Patient Perspectives of Barriers and Facilitators for the Uptake of Pharmacogenomic Testing in Veterans Affairs' Pharmacogenomic Testing for the Veterans (PHASER) Program.

We applied implementation science frameworks to identify barriers and facilitators to veterans' acceptance of pharmacogenomic testing (PGx), which was made available as a part of clinical care at 25 VA medical centers. We conducted 30 min interviews with veterans who accepted (n = 14), declined (n = 9), or were contemplating (n = 8) PGx testing. Six team members coded one transcript from each participant group to develop the codebook and finalize definitions. Three team members coded the remaining 28 transcripts and met regularly with the larger team to reach a consensus. The coders generated a matrix of implementation constructs by testing status to identify the similarities and differences between accepters, decliners, and contemplators. All groups understood the PGx testing procedures and possible benefits. In the decision-making, accepters prioritized the potential health benefits of PGx testing, such as reducing side effects or the number of medications. In contrast, decliners prioritized the possibilities of data breach or the negative impact on healthcare insurance or Veterans Affairs benefits. Contemplators desired to speak to a provider to learn more before making a decision. Efforts to improve the clarity of data security and the impact on benefits may improve veterans' abilities to make more informed decisions about whether to undergo PGx testing.

Inferring the disruption of rabies circulation in vampire bat populations using a betaherpesvirus-vectored transmissible vaccine.

Transmissible vaccines are an emerging biotechnology that hold prospects to eliminate pathogens from wildlife populations. Such vaccines would genetically modify naturally occurring, nonpathogenic viruses ("viral vectors") to express pathogen antigens while retaining their capacity to transmit. The epidemiology of candidate viral vectors within the target wildlife population has been notoriously challenging to resolve but underpins the selection of effective vectors prior to major investments in vaccine development. Here, we used spatiotemporally replicated deep sequencing to parameterize competing epidemiological mechanistic models of Desmodus rotundus betaherpesvirus (DrBHV), a proposed vector for a transmissible vaccine targeting vampire bat-transmitted rabies. Using 36 strain- and location-specific time series of prevalence collected over 6 y, we found that lifelong infections with cycles of latency and reactivation, combined with a high R0 (6.9; CI: 4.39 to 7.85), are necessary to explain patterns of DrBHV infection observed in wild bats. These epidemiological properties suggest that DrBHV may be suited to vector a lifelong, self-boosting, and transmissible vaccine. Simulations showed that inoculating a single bat with a DrBHV-vectored rabies vaccine could immunize >80% of a bat population, reducing the size, frequency, and duration of rabies outbreaks by 50 to 95%. Gradual loss of infectious vaccine from vaccinated individuals is expected but can be countered by inoculating larger but practically achievable proportions of bat populations. Parameterizing epidemiological models using accessible genomic data brings transmissible vaccines one step closer to implementation.

The invisible work of transfer centre nurses: A qualitative study of strategies to overcome communication challenges.

AIMS: To explore the role of transfer centre nurses and how they facilitate communication between referring and accepting providers during calls about interhospital transfers, including their strategies to overcome communication challenges. DESIGN: A qualitative interview study. METHODS: We conducted semi-structured interviews with 17 transfer centre nurses at one tertiary medical centre from March to August 2019, asking participants to describe their work. We performed content analysis, applying codes based on the Relational Coordination Framework and generating emergent codes, then organized codes in higher-order concepts. We followed the COREQ checklist. RESULTS: Transfer centre nurses employed multiple strategies to mitigate communication challenges. When referring providers had misconceptions about the transfer centre nurse's role and the accepting hospital's processes, the nurses informed referring providers why sharing information with them was necessary. If providers expressed frustrations or lacked understanding about their counterpart's caseload, the nurses managed providers' emotions by letting them "vent," explaining the other provider's situational context and describing the hospital's capabilities. Some nurses also mediated conflict and sought to break the tension if providers debated about the best course of action. When providers struggled to share complete and accurate information, the nurses hunted down details and 'filled in the blanks'. CONCLUSION: Transfer centre nurses perform invisible work throughout the lifespan of interhospital transfers. Nurses' expert knowledge of the transfer process and hospitals' capabilities can enhance provider communication. Meanwhile, providers' lack of knowledge of the nurse's role can impede respectful and efficient transfer conversations. Interventions to support and optimize the transfer centre nurses' critical work are needed. IMPACT: This study describes how transfer centre nurses facilitate communication and overcome challenges during calls about interhospital transfers. An intervention that supports this critical work has the potential to benefit nurses, providers and patients by ensuring accurate and complete information exchange in an effective, efficient manner that respects all parties. PATIENT OR PUBLIC CONTRIBUTION: This study was designed to capture the perspectives and experiences of transfer centre nurses themselves through interviews. Therefore, it was not conducted using input or suggestions from the public or the patient population served by the organization.

Ecological determinants of rabies virus dynamics in vampire bats and spillover to livestock.

The pathogen transmission dynamics in bat reservoirs underpin efforts to reduce risks to human health and enhance bat conservation, but are notoriously challenging to resolve. For vampire bat rabies, the geographical scale of enzootic cycles, whether environmental factors modulate baseline risk, and how within-host processes affect population-level dynamics remain unresolved. We studied patterns of rabies exposure using an 11-year, spatially replicated sero-survey of 3709 Peruvian vampire bats and co-occurring outbreaks in livestock. Seroprevalence was correlated among nearby sites but fluctuated asynchronously at larger distances. A generalized additive mixed model confirmed spatially compartmentalized transmission cycles, but no effects of bat demography or environmental context on seroprevalence. Among 427 recaptured bats, we observed long-term survival following rabies exposure and antibody waning, supporting hypotheses that immunological mechanisms influence viral maintenance. Finally, seroprevalence in bats was only weakly correlated with outbreaks in livestock, reinforcing the challenge of spillover prediction even with extensive data. Together our results suggest that rabies maintenance requires transmission among multiple, nearby bat colonies which may be facilitated by waning of protective immunity. However, the likelihood of incursions and dynamics of transmission within bat colonies appear largely independent of bat ecology. The implications of these results for spillover anticipation and controlling transmission at the source are discussed.

Longitudinal deep sequencing informs vector selection and future deployment strategies for transmissible vaccines.

Vaccination is a powerful tool in combating infectious diseases of humans and companion animals. In most wildlife, including reservoirs of emerging human diseases, achieving sufficient vaccine coverage to mitigate disease burdens remains logistically unattainable. Virally vectored "transmissible" vaccines that deliberately spread among hosts are a potentially transformative, but still theoretical, solution to the challenge of immunising inaccessible wildlife. Progress towards real-world application is frustrated by the absence of frameworks to guide vector selection and vaccine deployment prior to major in vitro and in vivo investments in vaccine engineering and testing. Here, we performed deep sequencing on field-collected samples of Desmodus rotundus betaherpesvirus (DrBHV), a candidate vector for a transmissible vaccine targeting vampire bat-transmitted rabies. We discovered 11 strains of DrBHV that varied in prevalence and geographic distribution across Peru. The phylogeographic structure of DrBHV strains was predictable from both host genetics and landscape topology, informing long-term DrBHV-vectored vaccine deployment strategies and identifying geographic areas for field trials where vaccine spread would be naturally contained. Multistrain infections were observed in 79% of infected bats. Resampling of marked individuals over 4 years showed within-host persistence kinetics characteristic of latency and reactivation, properties that might boost individual immunity and lead to sporadic vaccine transmission over the lifetime of the host. Further, strain acquisitions by already infected individuals implied that preexisting immunity and strain competition are unlikely to inhibit vaccine spread. Our results support the development of a transmissible vaccine targeting a major source of human and animal rabies in Latin America and show how genomics can enlighten vector selection and deployment strategies for transmissible vaccines.

An Implementation Assessment of the Virtual Acute Care for Elders Program From the Perspective of Key Stakeholders.

OBJECTIVE: The aim of this study was to obtain feedback from key stakeholders and end users to identify program strengths and weaknesses to plan for wider dissemination and implementation of the Virtual Acute Care for Elders (Virtual ACE) program, a novel intervention that improves outcomes for older surgical patients. BACKGROUND: Virtual ACE was developed to deliver evidence-based geriatric care without requiring daily presence of a geriatrician. Previous work demonstrated that Virtual ACE increased mobility and decreased delirium rates for surgical patients. METHODS: We conducted semi-structured interviews with 30 key stakeholders (physicians, nurses, hospital leadership, nurse managers, information technology staff, and physical/occupational therapists) involved in the implementation and use of the program. RESULTS: Our stakeholders indicated that Virtual ACE was extremely empowering for bedside nurses. The program helped nurses identify older patients who were at risk for a difficult postoperative recovery. Virtual ACE also gave them skills to manage complex older patients and more effectively communicate their needs to surgeons and other providers. Nurse managers felt that Virtual ACE helped them allocate limited resources and plan their unit staffing assignments to better manage the needs of older patients. The main criticism was that the Virtual ACE Tracker that displayed patient status was difficult to interpret and could be improved by a better design interface. Stakeholders also felt that program training needed to be improved to accommodate staff turnover. CONCLUSIONS: Although respondents identified areas for improvement, our stakeholders felt that Virtual ACE empowered them and provided effective tools to improve outcomes for older surgical patients.

The first case of Janibacter hoylei bacteremia in an adult.

The Janibacter species are Gram positive, coryneform bacteria that belong to the Actinobacteria phylum and have been linked to bacteremia in immunocompromised children. We present the first documented adult case of Janibacter hoylei bacteremia. The patient was a 52-year-old woman with a history of recurrent Clostridioides difficile infection, sinus tachycardia and high-risk AML who had been admitted one month prior to presentation for matched unrelated donor hematopoietic stem cell transplant with reduced intensity fludarabine-melphalan. Thirty days post-transplant, the infectious disease team was consulted because blood cultures grew Janibacter hoylei, from one of two blood cultures It took nine days to identify the species. She was treated with linezolid and imipenem. Janibacter are rarely implicated in human pathology, and therein, usually identified in the context of malignancy and relative immunosuppression. J. hoylei was only previously reported from the bloodstream of a previously healthy 8-week-old infant without underlying medical conditions. Antimicrobial susceptibility testing is challenging as only in vitro susceptibility testing of Janibacter terrae has been reported. Given these challenges, it is our hope to illustrate the clinical approach to diagnosis as well as subsequent recommendations for treatment in a particularly challenging case of bacteremia in an AML patient.

Qualitative Analysis of Single-Site Headache Surgery: Is It Different From Multiple-Site Surgery?

BACKGROUND: Migraine surgery has been shown to be efficacious, but nuanced effects of surgery on pain and individuals' lives remain incompletely understood. Surgery may be performed at a single or multiple "primary" sites. The aims of this study were to investigate patient perceptions following single-site surgery and compare themes in patients undergoing single-site surgery with those from a previously published conceptual framework generated with patients undergoing multisite surgery. METHODS: Patients who underwent single-site headache surgery participated in open-ended interviews at least 1 year after surgery. Participants (n = 14) had undergone either occipital, temporal, or nasoseptal site surgery. A multidisciplinary team analyzed transcripts. Recurring themes were identified and compared and contrasted to those observed in patients who underwent multiple-site surgery (n = 15) in a previous study (Plast Reconstr Surg 2019;144(4):956-964). RESULTS: Similar recurring themes emerged from the single-site cohort, and the conceptual framework was applicable to all participants. Two new themes emerged from the single-site analysis. First, 5 of 14 participants described being "migraine-free" postoperatively, a finding not observed in the multisite group. Second, several individuals described financial benefits after surgery, via decreased prescription medication requirements, raises at work, and improved productivity. CONCLUSIONS: Single-site headache surgery appears to positively impact patients' lives in ways that support and expand upon previously published outcomes. Patients undergoing surgery at a single site may be more likely to experience a "pain-free" state, which may relate to the underlying pathophysiology of chronic headache. The effect of surgery on finances appears to be an outcome of interest to patients, which should be explored further.