometry (SE) studies determined that the BCl 3 and HF reactions were self-limiting versus exposure. The WO 3 ALE etch rates increased with temperature from 0.55 Å/cycle at 128 °C to 4.19 Å/cycle at 207 °C. W served as an etch stop because BCl 3 and HF could not etch the underlying W film. W ALE was performed using a three-step "oxidation-conversion-fluorination" mechanism. In this ABC exposure sequence, the W surface is first oxidized to a WO 3 layer using O 2 /O 3 . Subsequently, the WO 3 layer is etched with BCl 3 and HF. SE could simultaneously monitor the W and WO 3 thicknesses and conversion of W to WO 3 . SE measurements showed that the W film thickness decreased linearly with number of ABC reaction cycles. W ALE was shown to be self-limiting with respect to each reaction in the ABC process. The etch rate for W ALE was ∼2.5 Å/cycle at 207 °C. An oxide thickness of ∼20 Å remained after W ALE, but could be removed by sequential BCl 3 and HF exposures without affecting the W layer. These new etching mechanisms will enable the thermal ALE of a variety of additional metal materials including those that have volatile metal fluorides.

A Model for Designing Adaptive Laboratory Evolution Experiments.

PubMed

LaCroix, Ryan A; Palsson, Bernhard O; Feist, Adam M

2017-04-15

The occurrence of mutations is a cornerstone of the evolutionary theory of adaptation, capitalizing on the rare chance that a mutation confers a fitness benefit. Natural selection is increasingly being leveraged in laboratory settings for industrial and basic science applications. Despite increasing deployment, there are no standardized procedures available for designing and performing adaptive laboratory evolution (ALE) experiments. Thus, there is a need to optimize the experimental design, specifically for determining when to consider an experiment complete and for balancing outcomes with available resources (i.e., laboratory supplies, personnel, and time). To design and to better understand ALE experiments, a simulator, ALEsim, was developed, validated, and applied to the optimization of ALE experiments. The effects of various passage sizes were experimentally determined and subsequently evaluated with ALEsim, to explain differences in experimental outcomes. Furthermore, a beneficial mutation rate of 10 -6.9 to 10 -8.4 mutations per cell division was derived. A retrospective analysis of ALE experiments revealed that passage sizes typically employed in serial passage batch culture ALE experiments led to inefficient production and fixation of beneficial mutations. ALEsim and the results described here will aid in the design of ALE experiments to fit the exact needs of a project while taking into account the resources required and will lower the barriers to entry for this experimental technique. IMPORTANCE ALE is a widely used scientific technique to increase scientific understanding, as well as to create industrially relevant organisms. The manner in which ALE experiments are conducted is highly manual and uniform, with little optimization for efficiency. Such inefficiencies result in suboptimal experiments that can take multiple months to complete. With the availability of automation and computer simulations, we can now perform these experiments in an optimized fashion and can design experiments to generate greater fitness in an accelerated time frame, thereby pushing the limits of what adaptive laboratory evolution can achieve. Copyright © 2017 American Society for Microbiology.

Effects of low-volume high-intensity interval training (HIT) on fitness in adults: a meta-analysis of controlled and non-controlled trials.

PubMed

Weston, Matthew; Taylor, Kathryn L; Batterham, Alan M; Hopkins, Will G

2014-07-01

Low-volume high-intensity interval training (HIT) appears to be an efficient and practical way to develop physical fitness. Our objective was to estimate meta-analysed mean effects of HIT on aerobic power (maximum oxygen consumption [VO(2max)] in an incremental test) and sprint fitness (peak and mean power in a 30-s Wingate test). Five databases (PubMed, MEDLINE, Scopus, BIOSIS and Web of Science) were searched for original research articles published up to January 2014. Search terms included 'high intensity', 'HIT', 'sprint', 'fitness' and 'VO(2max)'. Inclusion criteria were fitness assessed pre- and post-training; training period ≥2 weeks; repetition duration 30-60 s; work/rest ratio <1.0; exercise intensity described as maximal or near maximal; adult subjects aged >18 years. The final data set consisted of 55 estimates from 32 trials for VO(2max), 23 estimates from 16 trials for peak sprint power, and 19 estimates from 12 trials for mean sprint power. Effects on fitness were analysed as percentages via log transformation. Standard errors calculated from exact p values (where reported) or imputed from errors of measurement provided appropriate weightings. Fixed effects in the meta-regression model included type of study (controlled, uncontrolled), subject characteristics (sex, training status, baseline fitness) and training parameters (number of training sessions, repetition duration, work/rest ratio). Probabilistic magnitude-based inferences for meta-analysed effects were based on standardized thresholds for small, moderate and large changes (0.2, 0.6 and 1.2, respectively) derived from between-subject standard deviations (SDs) for baseline fitness. A mean low-volume HIT protocol (13 training sessions, 0.16 work/rest ratio) in a controlled trial produced a likely moderate improvement in the VO(2max) of active non-athletic males (6.2 %; 90 % confidence limits ±3.1 %), when compared with control. There were possibly moderate improvements in the VO(2max) of sedentary males (10.0 %; ±5.1 %) and active non-athletic females (3.6 %; ±4.3 %) and a likely small increase for sedentary females (7.3 %; ±4.8 %). The effect on the VO(2max) of athletic males was unclear (2.7 %; ±4.6 %). A possibly moderate additional increase was likely for subjects with a 10 mL·kg(-1)·min(-1) lower baseline VO(2max) (3.8 %; ±2.5 %), whereas the modifying effects of sex and difference in exercise dose were unclear. The comparison of HIT with traditional endurance training was unclear (-1.6 %; ±4.3 %). Unexplained variation between studies was 2.0 % (SD). Meta-analysed effects of HIT on Wingate peak and mean power were unclear. Low-volume HIT produces moderate improvements in the aerobic power of active non-athletic and sedentary subjects. More studies are needed to resolve the unclear modifying effects of sex and HIT dose on aerobic power and the unclear effects on sprint fitness.

[Development of an Excel spreadsheet for meta-analysis of indirect and mixed treatment comparisons].

PubMed

Tobías, Aurelio; Catalá-López, Ferrán; Roqué, Marta

2014-01-01

Meta-analyses in clinical research usually aimed to evaluate treatment efficacy and safety in direct comparison with a unique comparator. Indirect comparisons, using the Bucher's method, can summarize primary data when information from direct comparisons is limited or nonexistent. Mixed comparisons allow combining estimates from direct and indirect comparisons, increasing statistical power. There is a need for simple applications for meta-analysis of indirect and mixed comparisons. These can easily be conducted using a Microsoft Office Excel spreadsheet. We developed a spreadsheet for indirect and mixed effects comparisons of friendly use for clinical researchers interested in systematic reviews, but non-familiarized with the use of more advanced statistical packages. The use of the proposed Excel spreadsheet for indirect and mixed comparisons can be of great use in clinical epidemiology to extend the knowledge provided by traditional meta-analysis when evidence from direct comparisons is limited or nonexistent.

A Microsoft-Excel-based tool for running and critically appraising network meta-analyses—an overview and application of NetMetaXL

PubMed Central

2014-01-01

Background The use of network meta-analysis has increased dramatically in recent years. WinBUGS, a freely available Bayesian software package, has been the most widely used software package to conduct network meta-analyses. However, the learning curve for WinBUGS can be daunting, especially for new users. Furthermore, critical appraisal of network meta-analyses conducted in WinBUGS can be challenging given its limited data manipulation capabilities and the fact that generation of graphical output from network meta-analyses often relies on different software packages than the analyses themselves. Methods We developed a freely available Microsoft-Excel-based tool called NetMetaXL, programmed in Visual Basic for Applications, which provides an interface for conducting a Bayesian network meta-analysis using WinBUGS from within Microsoft Excel. . This tool allows the user to easily prepare and enter data, set model assumptions, and run the network meta-analysis, with results being automatically displayed in an Excel spreadsheet. It also contains macros that use NetMetaXL’s interface to generate evidence network diagrams, forest plots, league tables of pairwise comparisons, probability plots (rankograms), and inconsistency plots within Microsoft Excel. All figures generated are publication quality, thereby increasing the efficiency of knowledge transfer and manuscript preparation. Results We demonstrate the application of NetMetaXL using data from a network meta-analysis published previously which compares combined resynchronization and implantable defibrillator therapy in left ventricular dysfunction. We replicate results from the previous publication while demonstrating result summaries generated by the software. Conclusions Use of the freely available NetMetaXL successfully demonstrated its ability to make running network meta-analyses more accessible to novice WinBUGS users by allowing analyses to be conducted entirely within Microsoft Excel. NetMetaXL also allows for more efficient and transparent critical appraisal of network meta-analyses, enhanced standardization of reporting, and integration with health economic evaluations which are frequently Excel-based. PMID:25267416

Meta-analysis of magnitudes, differences and variation in evolutionary parameters.

PubMed

Morrissey, M B

2016-10-01

Meta-analysis is increasingly used to synthesize major patterns in the large literatures within ecology and evolution. Meta-analytic methods that do not account for the process of observing data, which we may refer to as 'informal meta-analyses', may have undesirable properties. In some cases, informal meta-analyses may produce results that are unbiased, but do not necessarily make the best possible use of available data. In other cases, unbiased statistical noise in individual reports in the literature can potentially be converted into severe systematic biases in informal meta-analyses. I first present a general description of how failure to account for noise in individual inferences should be expected to lead to biases in some kinds of meta-analysis. In particular, informal meta-analyses of quantities that reflect the dispersion of parameters in nature, for example, the mean absolute value of a quantity, are likely to be generally highly misleading. I then re-analyse three previously published informal meta-analyses, where key inferences were of aspects of the dispersion of values in nature, for example, the mean absolute value of selection gradients. Major biological conclusions in each original informal meta-analysis closely match those that could arise as artefacts due to statistical noise. I present alternative mixed-model-based analyses that are specifically tailored to each situation, but where all analyses may be implemented with widely available open-source software. In each example meta-re-analysis, major conclusions change substantially. © 2016 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2016 European Society For Evolutionary Biology.

Meta-analysis of Odds Ratios: Current Good Practices

PubMed Central

Chang, Bei-Hung; Hoaglin, David C.

2016-01-01

Background Many systematic reviews of randomized clinical trials lead to meta-analyses of odds ratios. The customary methods of estimating an overall odds ratio involve weighted averages of the individual trials’ estimates of the logarithm of the odds ratio. That approach, however, has several shortcomings, arising from assumptions and approximations, that render the results unreliable. Although the problems have been documented in the literature for many years, the conventional methods persist in software and applications. A well-developed alternative approach avoids the approximations by working directly with the numbers of subjects and events in the arms of the individual trials. Objective We aim to raise awareness of methods that avoid the conventional approximations, can be applied with widely available software, and produce more-reliable results. Methods We summarize the fixed-effect and random-effects approaches to meta-analysis; describe conventional, approximate methods and alternative methods; apply the methods in a meta-analysis of 19 randomized trials of endoscopic sclerotherapy in patients with cirrhosis and esophagogastric varices; and compare the results. We demonstrate the use of SAS, Stata, and R software for the analysis. Results In the example, point estimates and confidence intervals for the overall log-odds-ratio differ between the conventional and alternative methods, in ways that can affect inferences. Programming is straightforward in the three software packages; an appendix gives the details. Conclusions The modest additional programming required should not be an obstacle to adoption of the alternative methods. Because their results are unreliable, use of the conventional methods for meta-analysis of odds ratios should be discontinued. PMID:28169977

Is Operative Treatment of Achilles Tendon Ruptures Superior to Nonoperative Treatment?

PubMed Central

Erickson, Brandon J.; Mascarenhas, Randy; Saltzman, Bryan M.; Walton, David; Lee, Simon; Cole, Brian J.; Bach, Bernard R.

2015-01-01

Background: Multiple meta-analyses have been published in efforts to determine whether operative or nonoperative treatment of Achilles tendon ruptures affords superior outcomes. Purpose: To perform a systematic review of overlapping meta-analyses comparing operative and nonoperative treatment of Achilles tendon ruptures to determine which meta-analyses provide the highest level of evidence for treatment recommendations. Study Design: Systematic review; Level of evidence, 3. Methods: A systematic review of the literature was performed to identify meta-analyses that fit the study inclusion criteria. Data were extracted from these meta-analyses regarding patient outcomes and reruptures. Meta-analysis quality was assessed using the Oxman-Guyatt and QUOROM (Quality of Reporting of Meta-analyses) systems. The Jadad algorithm was applied to determine the meta-analyses with the highest level of evidence. Results: Nine meta-analyses met the eligibility criteria, with all but 1 study including level 1 evidence. A total of 5842 patients were included. Seven studies found a higher rate of rerupture in the nonoperative group but a higher rate of complications in the operative group. One study found no differences in rerupture or complication rates, and 1 study found surgery decreased rerupture rates only when compared with nonoperative treatment without a functional brace. Three studies also identified an earlier return to work in the operative group. Almost all (8 of 9) of the meta-analyses had Oxman-Guyatt scores >3, indicating no major flaws. Conclusion: Operative treatment of Achilles tendon ruptures decreases rerupture rates but increases the risk for minor complications when compared with nonoperative treatment. Additionally, surgical treatment may allow earlier return to work. PMID:26665055

Exploring changes over time and characteristics associated with data retrieval across individual participant data meta-analyses: systematic review.

PubMed

Nevitt, Sarah J; Marson, Anthony G; Davie, Becky; Reynolds, Sally; Williams, Lisa; Smith, Catrin Tudur

2017-04-05

Objective  To investigate whether the success rate of retrieving individual participant data (IPD) for use in IPD meta-analyses has increased over time, and to explore the characteristics associated with IPD retrieval. Design  Systematic review of published IPD meta-analyses, supplemented by a reflection of the Cochrane Epilepsy Group's 20 years' experience of requesting IPD. Data sources  Medline, CENTRAL, Scopus, Web of Science, CINAHL Plus, and PsycINFO. Eligibility criteria for study selection  IPD meta-analyses of studies of all designs and all clinical areas published in English. Results  760 IPD meta-analyses which identified studies by systematic methods that had been published between 1987 and 2015 were included. Only 188 (25%) of these IPD meta-analyses retrieved 100% of the eligible IPD for analysis, with 324 (43%) of these IPD meta-analyses retrieving 80% or more of relevant IPD. There is insufficient evidence to suggest that IPD retrieval rates have improved over time. IPD meta-analyses that included only randomised trials, had an authorship policy, included fewer eligible participants, and were conducted outside of the Cochrane Database of Systematic Reviews were associated with a high or complete IPD retrieval rate. There was no association between the source of funding of the IPD meta-analyses and IPD retrieval rate. The IPD retrieval rate of the Cochrane Epilepsy Group has declined from 83% (up to 2005) to 65% (between 2012 and 2015) and the reported reasons for lack of data availability have changed in recent years. Conclusions  IPD meta-analyses are considered to be the "gold standard" for the synthesis of data from clinical research studies; however, only 25% of published IPD meta-analyses have had access to all IPD. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for osteoporosis or low bone density

PubMed Central

Edwards, D. L.; Saleh, A. A.; Greenspan, S. L.

2015-01-01

Summary We performed a systematic review and meta-analysis of the performance of clinical risk assessment instruments for screening for DXA-determined osteoporosis or low bone density. Commonly evaluated risk instruments showed high sensitivity approaching or exceeding 90 % at particular thresholds within various populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. Introduction The purpose of the study is to systematically review the performance of clinical risk assessment instruments for screening for dual-energy X-ray absorptiometry (DXA)-determined osteoporosis or low bone density. Methods Systematic review and meta-analysis were performed. Multiple literature sources were searched, and data extracted and analyzed from included references. Results One hundred eight references met inclusion criteria. Studies assessed many instruments in 34 countries, most commonly the Osteoporosis Self-Assessment Tool (OST), the Simple Calculated Osteoporosis Risk Estimation (SCORE) instrument, the Osteoporosis Self-Assessment Tool for Asians (OSTA), the Osteoporosis Risk Assessment Instrument (ORAI), and body weight criteria. Meta-analyses of studies evaluating OST using a cutoff threshold of <1 to identify US postmenopausal women with osteoporosis at the femoral neck provided summary sensitivity and specificity estimates of 89 % (95%CI 82–96 %) and 41 % (95%CI 23–59 %), respectively. Meta-analyses of studies evaluating OST using a cutoff threshold of 3 to identify US men with osteoporosis at the femoral neck, total hip, or lumbar spine provided summary sensitivity and specificity estimates of 88 % (95%CI 79–97 %) and 55 % (95%CI 42–68 %), respectively. Frequently evaluated instruments each had thresholds and populations for which sensitivity for osteoporosis or low bone mass detection approached or exceeded 90 % but always with a trade-off of relatively low specificity. Conclusions Commonly evaluated clinical risk assessment instruments each showed high sensitivity approaching or exceeding 90 % for identifying individuals with DXA-determined osteoporosis or low BMD at certain thresholds in different populations but low specificity at thresholds required for high sensitivity. Simpler instruments, such as OST, generally performed as well as or better than more complex instruments. PMID:25644147

Matching visual and nonvisual signals: evidence for a mechanism to discount optic flow during locomotion

NASA Astrophysics Data System (ADS)

Thurrell, Adrian; Pelah, Adar

2005-03-01

We report on recent experiments to investigate the Arthrovisual Locomotor Effect (ALE), a mechanism based on non-visual signals postulated to discount or remove the self-generated visual motion signals during locomotion. It is shown that perceptual matches made by standing subjects to a constant motion optic flow stimulus that is viewed while walking on a treadmill are linearly reduced by walking speed, a measure of the reported ALE. The degree of reduction in perceived speed depends on the similarity of the motor activity to natural locomotion, thus for the four activities tested, ALE strength is ranked as follows: Walking > Cycling > Hand Pedalling > Finger Tapping = 0. Other variations and important controls for the ALE are described.

Coffee drinking and pancreatic cancer risk: a meta-analysis of cohort studies.

PubMed

Dong, Jie; Zou, Jian; Yu, Xiao-Feng

2011-03-07

To quantitatively assess the relationship between coffee consumption and incidence of pancreatic cancer in a meta-analysis of cohort studies. We searched MEDLINE, EMBASE, Science Citation Index Expanded and bibliographies of retrieved articles. Studies were included if they reported relative risks (RRs) and corresponding 95% CIs of pancreatic cancer with respect to frequency of coffee intake. We performed random-effects meta-analyses and meta-regressions of study-specific incremental estimates to determine the risk of pancreatic cancer associated with a 1 cup/d increment in coffee consumption. Fourteen studies met the inclusion criteria, which included 671,080 individuals (1496 cancer events) with an average follow-up of 14.9 years. Compared with individuals who did not drink or seldom drank coffee per day, the pooled RR of pancreatic cancer was 0.82 (95% CI: 0.69-0.95) for regular coffee drinkers, 0.86 (0.76-0.96) for low to moderate coffee drinkers, and 0.68 (0.51-0.84) for high drinkers. In subgroup analyses, we noted that, coffee drinking was associated with a reduced risk of pancreatic cancer in men, while this association was not seen in women. These associations were also similar in studies from North America, Europe, and the Asia-Pacific region. Findings from this meta-analysis suggest that there is an inverse relationship between coffee drinking and risk of pancreatic cancer.

Meta-analysis of alcohol price and income elasticities – with corrections for publication bias

PubMed Central

2013-01-01

Background This paper contributes to the evidence-base on prices and alcohol use by presenting meta-analytic summaries of price and income elasticities for alcohol beverages. The analysis improves on previous meta-analyses by correcting for outliers and publication bias. Methods Adjusting for outliers is important to avoid assigning too much weight to studies with very small standard errors or large effect sizes. Trimmed samples are used for this purpose. Correcting for publication bias is important to avoid giving too much weight to studies that reflect selection by investigators or others involved with publication processes. Cumulative meta-analysis is proposed as a method to avoid or reduce publication bias, resulting in more robust estimates. The literature search obtained 182 primary studies for aggregate alcohol consumption, which exceeds the database used in previous reviews and meta-analyses. Results For individual beverages, corrected price elasticities are smaller (less elastic) by 28-29 percent compared with consensus averages frequently used for alcohol beverages. The average price and income elasticities are: beer, -0.30 and 0.50; wine, -0.45 and 1.00; and spirits, -0.55 and 1.00. For total alcohol, the price elasticity is -0.50 and the income elasticity is 0.60. Conclusions These new results imply that attempts to reduce alcohol consumption through price or tax increases will be less effective or more costly than previously claimed. PMID:23883547

A Review of Meta-Analyses in Education: Methodological Strengths and Weaknesses

ERIC Educational Resources Information Center

Ahn, Soyeon; Ames, Allison J.; Myers, Nicholas D.

2012-01-01

The current review addresses the validity of published meta-analyses in education that determines the credibility and generalizability of study findings using a total of 56 meta-analyses published in education in the 2000s. Our objectives were to evaluate the current meta-analytic practices in education, identify methodological strengths and…

An improvement to the ligand optimisation method (LOM) for measuring the apparent dissociation constant and ligand purity in Ca2+ and Mg2+ buffer solutions.

PubMed

McGuigan, John A S; Kay, James W; Elder, Hugh Y

2014-01-01

In Ca(2+)/Mg(2+) buffers the calculated ionised concentrations ([X(2+)]) can vary by up to a factor of seven. Since there are no defined standards it is impossible to check calculated [X(2+)], making measurement essential. The ligand optimisation method (LOM) is an accurate method to measure [X(2+)] in Ca(2+)/Mg(2+) buffers; independent estimation of ligand purity extends the method to pK(/) < 4. To simplify calculation, Excel programs ALE and AEC were compiled for LOM and its extension. This paper demonstrates that the slope of the electrode in the pX range 2.000-3.301 deviates from Nernstian behaviour as it depends on the value of the lumped interference, Σ. ALE was modified to include this effect; this modified program SALE, and the programs ALE and AEC were used on simulated data for Ca(2+)-EGTA and Mg(2+)-ATP buffers, to calculate electrode and buffer characteristics as a function of Σ. Ca(2+)-electrodes have a Σ < 10(-6) mol/l and there was no difference amongst the three methods. The Σ for Mg(2+)-electrodes lies between 10(-5) and 1.5 (∗) 10(-5) mol/l and calculated [Mg(2+)] with ALE were around 3% less than the true value. SALE and AEC correctly predicted [Mg(2+)]. SALE was used to recalculate K(/) and pK(/) on measured data for Ca(2+)-EGTA and Mg(2+)-EDTA buffers. These results demonstrated that it is pK(/) that is normally distributed. Until defined standards are available, [X(2+)] in Ca(2+)/Mg(2+) buffers have to be measured. The most appropriate method is to use Ca(2+)/Mg(2) electrodes combined with the Excel programs SALE or AEC. Copyright © 2014 Elsevier Ltd. All rights reserved.

Panning for the gold in health research: incorporating studies' methodological quality in meta-analysis.

PubMed

Johnson, Blair T; Low, Robert E; MacDonald, Hayley V

2015-01-01

Systematic reviews now routinely assess methodological quality to gauge the validity of the included studies and of the synthesis as a whole. Although trends from higher quality studies should be clearer, it is uncertain how often meta-analyses incorporate methodological quality in models of study results either as predictors, or, more interestingly, in interactions with theoretical moderators. We survey 200 meta-analyses in three health promotion domains to examine when and how meta-analyses incorporate methodological quality. Although methodological quality assessments commonly appear in contemporary meta-analyses (usually as scales), they are rarely incorporated in analyses, and still more rarely analysed in interaction with theoretical determinants of the success of health promotions. The few meta-analyses (2.5%) that did include such an interaction analysis showed that moderator results remained significant in higher quality studies or were present only among higher quality studies. We describe how to model quality interactively with theoretically derived moderators and discuss strengths and weaknesses of this approach and in relation to current meta-analytic practice. In large literatures exhibiting heterogeneous effects, meta-analyses can incorporate methodological quality and generate conclusions that enable greater confidence not only about the substantive phenomenon but also about the role that methodological quality itself plays.

Exploring neural dysfunction in 'clinical high risk' for psychosis: a quantitative review of fMRI studies.

PubMed

Dutt, Anirban; Tseng, Huai-Hsuan; Fonville, Leon; Drakesmith, Mark; Su, Liang; Evans, John; Zammit, Stanley; Jones, Derek; Lewis, Glyn; David, Anthony S

2015-02-01

Individuals at clinical high risk (CHR) of developing psychosis present with widespread functional abnormalities in the brain. Cognitive deficits, including working memory (WM) problems, as commonly elicited by n-back tasks, are observed in CHR individuals. However, functional MRI (fMRI) studies, comprising a heterogeneous cluster of general and social cognition paradigms, have not necessarily demonstrated consistent and conclusive results in this population. Hence, a comprehensive review of fMRI studies, spanning almost one decade, was carried out to observe for general trends with respect to brain regions and cognitive systems most likely to be dysfunctional in CHR individuals. 32 studies were included for this review, out of which 22 met the criteria for quantitative analysis using activation likelihood estimation (ALE). Task related contrast activations were firstly analysed by comparing CHR and healthy control participants in the total pooled sample, followed by a comparison of general cognitive function studies (excluding social cognition paradigms), and finally by only looking at n-back working memory task based studies. Findings from the ALE implicated four key dysfunctional and distinct neural regions in the CHR group, namely the right inferior parietal lobule (rIPL), the left medial frontal gyrus (lmFG), the left superior temporal gyrus (lSTG) and the right fronto-polar cortex (rFPC) of the superior frontal gyrus (SFG). Narrowing down to relatively few significant dysfunctional neural regions is a step forward in reducing the apparent ambiguity of overall findings, which would help to target specific neural regions and pathways of interest for future research in CHR populations. Copyright © 2014. Published by Elsevier Ltd.

Garlic consumption and colorectal cancer risk in man: a systematic review and meta-analysis.

PubMed

Chiavarini, Manuela; Minelli, Liliana; Fabiani, Roberto

2016-02-01

Colorectal cancer shows large incidence variations worldwide that have been attributed to different dietary factors. We conducted a meta-analysis on the relationship between garlic consumption and colorectal cancer risk. We systematically reviewed publications obtained by searching ISI Web of Knowledge, MEDLINE and EMBASE literature databases. We extracted the risk estimate of the highest and the lowest reported categories of intake from each study and conducted meta-analysis using a random-effects model. The pooled analysis of all fourteen studies, seven cohort and seven case-control, indicated that garlic consumption was not associated with colorectal cancer risk (OR=0·93; 95 % CI 0·82, 1·06, P=0·281; I 2=83·6 %, P≤0·001). Separate analyses on the basis of cancer sites and sex also revealed no statistically significant effects on cancer risk. However, when separately analysed on the basis of study type, we found that garlic was associated with an approximately 37 % reduction in colorectal cancer risk in the case-control studies (combined risk estimate=0·63, 95 % CI 0·48, 0·82, P=0·001; I 2=75·6 %, P≤0·001). Our results suggest that consumption of garlic is not associated with a reduced colorectal cancer risk. Further investigations are necessary to clarify the discrepancy between results obtained from different types of epidemiological studies.

The epidemiology of hepatitis C virus in Afghanistan: systematic review and meta-analysis.

PubMed

Chemaitelly, Hiam; Mahmud, Sarwat; Rahmani, Ahmad Masoud; Abu-Raddad, Laith J

2015-11-01

To characterize hepatitis C virus (HCV) epidemiology and inform public health research, policy, and programming priorities in Afghanistan. Records of HCV incidence and prevalence were reviewed systematically and synthesized following PRISMA guidelines. Meta-analyses were implemented using a DerSimonian-Laird random effects model with inverse variance weighting to estimate HCV prevalence among various at risk populations. A risk of bias assessment was incorporated. The search identified one HCV incidence and 76 HCV prevalence measures. HCV incidence was only assessed among people who inject drugs (PWID), and was reported at 66.7 per 100 person-years. Meta-analyses estimated HCV prevalence at 0.7% among the general population (range 0-9.1%, 95% confidence interval (CI) 0.5-0.9%), 32.6% among PWID (range 9.5-70.0%, 95% CI 24.5-41.3%), and 2.3% among populations at intermediate risk (range 0.0-8.3%, 95% CI 1.3-3.7%). No data were available for other high risk populations such as hemodialysis, thalassemia, and hemophilia patients. HCV prevalence among the general population in Afghanistan is comparable to global levels. Data are needed for the level of infection among key clinical populations at high risk of infection. There is also an immediate need for expansion of harm reduction programs among PWID and prisoners. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

A review and meta-analysis of prospective studies of red and processed meat intake and prostate cancer

PubMed Central

2010-01-01

Over the past decade, several large epidemiologic investigations of meat intake and prostate cancer have been published. Therefore, a meta-analysis of prospective studies was conducted to estimate potential associations between red or processed meat intake and prostate cancer. Fifteen studies of red meat and 11 studies of processed meat were included in the analyses. High vs. low intake and dose-response analyses were conducted using random effects models to generate summary relative risk estimates (SRRE). No association between high vs. low red meat consumption (SRRE = 1.00, 95% CI: 0.96-1.05) or each 100 g increment of red meat (SRRE = 1.00, 95% CI: 0.95-1.05) and total prostate cancer was observed. Similarly, no association with red meat was observed for advanced prostate cancer (SRRE = 1.01, 95% CI: 0.94-1.09). A weakly elevated summary association between processed meat and total prostate cancer was found (SRRE = 1.05, 95% CI: 0.99-1.12), although heterogeneity was present, the association was attenuated in a sub-group analysis of studies that adjusted for multiple potential confounding factors, and publication bias likely affected the summary effect. In conclusion, the results of this meta-analysis are not supportive of an independent positive association between red or processed meat intake and prostate cancer. PMID:21044319

Prevalence of Transgender Depends on the “Case” Definition: A Systematic Review

PubMed Central

Collin, Lindsay; Reisner, Sari L.; Tangpricha, Vin; Goodman, Michael

2016-01-01

Background We conducted a systematic review and meta-analysis to evaluate how various definitions of “transgender” may affect prevalence estimates. Methods PubMed, Embase, and Medline were searched to identify studies reporting prevalence estimates of transgender in a population. All studies were grouped based on the case definition applied to the numerator. Summary estimates were derived using a random-effects model for total prevalence of transgender and for male-to-female (MTF) and female-to-male (FTM) subgroups. Overall and stratum-specific meta-prevalence estimates (mPs) and 95% confidence intervals (CIs) were accompanied by tests for heterogeneity, and meta-regressions to assess sources of heterogeneity. Results A total of 32 studies met the inclusion criteria for the systematic review. Of those, 27 studies provided necessary data for a meta-analysis. Overall mP (95% CI) per 100,000 population was 9.2 (4.9, 13.6) for surgical or hormonal gender affirmation therapy and 6.8 (4.6–9.1) for transgender-related diagnoses. Among studies assessing self-reported transgender identity, the mP was 871 (95% 519, 1224); however this result was influenced by a single outlier study. After removal of that study, the mP changed to 355 (95% CI 144, 566). Significant heterogeneity was observed in most analyses. Conclusions The empirical literature on the prevalence of transgender highlights the importance of adhering to specific case definitions because the results may range by orders of magnitude. Standardized and routine collection of transgender data is recommended. PMID:27045261

Perceptions of plagiarisers: The influence of target physical attractiveness, transgression severity, and sex on attributions of guilt and punishment.

PubMed

Swami, Viren; Arthey, Elizabeth; Furnham, Adrian

2017-09-01

The attractiveness-leniency effect (ALE) suggests that physically attractive targets are less likely to be perceived as guilty compared to less attractive targets. Here, we tested the ALE in relation to attributions of students who have committed plagiarism. British adults (N=165) were shown one of eight vignette-photograph pairings varying in target sex (female/male), physical attractiveness (high/low), and transgression severity (serious/minor), and provided attributions of guilt and severity of punishment. Analyses of variance revealed significant interactions between attractiveness and transgression severity for both dependent measures. Attractive targets were perceived as guiltier and deserving of more severe punishments in the serious transgression condition, but there was no significant difference between attractive and less attractive targets in the minor transgression condition. These results are discussed in terms of a reverse attribution bias, in which attractive individuals are judged more negatively when they fail to live up to higher standards of conduct. Copyright © 2017 Elsevier Ltd. All rights reserved.

Presentation approaches for enhancing interpretability of patient-reported outcomes (PROs) in meta-analysis: a protocol for a systematic survey of Cochrane reviews.

PubMed

Devji, Tahira; Johnston, Bradley C; Patrick, Donald L; Bhandari, Mohit; Thabane, Lehana; Guyatt, Gordon H

2017-09-27

Meta-analyses of clinical trials often provide sufficient information for decision-makers to evaluate whether chance can explain apparent differences between interventions. Interpretation of the magnitude and importance of treatment effects beyond statistical significance can, however, be challenging, particularly for patient-reported outcomes (PROs) measured using questionnaires with which clinicians have limited familiarity. The objectives of our study are to systematically evaluate Cochrane systematic review authors' approaches to calculation, reporting and interpretation of pooled estimates of patient-reported outcome measures (PROMs) in meta-analyses. We will conduct a methodological survey of a random sample of Cochrane systematic reviews published from 1 January 2015 to 1 April 2017 that report at least one statistically significant pooled result for at least one PRO in the abstract. Author pairs will independently review all titles, abstracts and full texts identified by the literature search, and they will extract data using a standardised data extraction form. We will extract the following: year of publication, number of included trials, number of included participants, clinical area, type of intervention(s) and control(s), type of meta-analysis and use of the Grading of Recommendations, Assessment, Development and Evaluation approach to rate the quality of evidence, as well as information regarding the characteristics of PROMs, calculation and presentation of PROM effect estimates and interpretation of PROM effect estimates. We will document and summarise the methods used for the analysis, reporting and interpretation of each summary effect measure. We will summarise categorical variables with frequencies and percentages and continuous outcomes as means and/or medians and associated measures of dispersion. Ethics approval for this study is not required. We will disseminate the results of this review in peer-reviewed publications and conference presentations. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Risk factors for Clostridium difficile infections - an overview of the evidence base and challenges in data synthesis.

PubMed

Eze, Paul; Balsells, Evelyn; Kyaw, Moe H; Nair, Harish

2017-06-01

Recognition of a broad spectrum of disease and development of Clostridium difficile infection (CDI) and recurrent CDI (rCDI) in populations previously considered to be at low risk has renewed attention on differences in the risk profile of patients. In the absence of primary prevention for CDI and limited treatment options, it is important to achieve a deep understanding of the multiple factors that influence the risk of developing CDI and rCDI. We conducted a review of systematic reviews and meta-analyses on risk factors for CDI and rCDI published between 1990 and October 2016. 22 systematic reviews assessing risk factors for CDI (n = 19) and rCDI (n = 6) were included. Meta-analyses were conducted in 17 of the systematic reviews. Over 40 risk factors have been associated with CDI and rCDI and can be classified into three categories: pharmacological risk factors, host-related risk factors, and clinical characteristics or interventions. Most systematic reviews and meta-analyses have focused on antibiotic use (n = 8 for CDI, 3 for rCDI), proton pump inhibitors (n = 8 for CDI, 4 for rCDI), and histamine 2 receptor antagonists (n = 4 for CDI) and chronic kidney disease (n = 4 for rCDI). However, other risk factors have been assessed. We discuss the state of the evidence, methods, and challenges for data synthesis. Several studies, synthesized in different systematic review, provide valuable insights into the role of different risk factors for CDI. Meta-analytic evidence of association has been reported for factors such as antibiotics, gastric acid suppressants, non-selective NSAID, and some co-morbidities. However, despite statistical significance, issues of high heterogeneity, bias and confounding remain to be addressed effectively to improve overall risk estimates. Large, prospective primary studies on risk factors for CDI with standardised case definitions and stratified analyses are required to develop more accurate and robust estimates of risk effects that can inform targeted-CDI clinical management procedures, prevention, and research.

Optimized adipose tissue engineering strategy based on a neo-mechanical processing method.

PubMed

He, Yunfan; Lin, Maohui; Wang, Xuecen; Guan, Jingyan; Dong, Ziqing; Feng, Lu; Xing, Malcolm; Feng, Chuanbo; Li, Xiaojian

2018-05-26

Decellularized adipose tissue (DAT) represents a promising scaffold for adipose tissue engineering. However, the unique and prolonged lipid removal process required for adipose tissue can damage extracellular matrix (ECM) constituents. Moreover, inadequate vascularization limits the recellularization of DAT in vivo. We proposed a neo-mechanical protocol for rapidly breaking adipocytes and removing lipid content from adipose tissue. The lipid-depleted adipose tissue was then subjected to a fast and mild decellularization to fabricate high-quality DAT (M-DAT). Adipose liquid extract (ALE) derived from this mechanical process was collected and incorporated into M-DAT to further optimize in vivo recellularization. Ordinary DAT was fabricated and served as a control. This developed strategy was evaluated based on decellularization efficiency, ECM quality, and recellularization efficiency. Angiogenic factor components and angiogenic potential of ALE were evaluated in vivo and in vitro. M-DAT achieved the same decellularization efficiency, but exhibited better retention of ECM components and recellularization, compared to those with ordinary DAT. Protein quantification revealed considerable levels of angiogenic factors (basic fibroblast growth factor, epidermal growth factor, transforming growth factor-β1, and vascular endothelial growth factor) in ALE. ALE promoted tube formation in vitro and induced intense angiogenesis in M-DAT in vivo; furthermore, higher expression of the adipogenic factor PPARγ and greater numbers of adipocytes were evident following ALE treatment, compared to those in the M-DAT group. Mechanical processing of adipose tissue led to the production of high-quality M-DAT and angiogenic factor-enriched ALE. The combination of ALE and M-DAT could be a promising strategy for engineered adipose tissue construction. This article is protected by copyright. All rights reserved. © 2018 by the Wound Healing Society.

Improved Mobilization of Exogenous Mesenchymal Stem Cells to Bone for Fracture Healing and Sex Difference

PubMed Central

Yao, Wei; Evan Lay, Yu-An; Kot, Alexander; Liu, Ruiwu; Zhang, Hongliang; Chen, Haiyan; Lam, Kit; Lane, Nancy E.

2017-01-01

Mesenchymal stem cell (MSC) transplantation has been tested in animal and clinical fracture studies. We have developed a bone-seeking compound, LLP2A-Alendronate (LLP2A-Ale) that augments MSC homing to bone. The purpose of this study was to determine whether treatment with LLP2A-Ale or a combination of LLP2A-Ale and MSCs would accelerate bone healing in a mouse closed fracture model and if the effects are sex dependent. A right mid-femur fracture was induced in two-month-old osterix-mCherry (Osx-mCherry) male and female reporter mice. The mice were subsequently treated with placebo, LLP2A-Ale (500 µg/kg, IV), MSCs derived from wild-type female Osx-mCherry adipose tissue (ADSC, 3 × 105, IV) or ADSC + LLP2A-Ale. In phosphate buffered saline-treated mice, females had higher systemic and surface-based bone formation than males. However, male mice formed a larger callus and had higher volumetric bone mineral density and bone strength than females. LLP2A-Ale treatment increased exogenous MSC homing to the fracture gaps, enhanced incorporation of these cells into callus formation, and stimulated endochondral bone formation. Additionally, higher engraftment of exogenous MSCs in fracture gaps seemed to contribute to overall fracture healing and improved bone strength. These effects were sex-independent. There was a sex-difference in the rate of fracture healing. ADSC and LLP2A-Ale combination treatment was superior to on callus formation, which was independent of sex. Increased mobilization of exogenous MSCs to fracture sites accelerated endochondral bone formation and enhanced bone tissue regeneration. PMID:27334693

78 FR 63479 - Meta-Analyses of Randomized Controlled Clinical Trials (RCTs) for the Evaluation of Risk To...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-10-24

... methodological issues that arise in the use of meta-analyses to evaluate safety risks, followed by a discussion... design, conduct and use of meta-analysis. Although many external stakeholders conduct meta-analyses, FDA... meeting. FDA expects that this meeting will build upon prior stakeholder feedback on the design, conduct...

Modeling of Complex Coupled Fluid-Structure Interaction Systems in Arbitrary Water Depth

DTIC Science & Technology

2008-01-01

model in a particle finite element method ( PFEM ) based framework for the ALE-RANS solver and submitted a journal paper recently [1]. In the paper, we...developing a fluid-flexible structure interaction model without free surface using ALE-RANS and k-ε turbulence closure model implemented by PFEM . In...the ALE_RANS and k-ε turbulence closure model based on the particle finite element Method ( PFEM ) and obtained some satisfying results [1-2]. The

Estimates of alcohol-related oesophageal cancer burden in Japan: systematic review and meta-analyses

PubMed Central

Shield, Kevin D; Higuchi, Susumu; Yoshimura, Atsushi; Larsen, Elisabeth; Rehm, Maximilien X; Rehm, Jürgen

2015-01-01

Abstract Objective To refine estimates of the burden of alcohol-related oesophageal cancer in Japan. Methods We searched PubMed for published reviews and original studies on alcohol intake, aldehyde dehydrogenase polymorphisms, and risk for oesophageal cancer in Japan, published before 2014. We conducted random-effects meta-analyses, including subgroup analyses by aldehyde dehydrogenase variants. We estimated deaths and loss of disability-adjusted life years (DALYs) from oesophageal cancer using exposure distributions for alcohol based on age, sex and relative risks per unit of exposure. Findings We identified 14 relevant studies. Three cohort studies and four case-control studies had dose–response data. Evidence from cohort studies showed that people who consumed the equivalent of 100 g/day of pure alcohol had an 11.71 fold, (95% confidence interval, CI: 2.67–51.32) risk of oesophageal cancer compared to those who never consumed alcohol. Evidence from case-control studies showed that the increase in risk was 33.11 fold (95% CI: 8.15–134.43) in the population at large. The difference by study design is explained by the 159 fold (95% CI: 27.2–938.2) risk among those with an inactive aldehyde dehydrogenase enzyme variant. Applying these dose–response estimates to the national profile of alcohol intake yielded 5279 oesophageal cancer deaths and 102 988 DALYs lost – almost double the estimates produced by the most recent global burden of disease exercise. Conclusion Use of global dose–response data results in an underestimate of the burden of disease from oesophageal cancer in Japan. Where possible, national burden of disease studies should use results from the population concerned. PMID:26229204

Comparison of updated Lagrangian FEM with arbitrary Lagrangian Eulerian method for 3D thermo-mechanical extrusion of a tube profile

NASA Astrophysics Data System (ADS)

Kronsteiner, J.; Horwatitsch, D.; Zeman, K.

2017-10-01

Thermo-mechanical numerical modelling and simulation of extrusion processes faces several serious challenges. Large plastic deformations in combination with a strong coupling of thermal with mechanical effects leads to a high numerical demand for the solution as well as for the handling of mesh distortions. The two numerical methods presented in this paper also reflect two different ways to deal with mesh distortions. Lagrangian Finite Element Methods (FEM) tackle distorted elements by building a new mesh (called re-meshing) whereas Arbitrary Lagrangian Eulerian (ALE) methods use an "advection" step to remap the solution from the distorted to the undistorted mesh. Another difference between conventional Lagrangian and ALE methods is the separate treatment of material and mesh in ALE, allowing the definition of individual velocity fields. In theory, an ALE formulation contains the Eulerian formulation as a subset to the Lagrangian description of the material. The investigations presented in this paper were dealing with the direct extrusion of a tube profile using EN-AW 6082 aluminum alloy and a comparison of experimental with Lagrangian and ALE results. The numerical simulations cover the billet upsetting and last until one third of the billet length is extruded. A good qualitative correlation of experimental and numerical results could be found, however, major differences between Lagrangian and ALE methods concerning thermo-mechanical coupling lead to deviations in the thermal results.

Class Size Reduction or Rapid Formative Assessment?: A Comparison of Cost-Effectiveness

ERIC Educational Resources Information Center

Yeh, Stuart S.

2009-01-01

The cost-effectiveness of class size reduction (CSR) was compared with the cost-effectiveness of rapid formative assessment, a promising alternative for raising student achievement. Drawing upon existing meta-analyses of the effects of student-teacher ratio, evaluations of CSR in Tennessee, California, and Wisconsin, and RAND cost estimates, CSR…

Childhood Attention-Deficit/Hyperactivity Disorder and Future Substance Use Disorders: Comparative Meta-Analyses

ERIC Educational Resources Information Center

Charach, Alice; Yeung, Emanuela; Climans, Troy; Lillie, Erin

2011-01-01

Objective: In recent years cohort studies have examined childhood attention-deficit/hyperactivity disorder (ADHD) as a risk factor for substance use disorders (SUDs) in adolescence and young adulthood. The long-term risk is estimated for development of alcohol, cannabis, combined alcohol and psychoactive SUDs, combined SUDs (nonalcohol), and…

The Prevalence of Comorbid Personality Disorders in Treatment-Seeking Problem Gamblers: A Systematic Review and Meta-Analysis.

PubMed

Dowling, Nicki A; Cowlishaw, S; Jackson, A C; Merkouris, S S; Francis, K L; Christensen, D R

2015-12-01

The aim of this study was to systematically review and meta-analyze the prevalence of comorbid personality disorders among treatment-seeking problem gamblers. Almost one half (47.9%) of problem gamblers displayed comorbid personality disorders. They were most likely to display Cluster B disorders (17.6%), with smaller proportions reporting Cluster C disorders (12.6%) and Cluster A disorders (6.1%). The most prevalent personality disorders were narcissistic (16.6%), antisocial (14.0%), avoidant (13.4%), obsessive-compulsive (13.4%), and borderline (13.1%) personality disorders. Sensitivity analyses suggested that these prevalence estimates were robust to the inclusion of clinical trials and self-selected samples. Although there was significant variability in reported rates, subgroup analyses revealed no significant differences in estimates of antisocial personality disorder according to problem gambling severity, measure of comorbidity employed, and study jurisdiction. The findings highlight the need for gambling treatment services to conduct routine screening and assessment of co-occurring personality disorders and to provide treatment approaches that adequately address these comorbid conditions.

Diffraction-limited Mid-infrared Integral Field Spectroscopy of Io's Volcanic Activity with ALES on the Large Binocular Telescope

NASA Astrophysics Data System (ADS)

Skrutskie, Michael F.; de Kleer, Katherine R.; Stone, Jordan; Conrad, Al; Davies, Ashley; de Pater, Imke; Leisenring, Jarron; Hinz, Philip; Skemer, Andrew; Veillet, Christian; Woodward, Charles E.; Ertel, Steve; Spalding, Eckhart

2017-10-01

The Arizona Lenslet for Exoplanet Spectroscopy (ALES) is an enhancement to the Large Binocular Telescope's mid-infrared imager, LMIRcam, that permits low-resolution (R~20) spectroscopy between 2.8 and 4.2 μm of every diffraction-limited resolution element in a 2.5"x2.5" field-of-view on a 2048x2048 HAWAII-2RG 5.2 μm-cutoff array. The 1" disk of Io, dotted with powerful self-luminous volcanic eruptions, provides an ideal target for ALES, where the single 8.4-meter aperture diffraction-limited scale for Io at opposition ranges from 240 kilometers (80 milliarcseconds) at 2.8 μm to 360 kilometers (120 milliarcseconds) at 4.2 μm. ALES provides the capability to assess the color temperature of each volcanic thermal emission site as well as map broadband absorbers such as SO2 frost. A monitoring campaign in the Spring 2017 semester provided two global snapshots of Io's volcanic activity with ALES as well as characterization of a new brightening episode at Loki Patera over four epochs between January and May 2017.

Prevalence of Transgender Depends on the "Case" Definition: A Systematic Review.

PubMed

Collin, Lindsay; Reisner, Sari L; Tangpricha, Vin; Goodman, Michael

2016-04-01

A systematic review and meta-analysis was conducted to evaluate how various definitions of transgender affect prevalence estimates. To evaluate the epidemiology of transgender and examine how various definitions of transgender affect prevalence estimates and to compare findings across studies that used different methodologies, in different countries, and over different periods. PubMed, EMBASE, and Medline were searched to identify studies reporting prevalence estimates of transgender in a population. All studies were grouped based on the case definition applied to the numerator. Summary estimates were derived using a random-effects model for total prevalence of transgender and for male-to-female and female-to-male subgroups. Overall and stratum-specific meta-prevalence estimates (mPs) and 95% confidence intervals (CIs) were accompanied by tests for heterogeneity and meta-regressions to assess sources of heterogeneity. The main outcome measure was population prevalence of transgender. Secondary outcomes included gender-specific prevalence estimates for male-to-female and female to male subgroups. Thirty-two studies met the inclusion criteria for systematic review. Of those, 27 studies provided necessary data for a meta-analysis. Overall mP estimates per 100,000 population were 9.2 (95% CI = 4.9-13.6) for surgical or hormonal gender affirmation therapy and 6.8 (95% CI = 4.6-9.1) for transgender-related diagnoses. Of studies assessing self-reported transgender identity, the mP was 871 (95% CI = 519-1,224); however, this result was influenced by a single outlier study. After removal of that study, the mP changed to 355 (95% CI = 144-566). Significant heterogeneity was observed in most analyses. The empirical literature on the prevalence of transgender highlights the importance of adhering to specific case definitions because the results can range by orders of magnitude. Standardized and routine collection of data on transgender status and gender identity is recommended. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

Trade-off of cerebello-cortical and cortico-cortical functional networks for planning in 6-year-old children.

PubMed

Kipping, Judy A; Margulies, Daniel S; Eickhoff, Simon B; Lee, Annie; Qiu, Anqi

2018-08-01

Childhood is a critical period for the development of cognitive planning. There is a lack of knowledge on its neural mechanisms in children. This study aimed to examine cerebello-cortical and cortico-cortical functional connectivity in association with planning skills in 6-year-olds (n = 76). We identified the cerebello-cortical and cortico-cortical functional networks related to cognitive planning using activation likelihood estimation (ALE) meta-analysis on existing functional imaging studies on spatial planning, and data-driven independent component analysis (ICA) of children's resting-state functional MRI (rs-fMRI). We investigated associations of cerebello-cortical and cortico-cortical functional connectivity with planning ability in 6-year-olds, as assessed using the Stockings of Cambridge task. Long-range functional connectivity of two cerebellar networks (lobules VI and lateral VIIa) with the prefrontal and premotor cortex were greater in children with poorer planning ability. In contrast, cortico-cortical association networks were not associated with the performance of planning in children. These results highlighted the key contribution of the lateral cerebello-frontal functional connectivity, but not cortico-cortical association functional connectivity, for planning ability in 6-year-olds. Our results suggested that brain adaptation to the acquisition of planning ability during childhood is partially achieved through the engagement of the cerebello-cortical functional connectivity. Copyright © 2018 Elsevier Inc. All rights reserved.

Disentangling the neural mechanisms involved in Hinduism- and Buddhism-related meditations.

PubMed

Tomasino, Barbara; Chiesa, Alberto; Fabbro, Franco

2014-10-01

The most diffuse forms of meditation derive from Hinduism and Buddhism spiritual traditions. Different cognitive processes are set in place to reach these meditation states. According to an historical-philological hypothesis (Wynne, 2009) the two forms of meditation could be disentangled. While mindfulness is the focus of Buddhist meditation reached by focusing sustained attention on the body, on breathing and on the content of the thoughts, reaching an ineffable state of nothigness accompanied by a loss of sense of self and duality (Samadhi) is the main focus of Hinduism-inspired meditation. It is possible that these different practices activate separate brain networks. We tested this hypothesis by conducting an activation likelihood estimation (ALE) meta-analysis of functional magnetic resonance imaging (fMRI) studies. The network related to Buddhism-inspired meditation (16 experiments, 263 subjects, and 96 activation foci) included activations in some frontal lobe structures associated with executive attention, possibly confirming the fundamental role of mindfulness shared by many Buddhist meditations. By contrast, the network related to Hinduism-inspired meditation (8 experiments, 54 activation foci and 66 subjects) triggered a left lateralized network of areas including the postcentral gyrus, the superior parietal lobe, the hippocampus and the right middle cingulate cortex. The dissociation between anterior and posterior networks support the notion that different meditation styles and traditions are characterized by different patterns of neural activation. Copyright © 2014. Published by Elsevier Inc.

High statistical heterogeneity is more frequent in meta-analysis of continuous than binary outcomes.

PubMed

Alba, Ana C; Alexander, Paul E; Chang, Joanne; MacIsaac, John; DeFry, Samantha; Guyatt, Gordon H

2016-02-01

We compared the distribution of heterogeneity in meta-analyses of binary and continuous outcomes. We searched citations in MEDLINE and Cochrane databases for meta-analyses of randomized trials published in 2012 that reported a measure of heterogeneity of either binary or continuous outcomes. Two reviewers independently performed eligibility screening and data abstraction. We evaluated the distribution of I(2) in meta-analyses of binary and continuous outcomes and explored hypotheses explaining the difference in distributions. After full-text screening, we selected 671 meta-analyses evaluating 557 binary and 352 continuous outcomes. Heterogeneity as assessed by I(2) proved higher in continuous than in binary outcomes: the proportion of continuous and binary outcomes reporting an I(2) of 0% was 34% vs. 52%, respectively, and reporting an I(2) of 60-100% was 39% vs. 14%. In continuous but not binary outcomes, I(2) increased with larger number of studies included in a meta-analysis. Increased precision and sample size do not explain the larger I(2) found in meta-analyses of continuous outcomes with a larger number of studies. Meta-analyses evaluating continuous outcomes showed substantially higher I(2) than meta-analyses of binary outcomes. Results suggest differing standards for interpreting I(2) in continuous vs. binary outcomes may be appropriate. Copyright © 2016 Elsevier Inc. All rights reserved.

Modelling multiple sources of dissemination bias in meta-analysis.

PubMed

Bowden, Jack; Jackson, Dan; Thompson, Simon G

2010-03-30

Asymmetry in the funnel plot for a meta-analysis suggests the presence of dissemination bias. This may be caused by publication bias through the decisions of journal editors, by selective reporting of research results by authors or by a combination of both. Typically, study results that are statistically significant or have larger estimated effect sizes are more likely to appear in the published literature, hence giving a biased picture of the evidence-base. Previous statistical approaches for addressing dissemination bias have assumed only a single selection mechanism. Here we consider a more realistic scenario in which multiple dissemination processes, involving both the publishing authors and journals, are operating. In practical applications, the methods can be used to provide sensitivity analyses for the potential effects of multiple dissemination biases operating in meta-analysis.

Morning sickness

MedlinePlus

... Bland foods, such as gelatin, frozen desserts, broth, ginger ale, and saltine crackers, also soothe the stomach. ... your stomach does not get too full. Seltzer, ginger ale, or other sparkling waters may help control ...

Marital status integration and suicide: A meta-analysis and meta-regression.

PubMed

Kyung-Sook, Woo; SangSoo, Shin; Sangjin, Shin; Young-Jeon, Shin

2018-01-01

Marital status is an index of the phenomenon of social integration within social structures and has long been identified as an important predictor suicide. However, previous meta-analyses have focused only on a particular marital status, or not sufficiently explored moderators. A meta-analysis of observational studies was conducted to explore the relationships between marital status and suicide and to understand the important moderating factors in this association. Electronic databases were searched to identify studies conducted between January 1, 2000 and June 30, 2016. We performed a meta-analysis, subgroup analysis, and meta-regression of 170 suicide risk estimates from 36 publications. Using random effects model with adjustment for covariates, the study found that the suicide risk for non-married versus married was OR = 1.92 (95% CI: 1.75-2.12). The suicide risk was higher for non-married individuals aged <65 years than for those aged ≥65 years, and higher for men than for women. According to the results of stratified analysis by gender, non-married men exhibited a greater risk of suicide than their married counterparts in all sub-analyses, but women aged 65 years or older showed no significant association between marital status and suicide. The suicide risk in divorced individuals was higher than for non-married individuals in both men and women. The meta-regression showed that gender, age, and sample size affected between-study variation. The results of the study indicated that non-married individuals have an aggregate higher suicide risk than married ones. In addition, gender and age were confirmed as important moderating factors in the relationship between marital status and suicide. Copyright © 2017 Elsevier Ltd. All rights reserved.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review.

PubMed

Demarzo, Marcelo M P; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-11-01

Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I(2) = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I(2) = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I(2) = 0; P >.05). Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. © 2015 Annals of Family Medicine, Inc.

Human papillomavirus vaccine and demyelinating diseases-A systematic review and meta-analysis.

PubMed

Mouchet, Julie; Salvo, Francesco; Raschi, Emanuel; Poluzzi, Elisabetta; Antonazzo, Ippazio Cosimo; De Ponti, Fabrizio; Bégaud, Bernard

2018-06-01

Approved in 2006, human papillomavirus (HPV) vaccines were initially targeted for girls aged 9-14 years. Although the safety of these vaccines has been monitored through post-licensure surveillance programmes, cases of neurological events have been reported worldwide. The present study aimed to assess the risk of developing demyelination after HPV immunization by meta-analysing risk estimates from pharmacoepidemiologic studies. A systematic review was conducted in Medline, Embase, ISI Web of Science and the Cochrane Library from inception to 10 May 2017, without language restriction. Only observational studies including a control group were retained. Study selection was performed by two independent reviewers with disagreements solved through discussion. This meta-analysis was performed using a generic inverse variance random-effect model. Outcomes of interest included a broad category of central demyelination, multiple sclerosis (MS), optic neuritis (ON), and Guillain-Barré syndrome (GBS), each being considered independently. Heterogeneity was investigated; sensitivity and subgroup analyses were performed when necessary. In parallel, post-licensure safety studies were considered for a qualitative review. This study followed the PRISMA statement and the MOOSE reporting guideline. Of the 2,863 references identified, 11 articles were selected for meta-analysis. No significant association emerged between HPV vaccination and central demyelination, the pooled odds ratio being 0.96 [95% CI 0.77-1.20], with a moderate but non-significant heterogeneity (I 2  = 29%). Similar results were found for MS and ON. Sensitivity analyses did not alter our conclusions. Findings from qualitative review of 14 safety studies concluded in an absence of a relevant signal. Owing to limited data on GBS, no meta-analysis was performed for this outcome. This study strongly supports the absence of association between HPV vaccines and central demyelination. Copyright © 2018 Elsevier Ltd. All rights reserved.

The Efficacy of Mindfulness-Based Interventions in Primary Care: A Meta-Analytic Review

PubMed Central

Demarzo, Marcelo M.P.; Montero-Marin, Jesús; Cuijpers, Pim; Zabaleta-del-Olmo, Edurne; Mahtani, Kamal R.; Vellinga, Akke; Vicens, Caterina; López-del-Hoyo, Yolanda; García-Campayo, Javier

2015-01-01

PURPOSE Positive effects have been reported after mindfulness-based interventions (MBIs) in diverse clinical and nonclinical populations. Primary care is a key health care setting for addressing common chronic conditions, and an effective MBI designed for this setting could benefit countless people worldwide. Meta-analyses of MBIs have become popular, but little is known about their efficacy in primary care. Our aim was to investigate the application and efficacy of MBIs that address primary care patients. METHODS We performed a meta-analytic review of randomized controlled trials addressing the effect of MBIs in adult patients recruited from primary care settings. The PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) and Cochrane guidelines were followed. Effect sizes were calculated with the Hedges g in random effects models. RESULTS The meta-analyses were based on 6 trials having a total of 553 patients. The overall effect size of MBI compared with a control condition for improving general health was moderate (g = 0.48; P = .002), with moderate heterogeneity (I2 = 59; P <.05). We found no indication of publication bias in the overall estimates. MBIs were efficacious for improving mental health (g = 0.56; P = .007), with a high heterogeneity (I2 = 78; P <.01), and for improving quality of life (g = 0.29; P = .002), with a low heterogeneity (I2 = 0; P >.05). CONCLUSIONS Although the number of randomized controlled trials applying MBIs in primary care is still limited, our results suggest that these interventions are promising for the mental health and quality of life of primary care patients. We discuss innovative approaches for implementing MBIs, such as complex intervention and stepped care. PMID:26553897

Maternal Colonization With Group B Streptococcus and Serotype Distribution Worldwide: Systematic Review and Meta-analyses.

PubMed

Russell, Neal J; Seale, Anna C; O'Driscoll, Megan; O'Sullivan, Catherine; Bianchi-Jassir, Fiorella; Gonzalez-Guarin, Juan; Lawn, Joy E; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Heath, Paul T; Le Doare, Kirsty; Madhi, Shabir A; Rubens, Craig E; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Saha, Samir K; Ip, Margaret

2017-11-06

Maternal rectovaginal colonization with group B Streptococcus (GBS) is the most common pathway for GBS disease in mother, fetus, and newborn. This article, the second in a series estimating the burden of GBS, aims to determine the prevalence and serotype distribution of GBS colonizing pregnant women worldwide. We conducted systematic literature reviews (PubMed/Medline, Embase, Latin American and Caribbean Health Sciences Literature [LILACS], World Health Organization Library Information System [WHOLIS], and Scopus), organized Chinese language searches, and sought unpublished data from investigator groups. We applied broad inclusion criteria to maximize data inputs, particularly from low- and middle-income contexts, and then applied new meta-analyses to adjust for studies with less-sensitive sampling and laboratory techniques. We undertook meta-analyses to derive pooled estimates of maternal GBS colonization prevalence at national and regional levels. The dataset regarding colonization included 390 articles, 85 countries, and a total of 299924 pregnant women. Our adjusted estimate for maternal GBS colonization worldwide was 18% (95% confidence interval [CI], 17%-19%), with regional variation (11%-35%), and lower prevalence in Southern Asia (12.5% [95% CI, 10%-15%]) and Eastern Asia (11% [95% CI, 10%-12%]). Bacterial serotypes I-V account for 98% of identified colonizing GBS isolates worldwide. Serotype III, associated with invasive disease, accounts for 25% (95% CI, 23%-28%), but is less frequent in some South American and Asian countries. Serotypes VI-IX are more common in Asia. GBS colonizes pregnant women worldwide, but prevalence and serotype distribution vary, even after adjusting for laboratory methods. Lower GBS maternal colonization prevalence, with less serotype III, may help to explain lower GBS disease incidence in regions such as Asia. High prevalence worldwide, and more serotype data, are relevant to prevention efforts. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

Endogenous pain modulation in chronic orofacial pain: a systematic review and meta-analysis.

PubMed

Moana-Filho, Estephan J; Herrero Babiloni, Alberto; Theis-Mahon, Nicole R

2018-06-15

Abnormal endogenous pain modulation was suggested as a potential mechanism for chronic pain, ie, increased pain facilitation and/or impaired pain inhibition underlying symptoms manifestation. Endogenous pain modulation function can be tested using psychophysical methods such as temporal summation of pain (TSP) and conditioned pain modulation (CPM), which assess pain facilitation and inhibition, respectively. Several studies have investigated endogenous pain modulation function in patients with nonparoxysmal orofacial pain (OFP) and reported mixed results. This study aimed to provide, through a qualitative and quantitative synthesis of the available literature, overall estimates for TSP/CPM responses in patients with OFP relative to controls. MEDLINE, Embase, and the Cochrane databases were searched, and references were screened independently by 2 raters. Twenty-six studies were included for qualitative review, and 22 studies were included for meta-analysis. Traditional meta-analysis and robust variance estimation were used to synthesize overall estimates for standardized mean difference. The overall standardized estimate for TSP was 0.30 (95% confidence interval: 0.11-0.49; P = 0.002), with moderate between-study heterogeneity (Q [df = 17] = 41.8, P = 0.001; I = 70.2%). Conditioned pain modulation's estimated overall effect size was large but above the significance threshold (estimate = 1.36; 95% confidence interval: -0.09 to 2.81; P = 0.066), with very large heterogeneity (Q [df = 8] = 108.3, P < 0.001; I = 98.0%). Sensitivity analyses did not affect the overall estimate for TSP; for CPM, the overall estimate became significant if specific random-effect models were used or if the most influential study was removed. Publication bias was not present for TSP studies, whereas it substantially influenced CPM's overall estimate. These results suggest increased pain facilitation and trend for pain inhibition impairment in patients with nonparoxysmal OFP.

The neural basis of kinesthetic and visual imagery in sports: an ALE meta - analysis.

PubMed

Filgueiras, Alberto; Quintas Conde, Erick Francisco; Hall, Craig R

2017-12-19

Imagery is a widely spread technique in the sport sciences that entails the mental rehearsal of a given situation to improve an athlete's learning, performance and motivation. Two modalities of imagery are reported to tap into distinct brain structures, but sharing common components: kinesthetic and visual imagery. This study aimed to investigate the neural basis of those types of imagery with Activation Likelihood Estimation algorithm to perform a meta - analysis. A systematic search was used to retrieve only experimental studies with athletes or sportspersons. Altogether, nine studies were selected and an ALE meta - analysis was performed. Results indicated significant activation of the premotor, somatosensory cortex, supplementary motor areas, inferior and superior parietal lobule, caudate, cingulate and cerebellum in both imagery tasks. It was concluded that visual and kinesthetic imagery share similar neural networks which suggests that combined interventions are beneficial to athletes whereas separate use of those two modalities of imagery may seem less efficient from a neuropsychological approach.

Interaction between the serotonin transporter gene (5-HTTLPR), stressful life events, and risk of depression: a meta-analysis.

PubMed

Risch, Neil; Herrell, Richard; Lehner, Thomas; Liang, Kung-Yee; Eaves, Lindon; Hoh, Josephine; Griem, Andrea; Kovacs, Maria; Ott, Jurg; Merikangas, Kathleen Ries

2009-06-17

Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region (5-HTTLPR) and stressful life events on an increased risk of major depression. To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, > or = 3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR, the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14,250 participants, 1769 were classified as having depression; 12,481 as not having depression. In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined.

Clinical and Molecular Epidemiology of Extended-Spectrum Beta-Lactamase-Producing Klebsiella spp.: A Systematic Review and Meta-Analyses

PubMed Central

Hendrik, Tirza C.; Voor in ‘t holt, Anne F.; Vos, Margreet C.

2015-01-01

Healthcare-related infections caused by extended-spectrum beta-lactamase (ESBL)-producing Klebsiella spp. are of major concern. To control transmission, deep understanding of the transmission mechanisms is needed. This systematic review aimed to identify risk factors and sources, clonal relatedness using molecular techniques, and the most effective control strategies for ESBL-producing Klebsiella spp. A systematic search of PubMed, Embase, and Outbreak Database was performed. We identified 2771 articles from November 25th, 1960 until April 7th, 2014 of which 148 were included in the systematic review and 23 in a random-effects meta-analysis study. The random-effects meta-analyses showed that underlying disease or condition (odds ratio [OR] = 6.25; 95% confidence interval [CI] = 2.85 to 13.66) generated the highest pooled estimate. ESBL-producing Klebsiella spp. were spread through person-to-person contact and via sources in the environment; we identified both monoclonal and polyclonal presence. Multi-faceted interventions are needed to prevent transmission of ESBL-producing Klebsiella spp. PMID:26485570

Weight and prognosis for influenza A(H1N1)pdm09 infection during the pandemic period between 2009 and 2011: a systematic review of observational studies with meta-analysis.

PubMed

Sun, Ying; Wang, Quanyi; Yang, Guoyan; Lin, Changying; Zhang, Yi; Yang, Peng

2016-01-01

In 2009, a novel influenza A(H1N1)pdm09 virus was detected and caused influenza pandemic. It is important to identify the risk factors for severe outcomes. However, inconsistent results regarding the effect of obesity were reported in previous studies. We conducted a systematic review to assess the association between obesity and poor prognosis for laboratory-confirmed A(H1N1)pdm09 influenza. We searched three English databases and three Chinese databases for relevant studies from April 2009 to October 2015: PubMed, the Cochrane library, Embase, CNKI, CBM, and Wanfang. Two investigators independently identified eligible articles, assessed quality using NOS, and extracted data. We performed meta-analyses and meta-regressions to estimate the association between weight and poor prognosis for influenza A(H1N1)pdm09 infection, when data were available. We identified 22 articles enrolling 25,189 laboratory confirmed patients. The pooled estimates indicated obesity significantly increased the risk of fatal and critical complications of influenza A(H1N1)pdm09 infection (for fatal, OR = 1.81, 95% CI: 1.23-2.65; for critical complications, OR = 1.67, 95% CI: 1.13-2.47). However, we found significant interaction between early antiviral treatment and obesity (β = -0.28). After adjustment for early antiviral treatment, relationship between obesity and poor outcomes disappeared (OR = 1.14, 95% CI: 0.94-1.39). The results of the meta-analyses showed obesity significantly increased the risk of death, critical complications, and severe complications for influenza A(H1N1)pdm09 infection, especially among high-quality studies and in Asia region. Importantly, the result from our meta-regression indicated that the conclusion should be interpreted with caution, because early antiviral treatment might be a key confounding factor.

Prevalence of placenta previa among deliveries in Mainland China

PubMed Central

Fan, Dazhi; Wu, Song; Wang, Wen; Xin, Lihong; Tian, Guo; Liu, Li; Feng, Jinping; Guo, Xiaoling; Liu, Zhengping

2016-01-01

Abstract Background: Placenta previa is characterized by the abnormal placenta overlying the endocervical os, and it is known as one of the most feared adverse maternal and fetal-neonatal complications in obstetrics. Objectives: We aimed to obtain overall and regional estimates of placenta previa prevalence among deliveries in Mainland China. Methods: The research was performed a systematic review, following the Meta-analysis of observational studies in epidemiology (MOOSE) guidelines for systematic reviews of observational studies, and the preferred reporting items for systematic reviews and meta-analysis (PRISMA) statement for reporting systematic reviews and meta-analysis. Electronic databases were searched and included hospital-based studies that reported placenta previa prevalence in Mainland China. Random-effects meta-analyses were used to pool prevalence estimates of placenta previa. Meta-regression analyses were performed to explore sources of heterogeneity across the included studies. For exploring the geographical distributions of placenta previa, the ArcGIS software (Esri) was used to construct the map of prevalence. Results: A total of 80 articles and 86 datasets (including 1,298,548 subjects and 14,199 placenta previa cases) from 1965 through 2015 were included. The pooled overall prevalence of placenta previa among deliveries was 1.24% (95% confidence interval [CI], 1.12–1.36) in Mainland China during 1965 to 2015. And, the trend in the prevalence of placenta previa was steady. The occurrence rate of placenta previa in the region groups Northeast, North, Northwest, Central China, East, South, and Southwest was 1.20%, 1.01%, 1.10%, 1.15%, 0.93%, 1.42%, and 2.01%, respectively. The prevalence map based on a geographic information system showed an unequal geographic distribution. Conclusions: The results showed that placenta previa is currently a high-burden disease in Mainland China. This review would be useful for the design of placenta previa planning and implementation adequate health care systems and treatment programs in Mainland China. PMID:27749592

A meta-analysis of interleukin-10-1082 promoter polymorphism associated with gastric cancer risk.

PubMed

Ni, Peihua; Xu, Hong; Xue, Huiping; Lin, Bing; Lu, Yang

2012-04-01

We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer.

A Meta-Analysis of Interleukin-10-1082 Promoter Polymorphism Associated with Gastric Cancer Risk

PubMed Central

Ni, Peihua; Xu, Hong; Xue, Huiping; Lin, Bing

2012-01-01

We aimed to explore the role of allele A/G single nucleotide polymorphism (SNP) of gene Interleukin 10 (IL-10) promoter-1082 in the susceptibility to gastric cancer through a systematic review and meta-analysis. Each initially included article was scored for quality appraisal. Desirable data were extracted and registered into databases. Twenty studies were ultimately eligible for the meta-analysis of IL-10-1082 A/G SNP. We adopted the most probably appropriate genetic model (dominant model), with the combined group of GG-plus-GA genotypes compared with the AA genotype. Potential sources of heterogeneity were sought out via subgroup analyses and sensitivity analyses, and publication biases were estimated. Between IL-10-1082 GG-plus-GA genotypes with the risk of developing gastric cancer, statistically significant association could be noted with overall gastric cancer, being mainly in Asian subgroup, large sample subgroup, high quality subgroup, intestinal-type subgroup, cardia-type subgroup, and some genotyping method subgroups. Our meta-analysis indicates that IL-10-1082 GG-plus-GA genotypes are associated with the overall risk of developing gastric cancer and seem to be more susceptible to overall gastric cancer in Asian populations. IL-10-1082 GG-plus-GA genotypes are more associated with the pathologically intestinal-type gastric cancer or anatomically cardia-type gastric cancer. PMID:22335769

Weighing Evidence “Steampunk” Style via the Meta-Analyser

PubMed Central

Bowden, Jack; Jackson, Chris

2016-01-01

ABSTRACT The funnel plot is a graphical visualization of summary data estimates from a meta-analysis, and is a useful tool for detecting departures from the standard modeling assumptions. Although perhaps not widely appreciated, a simple extension of the funnel plot can help to facilitate an intuitive interpretation of the mathematics underlying a meta-analysis at a more fundamental level, by equating it to determining the center of mass of a physical system. We used this analogy to explain the concepts of weighing evidence and of biased evidence to a young audience at the Cambridge Science Festival, without recourse to precise definitions or statistical formulas and with a little help from Sherlock Holmes! Following on from the science fair, we have developed an interactive web-application (named the Meta-Analyser) to bring these ideas to a wider audience. We envisage that our application will be a useful tool for researchers when interpreting their data. First, to facilitate a simple understanding of fixed and random effects modeling approaches; second, to assess the importance of outliers; and third, to show the impact of adjusting for small study bias. This final aim is realized by introducing a novel graphical interpretation of the well-known method of Egger regression. PMID:28003684

Kaplan-Meier survival analysis overestimates cumulative incidence of health-related events in competing risk settings: a meta-analysis.

PubMed

Lacny, Sarah; Wilson, Todd; Clement, Fiona; Roberts, Derek J; Faris, Peter; Ghali, William A; Marshall, Deborah A

2018-01-01

Kaplan-Meier survival analysis overestimates cumulative incidence in competing risks (CRs) settings. The extent of overestimation (or its clinical significance) has been questioned, and CRs methods are infrequently used. This meta-analysis compares the Kaplan-Meier method to the cumulative incidence function (CIF), a CRs method. We searched MEDLINE, EMBASE, BIOSIS Previews, Web of Science (1992-2016), and article bibliographies for studies estimating cumulative incidence using the Kaplan-Meier method and CIF. For studies with sufficient data, we calculated pooled risk ratios (RRs) comparing Kaplan-Meier and CIF estimates using DerSimonian and Laird random effects models. We performed stratified meta-analyses by clinical area, rate of CRs (CRs/events of interest), and follow-up time. Of 2,192 identified abstracts, we included 77 studies in the systematic review and meta-analyzed 55. The pooled RR demonstrated the Kaplan-Meier estimate was 1.41 [95% confidence interval (CI): 1.36, 1.47] times higher than the CIF. Overestimation was highest among studies with high rates of CRs [RR = 2.36 (95% CI: 1.79, 3.12)], studies related to hepatology [RR = 2.60 (95% CI: 2.12, 3.19)], and obstetrics and gynecology [RR = 1.84 (95% CI: 1.52, 2.23)]. The Kaplan-Meier method overestimated the cumulative incidence across 10 clinical areas. Using CRs methods will ensure accurate results inform clinical and policy decisions. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of residential dampness and mold with respiratory tract infections and bronchitis: a meta-analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fisk, William J.; Eliseeva, Ekaterina A.; Mendell, Mark J.

Dampness and mold have been shown in qualitative reviews to be associated with a variety of adverse respiratory health effects, including respiratory tract infections. Several published meta-analyses have provided quantitative summaries for some of these associations, but not for respiratory infections. Demonstrating a causal relationship between dampness-related agents, which are preventable exposures, and respiratory tract infections would suggest important new public health strategies. We report the results of quantitative meta-analyses of published studies that examined the association of dampness or mold in homes with respiratory infections and bronchitis. For primary studies meeting eligibility criteria, we transformed reported odds ratios (ORs)more » and confidence intervals (CIs) to the log scale. Both fixed and random effects models were applied to the log ORs and their variances. Most studies contained multiple estimated ORs. Models accounted for the correlation between multiple results within the studies analyzed. One set of analyses was performed with all eligible studies, and another set restricted to studies that controlled for age, gender, smoking, and socioeconomic status. Subgroups of studies were assessed to explore heterogeneity. Funnel plots were used to assess publication bias. The resulting summary estimates of ORs from random effects models based on all studies ranged from 1.38 to 1.50, with 95% CIs excluding the null in all cases. Use of different analysis models and restricting analyses based on control of multiple confounding variables changed findings only slightly. ORs (95% CIs) from random effects models using studies adjusting for major confounding variables were, for bronchitis, 1.45 (1.32-1.59); for respiratory infections, 1.44 (1.31-1.59); for respiratory infections excluding nonspecific upper respiratory infections, 1.50 (1.32-1.70), and for respiratory infections in children or infants, 1.48 (1.33-1.65). Little effect of publication bias was evident. Estimated attributable risk proportions ranged from 8% to 20%. Residential dampness and mold are associated with substantial and statistically significant increases in both respiratory infections and bronchitis. If these associations were confirmed as causal, effective control of dampness and mold in buildings would prevent a substantial proportion of respiratory infections.« less

Lifetime prevalence of non-suicidal self-injury in patients with eating disorders: a systematic review and meta-analysis.

PubMed

Cucchi, A; Ryan, D; Konstantakopoulos, G; Stroumpa, S; Kaçar, A Ş; Renshaw, S; Landau, S; Kravariti, E

2016-05-01

Against a backdrop of increasing research, clinical and taxonomic attention in non-suicidal self-injury (NSSI), evidence suggests a link between NSSI and eating disorders (ED). The frequency estimates of NSSI in ED vary widely. Little is known about the sources of this variation, and no meta-analysis has quantified the association between ED and NSSI. Using random-effects meta-analyses, meta-regression analyses, and 1816-6466 unique participants with various ED, we estimated the weighted average percentage of individuals with ED, those with anorexia nervosa (AN) and those with bulimia nervosa (BN) who are reported to have a lifetime history of NSSI across studies. We further examined predictors of NSSI in ED. The weighted average percentage of patients with a lifetime history of NSSI was 27.3% [95% confidence interval (CI) 23.8-31.0%] for ED, 21.8% (95% CI 18.5-25.6%) for AN, and 32.7% (95% CI 26.9-39.1%) for BN. The difference between BN and AN was statistically significant [odds ratio (OR) 1.77, 95% CI 1.14-2.77, p = 0.013]. The odds of NSSI increased by 24% for every 10% increase in the percentage of participants with histories of suicide attempts (OR 1.24, 95% CI 1.04-1.48, p = 0.020) and decreased by 26% for every 10% increase in the percentage of participants with histories of substance abuse (OR 0.74, 95% CI 0.58-0.95, p = 0.023). In the specific context of ED, NSSI is highly prevalent and correlates positively with attempted suicide, urging for NSSI-focused treatments. A novel finding is that NSSI is potentially antagonized by substance abuse.

Cross-education of muscular strength following unilateral resistance training: a meta-analysis.

PubMed

Manca, A; Dragone, D; Dvir, Z; Deriu, Franca

2017-11-01

Cross-education (CE) of strength is a well-known phenomenon whereby exercise of one limb can induce strength gains in the contralateral untrained limb. The only available meta-analyses on CE, which date back to a decade ago, estimated a modest 7.8% increase in contralateral strength following unilateral training. However, in recent years new evidences have outlined larger contralateral gains, which deserve to be systematically evaluated. Therefore, the aim of this meta-analysis was to appraise current data on CE and determine its overall magnitude of effect. Five databases were searched from inception to December 2016. All randomized controlled trials focusing on unilateral resistance training were carefully checked by two reviewers who also assessed the eligibility of the identified trials and extracted data independently. The risk of bias was assessed using the Cochrane Risk-of-Bias tool. Thirty-one studies entered the meta-analysis. Data from 785 subjects were pooled and subgroup analyses by body region (upper/lower limb) and type of training (isometric/concentric/eccentric/isotonic-dynamic) were performed. The pooled estimate of CE was a significant 11.9% contralateral increase (95% CI 9.1-14.8; p < 0.00001; upper limb: + 9.4%, p < 0.00001; lower limb: + 16.4%, p < 0.00001). Significant CE effects were induced by isometric (8.2%; p = 0.0003), concentric (11.3%; p < 0.00001), eccentric (17.7%; p = 0.003) and isotonic-dynamic training (15.9%; p < 0.00001), although a high risk of bias was detected across the studies. Unilateral resistance training induces significant contraction type-dependent gains in the contralateral untrained limb. Methodological issues in the included studies are outlined to provide guidance for a reliable quantification of CE in future studies.

Fruits, vegetables, and bladder cancer risk: a systematic review and meta-analysis.

PubMed

Vieira, Ana R; Vingeliene, Snieguole; Chan, Doris S M; Aune, Dagfinn; Abar, Leila; Navarro Rosenblatt, Deborah; Greenwood, Darren C; Norat, Teresa

2015-01-01

Smoking is estimated to cause about half of all bladder cancer cases. Case-control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose-response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose-response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95-0.99) I(2)  = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94-1.00, I(2)  = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96-1.00, I(2)  = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76-0.99, I(2)  = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Fruits, vegetables, and bladder cancer risk: a systematic review and meta-analysis

PubMed Central

Vieira, Ana R; Vingeliene, Snieguole; Chan, Doris S M; Aune, Dagfinn; Abar, Leila; Navarro Rosenblatt, Deborah; Greenwood, Darren C; Norat, Teresa

2015-01-01

Smoking is estimated to cause about half of all bladder cancer cases. Case–control studies have provided evidence of an inverse association between fruit and vegetable intake and bladder cancer risk. As part of the World Cancer Research/American Institute for Cancer Research Continuous Update Project, we conducted a systematic review and meta-analysis of prospective studies to assess the dose–response relationship between fruit and vegetables and incidence and mortality of bladder cancer. We searched PubMed up to December 2013 for relevant prospective studies. We conducted highest compared with lowest meta-analyses and dose–response meta-analyses using random effects models to estimate summary relative risks (RRs) and 95% confidence intervals (CIs), and used restricted cubic splines to examine possible nonlinear associations. Fifteen prospective studies were included in the review. The summary RR for an increase of 1 serving/day (80 g) were 0.97 (95% CI: 0.95–0.99) I2 = 0%, eight studies for fruits and vegetables, 0.97 (95% CI: 0.94–1.00, I2 = 10%, 10 studies) for vegetables and 0.98 (95% CI: 0.96–1.00, I2 = 0%, 12 studies) for fruits. Results were similar in men and women and in current, former and nonsmokers. Amongst fruits and vegetables subgroups, for citrus fruits the summary RR for the highest compared with the lowest intake was 0.87 (95% CI: 0.76–0.99, I2 = 0%, eight studies) and for cruciferous vegetables there was evidence of a nonlinear relationship (P = 0.001). The current evidence from cohort studies is not consistent with a role for fruits and vegetables in preventing bladder cancer. PMID:25461441

Cotrimoxazole prophylactic treatment prevents malaria in children in sub-Saharan Africa: systematic review and meta-analysis.

PubMed

Mbeye, Nyanyiwe M; ter Kuile, Feiko O; Davies, Mary-Ann; Phiri, Kamija S; Egger, Matthias; Wandeler, Gilles

2014-09-01

Cotrimoxazole prophylactic treatment (CPT) prevents opportunistic infections in HIV-infected or HIV-exposed children, but estimates of the effectiveness in preventing malaria vary. We reviewed studies that examined the effect of CPT on incidence of malaria in children in sub-Saharan Africa. We searched PubMed and EMBASE for randomised controlled trials (RCTs) and cohort studies on the effect of CPT on incidence of malaria and mortality in children and extracted data on the prevalence of sulphadoxine-pyrimethamine resistance-conferring point mutations. Incidence rate ratios (IRR) from individual studies were combined using random effects meta-analysis; confounder-adjusted estimates were used for cohort studies. The importance of resistance was examined in meta-regression analyses. Three RCTs and four cohort studies with 5039 children (1692 HIV-exposed; 2800 HIV-uninfected; 1486 HIV-infected) were included. Children on CPT were less likely to develop clinical malaria episodes than those without prophylaxis (combined IRR 0.37, 95% confidence interval: 0.21-0.66), but there was substantial between-study heterogeneity (I-squared = 94%, P < 0.001). The protective efficacy of CPT was highest in an RCT from Mali, where the prevalence of antifolate resistant plasmodia was low. In meta-regression analyses, there was some evidence that the efficacy of CPT declined with increasing levels of resistance. Mortality was reduced with CPT in an RCT from Zambia, but not in a cohort study from Côte d'Ivoire. Cotrimoxazole prophylactic treatment reduces incidence of malaria and mortality in children in sub-Saharan Africa, but study designs, settings and results were heterogeneous. CPT appears to be beneficial for HIV-infected and HIV-exposed as well as HIV-uninfected children. © 2014 John Wiley & Sons Ltd.

Meta-analysis of residential exposure to radon gas and lung cancer.

PubMed Central

Pavia, Maria; Bianco, Aida; Pileggi, Claudia; Angelillo, Italo F.

2003-01-01

OBJECTIVES: To investigate the relation between residential exposure to radon and lung cancer. METHODS: A literature search was performed using Medline and other sources. The quality of studies was assessed. Adjusted odds ratios with 95% confidence intervals (CI) for the risk of lung cancer among categories of levels of exposure to radon were extracted. For each study, a weighted log-linear regression analysis of the adjusted odds ratios was performed according to radon concentration. The random effect model was used to combine values from single studies. Separate meta-analyses were performed on results from studies grouped with similar characteristics or with quality scores above or equal to the median. FINDINGS: Seventeen case-control studies were included in the meta-analysis. Quality scoring for individual studies ranged from 0.45 to 0.77 (median, 0.64). Meta-analysis based on exposure at 150 Bq/m3 gave a pooled odds ratio estimate of 1.24 (95% CI, 1.11-1.38), which indicated a potential effect of residential exposure to radon on the risk of lung cancer. Pooled estimates of fitted odds ratios at several levels of randon exposure were all significantly different from unity--ranging from 1.07 at 50 Bq/m3 to 1.43 at 250 Bq/m3. No remarkable differences from the baseline analysis were found for odds ratios from sensitivity analyses of studies in which > 75% of eligible cases were recruited (1.12, 1.00-1.25) and studies that included only women (1.29, 1.04-1.60). CONCLUSION: Although no definitive conclusions may be drawn, our results suggest a dose-response relation between residential exposure to radon and the risk of lung cancer. They support the need to develop strategies to reduce human exposure to radon. PMID:14758433

A Quantitative Assessment of the Reporting Quality of Herbal Medicine Research: The Road to Improvement.

PubMed

Naumann, Ken

2018-02-01

To quantify different aspects of the quality of reporting of herbal medicine clinical trials, to determine how that quality is affecting the conclusions of meta-analyses, and to target areas for improvement in future herbal medicine research reporting. The Electronic databases PubMed, Academic Search Premier, ScienceDirect, and Alt HealthWatch were searched for meta-analyses of herbal medicines in refereed journals and Cochrane Reviews in the years 2000-2004 and 2010-2014. The search was limited to meta-analyses of randomized controlled trials involving humans and published in English. Judgments and descriptions within the meta-analyses were used to report on risks of bias in the included clinical trials and the meta-analyses themselves. Out of 3264 citations, 9 journal-published meta-analyses were selected from 2000 to 2004, 116 from 2010 to 2014, and 44 Cochrane Reviews from 2010 to 2014. Across both time frames and categories of publication, <42% of the trials included in the meta-analyses described adequate randomization; <19% described concealment methods; <26% described double blinding; <29% described outcome assessment blinding, ≤53% discussed incomplete data, and <36% were nonselective in their reporting. Less than 54% of trials reported on adverse events and 64% of meta-analyses did not include a single trial with a low risk of bias. Taxonomic verification and chemical characterization of test products were infrequent in trials. Only 40% of meta-analyses considered publication bias and, of those that did, 90% found evidence for it. Cochrane Reviews were more likely than other sources to make negative conclusions of efficacy or to defer conclusions because of the absence of high quality trials. Meta-analyses of herbal medicines include a significant number of clinical trials that do not meet the recommended standards for clinical trial reporting. This quantitative assessment identified significant publication bias and other bias risks that may be due to inadequate trial design or incomplete reporting of outcomes. Suggested improvements to herbal medicine clinical trial reporting are discussed.

The impact of multiple endpoint dependency on Q and I(2) in meta-analysis.

PubMed

Thompson, Christopher Glen; Becker, Betsy Jane

2014-09-01

A common assumption in meta-analysis is that effect sizes are independent. When correlated effect sizes are analyzed using traditional univariate techniques, this assumption is violated. This research assesses the impact of dependence arising from treatment-control studies with multiple endpoints on homogeneity measures Q and I(2) in scenarios using the unbiased standardized-mean-difference effect size. Univariate and multivariate meta-analysis methods are examined. Conditions included different overall outcome effects, study sample sizes, numbers of studies, between-outcomes correlations, dependency structures, and ways of computing the correlation. The univariate approach used typical fixed-effects analyses whereas the multivariate approach used generalized least-squares (GLS) estimates of a fixed-effects model, weighted by the inverse variance-covariance matrix. Increased dependence among effect sizes led to increased Type I error rates from univariate models. When effect sizes were strongly dependent, error rates were drastically higher than nominal levels regardless of study sample size and number of studies. In contrast, using GLS estimation to account for multiple-endpoint dependency maintained error rates within nominal levels. Conversely, mean I(2) values were not greatly affected by increased amounts of dependency. Last, we point out that the between-outcomes correlation should be estimated as a pooled within-groups correlation rather than using a full-sample estimator that does not consider treatment/control group membership. Copyright © 2014 John Wiley & Sons, Ltd.

Multilevel mixed effects parametric survival models using adaptive Gauss-Hermite quadrature with application to recurrent events and individual participant data meta-analysis.

PubMed

Crowther, Michael J; Look, Maxime P; Riley, Richard D

2014-09-28

Multilevel mixed effects survival models are used in the analysis of clustered survival data, such as repeated events, multicenter clinical trials, and individual participant data (IPD) meta-analyses, to investigate heterogeneity in baseline risk and covariate effects. In this paper, we extend parametric frailty models including the exponential, Weibull and Gompertz proportional hazards (PH) models and the log logistic, log normal, and generalized gamma accelerated failure time models to allow any number of normally distributed random effects. Furthermore, we extend the flexible parametric survival model of Royston and Parmar, modeled on the log-cumulative hazard scale using restricted cubic splines, to include random effects while also allowing for non-PH (time-dependent effects). Maximum likelihood is used to estimate the models utilizing adaptive or nonadaptive Gauss-Hermite quadrature. The methods are evaluated through simulation studies representing clinically plausible scenarios of a multicenter trial and IPD meta-analysis, showing good performance of the estimation method. The flexible parametric mixed effects model is illustrated using a dataset of patients with kidney disease and repeated times to infection and an IPD meta-analysis of prognostic factor studies in patients with breast cancer. User-friendly Stata software is provided to implement the methods. Copyright © 2014 John Wiley & Sons, Ltd.

A joint frailty-copula model between tumour progression and death for meta-analysis.

PubMed

Emura, Takeshi; Nakatochi, Masahiro; Murotani, Kenta; Rondeau, Virginie

2017-12-01

Dependent censoring often arises in biomedical studies when time to tumour progression (e.g., relapse of cancer) is censored by an informative terminal event (e.g., death). For meta-analysis combining existing studies, a joint survival model between tumour progression and death has been considered under semicompeting risks, which induces dependence through the study-specific frailty. Our paper here utilizes copulas to generalize the joint frailty model by introducing additional source of dependence arising from intra-subject association between tumour progression and death. The practical value of the new model is particularly evident for meta-analyses in which only a few covariates are consistently measured across studies and hence there exist residual dependence. The covariate effects are formulated through the Cox proportional hazards model, and the baseline hazards are nonparametrically modeled on a basis of splines. The estimator is then obtained by maximizing a penalized log-likelihood function. We also show that the present methodologies are easily modified for the competing risks or recurrent event data, and are generalized to accommodate left-truncation. Simulations are performed to examine the performance of the proposed estimator. The method is applied to a meta-analysis for assessing a recently suggested biomarker CXCL12 for survival in ovarian cancer patients. We implement our proposed methods in R joint.Cox package.

The efficacy and safety of medical leech therapy for osteoarthritis of the knee: A meta-analysis of randomized controlled trials.

PubMed

Wang, Haixia; Zhang, Jing; Chen, Liyan

2018-06-01

It is controversial on whether medical leech therapy is effective in improving pain and functional outcome in patients with knee osteoarthritis (OA). Therefore, we perform a meta-analysis from randomized controlled trials (RCTs) to evaluate the efficacy and safety of medical leech therapy in patients with knee OA. The PubMed, EMBASE, ScienceDirect, and Cochrane Library databases were systematically searched for literature up to January 2018. RCTs involving medical leech therapy in patients with knee OA were included. Two independent reviewers performed independent data abstraction. The I 2 statistic was used to assess heterogeneity. A fixed or random effects model was adopted for meta-analysis. All meta-analyses were performed by using STATA 12.0. Four RCTs with 264 patients were included in this meta-analysis. The current meta-analysis showed that there were significant differences in terms of visual analogue scale (VAS) scores and WOMAC scores at 1 week, 4weeks and 7 weeks compared with control groups. However, leech therapy was associated with a significantly higher incidence of adverse events. The overall evidence quality is moderate, which means that further research is likely to significantly change confidence in the effect estimate but may change the estimate. Medical leech therapy was associated with a significantly improved outcome in pain relief and functional recovery in patients with symptomatic knee OA. However, given the inherent limitations in the included studies, this conclusion should be interpreted cautiously. Copyright © 2018 IJS Publishing Group Ltd. Published by Elsevier Ltd. All rights reserved.

The Effect of Omega-3 on Circulating Adiponectin in Adults with Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

PubMed

Bahreini, Mehdi; Ramezani, Amir-Hossein; Shishehbor, Farideh; Mansoori, Anahita

2018-01-04

Whether consumption of omega-3 affects circulating adiponectin has not been established. The objective of this study was to evaluate the effect of omega-3 (food or supplement) on circulating adiponectin in patients with type 2 diabetes through a systematic review of meta-analyses of randomized controlled trials. PubMed, Scopus and Web of Science were searched for relevant studies through May 2016. Two researchers screened and abstracted the literature independently. Pooled estimates were obtained using the random-effects models. Overall, omega-3 increased adiponectin by 0.57 µg/mL (95% confidence interval [CI] 0.15 to 1.31; p=0.01, I-square=74.2% p for heterogeneity <0.001). The source of observed heterogeneity was explored by subgroup analyses. In subgroup analyses, adiponectin levels increased only in those who had consumed omega-3 for more than 8 weeks. This systematic review and meta-analysis of randomized, placebo-controlled clinical trials suggests that omega-3 in patients with type 2 diabetes increases circulating adiponectin. These findings support the potentially beneficial effects of dietary omega-3 in patients with type 2 diabetes on pathways related to adiponectin metabolism. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

Cohort profile: the chronic kidney disease prognosis consortium.

PubMed

Matsushita, Kunihiro; Ballew, Shoshana H; Astor, Brad C; Jong, Paul E de; Gansevoort, Ron T; Hemmelgarn, Brenda R; Levey, Andrew S; Levin, Adeera; Wen, Chi-Pang; Woodward, Mark; Coresh, Josef

2013-12-01

The Chronic Kidney Disease Prognosis Consortium (CKD-PC) was established in 2009 to provide comprehensive evidence about the prognostic impact of two key kidney measures that are used to define and stage CKD, estimated glomerular filtration rate (eGFR) and albuminuria, on mortality and kidney outcomes. CKD-PC currently consists of 46 cohorts with data on these kidney measures and outcomes from >2 million participants spanning across 40 countries/regions all over the world. CKD-PC published four meta-analysis articles in 2010-11, providing key evidence for an international consensus on the definition and staging of CKD and an update for CKD clinical practice guidelines. The consortium continues to work on more detailed analysis (subgroups, different eGFR equations, other exposures and outcomes, and risk prediction). CKD-PC preferably collects individual participant data but also applies a novel distributed analysis model, in which each cohort runs statistical analysis locally and shares only analysed outputs for meta-analyses. This distributed model allows inclusion of cohorts which cannot share individual participant level data. According to agreement with cohorts, CKD-PC will not share data with third parties, but is open to including further eligible cohorts. Each cohort can opt in/out for each topic. CKD-PC has established a productive and effective collaboration, allowing flexible participation and complex meta-analyses for studying CKD.

Methodological Quality Assessment of Meta-Analyses of Hyperthyroidism Treatment.

PubMed

Qin, Yahong; Yao, Liang; Shao, Feifei; Yang, Kehu; Tian, Limin

2018-01-01

Hyperthyroidism is a common condition that is associated with increased morbidity and mortality. A number of meta-analyses (MAs) have assessed the therapeutic measures for hyperthyroidism, including antithyroid drugs, surgery, and radioiodine, however, the methodological quality has not been evaluated. This study evaluated the methodological quality and summarized the evidence obtained from MAs of hyperthyroidism treatments for radioiodine, antithyroid drugs, and surgery. We searched the PubMed, EMBASE, Cochrane Library, Web of Science, and Chinese Biomedical Literature Database databases. Two investigators independently assessed the meta-analyses titles and abstracts for inclusion. Methodological quality was assessed using the validated AMSTAR (Assessing the Methodological Quality of Systematic Reviews) tool. A total of 26 MAs fulfilled the inclusion criteria. Based on the AMSTAR scores, the average methodological quality was 8.31, with large variability ranging from 4 to 11. The methodological quality of English meta-analyses was better than that of Chinese meta-analyses. Cochrane reviews had better methodological quality than non-Cochrane reviews due to better study selection and data extraction, the inclusion of unpublished studies, and better reporting of study characteristics. The authors did not report conflicts of interest in 53.8% meta-analyses, and 19.2% did not report the harmful effects of treatment. Publication bias was not assessed in 38.5% of meta-analyses, and 19.2% did not report the follow-up time. Large-scale assessment of methodological quality of meta-analyses of hyperthyroidism treatment highlighted methodological strengths and weaknesses. Consideration of scientific quality when formulating conclusions should be made explicit. Future meta-analyses should improve on reporting conflict of interest. © Georg Thieme Verlag KG Stuttgart · New York.

Incidence of bradycardia in pediatric patients receiving dexmedetomidine anesthesia: a meta-analysis.

PubMed

Gong, Maowei; Man, Yuanyuan; Fu, Qiang

2017-02-01

Background Dexmedetomidine, an α2-receptor agonist, provides potent sedation, analgesia, and anxiolysis without respiratory depression and is used in a variety of surgical and procedural situations. Aim of the review The aim of this study was to estimate the incidence of bradycardia in pediatric patients who received dexmedetomidine as a sole agent for any procedural, intensive care or surgical sedation. Method Literature was searched in electronic databases and studies were selected by following pre-determined eligibility criteria. Meta-analyses were carried out by pooling the percent incidence of bradycardia to attain a weighted overall effect size. Age-wise subgroup analyses and meta-regression analyses for the identification of factors affecting the incidence were also performed. Results Data of 2835 patients from 21 studies were included. The mean age was 62.21 ± 35.68 months. Initial, maintenance and total doses of dexmedetomidine (mean ± standard deviation) were 1.63 ± 0.33 μg/kg body weight, 0.86 ± 0.68 μg/kg/h, and 26.7 ± 20.8 μg/kg. The overall incidence of bradycardia (95% confidence interval) was 3.067 (2.863, 3.270)%; P < 0.0001. However, range was wider (0-22%) with 9 studies observed 0% incidence. The mean change in the heart rate was -17.26 (-21.60, -12.92); P < 0.00001. In the meta-regression analyses, age, body weight and dexmedetomidine dose were not significantly associated with the incidence of bradycardia. The minimum heart rate observed during the dexmedetomidine treatment period was positively associated with baseline heart rate. Conclusion Incidence of bradycardia in dexmedetomidine treated pediatric patients is 3%.

The march from early life food sensitization to allergic disease: a systematic review and meta-analyses of birth cohort studies.

PubMed

Alduraywish, S A; Lodge, C J; Campbell, B; Allen, K J; Erbas, B; Lowe, A J; Dharmage, S C

2016-01-01

There is growing evidence for an increase in food allergies. The question of whether early life food sensitization, a primary step in food allergies, leads to other allergic disease is a controversial but important issue. Birth cohorts are an ideal design to answer this question. We aimed to systematically investigate and meta-analyse the evidence for associations between early food sensitization and allergic disease in birth cohorts. MEDLINE and SCOPUS databases were searched for birth cohorts that have investigated the association between food sensitization in the first 2 years and subsequent wheeze/asthma, eczema and/or allergic rhinitis. We performed meta-analyses using random-effects models to obtain pooled estimates, stratified by age group. The search yielded fifteen original articles representing thirteen cohorts. Early life food sensitization was associated with an increased risk of infantile eczema, childhood wheeze/asthma, eczema and allergic rhinitis and young adult asthma. Meta-analyses demonstrated that early life food sensitization is related to an increased risk of wheeze/asthma (pooled OR 2.9; 95% CI 2.0-4.0), eczema (pooled OR 2.7; 95% CI 1.7-4.4) and allergic rhinitis (pooled OR 3.1; 95% CI 1.9-4.9) from 4 to 8 years. Food sensitization in the first 2 years of life can identify children at high risk of subsequent allergic disease who may benefit from early life preventive strategies. However, due to potential residual confounding in the majority of studies combined with lack of follow-up into adolescence and adulthood, further research is needed. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Active Learning in Engineering Education: a (re)introduction

NASA Astrophysics Data System (ADS)

Lima, Rui M.; Andersson, Pernille Hammar; Saalman, Elisabeth

2017-01-01

The informal network 'Active Learning in Engineering Education' (ALE) has been promoting Active Learning since 2001. ALE creates opportunity for practitioners and researchers of engineering education to collaboratively learn how to foster learning of engineering students. The activities in ALE are centred on the vision that learners construct their knowledge based on meaningful activities and knowledge. In 2014, the steering committee of the ALE network reinforced the need to discuss the meaning of Active Learning and that was the base for this proposal for a special issue. More than 40 submissions were reviewed by the European Journal of Engineering Education community and this theme issue ended up with eight contributions, which are different both in their research and Active Learning approaches. These different Active Learning approaches are aligned with the different approaches that can be increasingly found in indexed journals.

Adaptive reconnection-based arbitrary Lagrangian Eulerian method

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bo, Wurigen; Shashkov, Mikhail

We present a new adaptive Arbitrary Lagrangian Eulerian (ALE) method. This method is based on the reconnection-based ALE (ReALE) methodology of Refs. [35], [34] and [6]. The main elements in a standard ReALE method are: an explicit Lagrangian phase on an arbitrary polygonal (in 2D) mesh in which the solution and positions of grid nodes are updated; a rezoning phase in which a new grid is defined by changing the connectivity (using Voronoi tessellation) but not the number of cells; and a remapping phase in which the Lagrangian solution is transferred onto the new grid. Furthermore, in the standard ReALEmore » method, the rezoned mesh is smoothed by using one or several steps toward centroidal Voronoi tessellation, but it is not adapted to the solution in any way.« less

Adaptive reconnection-based arbitrary Lagrangian Eulerian method

DOE PAGES

Bo, Wurigen; Shashkov, Mikhail

2015-07-21

We present a new adaptive Arbitrary Lagrangian Eulerian (ALE) method. This method is based on the reconnection-based ALE (ReALE) methodology of Refs. [35], [34] and [6]. The main elements in a standard ReALE method are: an explicit Lagrangian phase on an arbitrary polygonal (in 2D) mesh in which the solution and positions of grid nodes are updated; a rezoning phase in which a new grid is defined by changing the connectivity (using Voronoi tessellation) but not the number of cells; and a remapping phase in which the Lagrangian solution is transferred onto the new grid. Furthermore, in the standard ReALEmore » method, the rezoned mesh is smoothed by using one or several steps toward centroidal Voronoi tessellation, but it is not adapted to the solution in any way.« less

Meta-analyses are no substitute for registered replications: a skeptical perspective on religious priming

PubMed Central

van Elk, Michiel; Matzke, Dora; Gronau, Quentin F.; Guan, Maime; Vandekerckhove, Joachim; Wagenmakers, Eric-Jan

2015-01-01

According to a recent meta-analysis, religious priming has a positive effect on prosocial behavior (Shariff et al., 2015). We first argue that this meta-analysis suffers from a number of methodological shortcomings that limit the conclusions that can be drawn about the potential benefits of religious priming. Next we present a re-analysis of the religious priming data using two different meta-analytic techniques. A Precision-Effect Testing–Precision-Effect-Estimate with Standard Error (PET-PEESE) meta-analysis suggests that the effect of religious priming is driven solely by publication bias. In contrast, an analysis using Bayesian bias correction suggests the presence of a religious priming effect, even after controlling for publication bias. These contradictory statistical results demonstrate that meta-analytic techniques alone may not be sufficiently robust to firmly establish the presence or absence of an effect. We argue that a conclusive resolution of the debate about the effect of religious priming on prosocial behavior – and about theoretically disputed effects more generally – requires a large-scale, preregistered replication project, which we consider to be the sole remedy for the adverse effects of experimenter bias and publication bias. PMID:26441741

A correlated meta-analysis strategy for data mining "OMIC" scans.

PubMed

Province, Michael A; Borecki, Ingrid B

2013-01-01

Meta-analysis is becoming an increasingly popular and powerful tool to integrate findings across studies and OMIC dimensions. But there is the danger that hidden dependencies between putatively "independent" studies can cause inflation of type I error, due to reinforcement of the evidence from false-positive findings. We present here a simple method for conducting meta-analyses that automatically estimates the degree of any such non-independence between OMIC scans and corrects the inference for it, retaining the proper type I error structure. The method does not require the original data from the source studies, but operates only on summary analysis results from these in OMIC scans. The method is applicable in a wide variety of situations including combining GWAS and or sequencing scan results across studies with dependencies due to overlapping subjects, as well as to scans of correlated traits, in a meta-analysis scan for pleiotropic genetic effects. The method correctly detects which scans are actually independent in which case it yields the traditional meta-analysis, so it may safely be used in all cases, when there is even a suspicion of correlation amongst scans.

Altitude training and haemoglobin mass from the optimised carbon monoxide rebreathing method determined by a meta-analysis

PubMed Central

Gore, Christopher J; Sharpe, Ken; Garvican-Lewis, Laura A; Saunders, Philo U; Humberstone, Clare E; Robertson, Eileen Y; Wachsmuth, Nadine B; Clark, Sally A; McLean, Blake D; Friedmann-Bette, Birgit; Neya, Mitsuo; Pottgiesser, Torben; Schumacher, Yorck O; Schmidt, Walter F

2013-01-01

Objective To characterise the time course of changes in haemoglobin mass (Hbmass) in response to altitude exposure. Methods This meta-analysis uses raw data from 17 studies that used carbon monoxide rebreathing to determine Hbmass prealtitude, during altitude and postaltitude. Seven studies were classic altitude training, eight were live high train low (LHTL) and two mixed classic and LHTL. Separate linear-mixed models were fitted to the data from the 17 studies and the resultant estimates of the effects of altitude used in a random effects meta-analysis to obtain an overall estimate of the effect of altitude, with separate analyses during altitude and postaltitude. In addition, within-subject differences from the prealtitude phase for altitude participant and all the data on control participants were used to estimate the analytical SD. The ‘true’ between-subject response to altitude was estimated from the within-subject differences on altitude participants, between the prealtitude and during-altitude phases, together with the estimated analytical SD. Results During-altitude Hbmass was estimated to increase by ∼1.1%/100 h for LHTL and classic altitude. Postaltitude Hbmass was estimated to be 3.3% higher than prealtitude values for up to 20 days. The within-subject SD was constant at ∼2% for up to 7 days between observations, indicative of analytical error. A 95% prediction interval for the ‘true’ response of an athlete exposed to 300 h of altitude was estimated to be 1.1–6%. Conclusions Camps as short as 2 weeks of classic and LHTL altitude will quite likely increase Hbmass and most athletes can expect benefit. PMID:24282204

A meta-analysis of acute alcohol use and the risk of suicide attempt

PubMed Central

Borges, Guilherme; Bagge, Courtney; Cherpitel, Cheryl J.; Conner, Kenneth; Orozco, Ricardo; Rossow, Ingeborg

2016-01-01

Background While there are reviews reporting on the prevalence of acute use of alcohol (AUA) prior to suicide attempts, no review has used a meta-analytic approach to estimate common odds ratios (OR) of the effect of AUA on suicide attempts. We aim to report the results of the first meta-analysis of controlled epidemiological studies on acute alcohol use and suicide attempt. Methods The English language literature on Medline, PsychInfo, Google Scholar, and public-use databases was searched for original articles and critical review reports on acute alcohol use and suicide attempt for the period ranging from 1996–2015. Studies had to report an OR estimate for this association. Common odds ratios and 95% Confidence Intervals (95%CI) from random effects in meta-analyses for any acute alcohol use and 2 levels of alcohol use on suicide attempt were calculated. Results We gathered 7 studies that provided OR estimates for the likelihood of suicide attempt by acute alcohol use, compared to those who did not drink alcohol. Studies used case-control (3) and case-crossover design (4). All studies found increased ORs for acute alcohol use on suicide attempt. Meta-analysis revealed a common OR of 6.97 (95%CI=4.77, 10.17) for any acute alcohol use. Evidence from 4 studies suggests that «low levels of acute drinking» resulted in an OR of 2.71 (95%CI=1.56, 4.71) and «high levels» had much greater odds of suicide attempt, OR of 37.18 (95%CI=17.38, 79.53). Conclusions Acute use of alcohol is associated with increased likelihood of a suicide attempt, particularly at high doses. Such data should be incorporated into estimates of the burden of disease associated with alcohol use, which are currently limited by a consideration of only alcohol’s chronic effects. Future research should focus on the mechanisms through which acute use of alcohol confers risk for attempt. PMID:27928972

Global-scale impacts of nitrogen deposition on tree carbon sequestration in tropical, temperate, and boreal forests: A meta-analysis.

PubMed

Schulte-Uebbing, Lena; de Vries, Wim

2018-02-01

Elevated nitrogen (N) deposition may increase net primary productivity in N-limited terrestrial ecosystems and thus enhance the terrestrial carbon (C) sink. To assess the magnitude of this N-induced C sink, we performed a meta-analysis on data from forest fertilization experiments to estimate N-induced C sequestration in aboveground tree woody biomass, a stable C pool with long turnover times. Our results show that boreal and temperate forests responded strongly to N addition and sequestered on average an additional 14 and 13 kg C per kg N in aboveground woody biomass, respectively. Tropical forests, however, did not respond significantly to N addition. The common hypothesis that tropical forests do not respond to N because they are phosphorus-limited could not be confirmed, as we found no significant response to phosphorus addition in tropical forests. Across climate zones, we found that young forests responded more strongly to N addition, which is important as many previous meta-analyses of N addition experiments rely heavily on data from experiments on seedlings and young trees. Furthermore, the C-N response (defined as additional mass unit of C sequestered per additional mass unit of N addition) was affected by forest productivity, experimental N addition rate, and rate of ambient N deposition. The estimated C-N responses from our meta-analysis were generally lower that those derived with stoichiometric scaling, dynamic global vegetation models, and forest growth inventories along N deposition gradients. We estimated N-induced global C sequestration in tree aboveground woody biomass by multiplying the C-N responses obtained from the meta-analysis with N deposition estimates per biome. We thus derived an N-induced global C sink of about 177 (112-243) Tg C/year in aboveground and belowground woody biomass, which would account for about 12% of the forest biomass C sink (1,400 Tg C/year). © 2017 John Wiley & Sons Ltd.

Global Birth Prevalence of Spina Bifida by Folic Acid Fortification Status: A Systematic Review and Meta-Analysis.

PubMed

Atta, Callie A M; Fiest, Kirsten M; Frolkis, Alexandra D; Jette, Nathalie; Pringsheim, Tamara; St Germaine-Smith, Christine; Rajapakse, Thilinie; Kaplan, Gilaad G; Metcalfe, Amy

2016-01-01

Birth defects remain a significant source of worldwide morbidity and mortality. Strong scientific evidence shows that folic acid fortification of a region's food supply leads to a decrease in spina bifida (a birth defect of the spine). Still, many countries around the world have yet to approve mandatory fortification through government legislation. We sought to perform a systematic review and meta-analysis of period prevalence of spina bifida by folic acid fortification status, geographic region, and study population. An expert research librarian used terms related to neural tube defects and epidemiology from primary research from 1985 to 2010 to search in EMBASE and MEDLINE. We searched the reference lists of included articles and key review articles identified by experts. Inclusion criteria included studies in English or French reporting on prevalence published between January 1985 and December 2010 that (1) were primary research, (2) were population-based, and (3) reported a point or period prevalence estimate of spina bifida (i.e., prevalence estimate with confidence intervals or case numerator and population denominator). Two independent reviewers screened titles and abstracts for eligible articles, then 2 authors screened full texts in duplicate for final inclusion. Disagreements were resolved through consensus or a third party. We followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses, or PRISMA, abstracting data related to case ascertainment, study population, folic acid fortification status, geographic region, and prevalence estimate independently and in duplicate. We extracted overall data and any subgroups reported by age, gender, time period, or type of spina bifida. We classified each period prevalence estimate as "mandatory" or "voluntary" folic acid fortification according to each country's folic acid fortification status at the time data were collected (as determined by a well-recognized fortification monitoring body, Food Fortification Initiative). We determined study quality on the basis of sample representativeness, standardization of data collection and birth defect assessment, and statistical analyses. We analyzed study-level period prevalence estimates by using a random effects model (α level of < 0.05) for all meta-analyses. We stratified pooled period prevalence estimates by birth population, fortification status, and continent. Of 4078 studies identified, we included 179 studies in the systematic review and 123 in a meta-analysis. In studies of live births (LBs) alone, period prevalences of spina bifida were (1) lower in geographical regions with mandatory (33.86 per 100,000 LBs) versus voluntary (48.35 per 100,000 LBs) folic acid fortification, and (2) lower in studies of LBs, stillbirths, and terminations of pregnancy in regions with mandatory (35.22 per 100,000 LBs) versus voluntary (52.29 per 100,000 LBs) fortification. In LBs, stillbirths, and terminations of pregnancy studies, the lowest pooled prevalence estimate was in North America (38.70 per 100,000). Case ascertainment, surveillance methods, and reporting varied across these population-based studies. Mandatory legislation enforcing folic acid fortification of the food supply lags behind the evidence, particularly in Asian and European countries. This extensive literature review shows that spina bifida is significantly more common in world regions without government legislation regulating full-coverage folic acid fortification of the food supply (i.e., Asia, Europe) and that mandatory folic acid fortification resulted in a lower prevalence of spina bifida regardless of the type of birth cohort. African data were scarce, but needed, as many African nations are beginning to adopt folic acid legislation.

Effectiveness of seasonal influenza vaccination in community-dwelling elderly people: an individual participant data meta-analysis of test-negative design case-control studies.

PubMed

Darvishian, Maryam; van den Heuvel, Edwin R; Bissielo, Ange; Castilla, Jesus; Cohen, Cheryl; Englund, Helene; Gefenaite, Giedre; Huang, Wan-Ting; la Bastide-van Gemert, Sacha; Martinez-Baz, Iván; McAnerney, Johanna M; Ntshoe, Genevie M; Suzuki, Motoi; Turner, Nikki; Hak, Eelko

2017-03-01

Several aggregate data meta-analyses have provided estimates of the effectiveness of influenza vaccination in community-dwelling elderly people. However, these studies ignored the effects of patient-level confounders such as sex, age, and chronic diseases that could bias effectiveness estimates. We aimed to assess the confounder-adjusted effectiveness of influenza vaccines on laboratory-confirmed influenza among elderly people by conducting a global individual participant data meta-analysis. In this individual participant data meta-analysis, we considered studies included in a previously conducted aggregate data meta-analysis that included test-negative design case-control studies published up to July 13, 2014. We contacted all authors of the included studies on Dec 1, 2014, to request individual participant data. Patients were excluded if their unique identifier was missing, their vaccination status was unknown, their outcome status was unknown, or they had had suspected influenza infection more than once in the same influenza season. Cases were patients with influenza-like illness symptoms who tested positive for at least one of A H1N1, A H1N1 pdm09, A H3N2, or B viruses; controls were patients with influenza-like illness symptoms who tested negative for these virus types or subtypes. Influenza vaccine effectiveness against overall and subtype-specific laboratory-confirmed influenza were the primary and secondary outcomes. We used a generalised linear mixed model to calculate adjusted vaccine effectiveness according to vaccine match to the circulating strains of influenza virus and intensity of the virus activity (epidemic or non-epidemic). Vaccine effectiveness was defined as the relative reduction in risk of laboratory-confirmed influenza in vaccinated patients compared with unvaccinated patients. We did subgroup analyses to estimate vaccine effectiveness according to hemisphere, age category, and health status. We received 23 of the 53 datasets included in the aggregate data meta-analysis. Furthermore, six additional datasets were provided by data collaborators, which resulted in individual participant data for a total of 5210 participants. A total of 4975 patients had the required data for analysis. Of these, 3146 (63%) were controls and 1829 (37%) were cases. Influenza vaccination was significantly effective during epidemic seasons irrespective of vaccine match status (matched adjusted vaccine effectiveness 44·38%, 95% CI 22·63-60·01; mismatched adjusted vaccine effectiveness 20·00%, 95% CI 3·46-33·68; analyses in the imputed dataset). Seasonal influenza vaccination did not show significant effectiveness during non-epidemic seasons. We found substantial variation in vaccine effectiveness across virus types and subtypes, with the highest estimate for A H1N1 pdm09 (53·19%, 10·25-75·58) and the lowest estimate for B virus types (-1·52%, -39·58 to 26·16). Although we observed no significant differences between subgroups in each category (hemisphere, age, and health status), influenza vaccination showed a protective effect among elderly people with cardiovascular disease, lung disease, or aged 75 years and younger. Influenza vaccination is moderately effective against laboratory-confirmed influenza in elderly people during epidemic seasons. More research is needed to investigate factors affecting vaccine protection (eg, brand-specific or type-specific vaccine effectiveness and repeated annual vaccination) in elderly people. University Medical Center Groningen. Copyright © 2017 Elsevier Ltd. All rights reserved.

Influence of genetic variants on toxicity to anti-tubercular agents: a systematic review and meta-analysis (protocol).

PubMed

Richardson, Marty; Kirkham, Jamie; Dwan, Kerry; Sloan, Derek; Davies, Geraint; Jorgensen, Andrea

2017-07-13

Tuberculosis patients receiving anti-tuberculosis treatment may experience serious adverse drug reactions, such as hepatotoxicity. Genetic risk factors, such as polymorphisms of the NAT2, CYP2E1 and GSTM1 genes, may increase the risk of experiencing such toxicity events. Many pharmacogenetic studies have investigated the association between genetic variants and anti-tuberculosis drug-related toxicity events, and several meta-analyses have synthesised data from these studies, although conclusions from these meta-analyses are conflicting. Many meta-analyses also have serious methodological limitations, such as applying restrictive inclusion criteria, or not assessing the quality of included studies. Most also only consider hepatotoxicity outcomes and specific genetic variants. The purpose of this systematic review and meta-analysis is to give a comprehensive evaluation of the evidence base for associations between any genetic variant and anti-tuberculosis drug-related toxicity. We will search for studies in MEDLINE, EMBASE, BIOSIS and Web of Science. We will also hand search reference lists from relevant studies and contact experts in the field. We will include cohort studies, case-control studies and randomised controlled trials that recruited patients with tuberculosis who were either already established on anti-tuberculosis treatment or were commencing treatment and who were genotyped to investigate the effect of genetic variants on any anti-tuberculosis drug-related toxicity outcome. One author will screen abstracts to identify potentially relevant studies and will then obtain the full text for each potentially relevant study in order to assess eligibility. At each of these stages, a second author will independently screen/assess 10% of studies. Two authors will independently extract data and assess the quality of studies using a pre-piloted data extraction form. If appropriate, we will pool estimates of effect for each genotype on each outcome using meta-analyses stratified by ethnicity. Our review and meta-analysis will update and add to the existing research in this field. By not restricting the scope of the review to a specific drug, genetic variant, or toxicity outcome, we hope to synthesise data for associations between genetic variants and anti-tuberculosis drug-related toxicity outcomes that have previously not been summarised in systematic reviews, and consequently, add to the knowledge base of the pharmacogenetics of anti-tuberculosis drugs. PROSPERO CRD42017068448.

Risk of solid cancer in low dose-rate radiation epidemiological studies and the dose-rate effectiveness factor.

PubMed

Shore, Roy; Walsh, Linda; Azizova, Tamara; Rühm, Werner

2017-10-01

Estimated radiation risks used for radiation protection purposes have been based primarily on the Life Span Study (LSS) of atomic bomb survivors who received brief exposures at high dose rates, many with high doses. Information is needed regarding radiation risks from low dose-rate (LDR) exposures to low linear-energy-transfer (low-LET) radiation. We conducted a meta-analysis of LDR epidemiologic studies that provide dose-response estimates of total solid cancer risk in adulthood in comparison to corresponding LSS risks, in order to estimate a dose rate effectiveness factor (DREF). We identified 22 LDR studies with dose-response risk estimates for solid cancer after minimizing information overlap. For each study, a parallel risk estimate was derived from the LSS risk model using matching values for sex, mean ages at first exposure and attained age, targeted cancer types, and accounting for type of dosimetric assessment. For each LDR study, a ratio of the excess relative risk per Gy (ERR Gy -1 ) to the matching LSS ERR risk estimate (LDR/LSS) was calculated, and a meta-analysis of the risk ratios was conducted. The reciprocal of the resultant risk ratio provided an estimate of the DREF. The meta-analysis showed a LDR/LSS risk ratio of 0.36 (95% confidence interval [CI] 0.14, 0.57) for the 19 studies of solid cancer mortality and 0.33 (95% CI 0.13, 0.54) when three cohorts with only incidence data also were added, implying a DREF with values around 3, but statistically compatible with 2. However, the analyses were highly dominated by the Mayak worker study. When the Mayak study was excluded the LDR/LSS risk ratios increased: 1.12 (95% CI 0.40, 1.84) for mortality and 0.54 (95% CI 0.09, 0.99) for mortality + incidence, implying a lower DREF in the range of 1-2. Meta-analyses that included only cohorts in which the mean dose was <100 mGy yielded a risk ratio of 1.06 (95% CI 0.30, 1.83) for solid cancer mortality and 0.58 (95% CI 0.10, 1.06) for mortality + incidence data. The interpretation of a best estimate for a value of the DREF depends on the appropriateness of including the Mayak study. This study indicates a range of uncertainty in the value of DREF between 1 and about 2 after protracted radiation exposure. The LDR data provide direct evidence regarding risk from exposures at low dose rates as an important complement to the LSS risk estimates used for radiation protection purposes.

Serum uric acid levels and multiple health outcomes: umbrella review of evidence from observational studies, randomised controlled trials, and Mendelian randomisation studies.

PubMed

Li, Xue; Meng, Xiangrui; Timofeeva, Maria; Tzoulaki, Ioanna; Tsilidis, Konstantinos K; Ioannidis, John PA; Campbell, Harry; Theodoratou, Evropi

2017-06-07

Objective  To map the diverse health outcomes associated with serum uric acid (SUA) levels. Design  Umbrella review. Data sources  Medline, Embase, Cochrane Database of Systematic Reviews, and screening of citations and references. Eligibility criteria  Systematic reviews and meta-analyses of observational studies that examined associations between SUA level and health outcomes, meta-analyses of randomised controlled trials that investigated health outcomes related to SUA lowering treatment, and Mendelian randomisation studies that explored the causal associations of SUA level with health outcomes. Results  57 articles reporting 15 systematic reviews and144 meta-analyses of observational studies (76 unique outcomes), 8 articles reporting 31 meta-analyses of randomised controlled trials (20 unique outcomes), and 36 articles reporting 107 Mendelian randomisation studies (56 unique outcomes) met the eligibility criteria. Across all three study types, 136 unique health outcomes were reported. 16 unique outcomes in meta-analyses of observational studies had P<10 -6 , 8 unique outcomes in meta-analyses of randomised controlled trials had P<0.001, and 4 unique outcomes in Mendelian randomisation studies had P<0.01. Large between study heterogeneity was common (80% and 45% in meta-analyses of observational studies and of randomised controlled trials, respectively). 42 (55%) meta-analyses of observational studies and 7 (35%) meta-analyses of randomised controlled trials showed evidence of small study effects or excess significance bias. No associations from meta-analyses of observational studies were classified as convincing; five associations were classified as highly suggestive (increased risk of heart failure, hypertension, impaired fasting glucose or diabetes, chronic kidney disease, coronary heart disease mortality with high SUA levels). Only one outcome from randomised controlled trials (decreased risk of nephrolithiasis recurrence with SUA lowering treatment) had P<0.001, a 95% prediction interval excluding the null, and no large heterogeneity or bias. Only one outcome from Mendelian randomisation studies (increased risk of gout with high SUA levels) presented convincing evidence. Hypertension and chronic kidney disease showed concordant evidence in meta-analyses of observational studies, and in some (but not all) meta-analyses of randomised controlled trials with respective intermediate or surrogate outcomes, but they were not statistically significant in Mendelian randomisation studies. Conclusion  Despite a few hundred systematic reviews, meta-analyses, and Mendelian randomisation studies exploring 136 unique health outcomes, convincing evidence of a clear role of SUA level only exists for gout and nephrolithiasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Is everything we eat associated with cancer? A systematic cookbook review.

PubMed

Schoenfeld, Jonathan D; Ioannidis, John P A

2013-01-01

Nutritional epidemiology is a highly prolific field. Debates on associations of nutrients with disease risk are common in the literature and attract attention in public media. We aimed to examine the conclusions, statistical significance, and reproducibility in the literature on associations between specific foods and cancer risk. We selected 50 common ingredients from random recipes in a cookbook. PubMed queries identified recent studies that evaluated the relation of each ingredient to cancer risk. Information regarding author conclusions and relevant effect estimates were extracted. When >10 articles were found, we focused on the 10 most recent articles. Forty ingredients (80%) had articles reporting on their cancer risk. Of 264 single-study assessments, 191 (72%) concluded that the tested food was associated with an increased (n = 103) or a decreased (n = 88) risk; 75% of the risk estimates had weak (0.05 > P ≥ 0.001) or no statistical (P > 0.05) significance. Statistically significant results were more likely than nonsignificant findings to be published in the study abstract than in only the full text (P < 0.0001). Meta-analyses (n = 36) presented more conservative results; only 13 (26%) reported an increased (n = 4) or a decreased (n = 9) risk (6 had more than weak statistical support). The median RRs (IQRs) for studies that concluded an increased or a decreased risk were 2.20 (1.60, 3.44) and 0.52 (0.39, 0.66), respectively. The RRs from the meta-analyses were on average null (median: 0.96; IQR: 0.85, 1.10). Associations with cancer risk or benefits have been claimed for most food ingredients. Many single studies highlight implausibly large effects, even though evidence is weak. Effect sizes shrink in meta-analyses.

Statistical methods for meta-analyses including information from studies without any events-add nothing to nothing and succeed nevertheless.

PubMed

Kuss, O

2015-03-30

Meta-analyses with rare events, especially those that include studies with no event in one ('single-zero') or even both ('double-zero') treatment arms, are still a statistical challenge. In the case of double-zero studies, researchers in general delete these studies or use continuity corrections to avoid them. A number of arguments against both options has been given, and statistical methods that use the information from double-zero studies without using continuity corrections have been proposed. In this paper, we collect them and compare them by simulation. This simulation study tries to mirror real-life situations as completely as possible by deriving true underlying parameters from empirical data on actually performed meta-analyses. It is shown that for each of the commonly encountered effect estimators valid statistical methods are available that use the information from double-zero studies without using continuity corrections. Interestingly, all of them are truly random effects models, and so also the current standard method for very sparse data as recommended from the Cochrane collaboration, the Yusuf-Peto odds ratio, can be improved on. For actual analysis, we recommend to use beta-binomial regression methods to arrive at summary estimates for the odds ratio, the relative risk, or the risk difference. Methods that ignore information from double-zero studies or use continuity corrections should no longer be used. We illustrate the situation with an example where the original analysis ignores 35 double-zero studies, and a superior analysis discovers a clinically relevant advantage of off-pump surgery in coronary artery bypass grafting. Copyright © 2014 John Wiley & Sons, Ltd.

Higher PUFA and n-3 PUFA, conjugated linoleic acid, α-tocopherol and iron, but lower iodine and selenium concentrations in organic milk: a systematic literature review and meta- and redundancy analyses.

PubMed

Średnicka-Tober, Dominika; Barański, Marcin; Seal, Chris J; Sanderson, Roy; Benbrook, Charles; Steinshamn, Håvard; Gromadzka-Ostrowska, Joanna; Rembiałkowska, Ewa; Skwarło-Sońta, Krystyna; Eyre, Mick; Cozzi, Giulio; Larsen, Mette Krogh; Jordon, Teresa; Niggli, Urs; Sakowski, Tomasz; Calder, Philip C; Burdge, Graham C; Sotiraki, Smaragda; Stefanakis, Alexandros; Stergiadis, Sokratis; Yolcu, Halil; Chatzidimitriou, Eleni; Butler, Gillian; Stewart, Gavin; Leifert, Carlo

2016-03-28

Demand for organic milk is partially driven by consumer perceptions that it is more nutritious. However, there is still considerable uncertainty over whether the use of organic production standards affects milk quality. Here we report results of meta-analyses based on 170 published studies comparing the nutrient content of organic and conventional bovine milk. There were no significant differences in total SFA and MUFA concentrations between organic and conventional milk. However, concentrations of total PUFA and n-3 PUFA were significantly higher in organic milk, by an estimated 7 (95 % CI -1, 15) % and 56 (95 % CI 38, 74) %, respectively. Concentrations of α-linolenic acid (ALA), very long-chain n-3 fatty acids (EPA+DPA+DHA) and conjugated linoleic acid were also significantly higher in organic milk, by an 69 (95 % CI 53, 84) %, 57 (95 % CI 27, 87) % and 41 (95 % CI 14, 68) %, respectively. As there were no significant differences in total n-6 PUFA and linoleic acid (LA) concentrations, the n-6:n-3 and LA:ALA ratios were lower in organic milk, by an estimated 71 (95 % CI -122, -20) % and 93 (95 % CI -116, -70) %. It is concluded that organic bovine milk has a more desirable fatty acid composition than conventional milk. Meta-analyses also showed that organic milk has significantly higher α-tocopherol and Fe, but lower I and Se concentrations. Redundancy analysis of data from a large cross-European milk quality survey indicates that the higher grazing/conserved forage intakes in organic systems were the main reason for milk composition differences.

International migration and gestational diabetes mellitus: a systematic review of the literature and meta-analysis.

PubMed

Gagnon, Anita J; McDermott, Sarah; Rigol-Chachamovich, Juliana; Bandyopadhyay, Mridula; Stray-Pedersen, Babill; Stewart, Donna

2011-11-01

Influxes of migrant women of childbearing age to receiving countries have made their perinatal health status a key priority for many governments. The international research collaboration Reproductive Outcomes And Migration (ROAM) reviewed published studies to assess whether migrants in countries of resettlement have a greater risk of gestational diabetes mellitus (GDM) than women in receiving countries. A systematic review of the literature from Medline, Embase, PsychInfo and CINAHL from 1990 to 2009 included studies of migrant women and GDM. Studies were excluded if there was no cross-border movement or comparison group or if the receiving country was not the country of resettlement. Studies were assessed for quality, analysed descriptively and meta-analysed. Twenty-four reports (representing >120,000 migrants) met our inclusion criteria. Migrants were described primarily by geographic origin; other relevant aspects (e.g. time in country, language fluency) were rarely studied. Migrants' results for GDM were worse than those for receiving-country women in 79% of all studies. Meta-analyses showed that, compared with receiving-country women, Caribbean, African, European and Northern European women were at greater risk of GDM, while North Africans and North Americans had risks similar to receiving-country women. Although results of the 31 comparisons of Asians, East Africans or non-Australian Oceanians were too heterogeneous to provide a single GDM risk estimate for migrant women, only one comparison was below the receiving-country comparison group, all others presented a higher risk estimate. The majority of women migrants to resettlement countries are at greater risk for GDM than women resident in receiving countries. Research using clear, specific migrant definitions, adjusting for relevant risk factors and including other aspects of migration experiences is needed to confirm and understand these findings. © 2011 Blackwell Publishing Ltd.

Methodological quality of meta-analyses of single-case experimental studies.

PubMed

Jamshidi, Laleh; Heyvaert, Mieke; Declercq, Lies; Fernández-Castilla, Belén; Ferron, John M; Moeyaert, Mariola; Beretvas, S Natasha; Onghena, Patrick; Van den Noortgate, Wim

2017-12-28

Methodological rigor is a fundamental factor in the validity and credibility of the results of a meta-analysis. Following an increasing interest in single-case experimental design (SCED) meta-analyses, the current study investigates the methodological quality of SCED meta-analyses. We assessed the methodological quality of 178 SCED meta-analyses published between 1985 and 2015 through the modified Revised-Assessment of Multiple Systematic Reviews (R-AMSTAR) checklist. The main finding of the current review is that the methodological quality of the SCED meta-analyses has increased over time, but is still low according to the R-AMSTAR checklist. A remarkable percentage of the studies (93.80% of the included SCED meta-analyses) did not even reach the midpoint score (22, on a scale of 0-44). The mean and median methodological quality scores were 15.57 and 16, respectively. Relatively high scores were observed for "providing the characteristics of the included studies" and "doing comprehensive literature search". The key areas of deficiency were "reporting an assessment of the likelihood of publication bias" and "using the methods appropriately to combine the findings of studies". Although the results of the current review reveal that the methodological quality of the SCED meta-analyses has increased over time, still more efforts are needed to improve their methodological quality. Copyright © 2017 Elsevier Ltd. All rights reserved.

Effectiveness of Knee Injury and Anterior Cruciate Ligament Tear Prevention Programs: A Meta-Analysis

PubMed Central

Collins, Jamie E.; Yang, Heidi Y.; Goczalk, Melissa G.; Katz, Jeffrey N.; Losina, Elena

2015-01-01

Objective Individuals frequently involved in jumping, pivoting or cutting are at increased risk of knee injury, including anterior cruciate ligament (ACL) tears. We sought to use meta-analytic techniques to establish whether neuromuscular and proprioceptive training is efficacious in preventing knee and ACL injury and to identify factors related to greater efficacy of such programs. Methods We performed a systematic literature search of studies published in English between 1996 and 2014. Intervention efficacy was ascertained from incidence rate ratios (IRRs) weighted by their precision (1/variance) using a random effects model. Separate analyses were performed for knee and ACL injury. We examined whether year of publication, study quality, or specific components of the intervention were associated with efficacy of the intervention in a meta-regression analysis. Results Twenty-four studies met the inclusion criteria and were used in the meta-analysis. The mean study sample was 1,093 subjects. Twenty studies reported data on knee injury in general terms and 16 on ACL injury. Maximum Jadad score was 3 (on a 0–5 scale). The summary incidence rate ratio was estimated at 0.731 (95% CI: 0.614, 0.871) for knee injury and 0.493 (95% CI: 0.285, 0.854) for ACL injury, indicating a protective effect of intervention. Meta-regression analysis did not identify specific intervention components associated with greater efficacy but established that later year of publication was associated with more conservative estimates of intervention efficacy. Conclusion The current meta-analysis provides evidence that neuromuscular and proprioceptive training reduces knee injury in general and ACL injury in particular. Later publication date was associated with higher quality studies and more conservative efficacy estimates. As study quality was generally low, these data suggest that higher quality studies should be implemented to confirm the preventive efficacy of such programs. PMID:26637173

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

PubMed

Dogo, Samson Henry; Clark, Allan; Kulinskaya, Elena

2017-06-01

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 τ 2 . In this paper, we propose the use of a retrospective cumulative sum (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 visualization 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. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd. © 2016 The Authors. Research Synthesis Methods published by John Wiley & Sons Ltd.

Apocynum venetum Attenuates Acetaminophen-Induced Liver Injury in Mice.

PubMed

Xie, Wenyan; Chen, Chen; Jiang, Zhihui; Wang, Jian; Melzig, Matthias F; Zhang, Xiaoying

2015-01-01

Apocynum venetum L. (A. venetum) has long been used in oriental folk medicine for the treatment of some liver diseases; however, the underlying mechanisms remain to be fully elucidated. Acetaminophen (APAP) is a widely used analgesic drug that can cause acute liver injury in overdose situations. In this study, we investigated the potential protective effect of A. venetum leaf extract (ALE) against APAP-induced hepatotoxicity. Mice were intragastrically administered with ALE once daily for 3 consecutive days prior to receiving a single intraperitoneal injection of APAP. The APAP group showed severe liver injury characterized by the noticeable fluctuations in the following parameters: serum aminotransferases; hepatic malondialdehyde (MDA), 3-nitrotyrosine (3-NT), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione reductase (GR) and glutathione (GSH). These liver damages induced by APAP were significantly attenuated by ALE pretreatments. A collective analysis of histopathological examination, DNA laddering and western blot for caspase-3 and cytochrome c indicated that the ALE is also capable of preventing APAP-induced hepatocyte death. Hyperoside, isoquercitrin and their derivatives have been identified as the major components of ALE using HPLC-MS/MS. Taken together, the A. venetum possesses hepatoprotective effects partially due to its anti-oxidant action.