Genotype-stratified treatment for monogenic insulin resistance: a systematic review

This is the final version. Available from Nature Research via the DOI in this record. Data availability: All data used in this review is available from publicly available and herein referenced sources. A list of included studies is provided in Supplementary Data 1. All data generated or analyzed during this study are included in this published article and its supplementary information files. Source data for the figures are available as Supplementary Data 2.BACKGROUND: Monogenic insulin resistance (IR) includes lipodystrophy and disorders of insulin signalling. We sought to assess the effects of interventions in monogenic IR, stratified by genetic aetiology. METHODS: Systematic review using PubMed, MEDLINE and Embase (1 January 1987 to 23 June 2021). Studies reporting individual-level effects of pharmacologic and/or surgical interventions in monogenic IR were eligible. Individual data were extracted and duplicates were removed. Outcomes were analysed for each gene and intervention, and in aggregate for partial, generalised and all lipodystrophy. RESULTS: 10 non-randomised experimental studies, 8 case series, and 23 case reports meet inclusion criteria, all rated as having moderate or serious risk of bias. Metreleptin use is associated with the lowering of triglycerides and haemoglobin A1c (HbA1c) in all lipodystrophy (n = 111), partial (n = 71) and generalised lipodystrophy (n = 41), and in LMNA, PPARG, AGPAT2 or BSCL2 subgroups (n = 72,13,21 and 21 respectively). Body Mass Index (BMI) is lowered in partial and generalised lipodystrophy, and in LMNA or BSCL2, but not PPARG or AGPAT2 subgroups. Thiazolidinediones are associated with improved HbA1c and triglycerides in all lipodystrophy (n = 13), improved HbA1c in PPARG (n = 5), and improved triglycerides in LMNA (n = 7). In INSR-related IR, rhIGF-1, alone or with IGFBP3, is associated with improved HbA1c (n = 17). The small size or absence of other genotype-treatment combinations preclude firm conclusions. CONCLUSIONS: The evidence guiding genotype-specific treatment of monogenic IR is of low to very low quality. Metreleptin and Thiazolidinediones appear to improve metabolic markers in lipodystrophy, and rhIGF-1 appears to lower HbA1c in INSR-related IR. For other interventions, there is insufficient evidence to assess efficacy and risks in aggregated lipodystrophy or genetic subgroups.Wellcome TrustWellcome Trus

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations

O-RADS US Risk Stratification and Management System: A Consensus Guideline from the ACR Ovarian-Adnexal Reporting and Data System Committee

The Ovarian-Adnexal Reporting and Data System (O-RADS) US risk stratification and management system is designed to provide consistent interpretations, to decrease or eliminate ambiguity in US reports resulting in a higher probability of accuracy in assigning risk of malignancy to ovarian and other adnexal masses, and to provide a management recommendation for each risk category. It was developed by an international multidisciplinary committee sponsored by the American College of Radiology and applies the standardized reporting tool for US based on the 2018 published lexicon of the O-RADS US working group. For risk stratification, the O-RADS US system recommends six categories (O-RADS 0-5), incorporating the range of normal to high risk of malignancy. This unique system represents a collaboration between the pattern-based approach commonly used in North America and the widely used, European-based, algorithmic-style International Ovarian Tumor Analysis (IOTA) Assessment of Different Neoplasias in the Adnexa model system, a risk prediction model that has undergone successful prospective and external validation. The pattern approach relies on a subgroup of the most predictive descriptors in the lexicon based on a retrospective review of evidence prospectively obtained in the IOTA phase 1-3 prospective studies and other supporting studies that assist in differentiating management schemes in a variety of almost certainly benign lesions. With O-RADS US working group consensus, guidelines for management in the different risk categories are proposed. Both systems have been stratified to reach the same risk categories and management strategies regardless of which is initially used. At this time, O-RADS US is the only lexicon and classification system that encompasses all risk categories with their associated management schemes.status: publishe