Search

Abstract Background Sustaining evidence-based practices (EBPs) is crucial to ensuring care quality and addressing health disparities. Approaches to identifying factors related to sustainability are critically needed. One such approach is Matrixed Multiple Case Study (MMCS), which identifies factors and their combinations that influence implementation. We applied MMCS to identify factors related to the sustainability of the evidence-based Collaborative Chronic Care Model (CCM) at nine Department of Veterans Affairs (VA) outpatient mental health clinics, 3–4 years after implementation support had concluded. Methods We conducted a directed content analysis of 30 provider interviews, using 6 CCM elements and 4 Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) domains as codes. Based on CCM code summaries, we designated each site as high/medium/low sustainability. We used i-PARIHS code summaries to identify relevant factors for each site, the extent of their presence, and the type of influence they had on sustainability (enabling/neutral/hindering/unclear). We organized these data into a sortable matrix and assessed sustainability-related cross-site trends. Results CCM sustainability status was distributed among the sites, with three sites each being high, medium, and low. Twenty-five factors were identified from the i-PARIHS code summaries, of which 3 exhibited strong trends by sustainability status (relevant i-PARIHS domain in square brackets): “Collaborativeness/Teamwork [Recipients],” “Staff/Leadership turnover [Recipients],” and “Having a consistent/strong internal facilitator [Facilitation]” during and after active implementation. At most high-sustainability sites only, (i) “Having a knowledgeable/helpful external facilitator [Facilitation]” was variably present and enabled sustainability when present, while (ii) “Clarity about what CCM comprises [Innovation],” “Interdisciplinary coordination [Recipients],” and “Adequate clinic space for CCM team members [Context]” were somewhat or less present with mixed influences on sustainability. Conclusions MMCS revealed that CCM sustainability in VA outpatient mental health clinics may be related most strongly to provider collaboration, knowledge retention during staff/leadership transitions, and availability of skilled internal facilitators. These findings have informed a subsequent CCM implementation trial that prospectively examines whether enhancing the above-mentioned factors within implementation facilitation improves sustainability. MMCS is a systematic approach to multi-site examination that can be used to investigate sustainability-related factors applicable to other EBPs and across multiple contexts.

Abstract Background Intimate partner violence (IPV) is a prevalent social determinant of health. The US Preventive Services Task Force recommends routine IPV screening of women, but uptake remains variable. The Veterans Health Administration (VHA) initiated implementation facilitation (IF) to support integration of IPV screening programs into primary care clinics. An evaluation of IF efforts showed variability in IPV screening rates across sites. The follow-up study presented here used a Matrixed Multiple Case Study (MMCS) approach to examine the multilevel factors impacting IPV screening program implementation across sites with varying levels of implementation success. Methods This mixed methods study is part of a larger cluster randomized stepped wedge Hybrid-II program evaluation. In the larger trial, participating sites received 6 months of IF consisting of an external facilitator from VHA’s Office of Women’s Health working closely with an internal facilitator and key site personnel. Recognizing the heterogeneity in implementation outcomes across sites, the MMCS approach was used to enable interpretation of qualitative and quantitative data within and across sites to help contextualize the primary findings from the larger study. Qualitative data collection was guided by the integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework and included interviews with key informants involved in IPV screening implementation at eight sites. Quantitative data on IPV screening uptake was derived from medical records and surveys completed by key personnel at the same eight sites to understand implementation facilitation activities. Results Fifteen factors influencing IPV screening implementation spanning all four i-PARIHS domains were identified and categorized into three distinct categories: (1) factors with enabling influence across all sites, (2) factors deemed important to implementation success, and (3) factors differentiating sites with high/medium versus low implementation success. Conclusions Understanding the influencing factors across multi-level domains contributing to variable success of IPV screening implementation can inform the tailoring of IF efforts to promote spread and quality of screening. Implementation of IPV screening programs in primary care with IF should consider consistent engagement of internal facilitators with clinic staff involved in implementation, the resourcefulness of external facilitators, and appending resources to IPV screening tools to help key personnel address positive screens. Trial registration ClinicalTrials.gov NCT04106193. Registered on September 26, 2019.

Background: Policymakers and payers are reevaluating the temporary telehealth flexibilities granted during the COVID-19 public health emergency, which will shape future teledermatology utilization. Objective: To summarize the recently expanded telehealth flexibilities in the United States, projected changes, and corresponding implications for dermatologists. Methods: Narrative review of the literature, United States policies and regulations, and white paper reports. Results: Key telehealth flexibilities included expansion of payment parity, relaxation of originating site requirements, loosening of state licensure requirements, and HIPAA (Health Insurance Portability and Accountability Act of 1996) enforcement discretion. These changes enabled widespread accessibility and adoption of teledermatology, which enhanced high-quality and cost-effective dermatologic care. Most waivers will end 151 days following the end of the public health emergency declaration. Notably, asynchronous telehealth was not included in the reimbursement expansion. Limitations: Only policies and regulations through December 2022 are included. Conclusion: It will be important for the field of dermatology to stay abreast of the upcoming changes in telemedicine policies and reimbursement, to demonstrate teledermatology’s value through evidence-based studies and to advocate for enduring policies that will promote the accessibility of teledermatology for patients.

Background Sustaining healthcare interventions once they have been implemented is a pivotal public health endeavor. Achieving sustainability requires context-sensitive adaptations to evidence-based practices (EBPs) or the implementation strategies used to ensure their adoption. For replicability of adaptations beyond the specific setting in question, the underlying logic needs to be clearly described, and adaptations themselves need to be plainly documented. The goal of this project was to describe the process by which implementation facilitation was adapted to improve the uptake of clinical care practices that are consistent with the collaborative chronic care model (CCM). Method Quantitative and qualitative data from a prior implementation trial found that CCM-consistent care practices were not fully sustained within outpatient general mental health teams that had received 1 year of implementation facilitation to support uptake. We undertook a multistep consensus process to identify adaptations to implementation facilitation based on these results, with the goal of enhancing the sustainability of CCM-based care in a subsequent trial. The logic for these adaptations, and the resulting adaptations themselves, were documented using two adaptation-oriented implementation frameworks (the iterative decision-making for evaluation of adaptations [IDEA] and the framework for reporting adaptations and modifications to evidence-based implementation strategies [FRAME-IS], respectively). Results Three adaptations emerged from this process and were documented using the FRAME-IS: (a) increasing the scope of implementation facilitation within the medical center, (b) having the internal facilitator take a greater role in the implementation process, and (c) shortening the implementation timeframe from 12 to 8 months, while increasing the intensity of facilitation support during that time. Conclusions EBP sustainability may require careful adaptation of EBPs or the implementation strategies used to get them into routine practice. Recently developed frameworks such as the IDEA and FRAME-IS may be used to guide decision-making and document resulting adaptations themselves. An ongoing funded study is investigating the utility of the resulting adaptations for improving healthcare.

Background:. We aimed to identify how Integra bilayer wound matrix has expanded facial reconstruction options after Mohs surgery due to its reliability in both single- and dual-stage reconstruction. Methods:. A retrospective review of patients undergoing Mohs surgery and alloplastic facial reconstruction with Integra between 2012 and 2022 was performed. Patients who underwent single-stage reconstruction and dual-stage reconstruction with skin graft with at least 90 days of follow-up were included. Results:. One hundred thirty patients with a median age of 76 years were included. Basal cell carcinoma was the most common malignancy (39%). One hundred forty-two lesions were treated and reconstructed same-day with Integra. Lesions most commonly involved the nose (34%) and forehead (22%). The mean postoperative defect size was 26.9 cm2. An estimated 45.5% (n = 60) of defect sites underwent single-stage reconstruction with healing by secondary intention, whereas 54.5% (n = 72) underwent dual-stage reconstruction with skin graft. Integra success rate was 90.2%. Average time to re-epithelialization was 32.2 + 7.3 days. Average time to repigmentation was 169.5 + 14.6 days. The complication rate was 12.8% (n = 17), with 12 undergoing debridement, three needing new Integra graft, and seven needing new skin grafts. Average size for successful healing without complication was 26.6 cm2. Nineteen sites (13.2%) underwent aesthetic improvement procedures, with the majority occurring after dual-stage reconstruction (n = 13). Conclusions:. Integra is a reliable outpatient reconstructive option for facial Mohs defects that can increase the threshold for autologous tissue harvesting and successfully reconstruct large defects of 26.6 cm2 on average with low complication and reoperation rates.

Abstract Background The evidence-based Collaborative Chronic Care Model (CCM), developed to help structure care for chronic health conditions, comprises six elements: work role redesign, patient self-management support, provider decision support, clinical information systems, linkages to community resources, and organizational/leadership support. As the CCM is increasingly implemented in real-world settings, there is heightened interest in understanding specific influences upon implementation. Therefore, guided by the Integrated Promoting Action on Research Implementation in Health Services (i-PARIHS) framework, we (i) identified innovation-, recipient-, context-, and facilitation-related influences on CCM implementation and (ii) assessed the influences’ relationship to each CCM element’s implementation. Methods Using semi-structured interviews, we examined interdisciplinary behavioral health providers’ experiences at nine VA medical centers that implemented the CCM. We used i-PARIHS constructs as a priori codes for directed content analysis, then analyzed the data for cross-coding by CCM element and i-PARIHS construct. Results Participants (31 providers) perceived the CCM innovation as enabling comprehensive care but challenging to coordinate with existing structures/procedures. As recipients, participants recounted not always having the authority to design CCM-consistent care processes. They perceived local leadership support to be indispensable to implementation success and difficult to garner when CCM implementation distracted from other organizational priorities. They found implementation facilitation helpful for keeping implementation on track. We identified key themes at the intersection of i-PARIHS constructs and core CCM elements, including (i) the CCM being an innovation that offers a formal structure to stepping down care intensity for patients to encourage their self-management, (ii) recipients accessing their multidisciplinary colleagues’ expertise for provider decision support, (iii) relationships with external services in the community (e.g., homelessness programs) being a helpful context for providing comprehensive care, and (iv) facilitators helping to redesign specific interdisciplinary team member roles. Conclusions Future CCM implementation would benefit from (i) facilitating strategic development of supportive maintenance plans for patients’ self-management, (ii) collocating multidisciplinary staff (on-site or virtually) to enhance provider decision support, (iii) keeping information on available community resources up to date, and (iv) making clearer the explicit CCM-consistent care processes that work roles can be designed around. This work can inform concrete tailoring of implementation efforts to focus on the more challenging CCM elements, which is crucial to better account for multiple influences that vary across diverse care settings in which the CCM is being implemented.

We measure the radius–velocity phase-space edge profile of A1063 using galaxy redshifts from Karman et al. and Mercurio et al. Combined with a cosmological model and after accounting for interlopers and sampling effects, we infer the escape velocity profile. Using the Poisson equation, we then directly constrain the gravitational potential profile and find excellent agreement between three different density models. For the Navarro–Frenk–White profile, we find log _10 ( M _200,crit ) = ${15.40}_{-0.12}^{+0.06}$ M _⊙ , consistent to within 1 σ of six recently published lensing masses. We argue that this consistency is due to the fact that the escape technique shares no common systematics with lensing other than radial binning. These masses are 2–4 σ lower than estimates made using X-ray data, in addition to the Gómezet al. velocity dispersion estimate. We measure the 1D velocity dispersion within r _200 to be ${\sigma }_{v}\,=\,{1477}_{-99}^{+87}$ km s ^−1 , which combined with our escape velocity mass, brings the dispersion for A1063 in-line with hydrodynamic cosmological simulations for the first time.

All-sky maps of the thermal Sunyaev–Zel’dovich effect (SZ) tend to suffer from systematic features arising from the component-separation techniques used to extract the signal. In this work, we investigate one of these methods, known as needlet internal linear combination (NILC), and test its performance on simulated data. We show that NILC estimates are strongly affected by the choice of the spatial localization parameter (Γ), which controls a bias-variance trade-off. Typically, NILC extractions assume a fixed value of Γ over the entire sky, but we show there exists an optimal Γ that depends on the SZ signal strength and local contamination properties. Then we calculate the NILC solutions for multiple values of Γ and feed the results into a neural network to predict the SZ signal. This extraction method, which we call Deep-NILC, is tested against a set of validation data, including recovered radial profiles of resolved systems. Our main result is that Deep-NILC offers significant improvements over choosing fixed values of Γ.

Abstract Background The coronavirus disease 2019 (COVID-19) pandemic dramatically increased the use of telemental health via videoconferencing (TMH-V). While TMH-V has been found to be effective and satisfactory to both patients and providers, little is known regarding factors that influence site-level uptake. We examined facilitators and barriers to TMH-V uptake at higher and lower adoption sites within the US Department of Veterans Affairs (VA). Methods We conducted twenty-four semi-structured qualitative interviews at four northeastern VA medical centers (two with higher TMH-V adoption and two with lower adoption). Six interviews were conducted per site (one member of mental health leadership, one facility telehealth coordinator/technician, and four mental health providers per site). We performed directed content analysis, guided by the Consolidated Framework for Implementation Research (CFIR), followed by a matrix rating process to rank the degree of influence of each of the 19 included CFIR constructs at the four sites. Positive overall influences, negative overall influences, and differentiators were then identified based on patterns in ratings across sites. Results Five CFIR constructs had positive overall influences across sites: Relative advantage, Patient needs and resources, Relative priority, Knowledge and beliefs, and Self-efficacy. Complexity had a negative overall influence across sites. Four constructs significantly differentiated between higher and lower adoption sites with regards to TMH-V use: Quality, Compatibility, Leadership engagement, and Champions. Conclusions Several positive overall influences on TMH-V uptake were identified across sites; respondents acknowledged multiple advantages of TMH-V (e.g., convenience), and providers’ attitudes towards TMH-V improved as they gained experience. In contrast, complexity was a negative overall influence; TMH-V platforms and processes must be simple and user friendly to promote use. The emergence of Quality, Leadership engagement, and Champions as differentiators speaks to the importance of educating frontline staff and leadership at lower adoption sites about the evidence base demonstrating that TMH-V is high-quality care. Compatibility also emerged as a differentiator; if TMH-V is not easily integrated into provider workflows, uptake will falter. Future work should draw from these findings to develop implementation strategies aiming to increase TMH-V uptake at lower adoption sites, thereby increasing access to high-quality mental health care.

Abstract E-cigarette usage (also known as e-cigarettes or vaping products) has increasingly been recognized as a global public health problem. One challenge in particular involves their marketing to minors (teenagers and children) and the rising prevalence of use in this population. E-cigarettes unnecessarily expose minors to health risks, these include respiratory health problems, such as exacerbations of asthma, bronchitis, and respiratory-tract irritation. Nicotine, commonly found in e-cigarettes, is also associated with cognitive impairment and neurodevelopmental problems. E-cigarettes are also risk factors for downstream substance use, including cigarettes and cannabis initiation (the gateway hypothesis), which compounds health risks in dual users. Current public health preventative and intervention studies are limited, and there is a clear need for more interventions that may prevent usage and assist with cessation in this vulnerable population. Physician education and screening uptake should also be enhanced. Stricter public health policy and protection measures are also needed on a global scale to limit e-cigarette exposure in minors.

Abstract Background Implementation strategies are necessary to ensure that evidence-based practices are successfully incorporated into routine clinical practice. Such strategies, however, are frequently modified to fit local populations, settings, and contexts. While such modifications can be crucial to implementation success, the literature on documenting and evaluating them is virtually nonexistent. In this paper, we therefore describe the development of a new framework for documenting modifications to implementation strategies. Discussion We employed a multifaceted approach to developing the Framework for Reporting Adaptations and Modifications to Evidence-based Implementation Strategies (FRAME-IS), incorporating multiple stakeholder perspectives. Development steps included presentations of initial versions of the FRAME-IS to solicit structured feedback from individual implementation scientists (“think-aloud” exercises) and larger, international groups of researchers. The FRAME-IS includes core and supplementary modules to document modifications to implementation strategies: what is modified, the nature of the modification (including the relationship to core elements or functions), the primary goal and rationale for the modification, timing of the modification, participants in the modification decision-making process, and how widespread the modification is. We provide an example of application of the FRAME-IS to an implementation project and provide guidance on how it may be used in future work. Conclusion Increasing attention is being given to modifications to evidence-based practices, but little work has investigated modifications to the implementation strategies used to implement such practices. To fill this gap, the FRAME-IS is meant to be a flexible, practical tool for documenting modifications to implementation strategies. Its use may help illuminate the pivotal processes and mechanisms by which implementation strategies exert their effects.

Abstract Background This paper reports on a qualitative evaluation of a hybrid type II stepped-wedge, cluster randomized trial using implementation facilitation to implement team-based care in the form of the collaborative chronic care model (CCM) in interdisciplinary outpatient mental health teams. The objective of this analysis is to compare the alignment of sites’ clinical processes with the CCM elements at baseline (time 1) and after 12 months of implementation facilitation (time 2) from the perspective of providers. Methods We conducted semi-structured interviews to assess the extent to which six CCM elements were in place: work role redesign, patient self-management support, provider decision support, clinical information systems, linkages to community resources, and organizational/leadership support. Interviews were transcribed and a priori CCM elements were coded using a directed content analysis approach at times 1 and 2. We sought consensus on, and compared, the extent to which each CCM element was in place at times 1 and 2. Results We conducted 27 and 31 telephone interviews at times 1 and 2, respectively, with outpatient mental health providers at nine participating sites. At time 1 and time 2, three CCM elements were most frequently present across the sites: work role redesign, patient self-management support, and provider decision support. The CCM elements with increased implementation from time 1 to time 2 were work role redesign, patient self-management support, and clinical information systems. For two CCM elements, linkages to community resources and organizational/leadership support, some sites had increased implementation at time 2 compared to time 1, while others had reductions. For the provider decision support element, we saw little change in the extent of its implementation. Conclusions Sites increased the extent of implementation on several CCM elements. The most progress was made in the CCM elements where sites had CCM-aligned processes in place at time 1. Teams made progress on elements they could more easily control, such as work role redesign. Our results suggest that maximizing the benefits of CCM-based outpatient mental health care may require targeting resources and training toward specific CCM elements—especially in the use of clinical information systems and linking with community resources. Trial registration Clinical Trials NCT02543840 .

Induction of CD4 T follicular helper (Tfh) cells is important for antibody responses to viral infections. Here, the authors show in a rhesus macaque model of mild COVID-19 that SARS-CoV-2 infection results in transient accumulation of proliferating Tfh cells with a Th1 profile in peripheral blood and generation of germinal center Tfh cells specific for viral proteins.

Background: Facilitation is an effective strategy to implement evidence-based practices, often involving external facilitators (EFs) bringing content expertise to implementation sites. Estimating time spent on multifaceted EF activities is complex. Furthermore, collecting continuous time–motion data for facilitation tasks is challenging. However, organizations need this information to allocate implementation resources to sites. Thus, our objectives were to conduct a time–motion analysis of external facilitation, and compare continuous versus noncontinuous approaches to collecting time–motion data. Methods: We analyzed EF time–motion data from six VA mental health clinics implementing the evidence-based Collaborative Chronic Care Model (CCM). We documented EF activities during pre-implementation (4–6 weeks) and implementation (12 months) phases. We collected continuous data during the pre-implementation phase, followed by data collection over a 2-week period (henceforth, “a two-week interval”) at each of three time points (beginning/middle/end) during the implementation phase. As a validity check, we assessed how closely interval data represented continuous data collected throughout implementation for two of the sites. Results: EFs spent 21.8 ± 4.5 h/site during pre-implementation off-site, then 27.5 ± 4.6 h/site site-visiting to initiate implementation. Based on the 2-week interval data, EFs spent 2.5 ± 0.8, 1.4 ± 0.6, and 1.2 ± 0.6 h/week toward the implementation’s beginning, middle, and end, respectively. Prevalent activities were preparation/planning, process monitoring, program adaptation, problem identification, and problem-solving. Across all activities, 73.6% of EF time involved email, phone, or video communication. For the two continuous data sites, computed weekly time averages toward the implementation’s beginning, middle, and end differed from the interval data’s averages by 1.0, 0.1, and 0.2 h, respectively. Activities inconsistently captured in the interval data included irregular assessment, stakeholder engagement, and network development. Conclusions: Time–motion analysis of CCM implementation showed initial higher-intensity EF involvement that tapered. The 2-week interval data collection approach, if accounting for its potential underestimation of irregular activities, may be promising/efficient for implementation studies collecting time–motion data.

Abstract Introduction: Scientific endeavors are increasingly carried out by teams of scientists. While there is growing literature on factors associated with effective science teams, little is known about processes that facilitate the success of dissemination and implementation (D&I) teams studying the uptake of healthcare innovations. This study aimed to identify strategies used by D&I scientists to promote team science. Methods: Using a nominal group technique, a sample of 27 D&I scholars responded to the question, “What strategies have you or others used to promote team science?” Participants were asked to individually respond and then discuss within a small group to determine the group’s top three strategies. Through a facilitated consensus discussion with the full sample, a rank-ordered list of three strategies was determined. Results: A total of 126 individual responses (M = 9; SD = 4.88) were submitted. Through small group discussion, six groups ranked their top three strategies to promote team science. The final ranked list of strategies determined by the full sample included: (1) developing and maintaining clear expectations, (2) promoting and modeling effective communication, and (3) establishing shared goals and a mission of the work to be accomplished. Conclusions: Because of its goal of translating knowledge to practice, D&I research necessitates the use of team science. The top strategies are in line with those found to be effective for teams in other fields and hold promise for improving D&I team cohesion and innovation, which may ultimately accelerate the translation of health innovations and the improvement of care quality and outcomes.

Abstract Background Intimate partner violence (IPV) against women in the United States (US) remains a complex public health crisis. Women who experience IPV are among the most vulnerable patients seen in primary care. Screening increases the detection of IPV and, when paired with appropriate response interventions, can mitigate the health effects of IPV. The Department of Veterans Affairs (VA) has encouraged evidence-based IPV screening programs since 2014, yet adoption is modest and questions remain regarding the optimal ways to implement these practices, which are not yet available within the majority of VA primary care clinics. Methods/design This paper describes the planned evaluation of VA’s nationwide implementation of IPV screening programs in primary care clinics through a randomized implementation-effectiveness hybrid type 2 trial. With the support of our VA operational partners, we propose a stepped wedge design to compare the impact of two implementation strategies of differing intensities (toolkit + implementation as usual vs. toolkit + implementation facilitation) and investigate the clinical effectiveness of IPV screening programs. Using balanced randomization, 16–20 VA Medical Centers will be assigned to receive implementation facilitation in one of three waves, with implementation support lasting 6 months. Implementation facilitation in this effort consists of the coordinated efforts of the two types of facilitators, external and internal. Implementation facilitation is compared to dissemination of a toolkit plus implementation as usual. We propose a mixed methods approach to collect quantitative (clinical records data) and qualitative (key informant interviews) implementation outcomes, as well as quantitative (clinical records data) clinical effectiveness outcomes. We will supplement these data collection methods with provider surveys to assess discrete implementation strategies used before, during, and following implementation facilitation. The integrated-Promoting Action on Research Implementation in Health Services (i-PARIHS) framework will guide the qualitative data collection and analysis. Summative data will be analyzed using the Reach Effectiveness Adoption Implementation Maintenance (RE-AIM) framework. Discussion This research will advance national VHA efforts by identifying the practices and strategies useful for enhancing the implementation of IPV screening programs, thereby ultimately improving services for and health of women seen in primary care. Trial registration NCT04106193 . Registered on 23 September 2019.

Abstract Background Facilitation is a key strategy that may contribute to successful implementation of healthcare innovations. In blended facilitation, external facilitators (EFs) guide and support internal facilitators (IFs) in directing implementation processes. Developers of the i-PARIHS framework propose that successful facilitation requires project management, team/process, and influencing/negotiating skills. It is unclear what IF skills are most important in real-world settings, which could inform recruitment and training efforts. As prior qualitative studies of IF skills have only interviewed IFs, the perspectives of their EF partners are needed. Furthermore, little is known regarding the distribution of implementation tasks between IFs and EFs, which could impact sustainability once external support is removed. In the context of an implementation trial, we therefore: 1) evaluated IFs’ use of i-PARIHS facilitation skills, from EFs’ perspectives; 2) identified attributes of IFs not encompassed within the i-PARIHS skills; and 3) investigated the relative contributions of IFs and EFs during facilitation. Methods Analyses were conducted within a hybrid type II trial utilizing blended facilitation to implement the collaborative chronic care model within mental health teams of nine VA medical centers. Each site committed one team and an IF to weekly process design meetings and additional implementation activities over 12 months. Three EFs worked with three sites each. Following study completion, the EFs completed semi-structured qualitative interviews reflecting on the facilitation process, informed by the i-PARIHS facilitation skill areas. Interviews were analyzed via directed content analysis. Results EFs emphasized the importance of IFs having strong project management, team/process, and influencing/negotiating skills. Prior experience in these areas and a mental health background were also benefits. Personal characteristics (e.g., flexible, assertive) were described as critical, particularly when faced with conflict. EFs discussed the importance of clear delineation of EF/IF roles, and the need to shift facilitation responsibilities to IFs. Conclusions Key IF skills, according to EFs, are aligned with i-PARIHS recommendations, but IFs’ personal characteristics were also emphasized as important factors. Findings highlight traits to consider when selecting IFs and potential training areas (e.g., conflict management). EFs and IFs must determine an appropriate distribution of facilitation tasks to ensure long-term sustainability of practices. Trial registration Clinicaltrials.gov, September 7, 2015, #NCT02543840.

ABSTRACT Human clinical studies investigating use of convalescent plasma (CP) for treatment of coronavirus disease 2019 (COVID-19) have produced conflicting results. Outcomes in these studies may vary at least partly due to different timing of CP administration relative to symptom onset. The mechanisms of action of CP include neutralizing antibodies but may extend beyond virus neutralization to include normalization of blood clotting and dampening of inflammation. Unresolved questions include the minimum therapeutic titer in the CP units or CP recipient as well as the optimal timing of administration. Here, we show that treatment of macaques with CP within 24 h of infection does not reduce viral shedding in nasal or lung secretions compared to controls and does not detectably improve any clinical endpoint. We also demonstrate that CP administration does not impact viral sequence diversity in vivo, although the selection of a viral sequence variant in both macaques receiving normal human plasma was suggestive of immune pressure. Our results suggest that CP, administered to medium titers, has limited efficacy, even when given very early after infection. Our findings also contribute information important for the continued development of the nonhuman primate model of COVID-19. These results should inform interpretation of clinical studies of CP in addition to providing insights useful for developing other passive immunotherapies and vaccine strategies. IMPORTANCE Antiviral treatment options for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain very limited. One treatment that was explored beginning early in the pandemic (and that is likely to be tested early in future pandemics) is plasma collected from people who have recovered from coronavirus disease 2019 (COVID-19), known as convalescent plasma (CP). We tested if CP reduces viral shedding or disease in a nonhuman primate model. Our results demonstrate that administration of CP 1 day after SARS-CoV-2 infection had no significant impact on viral loads, clinical disease, or sequence diversity, although treatment with normal human plasma resulted in selection of a specific viral variant. Our results demonstrate that passive immunization with CP, even during early infection, provided no significant benefit in a nonhuman primate model of SARS-CoV-2 infection.

ABSTRACT Bone marrow mesenchymal progenitor cells are precursors for various cell types including osteoblasts, adipocytes, and chondrocytes. The external environment and signals act to direct the pathway of differentiation. Importantly, situations such as aging and chronic kidney disease display alterations in the balance of osteoblast and adipocyte differentiation, adversely affecting bone integrity. Iron deficiency, which can often occur during aging and chronic kidney disease, is associated with reduced bone density. The purpose of this study was to assess the effects of iron deficiency on the capacity of progenitor cell differentiation pathways. Mouse and human progenitor cells, differentiated under standard osteoblast and adipocyte protocols in the presence of the iron chelator deferoxamine (DFO), were used. Under osteogenic conditions, 5μM DFO significantly impaired expression of critical osteoblast genes, including osteocalcin, type 1 collagen, and dentin matrix protein 1. This led to a reduction in alkaline phosphatase activity and impaired mineralization. Despite prolonged exposure to chronic iron deficiency, cells retained viability as well as normal hypoxic responses with significant increases in transferrin receptor and protein accumulation of hypoxia inducible factor 1α. Similar concentrations of DFO were used when cells were maintained in adipogenic conditions. In contrast to osteoblast differentiation, DFO modestly suppressed adipocyte gene expression of peroxisome‐proliferating activated receptor gamma, lipoprotein lipase, and adiponectin at earlier time points with normalization at later stages. Lipid accumulation was also similar in all conditions. These data suggest the critical importance of iron in osteoblast differentiation, and as long as the external stimuli are present, iron deficiency does not impede adipogenesis. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Here, Khan et al. show that enhanced Zika virus replication in the lower female reproductive tract of mice and macaques associates with low expression of RNA sensing pattern recognition receptors, while IFNAR signaling may be critical in preventing viral dissemination to distal tissues.

Abstract Background This paper describes the process and results of a refinement of a framework to characterize modifications to interventions. The original version did not fully capture several aspects of modification and adaptation that may be important to document and report. Additionally, the earlier framework did not include a way to differentiate cultural adaptation from adaptations made for other reasons. Reporting additional elements will allow for a more precise understanding of modifications, the process of modifying or adapting, and the relationship between different forms of modification and subsequent health and implementation outcomes. Discussion We employed a multifaceted approach to develop the updated FRAME involving coding documents identified through a literature review, rapid coding of qualitative interviews, and a refinement process informed by multiple stakeholders. The updated FRAME expands upon Stirman et al.’s original framework by adding components of modification to report: (1) when and how in the implementation process the modification was made, (2) whether the modification was planned/proactive (i.e., an adaptation) or unplanned/reactive, (3) who determined that the modification should be made, (4) what is modified, (5) at what level of delivery the modification is made, (6) type or nature of context or content-level modifications, (7) the extent to which the modification is fidelity-consistent, and (8) the reasons for the modification, including (a) the intent or goal of the modification (e.g., to reduce costs) and (b) contextual factors that influenced the decision. Methods of using the framework to assess modifications are outlined, along with their strengths and weaknesses, and considerations for research to validate these measurement strategies. Conclusion The updated FRAME includes consideration of when and how modifications occurred, whether it was planned or unplanned, relationship to fidelity, and reasons and goals for modification. This tool that can be used to support research on the timing, nature, goals and reasons for, and impact of modifications to evidence-based interventions.

Abstract Background Controlled implementation trials often randomize the intervention at the site level, enrolling relatively few sites (e.g., 6–20) compared to trials that randomize by subject. Trials with few sites carry a substantial risk of an imbalance between intervened (cases) and non-intervened (control) sites in important site characteristics, thereby threatening the internal validity of the primary comparison. A stepped wedge design (SWD) staggers the intervention at sites over a sequence of times or time waves until all sites eventually receive the intervention. We propose a new randomization method, sequential balance, to control time trend in site allocation by minimizing sequential imbalance across multiple characteristics. We illustrate the new method by applying it to a SWD implementation trial. Methods The trial investigated the impact of blended internal-external facilitation on the establishment of evidence-based teams in general mental health clinics in nine US Department of Veterans Affairs medical centers. Prior to randomization to start time, an expert panel of implementation researchers and health system program leaders identified by consensus a series of eight facility-level characteristics judged relevant to the success of implementation. We characterized each of the nine sites according to these consensus features. Using a weighted sum of these characteristics, we calculated imbalance scores for each of 1680 possible site assignments to identify the most sequentially balanced assignment schemes. Results From 1680 possible site assignments, we identified 34 assignments with minimal imbalance scores, and then randomly selected one assignment by which to randomize start time. Initially, the mean imbalance score was 3.10, but restricted to the 34 assignments, it declined to 0.99. Conclusions Sequential balancing of site characteristics across groups of sites in the time waves of a SWD strengthens the internal validity of study conclusions by minimizing potential confounding. Trial registration Registered at ClinicalTrials.gov as clinical trials # NCT02543840; entered 9/4/2015.

Zika virus (ZIKV) is an arthropod-borne virus (arbovirus) and is primarily transmitted by Aedes species mosquitoes; however, ZIKV can also be sexually transmitted. During the initial epidemic and in places where ZIKV is now considered endemic, it is difficult to disentangle the risks and contributions of sexual versus vector-borne transmission to adverse pregnancy outcomes. To examine the potential impact of sexual transmission of ZIKV on pregnancy outcome, we challenged three rhesus macaques (Macaca mulatta) three times intravaginally with 1 x 107 PFU of a low passage, African lineage ZIKV isolate (ZIKV-DAK) in the first trimester (~30 days gestational age). Samples were collected from all animals initially on days 3 through 10 post challenge, followed by twice, and then once weekly sample collection; ultrasound examinations were performed every 3-4 days then weekly as pregnancies progressed. All three dams had ZIKV RNA detectable in plasma on day 3 post-ZIKV challenge. At approximately 45 days gestation (17-18 days post-challenge), two of the three dams were found with nonviable embryos by ultrasound. Viral RNA was detected in recovered tissues and at the maternal-fetal interface (MFI) in both cases. The remaining viable pregnancy proceeded to near term (~155 days gestational age) and ZIKV RNA was detected at the MFI but not in fetal tissues. These results suggest that sexual transmission of ZIKV may represent an underappreciated risk of pregnancy loss during early gestation.

Abstract Background Some veterans face multiple barriers to VA mental healthcare service use. However, there is limited understanding of how veterans’ experiences and meaning systems shape their perceptions of barriers to VA mental health service use. In 2015, a participatory, mixed-methods project was initiated to elicit veteran-centered barriers to using mental healthcare services among a diverse sample of US rural and urban veterans. We sought to identify veteran-centric barriers to mental healthcare to increase initial engagement and continuation with VA mental healthcare services. Methods Cultural Domain Analysis, incorporated in a mixed methods approach, generated a cognitive map of veterans’ barriers to care. The method involved: 1) free lists of barriers categorized through participant pile sorting; 2) multi-dimensional scaling and cluster analysis for item clusters in spatial dimensions; and 3) participant review, explanation, and interpretation for dimensions of the cultural domain. Item relations were synthesized within and across domain dimensions to contextualize mental health help-seeking behavior. Results Participants determined five dimensions of barriers to VA mental healthcare services: concern about what others think; financial, personal, and physical obstacles; confidence in the VA healthcare system; navigating VA benefits and healthcare services; and privacy, security, and abuse of services. Conclusions These findings demonstrate the value of participatory methods in eliciting meaningful cultural insight into barriers of mental health utilization informed by military veteran culture. They also reinforce the importance of collaborations between the VA and Department of Defense to address the role of military institutional norms and stigmatizing attitudes in veterans’ mental health-seeking behaviors.

Abstract Background Healthcare is increasingly delivered in a team-based format emphasizing interdisciplinary coordination. While recent reviews have investigated team-building interventions primarily in acute healthcare settings (e.g. emergency or surgery departments), we aimed to systematically review the evidence base for team-building interventions in non-acute settings (e.g. primary care or rehabilitation clinics). Methods We conducted a systematic review in PubMed and Embase to identify team-building interventions, and conducted follow-up literature searches to identify articles describing empirical studies of those interventions. This process identified 14 team-building interventions for non-acute healthcare settings, and 25 manuscripts describing empirical studies of these interventions. We evaluated outcomes in four domains: trainee evaluations, teamwork attitudes/knowledge, team functioning, and patient impact. Results Trainee evaluations for team-building interventions were generally positive, but only one study associated team-building with statistically significant improvement in teamwork attitudes/knowledge. Similarly mixed results emerged for team functioning and patient impact. Conclusions The evidence base for healthcare team-building interventions in non-acute healthcare settings is much less developed than the parallel literature for short-term team function in acute care settings. Only one intervention we identified has been tested in multiple non-acute settings by distinct research teams. Positive findings regarding the utility of team-building interventions are tempered by a lack of control conditions, inconsistency in outcome measures, and high probability of bias. Considering these results alongside the well-recognized costs of poor healthcare teamwork suggests that additional research is sorely needed to develop the evidence base for team-building in non-acute settings.

Abstract Background Participant recruitment is an ongoing challenge in health research. Recruitment may be especially difficult for studies of access to health care because, even among those who are in care, people using services least often also may be hardest to contact and recruit. Opt-out recruitment methods (in which potential participants are given the opportunity to decline further contact about the study (opt out) following an initial mailing, and are then contacted directly if they have not opted out within a specified period) can be used for such studies. However, there is a dearth of literature on the effort needed for effective opt-out recruitment. Methods In this paper we describe opt-out recruitment procedures for two studies on access to health care within the U.S. Department of Veterans Affairs. We report resource requirements for recruitment efforts (number of opt-out packets mailed and number of phone calls made). We also compare the characteristics of study participants to potential participants via t-tests, Fisher’s exact tests, and chi-squared tests. Results Recruitment rates for our two studies were 12 and 21%, respectively. Across multiple study sites, we had to send between 4.3 and 9.2 opt-out packets to recruit one participant. The number of phone calls required to arrive at a final status for each potentially eligible Veteran (i.e. study participation or the termination of recruitment efforts) were 2.9 and 6.1 in the two studies, respectively. Study participants differed as expected from the population of potentially eligible Veterans based on planned oversampling of certain subpopulations. The final samples of participants did not differ statistically from those who were mailed opt-out packets, with one exception: in one of our two studies, participants had higher rates of mental health service use in the past year than did those mailed opt-out packets (64 vs. 47%). Conclusions Our results emphasize the practicality of using opt-out methods for studies of access to health care. Despite the benefits of these methods, opt-out alone may be insufficient to eliminate non-response bias on key variables. Researchers will need to balance considerations of sample representativeness and feasibility when designing studies investigating access to care.

Experimental studies have shown that the size and infectious-stage of viral inoculum influence disease outcomes in rhesus macaques infected with simian immunodeficiency virus. The possible contribution to disease outcome of antibody developed after transmission and/or present in the inoculum in free or bound form is not understood. In this study, we develop a mathematical model of virus-antibody immune complex formation and use it to predict their role in transmission and protection. The model exhibits a bistable switch between clearance and persistence states. We fitted it to temporal virus data and estimated the parameter values for free virus infectivity rate and antibody carrying capacity for which the model transitions between virus clearance and persistence when the initial conditions (in particular the ratio of immune complexes to free virus) vary. We used these results to quantify the minimum virus amount in the inoculum needed to establish persistent infections in the presence and absence of protective antibodies.

The reaction between Fe(II) and H2O2 to yield hydroxyl radicals (HO•), the Fenton reaction, is of interest due to its role in trace metal and natural organic matter biogeochemistry, its utility in water treatment and its role in oxidative cell degradation and associated human disease. There is significant dispute over whether HO•, the most reactive of the so-called reactive oxygen species, is formed in this reaction, particularly under circumneutral conditions relevant to natural systems. In this work we have studied the oxidation kinetics of Fe(II) complexed by L = citrate, ethylenediaminetetraacetic acid (EDTA) and diethylenetriaminepentaacetic acid (DTPA) and also measured HO• production using phthalhydrazide as a probe compound at pH 8.2. It is shown that HO• is the sole product of the Fe(II)L-H2O2 reaction for L = EDTA and DTPA, with kinetic modelling of the full reaction pathway utilized to confirm this finding. Quantitative HO• production also appears likely for L = citrate, although uncertainties with the speciation of Fe(II)-citrate complexes as well as difficulties in modelling the oxidation kinetics of these complexes has prevented a definitive conclusion. In the absence of ligands at circumneutral pH, inorganic Fe(II) reacts with H2O2 to yield a species other than HO•, contrary to the well-established production of HO• from inorganic Fe(II) at low pH. Our results suggest that at high pH Fe(II) must be complexed for HO• production to occur.

Background/Objectives. Vagal block therapy (vBloc) is effective for moderate to severe obesity at one year. Subjects/Methods. The ReCharge trial is a double-blind, randomized controlled clinical trial of 239 participants with body mass index (BMI) of 40 to 45 kg/m or 35 to 40 kg/m with one or more obesity-related conditions. Interventions were implantation of either vBloc or Sham devices and weight management counseling. Mixed models assessed percent excess weight loss (%EWL) and total weight loss (%TWL) in intent-to-treat analyses. At 18 months, 142 (88%) vBloc and 64 (83%) Sham patients remained enrolled in the study. Results. 18-month weight loss was 23% EWL (8.8% TWL) for vBloc and 10% EWL (3.8% TWL) for Sham (P

Despite the mounting evidence of the benefits of cognitive therapy for depression and suicidal behaviors over usual care, like other evidence-based psychosocial treatments (EBTs), it has not been widely adopted in clinical practice. Studies have shown that training followed by intensive consultation is needed to prepare providers to an appropriate level of competency in complex, multisession treatment packages such as cognitive therapy. Given the critical role of training in EBT implementation, more information on factors associated with the success and challenges of training programs is needed. To identify potential reasons for variation in training outcomes across ten agencies in a large, urban community mental health system, we explored program evaluation data and examined provider, consultant, and training program administrator perspectives through follow-up interviews. Perceptions of cognitive therapy, contextual factors, and reactions to feedback on audio recordings emerged as broad categories of themes identified from interviews. These factors may interact and impact clinician efforts to learn cognitive therapy and deliver it skillfully in their practice. The findings highlight experiences and stakeholder perspectives that may contribute to more or less successful training outcomes.