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1.
PLoS One ; 19(3): e0298818, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38507426

RESUMO

Sox2 is known for its roles in maintaining the stem cell state of embryonic stem cells and neural stem cells. In particular, it has been shown to slow the proliferation of these cell types. It is also known for its effects as an activating transcription factor. Despite this, analysis of published studies shows that it represses as many genes as it activates. Here, we identify a new set of target genes that Sox2 represses in neural stem cells. These genes are associated with centrosomes, centromeres and other aspects of cell cycle control. In addition, we show that SUMOylation of Sox2 is necessary for the repression of these genes and for its repressive effects on cell proliferation. Together, these data suggest that SUMO-dependent repression of this group of target genes is responsible for the role of Sox2 in regulating the proliferation of neural stem cells.


Assuntos
Células-Tronco Neurais , Células-Tronco Neurais/metabolismo , Transcrição Gênica , Células-Tronco Embrionárias , Regulação da Expressão Gênica no Desenvolvimento , Proliferação de Células , Fatores de Transcrição SOXB1/genética , Fatores de Transcrição SOXB1/metabolismo , Diferenciação Celular/genética
2.
Implement Sci Commun ; 5(1): 8, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216967

RESUMO

BACKGROUND: STRIDE is a supervised walking program designed to address the negative consequences of immobility during hospitalization for older adults. In an 8-hospital stepped wedge randomized controlled trial, STRIDE was associated with reduced odds of hospital discharge to skilled nursing facility. STRIDE has the potential to become a system-wide approach to address hospital-associated disability in Veteran's Affairs; however, critical questions remain about how best to scale and sustain the program. The overall study goal is to compare the impact of two strategies on STRIDE program penetration (primary), fidelity, and adoption implementation outcomes. METHODS: Replicating Effective Programs will be used as a framework underlying all implementation support activities. In a parallel, cluster randomized trial, we will use stratified blocked randomization to assign hospitals (n = 32) to either foundational support, comprised of standard, low-touch activities, or enhanced support, which includes the addition of tailored, high-touch activities if hospitals do not meet STRIDE program benchmarks at 6 and 8 months following start date. All hospitals begin with foundational support for 6 months until randomization occurs. The primary outcome is implementation penetration defined as the proportion of eligible hospitalizations with ≥ 1 STRIDE walks at 10 months. Secondary outcomes are fidelity and adoption with all implementation outcomes additionally examined at 13 and 16 months. Fidelity will be assessed for STRIDE hospitalizations as the percentage of eligible hospital days with "full dose" of the program, defined as two or more documented walks or one walk for more than 5 min. Program adoption is a binary outcome defined as ≥ 5 patients with a STRIDE walk or not. Analyses will also include patient-level effectiveness outcomes (e.g., discharge to nursing home, length of stay) and staffing and labor costs. We will employ a convergent mixed-methods approach to explore and understand pre-implementation contextual factors related to differences in hospital-level adoption. DISCUSSION: Our study results will dually inform best practices for promoting successful implementation of an evidence-based hospital-based walking program. This information may support other programs by advancing our understanding of how to apply and scale-up national implementation strategies. TRIAL REGISTRATION: This study was registered on June 1, 2021, at ClinicalTrials.gov (identifier NCT04868656 ).

3.
J Gen Intern Med ; 2023 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-37932543

RESUMO

BACKGROUND: Risk stratification and population management strategies are critical for providing effective and equitable care for the growing population of older adults in the USA. Both frailty and neighborhood disadvantage are constructs that independently identify populations with higher healthcare utilization and risk of adverse outcomes. OBJECTIVE: To examine the joint association of these factors on acute healthcare utilization using two pragmatic measures based on structured data available in the electronic health record (EHR). DESIGN: In this retrospective observational study, we used EHR data to identify patients aged ≥ 65 years at Atrium Health Wake Forest Baptist on January 1, 2019, who were attributed to affiliated Accountable Care Organizations. Frailty was categorized through an EHR-derived electronic Frailty Index (eFI), while neighborhood disadvantage was quantified through linkage to the area deprivation index (ADI). We used a recurrent time-to-event model within a Cox proportional hazards framework to examine the joint association of eFI and ADI categories with healthcare utilization comprising emergency visits, observation stays, and inpatient hospitalizations over one year of follow-up. KEY RESULTS: We identified a cohort of 47,566 older adults (median age = 73, 60% female, 12% Black). There was an interaction between frailty and area disadvantage (P = 0.023). Each factor was associated with utilization across categories of the other. The magnitude of frailty's association was larger than living in a disadvantaged area. The highest-risk group comprised frail adults living in areas of high disadvantage (HR 3.23, 95% CI 2.99-3.49; P < 0.001). We observed additive effects between frailty and living in areas of mid- (RERI 0.29; 95% CI 0.13-0.45; P < 0.001) and high (RERI 0.62, 95% CI 0.41-0.83; P < 0.001) neighborhood disadvantage. CONCLUSIONS: Considering both frailty and neighborhood disadvantage may assist healthcare organizations in effectively risk-stratifying vulnerable older adults and informing population management strategies. These constructs can be readily assessed at-scale using routinely collected structured EHR data.

4.
Implement Sci Commun ; 4(1): 125, 2023 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-37828564

RESUMO

BACKGROUND: Knee osteoarthritis (OA) is a leading cause of chronic pain and disability and one of the most common conditions treated in outpatient physical therapy (PT). Because of the high and growing prevalence of knee OA, there is a need for efficient approaches for delivering exercise-based PT to patients with knee OA. A prior randomized controlled trial (RCT) showed that a 6-session Group Physical Therapy Program for Knee OA (Group PT) yields equivalent or greater improvements in pain and functional outcomes compared with traditional individual PT, while requiring fewer clinician hours per patient to deliver. This manuscript describes the protocol for a hybrid type III effectiveness-implementation trial comparing two implementation packages to support delivery of Group PT. METHODS: In this 12-month embedded trial, a minimum of 16 Veterans Affairs Medical Centers (VAMCs) will be randomized to receive one of two implementation support packages for their Group PT programs: a standard, low-touch support based on Replicating Effective Programs (REP) versus enhanced REP (enREP), which adds tailored, high-touch support if sites do not meet Group PT adoption and sustainment benchmarks at 6 and 9 months following launch. Implementation outcomes, including penetration (primary), adoption, and fidelity, will be assessed at 6 and 12 months (primary assessment time point). Additional analyses will include patient-level effectiveness outcomes (pain, function, satisfaction) and staffing and labor costs. A robust qualitative evaluation of site implementation context and experience, as well as site-led adaptations to the Group PT program, will be conducted. DISCUSSION: To our knowledge, this study is the first to evaluate the impact of tailored, high-touch implementation support on implementation outcomes when compared to standardized, low-touch support for delivering a PT-based intervention. The Group PT program has strong potential to become a standard offering for PT, improving function and pain-related outcomes for patients with knee OA. Results will provide information regarding the effectiveness and value of this implementation approach and a deeper understanding of how healthcare systems can support wide-scale adoption of Group PT. TRIAL REGISTRATION: This study was registered on March 7, 2022 at ClinicalTrials.gov (identifier NCT05282927 ).

5.
Implement Sci Commun ; 4(1): 97, 2023 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-37587517

RESUMO

BACKGROUND: Family caregiver training decreases caregiver psychological burden and improves caregiver depressive symptoms and health-related quality of life. Caregivers FIRST is an evidence-based group skills training curriculum for family caregivers and was announced for national dissemination in partnership with the Veterans Health Administration (VHA) National Caregiver Support Program (CSP). Previous evaluations of Caregivers FIRST implementation highlighted that varying support was needed to successfully implement the program, ranging from minimal technical assistance to intensive assistance and support. However, we do not know the optimal level of support needed to inform cost-effective national scaling of the program. We describe a protocol for randomizing 24 non-adopting VA medical centers 1:1 to a tailored, high-touch implementation support or a standard, low-touch implementation support to test the primary hypothesis that high-touch support increases Caregivers FIRST penetration, fidelity, and adoption. Additionally, we describe the methods for evaluating the effect of Caregivers FIRST participation on Veteran outcomes using a quasi-experimental design and the methods for a business case analysis to examine cost of delivery differences among sites assigned to a low or high-touch implementation support. METHODS: We use a type III hybrid implementation-effectiveness study design enrolling VA medical centers that do not meet Caregivers FIRST adoption benchmarks following the announcement of the program as mandated within the CSP. Eligible medical centers will be randomized to receive a standard low-touch implementation support based on Replicating Effective Programs (REP) only or to an enhanced REP (high-touch) implementation support consisting of facilitation and tailored technical assistance. Implementation outcomes include penetration (primary), fidelity, and adoption at 12 months. Mixed methods will explore sites' perceptions and experiences of the high-touch intensification strategy. Additional analyses will include a patient-level effectiveness outcome (Veteran days at home and not in an institution) and a business case analysis using staffing and labor cost data. DISCUSSION: This pragmatic trial will lead to the development and refinement of implementation tools to support VA in spreading and sustaining Caregivers FIRST in the most efficient means possible. TRIAL REGISTRATION: This study was registered on April 8, 2022, at ClinicalTrials.gov (identifier NCT05319535).

6.
Implement Sci Commun ; 4(1): 69, 2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37337208

RESUMO

BACKGROUND: Caregivers FIRST is an evidence-based program addressing gaps in caregivers' skills. In 2020, the Veterans Health Administration Caregiver Support Program (CSP) nationally endorsed Caregivers FIRST, offering credit in leadership performance plans to encourage all VA medical centers (VAMCs) to implement locally. This study examines the association of organizational readiness with VAMC adoption of Caregivers FIRST. METHODS: In a cohort observational study, we surveyed CSP managers about their facilities' readiness to implement using the Organizational Readiness for Implementing Change (ORIC) instrument and compared change commitment and change efficacy domains among VAMCs "adopters" defined as delivering Caregivers FIRST within 1 year of the national announcement to those that did not ("non-adopters"). Within "adopters," we categorized time to adoption based on Rogers' diffusion of innovation theory including "innovators," "early adopters," "early majority," "late adopters," and "laggards." Organizational readiness and site characteristics (facility complexity, staffing levels, volume of applications for caregiver assistance services) were compared between "adopters," "non-adopters," and between time to adoption subcategories. Separate logistic regression models were used to assess whether ORIC and site characteristics were associated with early adoption among "adopters." RESULTS: Fifty-one of 63 (81%) VAMCs with CSP manager survey respondents adopted Caregivers FIRST during the first year. ORIC change commitment and efficacy were similar for "adopters" and "non-adopters." However, sites that adopted earlier (innovators and early adopters) had higher ORIC change commitment and efficacy scores than the rest of the "adopters." Logistic regression results indicated that higher ORIC change commitment (odds ratio [OR] = 2.57; 95% confidence interval [CI], 1.11-5.95) and ORIC change efficacy (OR = 2.60; 95% CI, 1.12-6.03) scores were associated with increased odds that a VAMC was an early adopter (categorized as an "innovator," "early adopter", or "early majority"). Site-level characteristics were not associated with Caregivers FIRST early adoption. CONCLUSIONS: To our knowledge, this study is the first to prospectively assess organizational readiness and the timing of subsequent program adoption. Early adoption was associated with higher ORIC change commitment and change efficacy and not site-level characteristics. These findings yield insights into the role of organizational readiness to accelerate program adoption. TRIAL REGISTRATION: ClinicalTrials.gov, NCT03474380. Registered on March 22, 2018.

7.
Gerontologist ; 63(3): 405-415, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-35797202

RESUMO

BACKGROUND AND OBJECTIVES: Dissemination-implementation.org outlines 110 theories, models, and frameworks (TMFs): we conducted a citation analysis on 83 TMFs, searching Web of Science and PubMed databases. RESEARCH DESIGN AND METHODS: Search terms were broad and included "aging," "older," "elderly," and "geriatric." We extracted each TMF in identified articles from inception through January 28, 2022. Included articles must have used a TMF in research or quality improvement work directly linked to older adults within the United States. RESULTS: We reviewed 2,681 articles of which 295 articles cited at least one of 56 TMFs. Five TMFs represented 50% of the citations: Reach, Effectiveness, Adoption, Implementation, and Maintenance 1.0, Consolidated Framework for Implementation Research, Greenhalgh Diffusion of Innovation in Service Organizations, Quality Enhancement Research Initiative, Community-Based Participatory Research, and Promoting Action on Research Implementation in Health Services. TMF application varied and there was a steady increase in TMF citations over time, with a 2- to 3-fold increase in citations in 2020-2021. We identified that only 41% of TMF use was meaningful. DISCUSSION AND IMPLICATIONS: Our results suggest TMF utilization is increasing in aging research, but there is a need to more meaningful utilize TMFs. As the population of older adults continues to grow, there will be increasing demand for effective evidence-based practices and models of care to be quickly and effectively translated into routine care. Use of TMFs is critical to building such evidence and to identifying and evaluating methods to support this translation.


Assuntos
Pesquisa Participativa Baseada na Comunidade , Gerociência , Humanos , Estados Unidos , Idoso , Gerenciamento de Dados
8.
Gerontologist ; 63(3): 604-613, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36029028

RESUMO

Implementation strategies are activities to support integration of evidence-based programs (EBPs) into routine care. Comprised of 170+ facilities, the Veterans Affairs Healthcare System is conducive to evaluating feasibility and scalability of implementation strategies on a national level. In previous work evaluating implementation of three EBPs for older Veterans (hospital-based walking, caregiver skills training, group physical therapy), we found facilities varied in their need for implementation support, with some needing minimal guidance and others requiring intensive support. Committed to national scalability, our team developed an implementation intensification model consisting of foundational (low-touch) and enhanced (high-touch) implementation support. This Forum article describes our multilevel and multistep process to develop and evaluate implementation intensification. Steps included (a) review completed trial data; (b) conduct listening sessions; (c) review literature; (d) draft foundational and enhanced implementation support packages; (e) iteratively refine packages; and (7) devise an evaluation plan. Our model of implementation intensification may be relevant to other health care systems seeking strategies that can adapt to diverse delivery settings, optimize resources, help build capacity, and ultimately enhance implementation outcomes. As more health care systems focus on spread of EBPs into routine care, identifying scalable and effective implementation strategies will be critical.


Assuntos
United States Department of Veterans Affairs , Veteranos , Estados Unidos , Humanos , Atenção à Saúde
9.
Gerontologist ; 63(3): 534-544, 2023 03 21.
Artigo em Inglês | MEDLINE | ID: mdl-36327120

RESUMO

BACKGROUND AND OBJECTIVES: A minority of family caregivers receive training, with implications for their own and their recipient's outcomes. Federal policy has supported the implementation and expansion of caregiver training and support. The Department of Veterans Affairs (VA) has developed a national Caregiver Support Program and collaborated with VA health services researchers to explore caregivers' acceptance of an evidence-based training program in preparation for system-wide dissemination. RESEARCH DESIGN AND METHODS: This approach entailed a convergent mixed-methods design, which involved separate analyses of quantitative and qualitative data. Survey questions based on the Kirkpatrick model for training evaluation measured caregivers' reaction and learning, and interview questions elicited caregivers' reports about the value of the program for them. RESULTS: Most caregivers reported satisfaction with the training when responding to survey questions, although qualitative interviews revealed caveats suggesting need to hone the best timing and specific group of caregivers for maximal benefit. DISCUSSION AND IMPLICATIONS: Our findings indicate that understanding program-user fit may be particularly critical when implementing training for caregivers as they come to the program at different points along their caregiving journey, needing differing types and intensities of support. While a general program may appeal to policymakers aiming to scale caregiver training within a large, heterogeneous system, there may be shortcomings in terms of end-user acceptance and subsequent downstream outcomes such as reach and ultimately program effectiveness. Good, iterative communication flow between program developers and policymakers facilitates this understanding and, in turn, decisions about scaling.


Assuntos
Cuidadores , Cuidadores/educação , Veteranos , Pesquisa Qualitativa , United States Department of Veterans Affairs
10.
Gerontologist ; 2022 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-36473052

RESUMO

Modifying unhealthy behaviors and/or environments may improve or maintain an older adult's health. However, achieving and sustaining behavior change is challenging and depends upon clinical, social, psychological, and political domains. In an effort to highlight the multidisciplinary nature of behavior change, the NIA Research Centers Collaborative Network (RCCN) held a two-day workshop, Achieving and sustaining behavior change for older adults. The workshop was informed by the socioecological model and designed to initiate dialogue around individual, community, and systems-level determinants of behavior change. This paper summarizes key topics presented during the workshop, discusses opportunities for future research, education, and training, and recommends how each of the six NIA research centers may pursue work in behavior change for older adults.

11.
Geriatrics (Basel) ; 7(3)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35645282

RESUMO

Deprescribing may be particularly beneficial in patients with medical complexity and suspected cognitive impairment (CI). We describe central nervous system (CNS) medication use and side effects in this population and explore the relationship between anticholinergic burden and sleep. We conducted a cross-sectional analysis of baseline data from a pilot randomized-controlled trial in older adult veterans with medical complexity (Care Assessment Need score > 90), and suspected CI (Telephone Interview for Cognitive Status score 20−31). CNS medication classes included antipsychotics, benzodiazepines, H2-receptor antagonists, hypnotics, opioids, and skeletal muscle relaxants. We also coded anticholinergic-active medications according to their Anticholinergic Cognitive Burden (ACB) score. Other measures included self-reported medication side effects and the Pittsburgh Sleep Quality Index (PSQI). ACB association with sleep (PSQI) was examined using adjusted linear regression. In this sample (N = 40), the mean number of prescribed CNS medications was 2.2 (SD 1.5), 65% experienced ≥ 1 side effect, and 50% had an ACB score ≥ 3 (high anticholinergic exposure). The ACB score ≥ 3 compared to ACB < 3 was not significantly associated with PSQI scores (avg diff in score = −0.1, 95% CI −2.1, 1.8). Although results did not demonstrate a clear relationship with worsened sleep, significant side effects and anticholinergic burden support the deprescribing need in this population.

12.
Pharmaceutics ; 14(5)2022 May 19.
Artigo em Inglês | MEDLINE | ID: mdl-35631671

RESUMO

Clostridioides difficile is an opportunistic gut pathogen which causes severe colitis, leading to significant morbidity and mortality due to its toxins, TcdA and TcdB. Two intra-muscular toxoid vaccines entered Phase III trials and strongly induced toxin-neutralising antibodies systemically but failed to provide local protection in the colon from primary C. difficile infection (CDI). Alternatively, by immunising orally, the ileum (main immune inductive site) can be directly targeted to confer protection in the large intestine. The gut commensal, non-toxigenic C. difficile (NTCD) was previously tested in animal models as an oral vaccine for natural delivery of an engineered toxin chimera to the small intestine and successfully induced toxin-neutralising antibodies. We investigated whether NTCD could be further exploited to induce antibodies that block the adherence of C. difficile to epithelial cells to target the first stage of pathogenesis. In NTCD strain T7, the colonisation factor, CD0873, and a domain of TcdB were overexpressed. Following oral immunisation of hamsters with spores of recombinant strain, T7-0873 or T7-TcdB, intestinal and systemic responses were investigated. Vaccination with T7-0873 successfully induced intestinal antibodies that significantly reduced adhesion of toxigenic C. difficile to Caco-2 cells, and these responses were mirrored in sera. Additional engineering of NTCD is now warranted to further develop this vaccine.

13.
Vaccines (Basel) ; 9(12)2021 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-34960199

RESUMO

Mucosal vaccination aims to prevent infection mainly by inducing secretory IgA (sIgA) antibody, which neutralises pathogens and enterotoxins by blocking their attachment to epithelial cells. We previously demonstrated that encapsulated protein antigen CD0873 given orally to hamsters induces neutralising antibodies locally as well as systemically, affording partial protection against Clostridioides difficile infection. The aim of this study was to determine whether displaying CD0873 on liposomes, mimicking native presentation, would drive a stronger antibody response. The recombinant form we previously tested resembles the naturally cleaved lipoprotein commencing with a cysteine but lacking lipid modification. A synthetic lipid (DHPPA-Mal) was designed for conjugation of this protein via its N-terminal cysteine to the maleimide headgroup. DHPPA-Mal was first formulated with liposomes to produce MalLipo; then, CD0873 was conjugated to headgroups protruding from the outer envelope to generate CD0873-MalLipo. The immunogenicity of CD0873-MalLipo was compared to CD0873 in hamsters. Intestinal sIgA and CD0873-specific serum IgG were induced in all vaccinated animals; however, neutralising activity was greatest for the CD0873-MalLipo group. Our data hold great promise for development of a novel oral vaccine platform driving intestinal and systemic immune responses.

14.
Geriatrics (Basel) ; 6(4)2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34842733

RESUMO

Hospitalization is common among older adults. Prolonged time in bed during hospitalization can lead to deconditioning and functional impairments. Our team is currently working with Department of Veterans Affairs (VA) medical centers across the United States to implement STRIDE (assiSTed eaRly mobIlity for hospitalizeD older vEterans), a hospital-based walking program designed to mitigate the risks of immobility during hospitalization. However, the COVID-19 pandemic made in-person, or face-to-face, walking challenging due to social distancing recommendations and infection control concerns. In response, our team applied principles of implementation science, including stakeholder engagement, prototype development and refinement, and rapid dissemination and feedback, to create STRIDE in Your Room (SiYR). Consisting of self-guided exercises, light exercise equipment (e.g., TheraBands, stress ball, foam blocks, pedometer), the SiYR program provided safe alternative activities when face-to-face walking was not available during the pandemic. We describe the methods used in developing the SiYR program; present feedback from participating sites; and share initial implementation experiences, lessons learned, and future directions.

15.
J Clin Med ; 10(10)2021 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-34068839

RESUMO

Multiple chronic conditions (MCC) are one of today's most pressing healthcare concerns, affecting 25% of all Americans and 75% of older Americans. Clinical care for individuals with MCC is often complex, condition-centric, and poorly coordinated across multiple specialties and healthcare services. There is an urgent need for innovative patient-centered research and intervention development to address the unique needs of the growing population of individuals with MCC. In this commentary, we describe innovative methods and strategies to conduct patient-centered MCC research guided by the goals and objectives in the Department of Health and Human Services MCC Strategic Framework. We describe methods to (1) increase the external validity of trials for individuals with MCC; (2) study MCC epidemiology; (3) engage clinicians, communities, and patients into MCC research; and (4) address health equity to eliminate disparities.

16.
J Prim Care Community Health ; 12: 21501327211008055, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33882736

RESUMO

The diagnosis, treatment, and management of chronic pain is complex, nuanced, and challenging in primary care settings. These challenges often give rise to internal provider conflicts around appropriate management strategies, perhaps avoiding diagnosis all together. Factors that contribute to internal provider conflict include knowledge, responsibility, and uncertainties surrounding chronic pain management. This piece acknowledges the complexity and competing priorities of chronic pain management from a provider perspective. We advocate for coordinated and committed care of patients with chronic pain and a sense of shared responsibility among providers to adequately address patient needs.


Assuntos
Dor Crônica , Dor Crônica/diagnóstico , Dor Crônica/terapia , Humanos , Atenção Primária à Saúde
17.
Microorganisms ; 9(2)2021 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-33540694

RESUMO

Clostridioides difficile is the main cause of health-care-associated infectious diarrhoea. Toxins, TcdA and TcdB, secreted by this bacterium damage colonic epithelial cells and in severe cases this culminates in pseudomembranous colitis, toxic megacolon and death. Vaccines in human trials have focused exclusively on the parenteral administration of toxin-based formulations. These vaccines promote toxin-neutralising serum antibodies but fail to confer protection from infection in the gut. An effective route to immunise against gut pathogens and stimulate a protective mucosal antibody response (secretory immunoglobulin A, IgA) at the infection site is the oral route. Additionally, oral immunisation generates systemic antibodies (IgG). Using this route, two different antigens were tested in the hamster model: The colonisation factor CD0873 and a TcdB fragment. Animals immunised with CD0873 generated a significantly higher titre of sIgA in intestinal fluid and IgG in serum compared to naive animals, which significantly inhibited the adherence of C. difficile to Caco-2 cells. Following challenge with a hypervirulent isolate, the CD0873-immunised group showed a mean increase of 80% in time to experimental endpoint compared to naïve animals. Survival and body condition correlated with bacterial clearance and reduced pathology in the cecum. Our findings advocate CD0873 as a promising oral vaccine candidate against C. difficile.

18.
J Am Geriatr Soc ; 69(1): 77-84, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32966603

RESUMO

OBJECTIVE: This pilot study assessed feasibility of video-enhanced care management for complex older veterans with suspected mild cognitive impairment (CI) and their care partners, compared with telephone delivery. DESIGN: Pilot randomized controlled trial. SETTING: Durham Veterans Affairs Health Care System. PARTICIPANTS: Participants were enrolled as dyads, consisting of veterans aged 65 years or older with complex medical conditions (Care Assessment Need score ≥90) and suspected mild CI (education-adjusted Modified Telephone Interview for Cognitive Status score 20-31) and their care partners. INTERVENTION: The 12-week care management intervention consisted of monthly calls from a study nurse covering medication management, cardiovascular disease risk reduction, physical activity, and sleep behaviors, delivered via video compared with telephone. MEASUREMENTS: Dyads completed baseline and follow-up assessments to assess feasibility, acceptability, and usability. RESULTS: Forty veterans (mean (standard deviation (SD)) age = 72.4 (6.1) years; 100% male; 37.5% Black) and their care partners (mean (SD) age = 64.7 (10.8) years) were enrolled and randomized to telephone or video-enhanced care management. About a third of veteran participants indicated familiarity with relevant technology (regular tablet use and/or experience with videoconferencing); 53.6% of internet users were comfortable or very comfortable using the internet. Overall, 43 (71.7%) care management calls were completed in the video arm and 52 (86.7%) were completed in the telephone arm. Usability of the video telehealth platform was rated higher for participants already familiar with technology used to deliver the intervention (mean (SD) System Usability Scale scores: 65.0 (17.0) vs 55.6 (19.6)). Veterans, care partners, and study nurses reported greater engagement, communication, and interaction in the video arm. CONCLUSION: Video-delivered care management calls were feasible and preferred over telephone for some complex older adults with mild CI and their care partners. Future research should focus on understanding how to assess and incorporate patient and family preferences related to uptake and maintenance of video telehealth interventions.


Assuntos
Administração dos Cuidados ao Paciente/tendências , Telemedicina/tendências , Telefone , Veteranos/estatística & dados numéricos , Comunicação por Videoconferência , Idoso , Cuidadores/estatística & dados numéricos , Doença Crônica/terapia , Disfunção Cognitiva/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Comportamento de Redução do Risco
19.
J Gen Intern Med ; 35(1): 79-86, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31489559

RESUMO

BACKGROUND: Little research has been done on primary care-based models to improve health care use after an emergency department (ED) visit. OBJECTIVE: To examine the effectiveness of a primary care-based, nurse telephone support intervention for Veterans treated and released from the ED. DESIGN: Randomized controlled trial with 1:1 assignment to telephone support intervention or usual care arms (ClinicalTrials.gov: NCT01717976). SETTING: Department of Veterans Affairs Health Care System (VAHCS) in Durham, NC. PARTICIPANTS: Five hundred thirteen Veterans who were at high risk for repeat ED visits. INTERVENTION: The telephone support intervention consisted of two core calls in the week following an ED visit. Call content focused on improving the ED to primary care transition, enhancing chronic disease management, and educating Veterans and family members about VHA and community services. MAIN MEASURES: The primary outcome was repeat ED use within 30 days. KEY RESULTS: Observed rates of repeat ED use at 30 days in usual care and intervention groups were 23.1% and 24.9%, respectively (OR = 1.1; 95% CI = 0.7, 1.7; P = 0.6). The intervention group had a higher rate of having at least 1 primary care visit at 30 days (OR = 1.6, 95% CI = 1.1-2.3). At 180 days, the intervention group had a higher rate of usage of a weight management program (OR = 3.5, 95% CI = 1.6-7.5), diabetes/nutrition (OR = 1.8, 95% CI = 1.0-3.0), and home telehealth services (OR = 1.7, 95% CI = 1.0-2.9) compared with usual care. CONCLUSIONS: A brief primary care-based nurse telephone support program after an ED visit did not reduce repeat ED visits within 30 days, despite intervention participants' increased engagement with primary care and some chronic disease management services. TRIALS REGISTRATION: ClinicalTrials.gov NCT01717976.


Assuntos
Serviço Hospitalar de Emergência , Alta do Paciente , Humanos , Transferência de Pacientes , Atenção Primária à Saúde , Telefone
20.
Med Care ; 57 Suppl 10 Suppl 3: S246-S252, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31517795

RESUMO

BACKGROUND: There is an increasing expectation for research to involve patient stakeholders. Yet little guidance exists regarding patient-engaged research in evidence synthesis. Embedded in a learning health care system, the Veteran Affairs Evidence Synthesis Program (ESP) provides an ideal environment for exploring patient-engaged research in a program of evidence synthesis. OBJECTIVE: The objective of this study was to explore views, barriers, resources, and perceived values of engaging patient advisors in a national program of evidence synthesis research. METHODS: We conducted 10 qualitative interviews with ESP researchers and 2 focus groups with patient stakeholder informants. We queried for challenges to patient involvement, resources needed to overcome barriers, and perceived values of patient engagement. We analyzed qualitative data using applied thematic and matrix techniques. RESULTS: Patient stakeholders and researchers expressed positive views on the potential role for patient engagement in the Veteran Affairs ESP. Possible contributions included topic prioritization, translating findings for lay audiences, and identifying clinically important outcomes relevant to patients. There were numerous barriers to patient involvement, which were more commonly noted by ESP researchers than by patient stakeholders. Although informants were able to articulate multiple values, we found a lack of clarity around measurable outcomes of patient involvement in systematic reviews. CONCLUSIONS: The research community increasingly seeks patient input. There are many perceived and actual barriers to seeking robust patient engagement in systematic reviews. This study outlines emerging practices that other evidence synthesis programs should consider, such as the careful selection of stakeholders; codeveloped expectations and goals; and adequate training and appropriate resources to ensure meaningful engagement.


Assuntos
Sistema de Aprendizagem em Saúde , Participação do Paciente , Participação dos Interessados , Revisões Sistemáticas como Assunto , Grupos Focais , Humanos , Entrevistas como Assunto , Pesquisa Qualitativa , Pesquisadores
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