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Aim: To increase understanding regarding the experiences and values of young adults with cerebral palsy (CP), and their caregivers, regarding pediatric rehabilitation-related care, including perceived barriers and potential facilitators to transition to adult care., Method: This was a qualitative descriptive study that used 20 semi-structured interviews (13 caregivers and seven patient-caregiver dyads)., Results: We identified four major themes: (1) the value and security of long-term relationships; (2) feeling 'rudderless' navigating the logistics of transition; (3) differences in pediatric versus adult models of care; and (4) perceived lack of provider expertise and comfort in adult care settings. Young adults with CP who had not yet transitioned to adult rehabilitation care and their caregivers placed high value on provider relationships and expertise, advanced planning, communication, and coordination of care., Interpretation: Identified barriers and potential facilitators to the transition to adult rehabilitation care reflected the uncertainty that accompanies leaving an established healthcare relationship. Challenges related to the logistics of this transition, differences in models of care, and perceived lack of provider comfort and expertise in adult care settings were also noted. Our findings could be used to develop and study patient-centered and family-centered transition processes for individuals with CP to promote age-appropriate and developmentally appropriate lifespan care., (© 2024 Mac Keith Press.)

Background: Myriad risk factors contribute to pediatric influenza vaccination disparities. Digital stories are compelling accounts of lived experience that have been useful in health promotion, especially in minoritized communities. Little is known about how they are perceived as a behavioral intervention to improve influenza vaccination confidence in safety-net healthcare systems., Objective: To explore staff and caregivers' perceptions of Digital Storytelling (DST) as a behavioral intervention to improve influenza vaccine confidence among caregivers of children., Methods: This qualitative study was set in two federally qualified health centers in historically Black neighborhoods in Denver, Colorado, USA. Informal group discussions with clinic staff probed perceptions of vaccine disparities, clinic priorities, and DST. Individual interviews with key staff and caregivers of children 6 months to 5 years old explored perceptions of and preferences for DST to improve vaccine confidence. Interviews were recorded and transcribed verbatim. Three researchers analyzed transcripts via directed content analysis using a deductive approach based off the IM4Equity framework. Final themes were member-checked with clinic staff, pediatric providers, and community advisors., Results: Approximately 70 staff attended informal group discussions; 13 staff and 12 caregivers participated in key informant interviews. Transcripts from group discussions (n = 6) and individual interviews (n = 23) were included in final analyses. Staff felt existing influenza vaccination strategies were inadequate, perceived digital stories meaningfully, and desired equitable implementation without responsibility for implementing them. Caregivers perceived DST as compelling, noted the importance of trusted storytellers, and suggested relatable stories from diverse caregivers could be sent via text messages in the winter to cue caregivers to action., Conclusions: In this qualitative study, staff and caregivers perceived DST favorably, with preferences specific to DST implementation in a large, diverse health system. Work to develop and implement text-based DST for pediatric influenza vaccination in this context is warranted., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Joshua T.B. Williams reports financial support was provided by National Institute of Child Health and Human Development. Research reported in this publication was supported by the Eunice Kennedy Shriver National Institute Of Child Health & Human Development of the National Institutes of Health under Award Number K23HD107184. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Joshua T.B. Williams reports a relationship with Colorado Children's Immunization Coalition that includes: consulting or advisory and speaking and lecture fees. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Lowering hepatitis B surface antigen (HBsAg) levels from covalently closed circular DNA (cccDNA) and the integrated genome could reduce the persistence of hepatitis B virus (HBV) infection. Since HBV replication occurs in the liver and to ameliorate the peripheral neuropathy observed with a first-generation tricyclic 4-pyridone PAPD5/7 inhibitor ( AB-452 ) having high systemic exposure, we focused on increasing the hepatocyte concentration and reducing plasma levels. Optimization of a novel series of PAPD5/7 inhibitors that decrease HBsAg levels led to the tetracyclic 2-pyridone AB-161 , which was similarly potent to AB-452 in vitro and in vivo but showed dramatically higher rodent liver-to-plasma ratios. There were no neurobehavioral effects with AB-161 in dogs up to 45 mg/kg after 60 days, unlike with AB-452 , where these were observed at lower doses by day 14. AB-161 was then advanced into 90-day GLP toxicology studies, where the improved neurotoxicity profile persisted, but reproductive issues emerged, leading to discontinuation.

Inhibition of Hepatitis B Virus (HBV) replication by small molecules that modulate capsid assembly and the encapsidation of pgRNA and viral polymerase by HBV core protein is a clinically validated approach toward the development of new antivirals. Through definition of a minimal pharmacophore, a series of isoquinolinone-based capsid assembly modulators (CAMs) was identified. Structural biology analysis revealed that lead molecules possess a unique binding mode, exploiting electrostatic interactions with accessible phenylalanine and tyrosine residues. Key analogs demonstrated excellent primary potency, absorption, distribution, metabolism, and excretion (ADME) and pharmacokinetic properties, and efficacy in a mouse model of HBV. The optimized lead also displayed potent inhibition of capsid uncoating in HBV-infected HepG2 cells expressing the sodium-taurocholate cotransporting polypeptide (NTCP) receptor, affecting the generation of HBsAg and cccDNA establishment. Based on these results, isoquinolinone derivative AB-836 was advanced into clinical development. In Phase 1b trials, AB-836 demonstrated >3 log 10 reduction in serum HBV DNA, however, further development was discontinued due to the observation of incidental alanine aminotransferase (ALT) elevations.

Isoquinolinone-based HBV capsid assembly modulators that bind at the dimer:dimer interface of HBV core protein have been shown to suppress viral replication in chronic hepatitis B patients. Analysis of their binding mode by protein X-ray crystallography has identified a region of the small molecule where the application of a constraint can lock the preferred binding conformation and has allowed for further optimization of this class of compounds. Key analogues demonstrated single digit nM EC 50 values in reducing HBV DNA in a HepDE19 cellular assay in addition to favorable ADME and pharmacokinetic properties, leading to a high degree of oral efficacy in a relevant in vivo hydrodynamic injection mouse model of HBV infection, with 12e effecting a 3 log 10 decline in serum HBV DNA levels at a once daily dose of 1 mg/kg. Additionally, maintenance of activity was observed in clinically relevant HBV core protein variants T33N and I105T., Competing Interests: The authors declare no competing financial interest., (© 2024 American Chemical Society.)

Objective: Explore factors influencing patient comfort with and perceived helpfulness of screening for health-related social needs., Methods: In a parallel secondary mixed-methods analysis of data from three primary care clinics, we used logistic regression to examine effects of practice- and patient-level factors on comfort with and perceived helpfulness of social needs screening. We applied narrative analysis to 20 patient interviews to further understand how patients' lived experiences influenced their perceptions of screening., Results: Among 511 patients, receiving an explanation about screening was associated with increased odds of comfort (OR 2.1, 95% CI [1.1-4.30]) and perceived helpfulness (OR 4.7 [2.8-7.8]). Those experiencing more needs were less likely to report comfort (3 + needs vs. 0: OR 0.2 [0.1-0.5]). Narratives elucidated how a history of stigmatizing experiences increased discomfort disclosing needs and captured how relationship quality with healthcare teams influenced perceptions of screening for patients with extensive needs., Conclusion: Practice-level (screening explanation and therapeutic rapport) and patient-level factors (history and extent of needs) are key influences on comfort with and perceived helpfulness of screening., Practice Implications: Good communication about screening benefits all patients. Patients with extensive social needs may require additional sensitivity to their past experiences., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: The hepatitis C virus (HCV) causes chronic and curable disease with a substantial burden of morbidity and mortality across the globe. In the United States (US) and other developed countries, incidence of HCV is increasing and people who inject drugs are disproportionately affected. However, HCV treatment rates amongst patients with substance use disorders (SUD) are suboptimal. In this study, we aimed to understand the perspectives of subspecialist physicians who care for substantial numbers of patients with HCV, including addiction medicine, infectious diseases, and hepatology physicians, to better understand barriers and facilitators of HCV treatment., Methods: We recruited subspecialty physicians via purposive and snowball sampling and conducted semi-structured interviews with 20 physicians at 12 institutions across the US. We used a mixed deductive and inductive approach to perform qualitative content analysis with a rapid matrix technique., Results: Three major themes emerged: (1) Perceptions of patient complexity; (2) Systemic barriers to care, and (3) Importance of multidisciplinary teams. Within these themes, we elicited subthemes on the effects of patient-level factors, provider-level factors, and insurance-based requirements., Conclusion: Our results suggest that additional strategies are needed to reach the "last mile" untreated patients for HCV care, including decentralization and leverage of telehealth-based interventions to integrate treatment within primary care clinics, SUD treatment facilities, and community harm reduction sites. Such programs are likely to be more successful when multidisciplinary teams including pharmacists and/or peer navigators are involved. However, burdensome regulatory requirements continue to hinder this expansion in care and should be eliminated., (© 2024. The Author(s).)

Purpose: There is a need to increase palliative care access for hospitalized older adults with cancer discharged to a skilled nursing facility (SNF) at risk of poor outcomes. Assessing and Listening to Individual Goals and Needs (ALIGN) is a palliative care intervention developed to address this gap. This study gathered perspectives from clinicians across care settings to describe perceptions on serious illness communication and care coordination for patients with cancer after discharge to a SNF to guide ALIGN refinements., Methods: We conducted 37 semistructured interviews with clinicians and leaders in hospital medicine (n = 12), oncology (n = 9), palliative care (n = 12), home health care (n = 6), and hospice (n = 4). Some participants had experience working in more than one specialty. The Practical Robust Implementation and Sustainability Model framework was used to develop the interview guide that explored barriers to care, prognosis discussions, and hospice recommendations. Interviews were coded and analyzed using thematic content analysis., Results: Analysis identified four themes: (1) discharge to a SNF is recognized as a time of worsening prognosis; (2) care silos create communication and information barriers during a period of increasing palliative care need; (3) family caregiver distress escalates following care transitions; and (4) lack of clarity of roles and respect for the patient-oncologist relationship limits prognostic communication and changes in focus of treatment., Conclusion: These findings suggest that acute and postacute care clinicians defer serious illness conversations to the oncologist when patients are on a steep trajectory of decline, experiencing multiple care transitions, and may have limited contact with their oncologist. There is a need to clarify roles among nononcology and oncology clinicians in discussing prognosis and recommending hospice for older adults discharged to SNF.

Background: Approximately 20-50% of adolescent and young adult-aged childhood cancer survivors (AYA-CCS) experience sexual dysfunction (SD), although this healthcare need is widely underrecognized. Previous research from both AYA-CCS patients and their providers report that SD needs are unaddressed despite patient desires for SD discussions to be incorporated as part of their care. Patients and providers agree that standardized use of a patient-reported outcome measure may facilitate SD discussions; an SD screening approach was developed with patient and provider input. This study will measure the effectiveness of a standardized SD screening intervention and assess implementation outcomes and multilevel barriers and facilitators to guide future research., Methods: This multi-site, mixed methods, type 1 effectiveness-implementation hybrid trial will be evaluated using a pre-post design (NCT05524610). The trial will enroll 86 AYA-CCS (ages 15-39) from two cancer centers in the United States. The SD intervention consists of core fundamental functions with a "menu" of intervention options to allow for flexibility in delivery and tailoring in variable contexts. Effectiveness of the intervention on facilitating SD communication will be measured through patient surveys and clinical data; multivariable logistic regression will be used for the binary outcome of self-reported SD screening, controlling for patient-level predictors. Implementation outcomes will be assessed using mixed methods (electronic health record abstraction, patient and provider surveys, and provider interviews. Quantitative and qualitative findings will be merged using a joint display to understand factors affecting intervention success., Implications: Identification and treatment of SD in AYA-CCS is an important and challenging quality of life concern. The type 1 hybrid design will facilitate rapid translation from research to practice by testing the effects of the intervention while simultaneously identifying multilevel barriers and facilitators to real-world implementation. This approach will inform future testing and dissemination of the SD screening intervention., Competing Interests: Declaration of Interests The authors have declared that no competing interests exist.

The recent COVID-19 pandemic underscored the limitations of currently available direct-acting antiviral treatments against acute respiratory RNA-viral infections and stimulated major research initiatives targeting anticoronavirus agents. Two novel nsp5 protease (MPro) inhibitors have been approved, nirmatrelvir and ensitrelvir, along with two existing nucleos(t)ide analogues repurposed as nsp12 polymerase inhibitors, remdesivir and molnupiravir, but a need still exists for therapies with improved potency and systemic exposure with oral dosing, better metabolic stability, and reduced resistance and toxicity risks. Herein, we summarize our research toward identifying nsp12 inhibitors that led to nucleoside analogues 10e and 10n , which showed favorable pan-coronavirus activity in cell-infection screens, were metabolized to active triphosphate nucleotides in cell-incubation studies, and demonstrated target (nsp12) engagement in biochemical assays.

Approved therapies for hepatitis B virus (HBV) treatment include nucleos(t)ides and interferon alpha (IFN-α) which effectively suppress viral replication, but they rarely lead to cure. Expression of viral proteins, especially surface antigen of the hepatitis B virus (HBsAg) from covalently closed circular DNA (cccDNA) and the integrated genome, is believed to contribute to the persistence of HBV. This work focuses on therapies that target the expression of HBV proteins, in particular HBsAg, which differs from current treatments. Here we describe the identification of AB-452 , a dihydroquinolizinone (DHQ) analogue. AB-452 is a potent HBV RNA destabilizer by inhibiting PAPD5/7 proteins in vitro with good in vivo efficacy in a chronic HBV mouse model. AB-452 showed acceptable tolerability in 28-day rat and dog toxicity studies, and a high degree of oral exposure in multiple species. Based on its in vitro and in vivo profiles, AB-452 was identified as a clinical development candidate.

Aim: To describe the complex roles of and crucial support provided by caregivers to young adults with cerebral palsy (CP) during the transition to adulthood., Method: This was a qualitative study. We conducted 20 semi-structured interviews (13 caregiver; 7 patient/caregiver dyad) and analyzed data using a qualitative descriptive approach informed by phenomenological principles., Results: We identified four major themes related to the roles that caregivers play during the transition to adulthood for young adults with CP: 1) caregivers as care coordinators; 2) navigating logistic and insurance barriers; 3) adjusting to adulthood and planning for an uncertain future; and 4) supporting maintenance of health, function, and quality of life. Overall, caregivers shared the many different ways that they act as advocates for young adults with CP. Many participants identified the extensive amount of time, energy, and financial resources required to appropriately provide care., Conclusions: The transition to adulthood for young adults with CP is a challenging, uncertain, complex process for both adults with CP and their caregivers. Throughout this transition, caregivers also prioritize the happiness and quality of life of their adult children with CP. Our findings could be used by clinicians and researchers to develop and study patient- and family-centered transition processes for individuals with CP that attend to the struggles and priorities of youth with CP and caregivers alike., Competing Interests: The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Cristina Sarmiento reports financial support was provided by Foundation for Physical Medicine and Rehabilitation and the Tai Foundation. Lisa Brenner reports grants from the VA, DOD, NIH, and the State of Colorado, editorial remuneration from Wolters Kluwer and the Rand Corporation, and royalties from the American Psychological Association and Oxford University Press. In addition, she consults with sports leagues via her university affiliation., (© 2023 The Authors.)

Disruption of the HBV capsid assembly process through small-molecule interaction with HBV core protein is a validated target for the suppression of hepatitis B viral replication and the development of new antivirals. Through combination of key structural features associated with two distinct series of capsid assembly modulators, a novel aminochroman-based chemotype was identified. Optimization of anti-HBV potency through generation of SAR in addition to further core modifications provided a series of related functionalized aminoindanes. Key compounds demonstrated excellent cellular potency in addition to favorable ADME and pharmacokinetic profiles and were shown to be highly efficacious in a mouse model of HBV replication. Aminoindane derivative AB-506 was subsequently advanced into clinical development., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Andrew G. Cole, Steven G. Kultgen, Nagraj Mani, Jorge G. Quintero, Kristi Yi Fan, Andrzej Ardzinski, Kim Stever, Bruce D. Dorsey, Janet R. Phelps, Amy C.H. Lee, Emily P. Thi, Tim Chiu, Sunny Tang, Troy O. Harasym and Michael J. Sofia are either current or former employees of Arbutus Biopharma, Inc. and may own company stock., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Abstract: Exposures to potentially morally injurious events (PMIEs) and possible moral injury are risk factors for a range of difficulties impacting individual functioning. Although exposure to PMIEs is a somewhat common product of war, qualitative methods to understand Veterans' experiences of moral injury and Veterans Affairs treatment are limited. To better characterize Veterans' experiences, 14 male warzone Veterans who reported moral injury post-warzone deployment and completed posttraumatic stress disorder treatment in the past year were asked to describe their military service as part of a qualitative study. Through thematic analysis, we found two moral injury-consistent themes and four subthemes. The first theme was "military experiences were associated with morally questioning one's self" with subthemes of "moral shift" and "depersonalization." The second theme was "military experiences were associated with morally questioning others" with subthemes of "disillusionment" and "resignation." Based on these findings, we conclude with a discussion of treatment implications for moral injury., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Despite the abundance of health information on the internet for people who identify as transgender and gender diverse (TGD), much of the content used is found on social media channels, requiring individuals to vet the information for relevance and quality., Objective: We developed a prototype transgender health information resource (TGHIR) delivered via a mobile app to provide credible health and wellness information for people who are TGD., Methods: We partnered with the TGD community and used a participatory design approach that included focus groups and co-design sessions to identify users' needs and priorities. We used the Agile software development methodology to build the prototype. A medical librarian and physicians with expertise in transgender health curated a set of 97 information resources that constituted the foundational content of the prototype. To evaluate the prototype TGHIR app, we assessed the app with test users, using a single item from the System Usability Scale to assess feature usability, cognitive walk-throughs, and the user version of the Mobile Application Rating Scale to evaluate the app's objective and subjective quality., Results: A total of 13 people who identified as TGD or TGD allies rated their satisfaction with 9 of 10 (90%) app features as good to excellent, and 1 (10%) of the features-the ability to filter to narrow TGHIR resources-was rated as okay. The overall quality score on the user version of the Mobile Application Rating Scale was 4.25 out of 5 after 4 weeks of use, indicating a good-quality mobile app. The information subscore received the highest rating, at 4.75 out of 5., Conclusions: Community partnership and participatory design were effective in the development of the TGHIR app, resulting in an information resource app with satisfactory features and overall high-quality ratings. Test users felt that the TGHIR app would be helpful for people who are TGD and their care partners., (©Brad Morse, Andrey Soares, Bethany M Kwan, Marvyn Allen, Rita S Lee, Kristen Desanto, Brooke Dorsey Holliman, Kate Ytell, Lisa M Schilling. Originally published in JMIR Human Factors (https://humanfactors.jmir.org), 15.06.2023.)

Objectives: We evaluated Colorado's paid family caregiver certified nursing assistant (CNA) program by assessing stakeholders' perceptions of the model's strengths and potential areas for improvement., Methods: A professional bilingual research assistant conducted key informant interviews of English- and Spanish-speaking certified nursing assistant (CNA) family caregivers (FCs), primary care providers, and pediatric home health administrators of children with medical complexity in the family caregiver CNA program. Interview questions focused on the program's benefits, drawbacks, and implications for the child and caregiver's quality of life. Transcripts were coded and analyzed, and themes summarizing program benefits and disadvantages were identified., Results: Semistructured interviews were completed by phone with 25 FCs, 10 home health administrators, and 10 primary care providers between September 2020 and June 2021. Overall, the program was highly valued and uniformly recommended for prospective families. Perceived benefits included: (1) fulfilling the desire to be a good parent, (2) providing stable and high-quality home health care, (3) benefitting the child's health and wellbeing, and (4) enhancing family financial stability. Perceived drawbacks included: (1) FCs experiencing mental and physical health burdens, (2) difficult access for some community members, (3) extraneous training requirements, and (4) low program visibility., Conclusions: Given the perceived benefits of the family CNA program, the model may be considered for future dissemination to other communities. However, additional research and program improvements are needed to help make this a more equitable and sustainable home health care model for children with medical complexity., (Copyright © 2023 by the American Academy of Pediatrics.)

Background: Access to credible and relevant health care information is an unmet need for the transgender and gender-diverse (TGD) community. This paper describes the community engagement methods and resulting community priorities as part of a codesign process for the development of a Transgender Health Information Resource (TGHIR) application., Methods: A lesbian, gay, bisexual, transgender, and queer advocacy organization and an academic health sciences team partnered to establish a community advisory board (CAB) of TGD individuals, parents of TGD individuals, and clinicians with expertise in transgender health to inform the project. The analytic-deliberative model and group facilitation strategies based on Liberating Structures guided procedures. Affinity grouping was used to synthesize insights from CAB meeting notes regarding roles and perspectives on the design of the TGHIR application. We used the Patient Engagement in Research Scale (PEIRS) to evaluate CAB members' experience with the project., Results: The CAB emphasized the importance of designing the application with and for the TGD community, including prioritizing intersectionality and diversity. CAB engagement processes benefited from setting clear expectations, staying focused on goals, synchronous and asynchronous work, and appreciating CAB member expertise. TGHIR application scope and priorities included a single source to access relevant, credible health information, the ability to use the app discreetly, and preserving privacy (i.e., safe use). An out-of-scope CAB need was the ability to identify both culturally and clinically competent TGD health care providers. PEIRS results showed CAB members experienced moderate to high levels of meaningful engagement (M[standard deviation] = 84.7[12] out of 100)., Conclusion: A CAB model was useful for informing TGHIR application priority features. In-person and virtual methods were useful for engagement. The CAB continues to be engaged in application development, dissemination, and evaluation. The TGHIR application may complement, but will not replace, the need for both culturally and clinically competent health care for TGD people., Competing Interests: None declared., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: There is an urgent and unmet need for accessible and credible health information within the transgender and gender-diverse (TGD) community. Currently, TGD individuals often seek and must find relevant resources by vetting social media posts. A resource that provides accessible and credible health-related resources and content via a mobile phone app may have a positive impact on and support the TGD population., Objective: COVID-19 stay-at-home orders forced a shift in the methods used in participatory design. In this paper, we aimed to describe the web-based participatory methods used to develop the Transgender Health Information Resource. We also described and characterized the web-based engagement that occurred during a single session of the overall design process., Methods: We planned and conducted web-based design sessions to replace the proposed in-person sessions. We used web-based collaborative tools, including Zoom (Zoom Video Communications), Mural (Mural), REDCap (Research Electronic Data Capture; Vanderbilt University), and Justinmind (Justinmind), to engage the participants in the design process. Zoom was used as an integrated platform for design activities. Mural was used to perform exercises, such as free listing, brainstorming, and grouping. REDCap allowed us to collect survey responses. Justinmind was used to create prototypes that were shared and discussed via Zoom. Recruitment was led by one of our community partners, One Colorado, who used private Facebook groups in which web-based flyers were dispersed. The design process took place in several workshops over a period of 10 months. We described and characterized engagement during a single design session by tracking the number of influential interactions among participants. We defined an influential interaction as communication, either verbal or web-based content manipulation, that advanced the design process., Results: We presented data from a single design session that lasted 1 hour and 48 minutes and included 4 participants. During the session, there were 301 influential interactions, consisting of 79 verbal comments and 222 web-based content manipulations., Conclusions: Web-based participatory design can elicit input and decisions from participants to develop a health information resource, such as a mobile app user interface. Overall, participants were highly engaged. This approach maintained the benefits and fidelity of traditional in-person design sessions, mitigated deficits, and exploited the previously unconsidered benefits of web-based methods, such as enhancing the ability to participate for those who live far from academic institutions. The web-based approach to participatory design was an efficient and feasible methodological design approach., (©Brad Morse, Andrey Soares, Kate Ytell, Kristen DeSanto, Marvyn Allen, Brooke Dorsey Holliman, Rita S Lee, Bethany M Kwan, Lisa M Schilling. Originally published in Journal of Participatory Medicine (https://jopm.jmir.org), 10.01.2023.)

Introduction: Lethal means safety counseling (LMSC) is an evidence-based suicide prevention intervention during which providers encourage patients to limit their access to lethal means (e.g., firearms, medications). Despite agreement about the importance of LMSC, it is underutilized in clinical practice., Methods: To better understand the individual and contextual factors that influence LMSC and its implementation, we conducted a systematic review of qualitative studies examining stakeholder perceptions of the intervention. PubMed and PsycInfo were searched up to February 2021 using terms related to: (1) LMSC, firearms, or medications; (2) suicide, safety, or injury; and (3) qualitative methodology. Two coders used thematic synthesis to analyze findings from eligible papers, including developing a codebook and coding using an inductive and iterative approach (reliability k > 0.70). Confidence in review findings were evaluated using the Confidence in the Evidence from Reviews of Qualitative Research (CERQual) Approach. Subthemes were assigned to domains in the Consolidated Framework for Implementation Research., Findings: Of the 19 papers identified, 18 discussed LMSC for firearms and 1 focused exclusively on LMSC for medications. The firearm-related studies explored perspectives of a variety of stakeholders (patients, providers, members of the firearms community, healthcare leaders, and family members) across multiple settings (emergency departments, pediatric and adult primary care, and outpatient mental health). Seven overarching themes emerged, including the: (1) importance of firearms to owners' identities and perceptions of ownership as a value and right, which can lead to perceived cultural tensions in clinical settings; (2) importance of patients understanding the context and rationale for LMSC; (3) value of providers showing cultural competency when discussing firearms; (4) influence of safety and risk beliefs on firearm behaviors; (5) need to navigate logistical concerns when implementing LMSC; (6) value of individualizing LMSC; (7) potential for trusted family members and friends to be involved in implementing LMSC., Conclusion: This synthesis of the qualitative literature informs clinical, operational, and research endeavors aimed at increasing the reach and effectiveness of LMSC. Future research should address the perspectives of individuals underrepresented in the literature (e.g., those from racial/ethnic minority groups) and further examine stakeholders' perceptions of LMSC for medication. [-2pt]., Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021237515], identifier [CRD42021237515]., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Khazanov, Keddem, Hoskins, Myhre, Sullivan, Mitchell, Holliman, Landes and Simonetti.)

Background: Recently, there has been increasing evidence that reducing burnout in healthcare providers requires significant organizational efforts that include the integration of leadership strategies., Methods: Focus groups were conducted across four health systems within the University of Colorado Department of Medicine in four affinity groups (administrative staff, medical trainees, research faculty, and clinical faculty). Authentic leadership theory was used for analysis to advance the understanding of the role of leadership style upon participants' work experiences and preferences, and to identify opportunities for translation of site-specific results to other academic medical settings., Results: Study participants from each affinity group believed their clinical leaders lacked objectivity with decision-making (lacking "balancing processing"), which contributed to their overall feeling of powerlessness. The experience of increasing work demands was salient throughout all twelve focus groups, and participants identified leadership that interacted in a more open and self-disclosing manner ("relational transparency") as alleviating at least some of this burden. Strong preference discernable alignment between their leaders' decision-making and their internal moral compass of values (demonstrating "internalized moral perspective") was described, as was clinical leaders demonstrating "self-awareness" (having a self-reflective process that informs the leader's decision-making). Comparing affinity group experiences within each authentic leadership theory construct identified the relevance of contextual factors, such as work setting and roles, upon employees' perceptions and expectations of their leaders., Conclusions: Use of authentic leadership theory advanced the understanding of the association between leadership traits and experiences of burnout amongst a large group of academic clinicians, researchers, trainees, and administrative staff. Leadership styles that promoted relationship transparency, openness, and support were preferred and fostering these traits may help address the demands in academic medicine, including symptoms of burnout., (© 2022. The Author(s).)

Background: The transfer of patients between hospitals (inter-hospital transfer, or IHT) is a common occurrence for patients, but guidelines to ensure safe and effective IHTs are lacking. Poor IHTs result in higher rates of mortality, longer lengths of stay, and higher hospitalization costs compared to admissions from the emergency department. Nurses are often the first point of contact for IHT patients and can provide valuable insights on key challenges to IHT processes., Objective: To characterize the experiences of inpatient floor-level bedside nurses caring for IHT patients and identify care coordination challenges and solutions., Design/participants/approach: Qualitative study using semi-structured focus groups and interviews conducted from October 2019 to July 2020 with 21 inpatient floor-level nurses caring for adult medicine patients at an academic hospital. Nurses were recruited using a purposive convenience sampling approach. A combined inductive and deductive coding approach guided by thematic analysis was used for data analysis., Key Results: Results from this study are mapped to the Agency for Healthcare Research and Quality Care Coordination Measurement Framework domains of communication, assessing needs and goals, and negotiating accountability. The following key themes characterize nurses' experiences with IHT related to these domains: (1) challenges with information exchange and team communication during IHT, (2) environmental and information preparation needed to anticipate transfers, and (3) determining responsibility and care plans after the IHT patient has arrived at the accepting facility., Conclusions: Nurses described the absence of standardized processes to coordinate care before or at the time of patient arrival. Challenges to communication and coordination during IHTs negatively impacted patient care and nursing professional satisfaction. To streamline care for IHT patients and reduce nursing stress, future IHT interventions should include standardized handoff reports, timely identification and easy access to admitting clinicians, and timely clinician evaluation and orders., (© 2021. The Author(s) under exclusive licence to Society of General Internal Medicine.)

Disruption of the HBV viral life cycle with small molecules that prevent the encapsidation of pregenomic RNA and viral polymerase through binding to HBV core protein is a clinically validated approach to inhibiting HBV viral replication. Herein we report the further optimisation of clinical candidate AB-506 through core modification with a focus on increasing oral exposure and oral half-life. Maintenance of high levels of anti-HBV cellular potency in conjunction with improvements in pharmacokinetic properties led to multi-log 10 reductions in serum HBV DNA following low, once-daily oral dosing for key analogues in a preclinical animal model of HBV replication., Competing Interests: AGC, SGK, NM, AA, KYF, EPT, KS, TH and MJS are current employees of Arbutus Biopharma, Inc. and may own company stock., (This journal is © The Royal Society of Chemistry.)

AB-506, a small-molecule inhibitor targeting the HBV core protein, inhibits viral replication in vitro (HepAD38 cells: EC 50 of 0.077 μM, CC 50  > 25 μM) and in vivo (HBV mouse model: ∼3.0 log 10 reductions in serum HBV DNA compared to the vehicle control). Binding of AB-506 to HBV core protein accelerates capsid assembly and inhibits HBV pgRNA encapsidation. Furthermore, AB-506 blocks cccDNA establishment in HBV-infected HepG2-hNTCP-C4 cells and primary human hepatocytes, leading to inhibition of viral RNA, HBsAg, and HBeAg production (EC 50 from 0.64 μM to 1.92 μM). AB-506 demonstrated activity across HBV genotypes A-H and maintains antiviral activity against nucleos(t)ide analog-resistant variants in vitro. Evaluation of AB-506 against a panel of core variants showed that T33N/Q substitutions results in >200-fold increase in EC 50 values, while L30F, L37Q, and I105T substitutions showed an 8 to 20-fold increase in EC 50 values in comparison to the wild-type. In vitro combinations of AB-506 with NAs or an RNAi agent were additive to moderately synergistic. AB-506 exhibits good oral bioavailability, systemic exposure, and higher liver to plasma ratios in rodents, a pharmacokinetic profile supporting clinical development for chronic hepatitis B., (Copyright © 2021 Elsevier B.V. All rights reserved.)