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1.
JMIR Form Res ; 8: e52729, 2024 Nov 01.
Artículo en Inglés | MEDLINE | ID: mdl-39486023

RESUMEN

BACKGROUND: The World Health Organization and the Centers for Disease Control and Prevention have set ambitious hepatitis C virus (HCV) elimination targets for 2030. Current estimates show that the United States is not on pace to meet elimination targets due to multiple patient, clinic, institutional, and societal level barriers that contribute to HCV testing and treatment gaps. Among these barriers are unawareness of testing and treatment needs, misinformation concerning adverse treatment reactions, need for substance use sobriety, and treatment efficacy. Strategies to improve viral hepatitis education are needed. OBJECTIVE: We aim to provide a high-quality HCV educational app for patients and health care workers, particularly nonprescriber staff. The app was vetted by health care providers and designed to guide users through the HCV testing and treatment stages in a self-exploratory way to promote engagement and knowledge retention. The app is comprised of five learning modules: (1) Testing for Hep C (hepatitis C), (2) Tests for Hep C Positive Patients, (3) Treatments Available to You, (4) What to Expect During Treatment, and (5) What to Expect After Treatment. METHODS: An HCV knowledge assessment survey was administered to providers and patients at the Yale School of Medicine and 11 Connecticut HIV clinics as part of a grant-funded activity. The survey findings and pilot testing feedback guided the app's design and content development. Data on app usage from November 2019 to November 2022 were analyzed, focusing on user demographics, engagement metrics, and module usage patterns. RESULTS: There were 561 app users; 216 (38.5%) accessed the training modules of which 151 (69.9%) used the app for up to 60 minutes. Of them, 65 (30.1%) users used it for >60 minutes with a median time spent of 5 (IQR 2-8) minutes; the median time between initial accession and last use was 39 (IQR 18-60) days. Users accessed one or more modules and followed a nonsequential pattern of use: module 1: 163 (75.4%) users; module 4: 82 (38%); module 5: 67 (31%); module 3: 49 (22.7%); module 2: 41 (19%). CONCLUSIONS: This app, created in an academic setting, is one of a few available in English and Spanish that provides content-vetted HCV education for patients and health care supportive staff. It offers the convenience of on-demand education, allowing users to access crucial information about HCV management and treatment in a self-directed fashion that acknowledges and promotes variable preferences in learning approaches. While app uptake was relatively limited, we propose that future efforts should focus on combined promotion efforts with marketing strategies experts aligned with academic experts. Incorporating ongoing user feedback and integrating personalized reminders and quizzes, will further enhance engagement, supporting the broader public health HCV elimination goals.


Asunto(s)
Hepatitis C , Aplicaciones Móviles , Humanos , Hepatitis C/terapia , Masculino , Femenino , Adulto , Encuestas y Cuestionarios , Persona de Mediana Edad , Conocimientos, Actitudes y Práctica en Salud , Estados Unidos , Personal de Salud/educación , Educación del Paciente como Asunto/métodos
2.
J Acquir Immune Defic Syndr ; 96(1): 40-50, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38324241

RESUMEN

BACKGROUND: Re-engaging people with HIV who are newly out-of-care remains challenging. Data-to-care (D2C) is a potential strategy to re-engage such individuals. METHODS: A prospective randomized controlled trial compared a D2C strategy using a disease intervention specialist (DIS) vs standard of care where 23 HIV clinics in 3 counties in Connecticut could re-engage clients using existing methods. Using a data reconciliation process to confirm being newly out-of-care, 655 participants were randomized to DIS (N = 333) or standard of care (N = 322). HIV care continuum outcomes included re-engagement at 90 days, retention in care, and viral suppression by 12 months. Multivariable regression models were used to assess factors predictive of attaining HIV care continuum outcomes. RESULTS: Participants randomized to DIS were more likely to be re-engaged at 90 days (adjusted odds ratios [aOR] = 1.42, P = 0.045). Independent predictors of re-engagement at 90 days were age older than 40 years (aOR = 1.84, P = 0.012) and perinatal HIV risk category (aOR = 3.19, P = 0.030). Predictors of retention at 12 months included re-engagement at 90 days (aOR = 10.31, P < 0.001), drug injection HIV risk category (aOR = 1.83, P = 0.032), detectable HIV-1 RNA before randomization (aOR = 0.40, P = 0.003), and county (Hartford aOR = 1.74, P = 0.049; New Haven aOR = 1.80, P = 0.030). Predictors of viral suppression included re-engagement at 90 days (aOR = 2.85, P < 0.001), retention in HIV care (aOR = 7.07, P < 0.001), and detectable HIV-1 RNA prerandomization (aOR = 0.23, P < 0.001). CONCLUSIONS: A D2C strategy significantly improved re-engagement at 90 days. Early re-engagement improved downstream benefits along the HIV care continuum like retention in care and viral suppression at 12 months. Moreover, other factors predictive of care continuum outcomes can be used to improve D2C strategies.


Asunto(s)
Infecciones por VIH , Embarazo , Femenino , Humanos , Adulto , Infecciones por VIH/tratamiento farmacológico , Connecticut , Estudios Prospectivos , Continuidad de la Atención al Paciente , ARN
3.
Public Health Rep ; 139(2): 208-217, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37232422

RESUMEN

OBJECTIVES: Highly effective direct-acting antiviral medications have made it feasible to achieve elimination of hepatis C virus (HCV), including for people with HIV and HCV coinfection. The Centers for Disease Control and Prevention offers guidance for a laboratory surveillance-based HCV viral clearance cascade, which allows public health departments to track the outcomes of people with HCV based on the following steps: ever infected, virally tested, initial infection, and cured or cleared. We examined the feasibility of this approach among people with HIV and HCV coinfection in Connecticut. METHODS: We matched an HIV surveillance database, which included cases from the enhanced HIV/AIDS Reporting System as of December 31, 2019, and the HCV surveillance database, the Connecticut Electronic Disease Surveillance System, to define a cohort of coinfected people. We used HCV laboratory results obtained from January 1, 2016, through August 3, 2020, to determine HCV status. RESULTS: Of 1361 people who were ever infected with HCV as of December 31, 2019, 1256 (92.3%) received HCV viral testing, 865 of 1256 people tested (68.9%) were HCV infected, and 336 of 865 infected people (38.8%) were cleared or cured. People who had undetectable HIV viral loads at most recent HIV test (<200 copies/mL) were more likely than those with detectable HIV viral loads to achieve HCV cure (P = .02). CONCLUSIONS: A surveillance-based approach that includes data based on the Centers for Disease Control and Prevention HCV viral clearance cascade is feasible to implement, can help track population-level outcomes longitudinally, and can help identify gaps to inform HCV elimination strategies.


Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Antivirales/uso terapéutico , Connecticut/epidemiología , Coinfección/epidemiología , Coinfección/tratamiento farmacológico , Hepatitis C Crónica/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/epidemiología , Infecciones por VIH/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/epidemiología , Hepatitis C/tratamiento farmacológico , Hepacivirus
4.
J Appalach Health ; 4(3): 111-114, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38026050

RESUMEN

In March 2021, grassroots leaders in two counties in northeast Tennessee formed a new network called Connections. Leaders are working to strengthen the capacity of the network and member organizations by promoting partnerships as vital to address effectively rural social determinants of health. Connections provides network members with capacity-building tools and resources, including two funding opportunities, to achieve their missions and sustain impact. Network members are also aligning around common goals to address the socioeconomic conditions affecting health outcomes. Connections will utilize findings from network activities and collaborations to identify synergies that can accelerate improvements in community health and well-being.

5.
Cytometry A ; 103(11): 839-850, 2023 11.
Artículo en Inglés | MEDLINE | ID: mdl-37768325

RESUMEN

High-dimensional immunoprofiling is essential for studying host response to immunotherapy, infection, and disease in murine model systems. However, the difficulty of multiparameter panel design combined with a lack of existing murine tools has prevented the comprehensive study of all major leukocyte phenotypes in a single assay. Herein, we present a 40-color flow cytometry panel for deep immunophenotyping of murine lymphoid tissues, including the spleen, blood, Peyer's patches, inguinal lymph nodes, bone marrow, and thymus. This panel uses a robust set of surface markers capable of differentiating leukocyte subsets without the use of intracellular staining, thus allowing for the use of cells in downstream functional experiments or multiomic analyses. Our panel classifies T cells, B cells, natural killer cells, innate lymphoid cells, monocytes, macrophages, dendritic cells, basophils, neutrophils, eosinophils, progenitors, and their functional subsets by using a series of co-stimulatory, checkpoint, activation, migration, and maturation markers. This tool has a multitude of systems immunology applications ranging from serial monitoring of circulating blood signatures to complex endpoint analysis, especially in pre-clinical settings where treatments can modulate leukocyte abundance and/or function. Ultimately, this 40-color panel resolves a diverse array of immune cells on the axes of time, tissue, and treatment, filling the niche for a modern tool dedicated to murine immunophenotyping.


Asunto(s)
Inmunidad Innata , Tejido Linfoide , Ratones , Animales , Citometría de Flujo/métodos , Linfocitos T , Células Asesinas Naturales , Inmunofenotipificación
6.
Health Promot Pract ; 24(5): 1039-1049, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37439600

RESUMEN

Highly effective direct-acting antiviral (DAA) treatments for hepatitis C have led to strategic goals promoting hepatitis C virus (HCV) cure particularly in focus populations including persons with HIV/HCV coinfection. Implementing treatment more broadly requires both clinic-level and public health approaches such as those inherent in Data to Care (D2C) originally developed to improve the treatment cascade for persons with HIV (PWH). We used D2C methods to characterize and improve HCV treatment for persons with HIV/HCV coinfection among 11 HIV clinics in Connecticut cities with high PWH prevalence. Providers who were local champions in HCV treatment were recruited to participate along with clinic data staff and were key to quality improvement via practice transformation. We developed a methodology whereby clinic-generated lists of PWH receiving care from 2009 to 2018 were matched by CT Department of Public Health (DPH) against the state-wide HCV surveillance system. The resultant coinfection list was reviewed by clinical staff who designated HCV treatment status, enabling creation of individual clinic-level HCV treatment cascades. Data from DPH, especially current residency and deaths, enabled better characterization and allowed for refinement of longitudinal cascades. There were 1,496 patients with HIV/HCV coinfection. Sustained virologic response (SVR) rates varied by clinic (range, 44%-100%) with an aggregate SVR rate of 71% in September 2020. SVR rates improved during the project through a combination of increased treatment initiation/completion as well as data clean-up including serial updates of patient treatment status. Lack of treatment initiation was associated with being female (odds ratio [OR] = 2.18) and not having HIV viral suppression (OR = 3.24).


Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Femenino , Masculino , Antivirales/uso terapéutico , Hepacivirus , Coinfección/tratamiento farmacológico , Coinfección/epidemiología , Coinfección/complicaciones , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología
7.
Health Promot Pract ; 24(5): 1018-1028, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37439759

RESUMEN

Introduction. National strategies to end the HIV epidemic and eliminate hepatitis c (HCV) through a syndemic approach require improvements in testing for HIV and HCV. Given the intersection of the opioid crisis with HIV and HCV acquisition, substance use disorder (SUD) treatment centers providing medications for opiate use disorder (MOUD) provide a critical opportunity to expand testing. Rates of testing in MOUD clinics have been suboptimal. Method. We employed the Nominal Group Technique (NGT), Ishikawa cause and effect diagrams, and individualized Quality Improvement (QI) efforts at two SUD clinics (SUD A and B) in Connecticut (CT) as part of an HRSA-funded grant focused on improving HCV cure in persons with HIV/HCV coinfection. Baseline and longitudinal data were collected on rates of HIV and HCV testing and positivity as well as linkage to treatment. Results. Between April 1, 2019, and May 31, 2021, for SUD A and B respectively, HIV testing increased from 13% to 90% and 33% to 83%; HCV testing increased from 4% to 90% and 30% to 82%, with few reported cases of HIV/HCV coinfection. HCV testing revealed new and prior diagnoses at both sites, with subsequent referrals for treatment. Qualitative assessments identified best practices which included the institution of formal policies and procedures, streamlining of testing logistics, designation of a site champion, and broadening relevant education to staff and clients. Conclusion. Strategic assessment of barriers and facilitators to HIV and HCV testing at MOUD clinics can lead to improved testing and referral rates that are key to improving the cascade of care for both diseases.


Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C , Alcaloides Opiáceos , Trastornos Relacionados con Sustancias , Humanos , Alcaloides Opiáceos/uso terapéutico , Hepatitis C/diagnóstico , Hepatitis C/epidemiología , Trastornos Relacionados con Sustancias/terapia , Hepacivirus , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología
8.
Health Promot Pract ; 24(5): 998-1008, 2023 09.
Artículo en Inglés | MEDLINE | ID: mdl-37440258

RESUMEN

The prevalence of HIV/HCV (hepatitis C virus) co-infection is high particularly in persons who inject drugs (PWID) and is increasing because of the evolving opioid epidemic in the United States. The introduction of effective antiviral medications for HCV has raised the strategic goal of HCV micro-elimination, and efforts to understand the barriers to treatment are critical. In this study, we explored the provider perspective of factors that inhibit HCV micro-elimination efforts in people with HIV (PWH), including the role of implicit bias and related stigma in providers' health care decision making. We used the mixed-methods approach of nominal group technique (NGT) with 14 participants from 11 different clinics engaged in two virtual focus group sessions (n = 5 and n = 9). Responses from the NGTs were rank ordered during the sessions to identify providers' perspectives of major barriers and facilitators, then identified possible implicit bias after the NGTs concluded. There were 12 responses given for micro-elimination barriers with the three most prioritized being housing instability, medication nonadherence concerns, and inability to motivate patients. Of these, eight were categorized as potential implicit biases. Among the 14 responses given for facilitators of treatment, the three major solutions included distributive models of care, improved provider knowledge, and increased patient engagement. Although the solutions offered were insightful, there was consensus that the individual lives of patients were the root cause of most barriers to care. We recommend further research on behavioral design interventions that promote patients' involvement in decision making and focus on patients' eligibility criteria for HCV treatment as opposed to providers' perceived barriers to treatment.


Asunto(s)
Consumidores de Drogas , Infecciones por VIH , Hepatitis C , Abuso de Sustancias por Vía Intravenosa , Humanos , Estados Unidos , Hepacivirus , Sesgo Implícito , Abuso de Sustancias por Vía Intravenosa/complicaciones , Abuso de Sustancias por Vía Intravenosa/terapia , Abuso de Sustancias por Vía Intravenosa/epidemiología , Hepatitis C/tratamiento farmacológico , Hepatitis C/epidemiología , Infecciones por VIH/tratamiento farmacológico
9.
J Int AIDS Soc ; 26(1): e26040, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36682053

RESUMEN

INTRODUCTION: Data-to-care programmes utilize surveillance data to identify persons who are out of HIV care, re-engage them in care and improve HIV care outcomes. We assess the costs and cost-effectiveness of re-engagement in an HIV care intervention in the United States. METHODS: The Cooperative Re-engagement Control Trial (CoRECT) employed a data-to-care collaborative model between health departments and HIV care providers, August 2016-July 2018. The health departments in Connecticut (CT), Massachusetts (MA) and Philadelphia (PHL) collaborated with HIV clinics to identify newly out-of-care patients and randomize them to receive usual linkage and engagement in care services (standard-of-care control arm) or health department-initiated active re-engagement services (intervention arm). We used a microcosting approach to identify the activities and resources involved in the CoRECT intervention, separate from the standard-of-care, and quantified the costs. The cost data were collected at the start-up and recurrent phases of the trial to incorporate potential variation in the intervention costs. The costs were estimated from the healthcare provider perspective. RESULTS: The CoRECT trial in CT, MA and PHL randomly assigned on average 327, 316 and 305 participants per year either to the intervention arm (n = 166, 159 and 155) or the standard-of-care arm (n = 161, 157 and 150), respectively. Of those randomized, the number of participants re-engaged in care within 90 days in the intervention and standard-of-care arms was 85 and 70 in CT, 84 and 70 in MA, and 98 and 67 in PHL. The additional number of participants re-engaged in care in the intervention arm compared with those in the standard-of-care arm was 15 (CT), 14 (MA) and 31 (PHL). We estimated the annual total cost of the CoRECT intervention at $490,040 in CT, $473,297 in MA and $439,237 in PHL. The average cost per participant enrolled was $2952, $2977 and $2834 and the average cost per participant re-engaged in care was $5765, $5634 and $4482. We estimated an incremental cost per participant re-engaged in care at $32,669 (CT), $33,807 (MA) and $14,169 (PHL). CONCLUSIONS: The costs of the CoRECT intervention that identified newly out-of-care patients and re-engaged them in HIV care are comparable with other similar interventions, suggesting a potential for its cost-effectiveness in the US context.


Asunto(s)
Infecciones por VIH , Humanos , Estados Unidos , Infecciones por VIH/tratamiento farmacológico , Análisis Costo-Beneficio , Personal de Salud
10.
AIDS Behav ; 27(1): 119-133, 2023 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-35776253

RESUMEN

In the United States, approximately 25% of people with HIV (PWH) are co-infected with hepatitis C (HCV). Since 2014, highly effective and well-tolerated direct-acting antivirals (DAAs) have revolutionized HCV treatment. Uptake of DAAs by people with HIV/HCV co-infection has improved but remains suboptimal due to system, provider, and patient-level barriers. To explore patient-level issues by better understanding their attitudes towards DAA treatment, we conducted qualitative interviews with 21 persons with HIV/HCV co-infection who did not consent to DAA treatment or delayed treatment for at least 1 year after diagnosis. We found PWH perceived DAA treatment barriers and facilitators on multiple levels of the social-ecological environment: the individual (HCV disease and treatment literacy), interpersonal (peer influence), institutional (media and healthcare provider relationship), and structural levels (treatment cost and adherence support). Recommendations to improve DAA treatment uptake include HCV-treatment adherence support, HCV disease and treatment literacy training (particularly for substance use and DAA treatment interactions), and encouraging PWH who have successfully completed DAA treatment to speak with their peers.


Asunto(s)
Coinfección , Infecciones por VIH , Hepatitis C Crónica , Hepatitis C , Humanos , Estados Unidos , Antivirales/uso terapéutico , Coinfección/tratamiento farmacológico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Hepatitis C Crónica/complicaciones , Hepatitis C Crónica/tratamiento farmacológico , Hepatitis C/complicaciones , Hepatitis C/tratamiento farmacológico , Hepacivirus
11.
Semin Pediatr Surg ; 31(5): 151214, 2022 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-36371842

RESUMEN

Despite advances in the delivery of trauma care, trauma remains the leading cause of death amongst the pediatric population within the United States and is one of the leading causes of death in children worldwide.  Accurately triaging pediatric trauma patients is essential to minimize preventable mortality without burdening the system by utilizing unnecessary resources.  This article will review the accuracy of current pediatric trauma triage practices and how it will evolve in the future including moving away from mechanism of injury towards physiologic scoring tools such as the pediatric age-adjust shock index, and intervention-based systems including. Need for Surgeon Presence and Need For Trauma Intervention. This paper will also present evidence regarding over-utilization of air transport for pediatric trauma patients and the associated unnecessary costs placed on the trauma system.


Asunto(s)
Triaje , Heridas y Lesiones , Niño , Humanos , Estados Unidos , Heridas y Lesiones/diagnóstico , Heridas y Lesiones/terapia
12.
PLoS One ; 17(5): e0267903, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35511958

RESUMEN

BACKGROUND: UN AIDS has set ambitious 95-95-95 HIV care continuum targets for global HIV elimination by 2030. The U.S. HIV Care Continuum in 2018 showed that 65% of persons with HIV(PWH) are virally suppressed and 58% retained in care. Incomplete care-engagement not only affects individual health but drives ongoing HIV transmission. Data to Care (D2C) is a strategy using public health surveillance data to identify and re-engage out-of-care (OOC) PWH. Optimization of this strategy is needed. SETTING: Statewide partnership with Connecticut Department of Public Health (CT DPH), 23 HIV clinics and Yale University School of Medicine (YSM). Our site was one of 3 participants in the CDC-sponsored RCT evaluating the efficacy of DPH-employed Disease Intervention Specialists (DIS) for re-engagement in care. METHODS: From 11/2016-7/2018, a data reconciliation process using public health surveillance and clinic visit data was used to identify patients eligible for randomization (defined as in-Care for 12 months and OOC for subsequent 6-months) to receive DIS intervention. Clinic staff further reviewed this list and designated those who would not be randomized based on established criteria. RESULTS: 2958 patients were eligible for randomization; 655 (22.1%) were randomized. Reasons for non-randomizing included: well patient [499 (16.9%)]; recent visit [946 (32.0%)]; upcoming visit [398 (13.5%)]. Compared to non-randomized patients, those who were randomized were likely to be younger (mean age 46.1 vs. 51.6, p < .001), Black (40% vs 35%)/Hispanic (37% vs 32.8%) [(p < .001)], have CD4<200 cells/ul (15.9% vs 8.5%, p < .001) and viral load >20 copies/ml (43.8% vs. 24.1%, 0<0.001). Extrapolating these estimates to a statewide HIV care continuum suggests that only 8.3% of prevalent PWH are truly OOC. CONCLUSIONS: A D2C process that integrated DPH surveillance and clinic data successfully refined the selection of newly OOC PWH eligible for DIS intervention. This approach more accurately reflects real world care engagement and can help prioritize DPH resources.


Asunto(s)
Infecciones por VIH , Instituciones de Atención Ambulatoria , Continuidad de la Atención al Paciente , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/epidemiología , Humanos , Persona de Mediana Edad , Vigilancia en Salud Pública , Carga Viral
13.
Biomaterials ; 281: 121339, 2022 02.
Artículo en Inglés | MEDLINE | ID: mdl-35078042

RESUMEN

Ex vivo programming of T cells can be efficacious but is complex and expensive; therefore, the development of methods to transfect T cells in situ is important. We developed and optimized anti-CD3-targeted lipid nanoparticles (aCD3-LNPs) to deliver tightly packed, reporter gene mRNA specifically to T cells. In vitro, targeted LNPs efficiently delivered mCherry mRNA to Jurkat T cells, and T-cell activation and depletion were associated with aCD3 antibody coating on the surface of LNPs. aCD3-LNPs, but not non-targeted LNPs, accumulated within the spleen following systemic injection, with mCherry and Fluc signals visible within 30 min after injection. At 24 h after aCD3-LNP injection, 2-4% of all splenic T cells and 2-7% of all circulating T cells expressed mCherry, and this was dependent on aCD3 coating density. Targeting and transfection were accompanied by systemic CD25+, OX40+, and CD69+ T-cell activation with temporary CD3e ligand loss and depletion of splenic and circulating subsets. Migration of splenic CD8a+ T cells from the white-pulp to red-pulp, and differentiation from naïve to memory and effector phenotypes, followed upon aCD3-LNP delivery. Additionally, aCD3-LNP injection stimulated the secretion of myeloid-derived chemokines and T-helper cytokines into plasma. Lastly, we administered aCD3-LNPs to tumor bearing mice and found that transfected T cells localized within tumors and tumor-draining lymph nodes following immunotherapy treatment. In summary, we show that CD3-targeted transfection is feasible, yet associated with complex immunological consequences that must be further studied for potential therapeutic applications.


Asunto(s)
Lípidos , Nanopartículas , Animales , Liposomas , Ratones , Fenotipo , ARN Mensajero/genética , Transfección
14.
J Trauma Nurs ; 28(6): 378-385, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34766932

RESUMEN

BACKGROUND: Optimal outcomes have been reported for children treated at pediatric trauma centers; however, most children are treated at nonpediatric trauma centers or nonpediatric general hospitals. Hospitals that are not verified or designated pediatric trauma centers may lack the training and level of comfort and skill when treating severely injured children. OBJECTIVE: This study focused on identifying common pediatric guidelines for standardization across all trauma centers to inform a pediatric trauma toolkit. METHODS: A needs assessment survey was developed highlighting the guidelines from an expert committee review. The purpose of the survey was to prioritize needed items for the development of a pediatric trauma toolkit. Professional trauma organizations distributed the survey to their respective memberships to ensure good representation of people who care for traumatically injured children and work in trauma centers. Deidentified survey results were analyzed with frequencies and descriptive statistics provided. Data were compared by hospital trauma verification level using a chi-square test. The value of p < .05 was considered statistically significant. RESULTS: A total of 303 people responded to the survey. The majority of respondents reported a high value in the creation of a pediatric trauma toolkit for the guidelines that were included. There was variability in the reported access to the guidelines, indicating a significant need for the toolkit development and dissemination. CONCLUSION: As expected, Level III centers reported the largest gaps in access to standardized pediatric guidelines and demonstrated high levels of interest and need.


Asunto(s)
Hospitales de Alto Volumen , Centros Traumatológicos , Niño , Hospitales Pediátricos , Humanos , Evaluación de Necesidades
15.
Proc Natl Acad Sci U S A ; 118(30)2021 07 27.
Artículo en Inglés | MEDLINE | ID: mdl-34301870

RESUMEN

Genome-wide association studies have identified the chromosome 10q26 (Chr10) locus, which contains the age-related maculopathy susceptibility 2 (ARMS2) and high temperature requirement A serine peptidase 1 (HTRA1) genes, as the strongest genetic risk factor for age-related macular degeneration (AMD) [L.G. Fritsche et al., Annu. Rev. Genomics Hum. Genet. 15, 151-171, (2014)]. To date, it has been difficult to assign causality to any specific single nucleotide polymorphism (SNP), haplotype, or gene within this region because of high linkage disequilibrium among the disease-associated variants [J. Jakobsdottir et al. Am. J. Hum. Genet. 77, 389-407 (2005); A. Rivera et al. Hum. Mol. Genet. 14, 3227-3236 (2005)]. Here, we show that HTRA1 messenger RNA (mRNA) is reduced in retinal pigment epithelium (RPE) but not in neural retina or choroid tissues derived from human donors with homozygous risk at the 10q26 locus. This tissue-specific decrease is mediated by the presence of a noncoding, cis-regulatory element overlapping the ARMS2 intron, which contains a potential Lhx2 transcription factor binding site that is disrupted by risk variant rs36212733. HtrA1 protein increases with age in the RPE-Bruch's membrane (BM) interface in Chr10 nonrisk donors but fails to increase in donors with homozygous risk at the 10q26 locus. We propose that HtrA1, an extracellular chaperone and serine protease, functions to maintain the optimal integrity of the RPE-BM interface during the aging process and that reduced expression of HTRA1 mRNA and protein in Chr10 risk donors impairs this protective function, leading to increased risk of AMD pathogenesis. HtrA1 augmentation, not inhibition, in high-risk patients should be considered as a potential therapy for AMD.


Asunto(s)
Predisposición Genética a la Enfermedad , Serina Peptidasa A1 que Requiere Temperaturas Altas/metabolismo , Degeneración Macular/genética , Epitelio Pigmentado de la Retina/metabolismo , Coroides/metabolismo , Variación Genética , Serina Peptidasa A1 que Requiere Temperaturas Altas/genética , Humanos , Desequilibrio de Ligamiento , ARN Mensajero/genética , ARN Mensajero/metabolismo , Retina/metabolismo
16.
Lab Chip ; 20(12): 2062-2074, 2020 06 21.
Artículo en Inglés | MEDLINE | ID: mdl-32417874

RESUMEN

Droplet microfluidics has made large impacts in diverse areas such as enzyme evolution, chemical product screening, polymer engineering, and single-cell analysis. However, while droplet reactions have become increasingly sophisticated, phenotyping droplets by a fluorescent signal and sorting them to isolate individual variants-of-interest at high-throughput remains challenging. Here, we present sdDE-FACS (s[combining low line]ingle d[combining low line]roplet D[combining low line]ouble E[combining low line]mulsion-FACS), a new method that uses a standard flow cytometer to phenotype, select, and isolate individual double emulsion droplets of interest. Using a 130 µm nozzle at high sort frequency (12-14 kHz), we demonstrate detection of droplet fluorescence signals with a dynamic range spanning 5 orders of magnitude and robust post-sort recovery of intact double emulsion (DE) droplets using 2 commercially-available FACS instruments. We report the first demonstration of single double emulsion droplet isolation with post-sort recovery efficiencies >70%, equivalent to the capabilities of single-cell FACS. Finally, we establish complete downstream recovery of nucleic acids from single, sorted double emulsion droplets via qPCR with little to no cross-contamination. sdDE-FACS marries the full power of droplet microfluidics with flow cytometry to enable a variety of new droplet assays, including rare variant isolation and multiparameter single-cell analysis.


Asunto(s)
Ácidos Nucleicos , Emulsiones , Citometría de Flujo , Microfluídica , Análisis de la Célula Individual
17.
Prog Community Health Partnersh ; 14(1): 43-54, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32280122

RESUMEN

BACKGROUND: Medication-assisted treatment (MAT) is an evidence-based program for patients with opioid use disorders. Yet, within the state of Utah, MAT had not been widely available, promoted, or adopted within the public sector. Recognizing the potential benefit, a collective impact approach was used to promote social change and increase the use of MAT in the community for treatment of opioid use disorders. OBJECTIVE: Conduct a retrospective, observational case series study to measure the effect of a community-based, collective impact approach implementing the MAT program to improve the rate of abstinence and retention among individuals identified with an opioid use disorder in three Utah counties. METHODS: The study was designed and implemented by the Utah Opioid Community Collaborative (OCC) using a collective impact approach, which included broad sector coordination (public-private collaboration), a common agenda, participation in mutually reinforcing activities, continuous communication, consistent measurement of results, and identification of a backbone organization. The MAT intervention program includes use of medications approved by the U.S. Food and Drug Administration in combination with counseling and behavioral therapies delivered within two community sites. Analysis was performed over time to describe the rate of abstinence and retention associated with participation in the MAT program during 2015 through 2017. RESULTS: Of the 339 identified with risk of an opioid use disorders, 228 enrolled in the MAT Program. At MAT enrollment, average age was 32.6 ± 8.2 years old and 58.0% were female. At 365 days after MAT enrollment, 84% of participants were abstinent from opioid substances and 62% from all illicit substances. CONCLUSIONS: Use of a collective impact approach provides a successful mobilization framework in Utah for increasing community engagement and expanding patient access to underresourced MAT programs while suggesting a high rate of abstinence from illicit substances at 12 months.


Asunto(s)
Investigación Participativa Basada en la Comunidad/organización & administración , Tratamiento de Sustitución de Opiáceos/métodos , Trastornos Relacionados con Opioides/tratamiento farmacológico , Adulto , Comunicación , Femenino , Evaluación del Impacto en la Salud/métodos , Humanos , Masculino , Estudios Retrospectivos
18.
J Acquir Immune Defic Syndr ; 82 Suppl 1: S57-S61, 2019 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-31425397

RESUMEN

BACKGROUND: The Cooperative Re-Engagement Controlled Trial (CoRECT) is a randomized controlled trial that uses a combined health department-provider data to care (D2C) model to identify out-of-care HIV-infected persons. We present cost data for programmatic aspects of the trial during the start-up period (first 30 days of the study). METHODS: We used microcosting methods to estimate health department start-up costs. We collected start-up cost data between September 2016 and December 2016; 3 health departments completed a form to capture expenses for the initial 30 days of study implementation; the start date varied by health department. All costs are expressed in 2016 US dollars. RESULTS: Among the 3 health departments, the total start-up costs ranged from $14,145 to $26,058. Total start-up labor hours ranged from 224 to 640 hours. CONCLUSIONS: As D2C expands nationally with cooperative agreement, PS 18-1802 health departments may be able to use a similar analysis to consider the labor, time, and resources needed to implement D2C within their jurisdiction.


Asunto(s)
Infecciones por VIH/tratamiento farmacológico , Costos de la Atención en Salud , Administración en Salud Pública/economía , Infecciones por VIH/economía , Infecciones por VIH/epidemiología , Humanos , Estados Unidos/epidemiología
20.
Science ; 361(6399): 233-235, 2018 Jul 20.
Artículo en Inglés | MEDLINE | ID: mdl-30026216
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