Measuring Time Costs in Interventions Designed to Reduce Behavior Problems Among Children and Youth

The economic evaluation of psychosocial interventions is a growing area of research. Though time costs are central to the economist’s understanding of social costs, these costs generally have been ignored by prevention scientists. This article highlights the need to measure such costs and then reviews the principles economists use in valuing time. It then considers the specific time costs that often arise in interventions designed to reduce behavior problems among children and youth. These include classroom time devoted to program activities, the time of parents or other caregivers, the time of teachers (outside of the classroom), and the time of volunteers. We consider the economic principles that govern how economists value these inputs and then apply these principles to data from an evaluation of a prominent intervention in the field, the Incredible Years Program. We find that the time costs are potentially rather large and consider the implications for public policy of ignoring them

Fulfilling the Hope of ICWA: The Role of Community Context

28 pagesThis paper suggests that long-term foster care, especially when it is provided within an American Indian Cultural Environment (AICE), may be a culturally appropriate alternative form of permanency for American Indian children. Administrative data on foster care placements of children from four California counties over a five-year period indicate that children in the county with the strongest AICE had fewer placements and placements that were, on average, significantly longer. Within counties that had recognized tribes, children from local tribes had longer placements. Data on individual placements were available for one county and indicated that children whose home tribes were within that county and who were placed on Rancherias had significantly longer placements than other children. These relationships remained significant when children’s demographic characteristics were controlled. Implications for policy and practice related to ICWA are discussed

Discovery of Small Molecule Mer Kinase Inhibitors for the Treatment of Pediatric Acute Lymphoblastic Leukemia

Ectopic Mer expression promotes pro-survival signaling and contributes to leukemogenesis and chemoresistance in childhood acute lymphoblastic leukemia (ALL). Consequently, Mer kinase inhibitors may promote leukemic cell death and further act as chemosensitizers increasing efficacy and reducing toxicities of current ALL regimens. We have applied a structure-based design approach to discover novel small molecule Mer kinase inhibitors. Several pyrazolopyrimidine derivatives effectively inhibit Mer kinase activity at sub-nanomolar concentrations. Furthermore, the lead compound shows a promising selectivity profile against a panel of 72 kinases and has excellent pharmacokinetic properties. We also describe the crystal structure of the complex between the lead compound and Mer, opening new opportunities for further optimization and new template design

Effects of antiplatelet therapy on stroke risk by brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases: subgroup analyses of the RESTART randomised, open-label trial

Background Findings from the RESTART trial suggest that starting antiplatelet therapy might reduce the risk of recurrent symptomatic intracerebral haemorrhage compared with avoiding antiplatelet therapy. Brain imaging features of intracerebral haemorrhage and cerebral small vessel diseases (such as cerebral microbleeds) are associated with greater risks of recurrent intracerebral haemorrhage. We did subgroup analyses of the RESTART trial to explore whether these brain imaging features modify the effects of antiplatelet therapy

UNC569, a Novel Small-Molecule Mer Inhibitor with Efficacy against Acute Lymphoblastic Leukemia In Vitro and In Vivo

Acute lymphoblastic leukemia (ALL) is the most common malignancy in children. Although survival rates have improved, patients with certain biological subtypes still have suboptimal outcomes. Current chemotherapeutic regimens are associated with short- and long-term toxicities and novel, less toxic therapeutic strategies are needed. Mer receptor tyrosine kinase is ectopically expressed in ALL patient samples and cell lines. Inhibition of Mer expression reduces pro-survival signaling, increases chemosensitivity, and delays development of leukaemia in vivo suggesting that Mer tyrosine kinase inhibitors are excellent candidates for targeted therapies. Brain and spinal tumors are the second most common malignancies in childhood. Multiple chemotherapy approaches and radiation have been attempted, yet overall survival remains dismal. Mer is also abnormally expressed in atypical teratoid/rhabdoid tumors (ATRT), providing a rationale for targeting Mer as a therapeutic strategy. We have previously described UNC569, the first small molecule Mer inhibitor. This manuscript describes the biochemical and biological effects of UNC569 in ALL and ATRT. UNC569 inhibited Mer activation and downstream signaling through ERK1/2 and AKT, determined by western blot analysis. Treatment with UNC569 reduced proliferation/survival in liquid culture, decreased colony formation in methylcellulose/soft agar, and increased sensitivity to cytotoxic chemotherapies. MYC transgenic zebrafish with T-ALL were treated with UNC569 (4 µM for 2 weeks). Fluorescence was quantified as indicator of the distribution of lymphoblasts, which express Mer and enhanced green fluorescent protein. UNC569 induced >50% reduction in tumor burden compared to vehicle- and mock-treated fish. These data support further development of Mer inhibitors as effective therapies in ALL and ATRT

Dynamic Reprogramming of the Kinome in Response to Targeted MEK Inhibition in Triple-Negative Breast Cancer

Kinase inhibitors have limited success in cancer treatment because tumors circumvent their action. Using a quantitative proteomics approach, we assessed kinome activity in response to MEK inhibition in triple negative breast cancer (TNBC) cells and genetically engineered mice (GEMMs). MEK inhibition caused acute ERK activity loss, resulting in rapid c-Myc degradation that induced expression and activation of several receptor tyrosine kinases (RTKs). RNAi knockdown of ERK or c-Myc mimicked RTK induction by MEK inhibitors, whereas prevention of proteasomal c-Myc degradation blocked kinome reprogramming. MEK inhibitor-induced RTK stimulation overcame MEK2 but not MEK1 inhibition, reactivating ERK and producing drug resistance. The C3Tag GEMM for TNBC similarly induced RTKs in response to MEK inhibition. The inhibitor-induced RTK profile suggested a kinase inhibitor combination therapy that produced GEMM tumor apoptosis and regression where single agents were ineffective. This approach defines mechanisms of drug resistance, allowing rational design of combination therapies for cancer

COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

BACKGROUND: Updatable estimates of COVID-19 onset, progression, and trajectories underpin pandemic mitigation efforts. To identify and characterise disease trajectories, we aimed to define and validate ten COVID-19 phenotypes from nationwide linked electronic health records (EHR) using an extensible framework. METHODS: In this cohort study, we used eight linked National Health Service (NHS) datasets for people in England alive on Jan 23, 2020. Data on COVID-19 testing, vaccination, primary and secondary care records, and death registrations were collected until Nov 30, 2021. We defined ten COVID-19 phenotypes reflecting clinically relevant stages of disease severity and encompassing five categories: positive SARS-CoV-2 test, primary care diagnosis, hospital admission, ventilation modality (four phenotypes), and death (three phenotypes). We constructed patient trajectories illustrating transition frequency and duration between phenotypes. Analyses were stratified by pandemic waves and vaccination status. FINDINGS: Among 57 032 174 individuals included in the cohort, 13 990 423 COVID-19 events were identified in 7 244 925 individuals, equating to an infection rate of 12·7% during the study period. Of 7 244 925 individuals, 460 737 (6·4%) were admitted to hospital and 158 020 (2·2%) died. Of 460 737 individuals who were admitted to hospital, 48 847 (10·6%) were admitted to the intensive care unit (ICU), 69 090 (15·0%) received non-invasive ventilation, and 25 928 (5·6%) received invasive ventilation. Among 384 135 patients who were admitted to hospital but did not require ventilation, mortality was higher in wave 1 (23 485 [30·4%] of 77 202 patients) than wave 2 (44 220 [23·1%] of 191 528 patients), but remained unchanged for patients admitted to the ICU. Mortality was highest among patients who received ventilatory support outside of the ICU in wave 1 (2569 [50·7%] of 5063 patients). 15 486 (9·8%) of 158 020 COVID-19-related deaths occurred within 28 days of the first COVID-19 event without a COVID-19 diagnoses on the death certificate. 10 884 (6·9%) of 158 020 deaths were identified exclusively from mortality data with no previous COVID-19 phenotype recorded. We observed longer patient trajectories in wave 2 than wave 1. INTERPRETATION: Our analyses illustrate the wide spectrum of disease trajectories as shown by differences in incidence, survival, and clinical pathways. We have provided a modular analytical framework that can be used to monitor the impact of the pandemic and generate evidence of clinical and policy relevance using multiple EHR sources. FUNDING: British Heart Foundation Data Science Centre, led by Health Data Research UK

Proceedings of the 8th Annual Conference on the Science of Dissemination and Implementation

A1 Introduction to the 8(th) Annual Conference on the Science of Dissemination and Implementation: Optimizing Personal and Population Health David Chambers, Lisa Simpson D1 Discussion forum: Population health D&I research Felicia Hill-Briggs D2 Discussion forum: Global health D&I research Gila Neta, Cynthia Vinson D3 Discussion forum: Precision medicine and D&I research David Chambers S1 Predictors of community therapists’ use of therapy techniques in a large public mental health system Rinad Beidas, Steven Marcus, Gregory Aarons, Kimberly Hoagwood, Sonja Schoenwald, Arthur Evans, Matthew Hurford, Ronnie Rubin, Trevor Hadley, Frances Barg, Lucia Walsh, Danielle Adams, David Mandell S2 Implementing brief cognitive behavioral therapy (CBT) in primary care: Clinicians' experiences from the field Lindsey Martin, Joseph Mignogna, Juliette Mott, Natalie Hundt, Michael Kauth, Mark Kunik, Aanand Naik, Jeffrey Cully S3 Clinician competence: Natural variation, factors affecting, and effect on patient outcomes Alan McGuire, Dominique White, Tom Bartholomew, John McGrew, Lauren Luther, Angie Rollins, Michelle Salyers S4 Exploring the multifaceted nature of sustainability in community-based prevention: A mixed-method approach Brittany Cooper, Angie Funaiole S5 Theory informed behavioral health integration in primary care: Mixed methods evaluation of the implementation of routine depression and alcohol screening and assessment Julie Richards, Amy Lee, Gwen Lapham, Ryan Caldeiro, Paula Lozano, Tory Gildred, Carol Achtmeyer, Evette Ludman, Megan Addis, Larry Marx, Katharine Bradley S6 Enhancing the evidence for specialty mental health probation through a hybrid efficacy and implementation study Tonya VanDeinse, Amy Blank Wilson, Burgin Stacey, Byron Powell, Alicia Bunger, Gary Cuddeback S7 Personalizing evidence-based child mental health care within a fiscally mandated policy reform Miya Barnett, Nicole Stadnick, Lauren Brookman-Frazee, Anna Lau S8 Leveraging an existing resource for technical assistance: Community-based supervisors in public mental health Shannon Dorsey, Michael Pullmann S9 SBIRT implementation for adolescents in urban federally qualified health centers: Implementation outcomes Shannon Mitchell, Robert Schwartz, Arethusa Kirk, Kristi Dusek, Marla Oros, Colleen Hosler, Jan Gryczynski, Carolina Barbosa, Laura Dunlap, David Lounsbury, Kevin O'Grady, Barry Brown S10 PANEL: Tailoring Implementation Strategies to Context - Expert recommendations for tailoring strategies to context Laura Damschroder, Thomas Waltz, Byron Powell S11 PANEL: Tailoring Implementation Strategies to Context - Extreme facilitation: Helping challenged healthcare settings implement complex programs Mona Ritchie S12 PANEL: Tailoring Implementation Strategies to Context - Using menu-based choice tasks to obtain expert recommendations for implementing three high-priority practices in the VA Thomas Waltz S13 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Siri, rate my therapist: Using technology to automate fidelity ratings of motivational interviewing David Atkins, Zac E. Imel, Bo Xiao, Doğan Can, Panayiotis Georgiou, Shrikanth Narayanan S14 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Identifying indicators of implementation quality for computer-based ratings Cady Berkel, Carlos Gallo, Irwin Sandler, C. Hendricks Brown, Sharlene Wolchik, Anne Marie Mauricio S15 PANEL: The Use of Technology to Improve Efficient Monitoring of Implementation of Evidence-based Programs - Improving implementation of behavioral interventions by monitoring emotion in spoken speech Carlos Gallo, C. Hendricks Brown, Sanjay Mehrotra S16 Scorecards and dashboards to assure data quality of health management information system (HMIS) using R Dharmendra Chandurkar, Siddhartha Bora, Arup Das, Anand Tripathi, Niranjan Saggurti, Anita Raj S17 A big data approach for discovering and implementing patient safety insights Eric Hughes, Brian Jacobs, Eric Kirkendall S18 Improving the efficacy of a depression registry for use in a collaborative care model Danielle Loeb, Katy Trinkley, Michael Yang, Andrew Sprowell, Donald Nease S19 Measurement feedback systems as a strategy to support implementation of measurement-based care in behavioral health Aaron Lyon, Cara Lewis, Meredith Boyd, Abigail Melvin, Semret Nicodimos, Freda Liu, Nathanial Jungbluth S20 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Common loop assay: Methods of supporting learning collaboratives Allen Flynn S21 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Innovating audit and feedback using message tailoring models for learning health systems Zach Landis-Lewis S22 PANEL: Implementation Science and Learning Health Systems: Intersections and Commonalities - Implementation science and learning health systems: Connecting the dots Anne Sales S23 Facilitation activities of Critical Access Hospitals during TeamSTEPPS implementation Jure Baloh, Marcia Ward, Xi Zhu S24 Organizational and social context of federally qualified health centers and variation in maternal depression outcomes Ian Bennett, Jurgen Unutzer, Johnny Mao, Enola Proctor, Mindy Vredevoogd, Ya-Fen Chan, Nathaniel Williams, Phillip Green S25 Decision support to enhance treatment of hospitalized smokers: A randomized trial Steven Bernstein, June-Marie Rosner, Michelle DeWitt, Jeanette Tetrault, James Dziura, Allen Hsiao, Scott Sussman, Patrick O’Connor, Benjamin Toll S26 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A patient-centered approach to successful community transition after catastrophic injury Michael Jones, Julie Gassaway S27 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - Conducting PCOR to integrate mental health and cancer screening services in primary care Jonathan Tobin S28 PANEL: Developing Sustainable Strategies for the Implementation of Patient-Centered Care across Diverse US Healthcare Systems - A comparative effectiveness trial of optimal patient-centered care for US trauma care systems Douglas Zatzick S29 Preferences for in-person communication among patients in a multi-center randomized study of in-person versus telephone communication of genetic test results for cancer susceptibility Angela R Bradbury, Linda Patrick-Miller, Brian Egleston, Olufunmilayo I Olopade, Michael J Hall, Mary B Daly, Linda Fleisher, Generosa Grana, Pamela Ganschow, Dominique Fetzer, Amanda Brandt, Dana Farengo-Clark, Andrea Forman, Rikki S Gaber, Cassandra Gulden, Janice Horte, Jessica Long, Rachelle Lorenz Chambers, Terra Lucas, Shreshtha Madaan, Kristin Mattie, Danielle McKenna, Susan Montgomery, Sarah Nielsen, Jacquelyn Powers, Kim Rainey, Christina Rybak, Michelle Savage, Christina Seelaus, Jessica Stoll, Jill Stopfer, Shirley Yao and Susan Domchek S30 Working towards de-implementation: A mixed methods study in breast cancer surveillance care Erin Hahn, Corrine Munoz-Plaza, Jianjin Wang, Jazmine Garcia Delgadillo, Brian Mittman Michael Gould S31Integrating evidence-based practices for increasing cancer screenings in safety-net primary care systems: A multiple case study using the consolidated framework for implementation research Shuting (Lily) Liang, Michelle C. Kegler, Megan Cotter, Emily Phillips, April Hermstad, Rentonia Morton, Derrick Beasley, Jeremy Martinez, Kara Riehman S32 Observations from implementing an mHealth intervention in an FQHC David Gustafson, Lisa Marsch, Louise Mares, Andrew Quanbeck, Fiona McTavish, Helene McDowell, Randall Brown, Chantelle Thomas, Joseph Glass, Joseph Isham, Dhavan Shah S33 A multicomponent intervention to improve primary care provider adherence to chronic opioid therapy guidelines and reduce opioid misuse: A cluster randomized controlled trial protocol Jane Liebschutz, Karen Lasser S34 Implementing collaborative care for substance use disorders in primary care: Preliminary findings from the summit study Katherine Watkins, Allison Ober, Sarah Hunter, Karen Lamp, Brett Ewing S35 Sustaining a task-shifting strategy for blood pressure control in Ghana: A stakeholder analysis Juliet Iwelunmor, Joyce Gyamfi, Sarah Blackstone, Nana Kofi Quakyi, Jacob Plange-Rhule, Gbenga Ogedegbe S36 Contextual adaptation of the consolidated framework for implementation research (CFIR) in a tobacco cessation study in Vietnam Pritika Kumar, Nancy Van Devanter, Nam Nguyen, Linh Nguyen, Trang Nguyen, Nguyet Phuong, Donna Shelley S37 Evidence check: A knowledge brokering approach to systematic reviews for policy Sian Rudge S38 Using Evidence Synthesis to Strengthen Complex Health Systems in Low- and Middle-Income Countries Etienne Langlois S39 Does it matter: timeliness or accuracy of results? The choice of rapid reviews or systematic reviews to inform decision-making Andrea Tricco S40 Evaluation of the veterans choice program using lean six sigma at a VA medical center to identify benefits and overcome obstacles Sherry Ball, Anne Lambert-Kerzner, Christine Sulc, Carol Simmons, Jeneen Shell-Boyd, Taryn Oestreich, Ashley O'Connor, Emily Neely, Marina McCreight, Amy Labebue, Doreen DiFiore, Diana Brostow, P. Michael Ho, David Aron S41 The influence of local context on multi-stakeholder alliance quality improvement activities: A multiple case study Jillian Harvey, Megan McHugh, Dennis Scanlon S42 Increasing physical activity in early care and education: Sustainability via active garden education (SAGE) Rebecca Lee, Erica Soltero, Nathan Parker, Lorna McNeill, Tracey Ledoux S43 Marking a decade of policy implementation: The successes and continuing challenges of a provincial school food and nutrition policy in Canada Jessie-Lee McIsaac, Kate MacLeod, Nicole Ata, Sherry Jarvis, Sara Kirk S44 Use of research evidence among state legislators who prioritize mental health and substance abuse issues Jonathan Purtle, Elizabeth Dodson, Ross Brownson S45 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 1 designs Brian Mittman, Geoffrey Curran S46 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 2 designs Geoffrey Curran S47 PANEL: Effectiveness-Implementation Hybrid Designs: Clarifications, Refinements, and Additional Guidance Based on a Systematic Review and Reports from the Field - Hybrid type 3 designs Jeffrey Pyne S48 Linking team level implementation leadership and implementation climate to individual level attitudes, behaviors, and implementation outcomes Gregory Aarons, Mark Ehrhart, Elisa Torres S49 Pinpointing the specific elements of local context that matter most to implementation outcomes: Findings from qualitative comparative analysis in the RE-inspire study of VA acute stroke care Edward Miech S50 The GO score: A new context-sensitive instrument to measure group organization level for providing and improving care Edward Miech S51 A research network approach for boosting implementation and improvement Kathleen Stevens, I.S.R.N. Steering Council S52 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - The value of qualitative methods in implementation research Alison Hamilton S53 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Learning evaluation: The role of qualitative methods in dissemination and implementation research Deborah Cohen S54 PANEL: Qualitative methods in D&I Research: Value, rigor and challenge - Qualitative methods in D&I research Deborah Padgett S55 PANEL: Maps & models: The promise of network science for clinical D&I - Hospital network of sharing patients with acute and chronic diseases in California Alexandra Morshed S56 PANEL: Maps & models: The promise of network science for clinical D&I - The use of social network analysis to identify dissemination targets and enhance D&I research study recruitment for pre-exposure prophylaxis for HIV (PrEP) among men who have sex with men Rupa Patel S57 PANEL: Maps & models: The promise of network science for clinical D&I - Network and organizational factors related to the adoption of patient navigation services among rural breast cancer care providers Beth Prusaczyk S58 A theory of de-implementation based on the theory of healthcare professionals’ behavior and intention (THPBI) and the becker model of unlearning David C. Aron, Divya Gupta, Sherry Ball S59 Observation of registered dietitian nutritionist-patient encounters by dietetic interns highlights low awareness and implementation of evidence-based nutrition practice guidelines Rosa Hand, Jenica Abram, Taylor Wolfram S60 Program sustainability action planning: Building capacity for program sustainability using the program sustainability assessment tool Molly Hastings, Sarah Moreland-Russell S61 A review of D&I study designs in published study protocols Rachel Tabak, Alex Ramsey, Ana Baumann, Emily Kryzer, Katherine Montgomery, Ericka Lewis, Margaret Padek, Byron Powell, Ross Brownson S62 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Model simulation techniques to estimate the cost of implementing foundational public health services Cezar Brian Mamaril, Glen Mays, Keith Branham, Lava Timsina S63 PANEL: Geographic variation in the implementation of public health services: Economic, organizational, and network determinants - Inter-organizational network effects on the implementation of public health services Glen Mays, Rachel Hogg S64 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Implementation fidelity, coalition functioning, and community prevention system transformation using communities that care Abigail Fagan, Valerie Shapiro, Eric Brown S65 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Expanding capacity for implementation of communities that care at scale using a web-based, video-assisted training system Kevin Haggerty, David Hawkins S66 PANEL: Building capacity for implementation and dissemination of the communities that care prevention system at scale to promote evidence-based practices in behavioral health - Effects of communities that care on reducing youth behavioral health problems Sabrina Oesterle, David Hawkins, Richard Catalano S68 When interventions end: the dynamics of intervention de-adoption and replacement Virginia McKay, M. Margaret Dolcini, Lee Hoffer S69 Results from next-d: can a disease specific health plan reduce incident diabetes development among a national sample of working-age adults with pre-diabetes? Tannaz Moin, Jinnan Li, O. Kenrik Duru, Susan Ettner, Norman Turk, Charles Chan, Abigail Keckhafer, Robert Luchs, Sam Ho, Carol Mangione S70 Implementing smoking cessation interventions in primary care settings (STOP): using the interactive systems framework Peter Selby, Laurie Zawertailo, Nadia Minian, Dolly Balliunas, Rosa Dragonetti, Sarwar Hussain, Julia Lecce S71 Testing the Getting To Outcomes implementation support intervention in prevention-oriented, community-based settings Matthew Chinman, Joie Acosta, Patricia Ebener, Patrick S Malone, Mary Slaughter S72 Examining the reach of a multi-component farmers’ market implementation approach among low-income consumers in an urban context Darcy Freedman, Susan Flocke, Eunlye Lee, Kristen Matlack, Erika Trapl, Punam Ohri-Vachaspati, Morgan Taggart, Elaine Borawski S73 Increasing implementation of evidence-based health promotion practices at large workplaces: The CEOs Challenge Amanda Parrish, Jeffrey Harris, Marlana Kohn, Kristen Hammerback, Becca McMillan, Peggy Hannon S74 A qualitative assessment of barriers to nutrition promotion and obesity prevention in childcare Taren Swindle, Geoffrey Curran, Leanne Whiteside-Mansell, Wendy Ward S75 Documenting institutionalization of a health communication intervention in African American churches Cheryl Holt, Sheri Lou Santos, Erin Tagai, Mary Ann Scheirer, Roxanne Carter, Janice Bowie, Muhiuddin Haider, Jimmie Slade, Min Qi Wang S76 Reduction in hospital utilization by underserved patients through use of a community-medical home Andrew Masica, Gerald Ogola, Candice Berryman, Kathleen Richter S77 Sustainability of evidence-based lay health advisor programs in African American communities: A mixed methods investigation of the National Witness Project Rachel Shelton, Lina Jandorf, Deborah Erwin S78 Predicting the long-term uninsured population and analyzing their gaps in physical access to healthcare in South Carolina Khoa Truong S79 Using an evidence-based parenting intervention in churches to prevent behavioral problems among Filipino youth: A randomized pilot study Joyce R. Javier, Dean Coffey, Sheree M. Schrager, Lawrence Palinkas, Jeanne Miranda S80 Sustainability of elementary school-based health centers in three health-disparate southern communities Veda Johnson, Valerie Hutcherson, Ruth Ellis S81 Childhood obesity prevention partnership in Louisville: creative opportunities to engage families in a multifaceted approach to obesity prevention Anna Kharmats, Sandra Marshall-King, Monica LaPradd, Fannie Fonseca-Becker S82 Improvements in cervical cancer prevention found after implementation of evidence-based Latina prevention care management program Deanna Kepka, Julia Bodson, Echo Warner, Brynn Fowler S83 The OneFlorida data trust: Achieving health equity through research & training capacity building Elizabeth Shenkman, William Hogan, Folakami Odedina, Jessica De Leon, Monica Hooper, Olveen Carrasquillo, Renee Reams, Myra Hurt, Steven Smith, Jose Szapocznik, David Nelson, Prabir Mandal S84 Disseminating and sustaining medical-legal partnerships: Shared value and social return on investment James Teufe

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention

Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial

Background: Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods: The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings: Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation: These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention