Assessing COVID-19 testing strategies in K-12 schools in underserved populations: Study protocol for a cluster-randomized trial

BACKGROUND: Since March 2020, COVID-19 has disproportionately impacted communities of color within the United States. As schools have shifted from virtual to in-person learning, continual guidance is necessary to understand appropriate interventions to prevent SARS-CoV-2 transmission. Weekly testing of students and staff for SARS-CoV-2 within K-12 school setting could provide an additional barrier to school-based transmission, especially within schools unable to implement additional mitigation strategies and/or are in areas of high transmission. This study seeks to understand the role that weekly SARS-CoV-2 testing could play in K-12 schools. In addition, through qualitative interviews and listening sessions, this research hopes to understand community concerns and barriers regarding COVID-19 testing, COVID-19 vaccine, and return to school during the COVID-19 pandemic. METHODS/DESIGN: Sixteen middle and high schools from five school districts have been randomized into one of the following categories: (1) Weekly screening + symptomatic testing or (2) Symptomatic testing only. The primary outcome for this study will be the average of the secondary attack rate of school-based transmission per case. School-based transmission will also be assessed through qualitative contact interviews with positive contacts identified by the school contact tracers. Lastly, new total numbers of weekly cases and contacts within a school-based quarantine will provide guidance on transmission rates. Qualitative focus groups and interviews have been conducted to provide additional understanding to the acceptance of the intervention and barriers faced by the community regarding SARS-CoV-2 testing and vaccination. DISCUSSION: This study will provide greater understanding of the benefit that weekly screening testing can provide in reducing SARS-CoV-2 transmission within K-12 schools. Close collaboration with community partners and school districts will be necessary for the success of this and similar studies. TRIAL REGISTRATION: NCT04875520 . Registered May 6, 2021

A systematic review of influences on implementation of peer support work for adults with mental health problems

© 2019, The Author(s). Purpose: The evidence base for peer support work in mental health is established, yet implementation remains a challenge. The aim of this systematic review was to identify influences which facilitate or are barriers to implementation of mental health peer support work. Methods: Data sources comprised online databases (n = 11), journal table of contents (n = 2), conference proceedings (n = 18), peer support websites (n = 2), expert consultation (n = 38) and forward and backward citation tracking. Publications were included if they reported on implementation facilitators or barriers for formal face-to-face peer support work with adults with a mental health problem, and were available in English, French, German, Hebrew, Luganda, Spanish or Swahili. Data were analysed using narrative synthesis. A six-site international survey [Germany (2 sites), India, Israel, Tanzania, Uganda] using a measure based on the strongest influences was conducted. The review protocol was pre-registered (Prospero: CRD42018094838). Results: The search strategy identified 5813 publications, of which 53 were included. Fourteen implementation influences were identified, notably organisational culture (reported by 53% of papers), training (42%) and role definition (40%). Ratings on a measure using these influences demonstrated preliminary evidence for the convergent and discriminant validity of the identified influences. Conclusion: The identified influences provide a guide to implementation of peer support. For services developing a peer support service, organisational culture including role support (training, role clarity, resourcing and access to a peer network) and staff attitudes need to be considered. The identified influences provide a theory base to prepare research sites for implementing peer support worker interventions

Implementation of peer support for people with severe mental health conditions in high-, middle- and low-income-countries: a theory of change approach

BackgroundStakeholder engagement is essential to the design, implementation and evaluation of complex mental health interventions like peer support. Theory of Change (ToC) is commonly used in global health research to help structure and promote stakeholder engagement throughout the project cycle. Stakeholder insights are especially important in the context of a multi-site trial, in which an intervention may need to be adapted for implementation across very different settings while maintaining fidelity to a core model. This paper describes the development of a ToC for a peer support intervention to be delivered to people with severe mental health conditions in five countries as part of the UPSIDES trial.MethodsOne hundred thirty-four stakeholders from diverse backgrounds participated in a total of 17 workshops carried out at six UPSIDES implementing sites across high-, middle- and low-income settings (one site each in India, Israel, Uganda and Tanzania; two sites in Germany). The initial ToC maps created by stakeholders at each site were integrated into a cross-site ToC map, which was then revised to incorporate additional insights from the academic literature and updated iteratively through multiple rounds of feedback provided by the implementers.ResultsThe final ToC map divides the implementation of the UPSIDES peer support intervention into three main stages: preparation, implementation, and sustainability. The map also identifies three levels of actors involved in peer support: individuals (service users and peer support workers), organisations (and their staff members), and the public. In the UPSIDES trial, the ToC map proved especially helpful in characterising and distinguishing between (a) common features of peer support, (b) shared approaches to implementation and (c) informing adaptations to peer support or implementation to account for contextual differences.ConclusionsUPSIDES is the first project to develop a multi-national ToC for a mental health peer support intervention. Stakeholder engagement in the ToC process helped to improve the cultural and contextual appropriateness of a complex intervention and ensure equivalence across sites for the purposes of a multi-site trial. It may serve as a blueprint for implementing similar interventions with a focus on recovery and social inclusion among people with mental ill-health across diverse settings.Trial registrationISRCTN26008944 (Registration Date: 30/10/2019)

Peer support for people with severe mental illness versus usual care in high-, middle- A nd low-income countries: Study protocol for a pragmatic, multicentre, randomised controlled trial (UPSIDES-RCT)

© 2020 The Author(s). Background: Peer support is an established intervention involving a person recovering from mental illness supporting others with mental illness. Peer support is an under-used resource in global mental health. Building upon comprehensive formative research, this study will rigorously evaluate the impact of peer support at multiple levels, including service user outcomes (psychosocial and clinical), peer support worker outcomes (work role and empowerment), service outcomes (cost-effectiveness and return on investment), and implementation outcomes (adoption, sustainability and organisational change). Methods: UPSIDES-RCT is a pragmatic, parallel-group, multicentre, randomised controlled trial assessing the effectiveness of using peer support in developing empowering mental health services (UPSIDES) at four measurement points over 1 year (baseline, 4-, 8- A nd 12-month follow-up), with embedded process evaluation and cost-effectiveness analysis. Research will take place in a range of high-, middle- A nd low-income countries (Germany, UK, Israel, India, Uganda and Tanzania). The primary outcome is social inclusion of service users with severe mental illness (N = 558; N = 93 per site) at 8-month follow-up, measured with the Social Inclusion Scale. Secondary outcomes include empowerment (using the Empowerment Scale), hope (using the HOPE scale), recovery (using Stages of Recovery) and health and social functioning (using the Health of the Nations Outcome Scales). Mixed-methods process evaluation will investigate mediators and moderators of effect and the implementation experiences of four UPSIDES stakeholder groups (service users, peer support workers, mental health workers and policy makers). A cost-effectiveness analysis examining cost-utility and health budget impact will estimate the value for money of UPSIDES peer support. Discussion: The UPSIDES-RCT will explore the essential components necessary to create a peer support model in mental health care, while providing the evidence required to sustain and eventually scale-up the intervention in different cultural, organisational and resource settings. By actively involving and empowering service users, UPSIDES will move mental health systems toward a recovery orientation, emphasising user-centredness, community participation and the realisation of mental health as a human right

Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

Advances in the surgical management of the axilla in patients treated with neoadjuvant chemotherapy, especially those with node positive disease at diagnosis, have led to changes in practice and more judicious use of axillary lymph node dissection that may minimize morbidity from surgery. However, there is still significant confusion about how to optimally manage the axilla, resulting in variation among practices. From the viewpoint of drug development, assessment of response to neoadjuvant chemotherapy remains paramount and appropriate assessment of residual disease-the primary endpoint of many drug therapy trials in the neoadjuvant setting-is critical. Therefore decreasing the variability, especially in a multicenter clinical trial setting, and establishing a minimum standard to ensure consistency in clinical trial data, without mandating axillary lymph node dissection, for all patients is necessary. The key elements which include proper staging and identification of nodal involvement at diagnosis, and appropriately targeted management of the axilla at the time of surgical resection are presented. The following protocols have been adopted as standard procedure by the I-SPY2 trial for management of axilla in patients with node positive disease, and present a framework for prospective clinical trials and practice

Erratum: Author Correction: Surgical Standards for Management of the Axilla in Breast Cancer Clinical Trials with Pathological Complete Response Endpoint.

[This corrects the article DOI: 10.1038/s41523-018-0074-6.]

Functional annotation of human long noncoding RNAs via molecular phenotyping

Long noncoding RNAs (lncRNAs) constitute the majority of transcripts in the mammalian genomes, and yet, their functions remain largely unknown. As part of the FANTOM6 project, we systematically knocked down the expression of 285 lncRNAs in human dermal fibroblasts and quantified cellular growth, morphological changes, and transcriptomic responses using Capped Analysis of Gene Expression (CAGE). Antisense oligonucleotides targeting the same lncRNAs exhibited global concordance, and the molecular phenotype, measured by CAGE, recapitulated the observed cellular phenotypes while providing additional insights on the affected genes and pathways. Here, we disseminate the largest-todate lncRNA knockdown data set with molecular phenotyping (over 1000 CAGE deep-sequencing libraries) for further exploration and highlight functional roles for ZNF213-AS1 and lnc-KHDC3L-2.Peer reviewe

Estimates, trends, and drivers of the global burden of type 2 diabetes attributable to PM2.5 air pollution, 1990-2019 : an analysis of data from the Global Burden of Disease Study 2019

Background Experimental and epidemiological studies indicate an association between exposure to particulate matter (PM) air pollution and increased risk of type 2 diabetes. In view of the high and increasing prevalence of diabetes, we aimed to quantify the burden of type 2 diabetes attributable to PM2.5 originating from ambient and household air pollution.Methods We systematically compiled all relevant cohort and case-control studies assessing the effect of exposure to household and ambient fine particulate matter (PM2.5) air pollution on type 2 diabetes incidence and mortality. We derived an exposure-response curve from the extracted relative risk estimates using the MR-BRT (meta-regression-Bayesian, regularised, trimmed) tool. The estimated curve was linked to ambient and household PM2.5 exposures from the Global Burden of Diseases, Injuries, and Risk Factors Study 2019, and estimates of the attributable burden (population attributable fractions and rates per 100 000 population of deaths and disability-adjusted life-years) for 204 countries from 1990 to 2019 were calculated. We also assessed the role of changes in exposure, population size, age, and type 2 diabetes incidence in the observed trend in PM2.5-attributable type 2 diabetes burden. All estimates are presented with 95% uncertainty intervals.Findings In 2019, approximately a fifth of the global burden of type 2 diabetes was attributable to PM2.5 exposure, with an estimated 3.78 (95% uncertainty interval 2.68-4.83) deaths per 100 000 population and 167 (117-223) disability-adjusted life-years (DALYs) per 100 000 population. Approximately 13.4% (9.49-17.5) of deaths and 13.6% (9.73-17.9) of DALYs due to type 2 diabetes were contributed by ambient PM2.5, and 6.50% (4.22-9.53) of deaths and 5.92% (3.81-8.64) of DALYs by household air pollution. High burdens, in terms of numbers as well as rates, were estimated in Asia, sub-Saharan Africa, and South America. Since 1990, the attributable burden has increased by 50%, driven largely by population growth and ageing. Globally, the impact of reductions in household air pollution was largely offset by increased ambient PM2.5.Interpretation Air pollution is a major risk factor for diabetes. We estimated that about a fifth of the global burden of type 2 diabetes is attributable PM2.5 pollution. Air pollution mitigation therefore might have an essential role in reducing the global disease burden resulting from type 2 diabetes. Copyright (C) 2022 The Author(s). Published by Elsevier Ltd.Peer reviewe