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      Behavioural effects of methylphenidate in the spontaneously hypertensive rat model of attention-deficit/hyperactivity disorder: a systematic review and meta-analysis protocol

      systematic-review

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          Abstract

          Introduction

          Attention-deficit/hyperactivity disorder (ADHD) is a prevalent condition related to several negative outcomes, and its pathophysiology is still poorly understood. The spontaneously hypertensive rats (SHRs) are the most commonly used animal model of ADHD. How ever, its validity, and especially its predictive validity, has been questioned. Therefore, the current protocol discloses the background, aims and methods of a systematic review and meta-analysis of studies reporting the behavioural effects of methylphenidate (MPH), the most commonly prescribed treatment for ADHD, in the SHR.

          Search strategy

          Studies will be identified through a literature search using three different electronic databases: Medline, Embase and Web of Science. There will be no language restrictions. All s tudies that administered MPH to SHR and evaluated locomotion, attention, impulsivity or memory will be included.

          Screening and annotation

          Studies will be prescreened based on title and abstract, and a full-text review will be performed if necessary. Screening will be performed by two authors, and any disagreement will be discussed with a third author.

          Data management and reporting

          Data extraction will be performed by two independent authors according to a standardised form. Studies will be grouped according to the behavioural outcomes reported, and a meta-analysis will be performed for each group. The influence of predefined covariates on the effects of MPH will be evaluated using meta-regression and sensitivity analyses. Data will be reported following PRISMA guidelines.

          Most cited references45

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          Quantifying heterogeneity in a meta-analysis.

          The extent of heterogeneity in a meta-analysis partly determines the difficulty in drawing overall conclusions. This extent may be measured by estimating a between-study variance, but interpretation is then specific to a particular treatment effect metric. A test for the existence of heterogeneity exists, but depends on the number of studies in the meta-analysis. We develop measures of the impact of heterogeneity on a meta-analysis, from mathematical criteria, that are independent of the number of studies and the treatment effect metric. We derive and propose three suitable statistics: H is the square root of the chi2 heterogeneity statistic divided by its degrees of freedom; R is the ratio of the standard error of the underlying mean from a random effects meta-analysis to the standard error of a fixed effect meta-analytic estimate, and I2 is a transformation of (H) that describes the proportion of total variation in study estimates that is due to heterogeneity. We discuss interpretation, interval estimates and other properties of these measures and examine them in five example data sets showing different amounts of heterogeneity. We conclude that H and I2, which can usually be calculated for published meta-analyses, are particularly useful summaries of the impact of heterogeneity. One or both should be presented in published meta-analyses in preference to the test for heterogeneity. Copyright 2002 John Wiley & Sons, Ltd.
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            SYRCLE’s risk of bias tool for animal studies

            Background Systematic Reviews (SRs) of experimental animal studies are not yet common practice, but awareness of the merits of conducting such SRs is steadily increasing. As animal intervention studies differ from randomized clinical trials (RCT) in many aspects, the methodology for SRs of clinical trials needs to be adapted and optimized for animal intervention studies. The Cochrane Collaboration developed a Risk of Bias (RoB) tool to establish consistency and avoid discrepancies in assessing the methodological quality of RCTs. A similar initiative is warranted in the field of animal experimentation. Methods We provide an RoB tool for animal intervention studies (SYRCLE’s RoB tool). This tool is based on the Cochrane RoB tool and has been adjusted for aspects of bias that play a specific role in animal intervention studies. To enhance transparency and applicability, we formulated signalling questions to facilitate judgment. Results The resulting RoB tool for animal studies contains 10 entries. These entries are related to selection bias, performance bias, detection bias, attrition bias, reporting bias and other biases. Half these items are in agreement with the items in the Cochrane RoB tool. Most of the variations between the two tools are due to differences in design between RCTs and animal studies. Shortcomings in, or unfamiliarity with, specific aspects of experimental design of animal studies compared to clinical studies also play a role. Conclusions SYRCLE’s RoB tool is an adapted version of the Cochrane RoB tool. Widespread adoption and implementation of this tool will facilitate and improve critical appraisal of evidence from animal studies. This may subsequently enhance the efficiency of translating animal research into clinical practice and increase awareness of the necessity of improving the methodological quality of animal studies.
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              The adolescent brain and age-related behavioral manifestations.

              L Spear (2000)
              To successfully negotiate the developmental transition between youth and adulthood, adolescents must maneuver this often stressful period while acquiring skills necessary for independence. Certain behavioral features, including age-related increases in social behavior and risk-taking/novelty-seeking, are common among adolescents of diverse mammalian species and may aid in this process. Reduced positive incentive values from stimuli may lead adolescents to pursue new appetitive reinforcers through drug use and other risk-taking behaviors, with their relative insensitivity to drugs supporting comparatively greater per occasion use. Pubertal increases in gonadal hormones are a hallmark of adolescence, although there is little evidence for a simple association of these hormones with behavioral change during adolescence. Prominent developmental transformations are seen in prefrontal cortex and limbic brain regions of adolescents across a variety of species, alterations that include an apparent shift in the balance between mesocortical and mesolimbic dopamine systems. Developmental changes in these stressor-sensitive regions, which are critical for attributing incentive salience to drugs and other stimuli, likely contribute to the unique characteristics of adolescence.
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                Author and article information

                Journal
                BMJ Open Sci
                BMJ Open Sci
                bmjos
                bmjos
                BMJ Open Science
                BMJ Publishing Group (BMA House, Tavistock Square, London, WC1H 9JR )
                2398-8703
                2018
                19 October 2018
                : 2
                : 1
                : e000001
                Affiliations
                [1 ] departmentPost-Graduate Program in Medicine: Medical Sciences , School of Medicine, Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil
                [2 ] departmentLaboratory of Pain Pharmacology and Neuromodulation: Preclinical Studies - Pharmacology Department , Institute of Basic Health Sciences, Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil
                [3 ] departmentDepartment of Genetics , Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil
                [4 ] departmentADHD Outpatient Program , Hospital de Clínicas de Porto Alegre , Porto Alegre, Brazil
                [5 ] departmentDepartment of Psychiatry , Universidade Federal do Rio Grande do Sul , Porto Alegre, Brazil
                [6 ] National Institute of Developmental Psychiatry for Children and Adolescents , São Paulo, Brazil
                [7 ] departmentDepartamento de Psicobiologia , Universidade Federal de São Paulo , São Paulo, Brazil
                [8 ] departmentDepartment of Physiological Sciences , Santa Casa de São Paulo School of Medical Sciences , São Paulo, Brazil
                Author notes
                [Correspondence to ] Douglas Teixeira Leffa; douglasleffa@ 123456hotmail.com
                Author information
                http://orcid.org/0000-0002-4890-8451
                http://orcid.org/0000-0002-8844-3468
                http://orcid.org/0000-0002-8910-4927
                http://orcid.org/0000-0001-5644-3845
                http://orcid.org/0000-0002-4552-4188
                http://orcid.org/0000-0002-6898-7126
                Article
                bmjos-2018-000001
                10.1136/bmjos-2018-000001
                8715948
                b2a91077-b19e-474b-8e8f-de517c87b36c
                © Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY. Published by BMJ.

                This is an open access article distributed in accordance with the Creative Commons Attribution 4.0 Unported (CC BY 4.0) license, which permits others to copy, redistribute, remix, transform and build upon this work for any purpose, provided the original work is properly cited, a link to the licence is given, and indication of whether changes were made. See: https://creativecommons.org/licenses/by/4.0/.

                History
                : 05 January 2018
                : 13 June 2018
                Categories
                Protocol
                1506
                Custom metadata
                unlocked

                attention deficit disorder with hyperactivity,rats, inbred shr,meta-analysis as topic,methylphenidate

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