Rheumatoid arthritis (RA) is an inflammatory immune-triggered disease that causes synovitis, cartilage degradation, and joint injury. In nanotechnology, conventional liposomes were extensively investigated for RA. However, they frequently undergo rapid clearance, reducing circulation time and therapeutic efficacy. Additionally, their stability in the bloodstream is often compromised, resulting in premature drug release. The current review explores the potential of targeted liposomal-based nanosystems in the treatment of RA. It highlights the pathophysiology of RA, explores selective targeting sites, and elucidates diverse mechanisms of novel liposomal types and their applications. Furthermore, the targeting strategies of pH-sensitive, flexible, surface-modified, PEGylated, acoustic, ROS-mediated, and biofunctionalized liposomes are addressed. Targeted nanoliposomes showed potential in precisely delivering drugs to CD44, SR-A, FR-β, FLS, and toll-like receptors through the high affinity of ligands. In vitro studies interpreted stable release profiles and improved stability. Ex vivo studies on skin demonstrated that ultradeformable and glycerol-conjugated liposomes enhanced drug penetrability. In vivo experiments for liposomal types in the arthritis rat model depicted remarkable efficacy in reducing joint swelling, pro-inflammatory cytokines, and synovial hyperplasia. In conclusion, these targeted liposomes represented a significant leap forward in drug delivery, offering effective therapeutic options for RA. In the future, integrating these advanced liposomes with artificial intelligence, immunotherapy, and precision medicine holds great promise.
Abstract Objective To examine the relationship between site‐level adaptation and early adoption of Caregivers Finding Important Resources, Support, and Training (FIRST) training during national implementation across diverse Veteran Health Administration (VA) medical centers. Data Sources and Study Setting We enrolled and evaluated 25 VA medical centers (VAMCs). Along with administrative data on site characteristics, we examined site‐reported data on adaptations and intervention adoption, defined as ≥4 training classes delivered to ≥5 caregivers at 6 months from April through October 2022. Study Design A type III hybrid implementation‐effectiveness cluster randomized controlled trial, randomized VAMCs 1:1 to receive foundational (low‐touch) implementation support ( n = 12) or the addition of enhanced (high‐touch) implementation support ( n = 13). Data Collection/Extraction Methods At key implementation phases, VAMCs were asked to report adaptations including content, contextual modifications (format, setting, personnel, and population), and training of providers. We describe site‐level adaptations by arm and by organizational characteristics that included VAMC complexity level, staffing, rurality, and organizational readiness to change. We used qualitative comparative analysis to identify unique adaptations that contributed to intervention adoption at 6 months. Principal Finding s VAMCs randomized to receive enhanced support reported slightly more adaptations than those randomized to foundational support. At 6 months, VAMCs with two or more adaptations adopted Caregivers FIRST at a higher rate than those with fewer adaptations (90% vs. 44%). Staffing adaptations (e.g., who delivered the intervention), format and content (e.g., modified delivery pace), and referring provider training were unique adaptations to adopting sites. Conclusions Site‐level adaptations were diverse and occurred more frequently in sites with early adoption of Caregivers FIRST. Future research should identify best practices of supporting and monitoring intervention adaptation. Understanding the role of adaptation in early adoption success could assist other healthcare systems in implementing interventions for caregivers.
As the population ages there is an increasing need for caregiver training programs, but little is known about how to deliver implementation support for diverse sites in large-scale implementation efforts. External group-based implementation facilitation may be one promising approach. This study's objective is to detail the development and delivery of a pragmatic implementation facilitation approach to support the national rollout of caregiver training, Caregivers FIRST, at over 140 Veterans Health Administration (VHA) sites. Using administrative, survey, and project data, we describe the process of developing and delivering enhanced support to 13 VHA sites unable to meet adoption benchmarks as part of a national mandate. Enhanced support consisted of 4 group-based calls delivered within a 12-week period that used tailored external facilitation to address barriers, facilitators, and strategies for program implementation. We present key implementation barriers, implementation strategies, and sites' perceptions of highly valued elements of enhanced support. Enhanced support calls focused on 3 implementation barriers commonly identified by implementing staff (n = 25) in a site-level needs assessment survey: recruiting and retaining caregivers (83%), balancing program delivery alongside competing demands (57%), and support from other departments in program delivery (44%). Sites attended a median of 3 out of 4 enhanced support calls. In postimplementation quantitative surveys, the average response of perceived helpfulness of enhanced support (ranging from 1 to 5) was 3.4 at 6 months, increasing to 4.2 at 12 months. Respondents valued collaborative problem-solving and the ability to learn best practices from other implementing sites during enhanced support calls. Describing the process of developing and delivering enhanced support via group-based external facilitation for Caregivers FIRST in VHA may provide useful information to guide similar efforts in other healthcare systems as they broadly disseminate interventions to support caregivers across diverse sites. NCT05319535.
Abstract Objective To assess whether a team collaboration strategy (CONNECT) improves implementation outcomes of a family caregiver skills training program (iHI‐FIVES). Data Sources and Study Setting iHI‐FIVES was delivered to caregivers at eight Veterans Affairs (VA) medical centers. Data sources were electronic health records, staff surveys, and interviews. Study Design In a stepped wedge cluster randomized trial, sites were randomized to a 6‐month time interval start date for iHI‐FIVES launch. Sites were then randomized 1:1 to either (i) CONNECT, a team collaboration training strategy plus Replicating Effective Programs (REP), brief technical support training for staff, or (ii) REP only (non‐CONNECT arm). Implementation outcomes included reach (proportion of eligible caregivers enrolled) and fidelity (proportion of expected trainings delivered). Staff interviews and surveys assessed team function including communication, implementation experience, and their relation to CONNECT and iHI‐FIVES implementation outcomes. Data Collection/Extraction Methods The sample for assessing implementation outcomes included 571 Veterans referred to VA home‐ and community‐based services and their family caregivers eligible for iHI‐FIVES. Prior to iHI‐FIVES launch, staff completed 65 surveys and 62 interviews. After the start of iHI‐FIVES, staff completed 52 surveys and 38 interviews. Mixed methods evaluated reach and fidelity by arm. Principal Findings Fidelity was high overall with 88% of expected iHI‐FIVES trainings delivered, and higher among REP only (non‐CONNECT) compared with CONNECT sites (95% vs. 80%). Reach was 18% (average proportion of reach across eight sites) and higher among non‐CONNECT compared with CONNECT sites (22% vs. 14%). Qualitative interviews revealed strong leadership support at high‐reach sites. CONNECT did not influence self‐reported team function. Conclusions A team collaboration strategy (CONNECT), added to REP, required more resources to implement iHI‐FIVES than REP only and did not substantially enhance reach or fidelity. Leadership support was a key condition of implementation success and may be an important factor for improving iHI‐FIVES reach with national expansion.
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