Systematic reviews of animal studies – Report of an international symposium

Objective: The Symposium on Animal Systematic Reviews held 24 May 2022, sought to bring organisations working on animal literature searching and systematic reviews together into the same virtual space for introductions and discussion.Background: Groups working on animal research synthesis are often siloed into preclinical, veterinary, and One Health settings. This symposium sought to define commonalities and differences in methodologies, resources, and philosophies and to discuss future needs.Methods: The 3-hour virtual symposium for veterinarians, researchers, and information specialists began with introductions by panelists from organisations involved in searching the literature for animal studies and conducting systematic reviews. This was followed by a panel discussion and question and answer period.Results: Panelists identified a need to ensure planning and accurate description of primary animal studies as a precursor to quality systematic reviews. They acknowledged and discussed differences in evidence synthesis expectations and tools based on the type of review, the types of studies available on the topic, and the focus on preclinical, veterinary, or One Health topics.Conclusion: The need to increase the speed and quality of evidence reviews, and to automate updates, requires investing in the development of both skilled teams and platforms. The symposium provided a chance to identify existing resources, define challenges, and note gaps unique to systematic reviews of animal studies.Application: This symposium acts as a baseline for ongoing discussions centred on improving the culture and pipeline for evidence syntheses of animal studies that inform decision-making

Current status of clinical outcome measures in inclusion body myositis: a systematised review

OBJECTIVES: Sporadic inclusion body myositis (IBM) is a debilitating idiopathic inflammatory myopathy (IIM) which affects hand function, ambulation, and swallowing. There is no approved pharmacological therapy for IBM, and there is a lack of suitable outcome measure to assess the effect of an intervention. The IBM scientific interest group under IMACS reviewed the previously used outcome measures in IBM clinical studies to lay the path for developing a core set of outcome measures in IBM. METHODS: In this systematised review, we have extracted all outcome measures reported in IBM clinical studies to determine what measures were being used and to assess the need for optimising outcome measures in IBM. RESULTS: We found 13 observational studies, 17 open-label clinical trials, and 15 randomised control trials (RCTs) in IBM. Six-minute walk distance, IBM-functional rating scale (IBM-FRS), quantitative muscle testing, manual muscle testing, maximal voluntary isometric contraction testing, and thigh muscle volume measured by MRI were used as primary outcome measures. Twelve different outcome measures of motor function were used in IBM clinical trials. IBM-FRS was the most used measure of functionality. Swallowing function was reported as a secondary outcome measure in only 3 RCTs. CONCLUSIONS: There are inconsistencies in using outcome measures in clinical studies in IBM. The core set measures developed by the IMACS group for other IIMs are not directly applicable to IBM. As a result, there is an unmet need for an IBM-specific core set of measures to facilitate the evaluation of new potential therapeutics for IBM

Neural circuit disruptions of eye gaze processing in autism spectrum disorder and schizophrenia: An activation likelihood estimation meta-analysis

BackgroundImpairment in social cognition, particularly eye gaze processing, is a shared feature common to autism spectrum disorder (ASD) and schizophrenia. However, it is unclear if a convergent neural mechanism also underlies gaze dysfunction in these conditions. The present study examined whether this shared eye gaze phenotype is reflected in a profile of convergent neurobiological dysfunction in ASD and schizophrenia.MethodsActivation likelihood estimation (ALE) meta-analyses were conducted on peak voxel coordinates across the whole brain to identify spatial convergence. Functional coactivation with regions emerging as significant was assessed using meta-analytic connectivity modeling. Functional decoding was also conducted.ResultsFifty-six experiments (n = 30 with schizophrenia and n = 26 with ASD) from 36 articles met inclusion criteria, which comprised 354 participants with ASD, 275 with schizophrenia and 613 healthy controls (1242 participants in total). In ASD, aberrant activation was found in the left amygdala relative to unaffected controls during gaze processing. In schizophrenia, aberrant activation was found in the right inferior frontal gyrus and supplementary motor area. Across ASD and schizophrenia, aberrant activation was found in the right inferior frontal gyrus and right fusiform gyrus during gaze processing. Functional decoding mapped the left amygdala to domains related to emotion processing and cognition, the right inferior frontal gyrus to cognition and perception, and the right fusiform gyrus to visual perception, spatial cognition, and emotion perception. These regions also showed meta-analytic connectivity to frontoparietal and frontotemporal circuitry.ConclusionAlterations in frontoparietal and frontotemporal circuitry emerged as neural markers of gaze impairments in ASD and schizophrenia. These findings have implications for advancing transdiagnostic biomarkers to inform targeted treatments for ASD and schizophrenia. Previous article in issu

Personal Recovery Among People at Risk for Developing Serious Mental Health Problems:A Qualitative Systematic Review

OBJECTIVE: Personal recovery refers to a person's pursuit of a full, meaningful life despite the potentially debilitating impact of a mental illness. An evidence base describing personal recovery among people at risk for developing a mental illness is lacking, limiting the potential for mental health services to support personal recovery. To address this gap, the authors synthesized the extant research describing personal recovery among people at risk for developing a mental illness.METHODS: A systematic search of several literature databases (MEDLINE, Embase, APA PsycInfo, Web of Science Core Collection, and Cochrane Library) was conducted to retrieve qualitative and case studies and first-person accounts. The Joanna Briggs Institute guidelines for systematic reviews were followed. Included studies reported on participants at variable risk for developing a schizophrenia spectrum, bipolar, major depressive, or borderline personality disorder. Articles were retrieved through a librarian-assisted search and through use of additional strategies (e.g., expert consultation). Abstracts were screened by the research team, and themes were developed by using thematic synthesis.RESULTS: The 36 included articles were synthesized, and six themes were generated: difficulties and challenges; establishing an understanding of, and finding ways to cope with, one's mental health challenges; reestablishing a sense of agency and personhood; receiving support from people and services, as well as restoring relationships; reestablishing hope, meaning, and purpose; and overcoming stigma and destigmatizing mental illness in others.CONCLUSIONS: These findings provide a conceptual foundation that can guide future research on personal recovery and clinical interventions that foster it among people at risk for mental illness.</p

The Common Pathways of Epileptogenesis in Patients With Epilepsy Post-Brain Injury: Findings From a Systematic Review and Meta-analysis.

BACKGROUND AND OBJECTIVE: Epilepsy may result from various brain injuries, including stroke (ischemic and hemorrhagic), traumatic brain injury, and infections. Identifying shared common biological pathways and biomarkers of the epileptogenic process initiated by the different injuries may lead to novel targets for preventing the development of epilepsy. We systematically reviewed biofluid biomarkers to test their association with the risk of post-brain injury epilepsy. METHODS: We searched articles until January 25, 2022, in MEDLINE, Embase, PsycINFO, Web of Science, and Cochrane. The primary outcome was the difference in mean biomarker levels in patients with and without post-brain injury epilepsy. We used the modified quality score on prognostic studies for risk of bias assessment. We calculated each biomarker\u27s pooled standardized mean difference (SMD) and 95% confidence intervals (CI). Molecular interaction network and enrichment analyses were conducted in Cytoscape. (PROSPERO CRD42021297110) RESULTS: We included 22 studies with 1499 cases with post-brain injury epilepsy and 7929 controls without post-brain injury epilepsy. Forty-five biomarkers in blood or cerebrospinal fluid (CSF) were investigated with samples collected at disparate time points. Of 22 studies, 21 had a moderate-to-high risk of bias. Most biomarkers (28/45) were investigated in single studies; only nine provided validation data, and studies used variable definitions for early and late-onset seizures. A meta-analysis was possible for 19 biomarkers. Blood glucose levels in four studies were significantly higher in patients with post-stroke epilepsy (PSE) than without PSE (SMD 0.44; CI 0.19 to 0.69). From individual studies, 15 biomarkers in blood and seven in CSF were significantly associated with post-brain injury epilepsy. Enrichment analysis identified that the significant biomarkers (IL6, IL1β) were predominantly inflammation related. DISCUSSION: We cannot yet recommend using the reported biomarkers for designing anti-epileptogenesis trials or use in the clinical setting because of methodological heterogeneity, bias in the included studies, and insufficient validation studies. Even though our analyses indicate the plausible role of inflammation in epileptogenesis, this is likely not the only mechanism. For example, an individual\u27s genetic susceptibilities might contribute to his risk of epileptogenesis after brain injury. Rigorously designed biomarker studies with methods acceptable to the regulatory bodies should be conducted