Cross-cultural adaptation and psychometric validation of point-of-care outcome assessment tools in Chinese palliative care clinical practice.

BACKGROUND: A standardized national approach to routinely assessing palliative care patients helps improve patient outcomes. However, a quality improvement program-based on person centered outcomes within palliative care is lacking in Mainland China. The well-established Australian Palliative Care Outcome Collaboration (PCOC) national model improves palliative care quality. This study aimed to culturally adapt and validate three measures that form part of the PCOC program for palliative care clinical practice in China: The PCOC Symptom Assessment Scale (PCOC SAS), Palliative Care Problem Severity Scale (PCPSS), Palliative Care Phase. METHODS: A study was conducted on cross-cultural adaptation and validation of PCOC SAS, PCPSS and Palliative Care Phase, involving translation methods, cognitive interviewing, and psychometric testing through paired assessments. RESULTS: Cross-cultural adaptation highlighted the need to strengthen the link between the patient's care plan and the outcome measures to improve outcomes, and the concept of distress in PCOC SAS. Analysis of 368 paired assessments (n = 135 inpatients, 22 clinicians) demonstrated that the PCOC SAS and PCPSS had good and acceptable coherence (Cronbach's a = 0.85, 0.75 respectively). Palliative Care Phase detected patients' urgent needs. PCOC SAS and PCPSS showed fair discriminant and concurrent validity. Inter-rater reliability was fair for Palliative Care Phase (k = 0.31) and PCPSS (k = 0.23-0.30), except for PCPSS-pain, which was moderate (k = 0.53). CONCLUSIONS: The Chinese version of PCOC SAS, PCPSS, and Palliative Care Phase can be used to assess outcomes as part of routine clinical practice in Mainland China. Comprehensive clinical education regarding the assessment tools is necessary to help improve the inter-rater reliability.

Educational content and strategies to support nurses from culturally and linguistically diverse backgrounds caring for patients considering voluntary assisted dying: The Australian experience.

OBJECTIVES: Drawing on findings from a qualitative study that aimed to explore the knowledge and attitudes of nurses from culturally and linguistically diverse (CALD) backgrounds about voluntary assisted dying (VAD). The study also aimed to identify the strategies that assist nurses in their readiness and preparation for exposure to VAD. This paper reports on the educational content and strategies that could assist nurses from CALD backgrounds to be better prepared when they encounter VAD requests. BACKGROUND: Around the world, healthcare professionals have roles to play in caring for patients requesting voluntary assisted dying. Nurses, particularly those from diverse geographic and clinical settings, have voiced inadequate knowledge and understanding about voluntary assisted dying. DESIGN: A qualitative descriptive approach was undertaken. METHODS: Data collection involved one focus group and 16 in-depth interviews. A total of 21 nurses from CALD backgrounds were recruited from one Australian state. Thematic analysis was conducted to interpret the data. FINDINGS: Nurses identified their knowledge gaps and specified the need for education and workplace training on VAD, its legal and ethical aspects, clarity on their role, communication techniques and how VAD intersects with their practice. They suggested various teaching strategies that could prepare nurses to work safely and confidently in a clinical environment where voluntary assisted dying is an option for patients. CONCLUSION: Given the high number of nurses from diverse backgrounds working in the Australian health sector, these nurses need to be fully prepared to care for patients requesting VAD.

Are Socioeconomic Factors Associated with Atrial Fibrillation Sex-dependent?

Atrial Fibrillation (AF), the most prevalent cardiac arrhythmia, poses a significant public health and economic burden. While socioeconomic factors like income and education have been implicated in AF incidence and outcomes, the potential sex-specific associations remained underexplored. This narrative review aimed to fill this gap by synthesizing existing literature on the sex-specific impact of socioeconomic factors on AF incidence, treatment and outcome. Among these socioeconomic factors, we identified income and education as the most frequently cited determinants.. Nevertheless, the magnitude and direction of these sex differences remained inconsistent across studies. The review uncovered that many studies did not include sex in the analysis when assessing the impact of socioeconomic factors on AF. We highlighted that the paucity of studies employing sex stratified reporting and sex interaction analyses, thereby hindering a deeper understanding of these relationships.

Global status of chiropractic education research: a scoping review protocol.

OBJECTIVE: The objective of this scoping review is to map the volume and nature (topics, study designs, regions) of chiropractic education research relating to chiropractic learners and programs worldwide. INTRODUCTION: Education of the health workforce is critical to reach population health goals. Chiropractic educational programs are expanding globally; however, the state of chiropractic education research is not known. A better understanding of the volume and nature of chiropractic education research will inform education research priorities and development of chiropractic programs, and assist with preparing a stronger chiropractic workforce to address world health goals. INCLUSION CRITERIA: This scoping review will consider articles that study students, faculty, administration, staff, graduates, and programs in any chiropractic education setting, including graduate, clinical, postgraduate, and specialty training, in any country. Articles on non-educational topics or clinical research will be excluded. METHODS: This review will follow the JBI scoping review methodology and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses extension for Scoping Reviews (PRISMA-ScR). The databases to be searched include PubMed, Scopus, CINAHL, Index to Chiropractic Literature, Biblioteca Virtual em Saúde, and Educational Resources Information Center from their inception. All languages will be considered. Two reviewers will independently screen records using predefined eligibility criteria and extract data using tables. Data extracted from eligible articles will include study design, participants, region, and topics. The results will be presented in a narrative summary with data presented in tabular and diagrammatic formats. REVIEW REGISTRATION: Open Science Framework https://osf.io/9b3ap.

Dynamic, multi-scale analyses indicate site- and landscape-level forest cover drive Yellow-billed and Black-billed Cuckoo interannual turnover.

Studies of habitat use in breeding birds often assume species have relatively stable breeding distributions. Some species, however, display considerable year-to-year variability, complicating efforts to determine suitable or preferred habitats. After returning to their breeding range, Black-billed Cuckoos (Coccyzus erythropthalmus) and Yellow-billed Cuckoos (C. americanus) are thought to range widely before nesting, resulting in high rates of interannual breeding-site turnover, potentially contributing to conflicting habitat associations found in past studies. However, difficulty detecting these rare and declining species could lead to overinflated estimates of interannual turnover. Using broadcast surveys to increase detection probability, we collected detection/non-detection data in 2019 and 2020 at 41 publicly owned sites in Illinois and performed a dynamic, multi-scale occupancy analysis for each species to separate detection probability from potential interannual turnover and determine landscape and small-scale variables driving habitat use and occupancy dynamics. We found strong support for interannual turnover for both species based on poor performance of non-dynamic models and variation in estimated annual occupancy (20% and 21% increase between years for Black-billed and Yellow-billed Cuckoos, respectively). Black-billed Cuckoos persisted at sites with less forest in the surrounding landscape and used areas with denser understory vegetation. Yellow-billed Cuckoos colonized sites with greater canopy cover, avoided developed landscapes, and used areas with a shorter subcanopy layer. The dynamic nature of habitat use in these two cuckoo species suggests the importance of coordinating management and conservation across a broader spatial scale. Managing for larger patches of dense shrubs in less forested landscapes would benefit Black-billed Cuckoos while Yellow-billed cuckoos would benefit from management creating forested areas with open understories in less-developed landscapes.

Impact of knockout of dual-specificity protein phosphatase 5 on structural and mechanical properties of rat middle cerebral arteries: implications for vascular aging.

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable between Dusp5 KO and control rats. The internal elastic lamina in the MCA of Dusp5 KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA in Dusp5 KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that while Dusp5 KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging.

Stages of readiness for advance care planning: Systematic review and meta-analysis of prevalence rates and associated factors.

BACKGROUND: Advance care planning has been widely recommended to respect the medical care preferences of patients in the final stages of life. However, uptake of advance care planning in healthcare settings remains suboptimal. It may be beneficial to take into account individuals' readiness for advance care planning based on the stages to change identified in the Transtheoretical Model. OBJECTIVE: To identify the measurements used to assess readiness of advance care planning based on the Transtheoretical Model, to pool the prevalence of readiness stages, and to summarize the factors affecting people's readiness for advance care planning. DESIGN: Systematic review and meta-analysis. METHODS: We systematically searched the databases of PubMed, EMBASE, The Cochrane Library, CINAHL, and Web of Science for relevant studies from inception to February 2023. A random effects model was used to estimate the pooled prevalence. And a narrative review on the factors associated with stages of readiness was conducted. RESULTS: This meta-analysis included 25 studies involving a total of 4237 individuals. The precontemplation stage was the most commonly identified stage of readiness among advance care planning behaviors (26-72 %). The prevalence of readiness stages for advance care planning varied among different types of behavior. The behavior of "talking to health care proxy/family/loved ones about thoughts on quality versus quantity of life" had the highest level of readiness among all listed behaviors, followed by "talking to health care proxy/family/loved ones about living will", "signing a health care proxy form" and "signing a living will", "signing an advance directive", as well as "talking to doctors about living will". Regarding to influencing factors, a majority of sociodemographic and clinical factors did not show consistent associations with readiness, but some studies did suggest potential links with age, health status, countries, type of assessment, core structures of the Transtheoretical Model, and intervention modalities. CONCLUSIONS: A majority of individuals were unaware of advance care planning. There is an urgent need to promote readiness for such planning. Starting with preliminary activities such as "talking to health care proxy/family/loved ones about thoughts on quality versus quantity of life" can help initiate advance care planning. Better integration of the Transtheoretical Model and interventions into the research of advance care planning readiness are needed. REGISTRATION: Not registered.

The experience of Australian aged care workers during a trial implementation of a palliative care outcomes programme.

End of life care is an essential part of the role of Australian aged care homes (ACHs). However, there is no national framework to support aged care staff in systematically identifying residents with palliative care needs or to routinely assess, respond to, and measure end of life needs. The Palliative Care Outcomes Collaboration (PCOC) is a national outcomes and benchmarking programme which aims to systematically improve palliative care for people who are approaching the end of life, and for their families and carers. The PCOC Wicking Model for Residential Aged Care was developed and piloted in four Australian ACHs. This paper reports on the qualitative findings from semi-structured interviews and focus groups conducted with ACH staff (N = 37) to examine feasibility. Thematic analysis identified three overarching themes about the pilot: (i) processes to successfully prepare and support ACHs; (ii) appropriateness of PCOC tools for the ACH setting; and (iii) realised and potential benefits of the model for ACHs. The lessons presented valuable insights to refine the PCOC Wicking Model and enrich understanding of the potential challenges and solutions for implementing similar programs within ACHs in future. The results suggest that key to successfully preparing ACHs for implementation of the PCOC Wicking Model is an authentic and well-paced collaborative approach with ACHs to ensure the resources, structures and systems are in place and appropriate for the setting. The PCOC Wicking Model for Residential Aged Care is a promising prototype to support ACHs in improving palliative and end of life care outcomes for residents and their carers.

Role of Dusp5 KO on Vascular Properties of Middle Cerebral Artery in Rats.

Vascular aging influences hemodynamics, elevating risks for vascular diseases and dementia. We recently demonstrated that knockout (KO) of Dusp5 enhances cerebral and renal hemodynamics and cognitive function. This improvement correlates with elevated pPKC and pERK1/2 levels in the brain and kidneys. Additionally, we observed that Dusp5 KO modulates the passive mechanical properties of cerebral and renal arterioles, associated with increased myogenic tone at low pressure, enhanced distensibility, greater compliance, and reduced stiffness. The present study evaluates the structural and mechanical properties of the middle cerebral artery (MCA) in Dusp5 KO rats. We found that vascular smooth muscle cell layers and the collagen content in the MCA wall are comparable between Dusp5 KO and control rats. The internal elastic lamina in the MCA of Dusp5 KO rats exhibits increased thickness, higher autofluorescence intensity, smaller fenestrae areas, and fewer fenestrations. Despite an enhanced myogenic response and tone of the MCA in Dusp5 KO rats, other passive mechanical properties, such as wall thickness, cross-sectional area, wall-to-lumen ratio, distensibility, incremental elasticity, circumferential wall stress, and elastic modulus, do not significantly differ between strains. These findings suggest that while Dusp5 KO has a limited impact on altering the structural and mechanical properties of MCA, its primary role in ameliorating hemodynamics and cognitive functions is likely attributable to its enzymatic activity on cerebral arterioles. Further research is needed to elucidate the specific enzymatic mechanisms and explore potential clinical applications in the context of vascular aging.

Association between spinal and non-spinal health conditions reported in epidemiological studies: a scoping review protocol.

INTRODUCTION: The increasing prevalence of coexisting health conditions poses a challenge to healthcare providers and healthcare systems. Spinal pain (eg, neck and back pain) and spinal pathologies (eg, osteoporotic fractures and degenerative spinal disease) exist concurrently with other non-spinal health conditions (NSHC). However, the scope of what associations may exist among these co-occurring conditions is unclear. Therefore, this scoping review aims to map the epidemiological literature that reports associations between spine-related pain and pathologies (SPPs) and NSHCs. METHODS AND ANALYSIS: This scoping review will follow the JBI protocol and Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Reviews. We will systematically search the literature using key words and MeSH terms for SPPs and NSHCs. Terminology/vocabulary for NSHCs will include those for communicable and non-communicable diseases as reported by WHO Global Burden of Disease reports. Five databases will be searched from inception: MEDLINE, EMBASE, APA PsycInfo, Scopus and Web of Science Core Collection. Papers published in English, in peer-reviewed journals, including measures of association between SPPs and NSHCs and using observational epidemiologic study designs will be included. Excluded will be studies of cadaveric, animal or health behaviours; studies with no measures of association and non-observational epidemiologic studies. Results will include the number of studies, the studies that have evaluated the measures of association and the frequency of the studied associations between SPPs and NSHCs. Results will be reported in tables and diagrams. Themes of comorbidities will be synthesised into a descriptive report. ETHICS AND DISSEMINATION: This scoping review was deemed exempt from ethics review. This review will provide a comprehensive overview of the literature that reports associations between SPPs and NSHCs to inform future research initiatives and practices. Results will be disseminated through publication in peer-reviewed journals and research conferences. REGISTRATION DETAILS: https://osf.io/w49u3.

Chiropractic Day 2023: A Report and Qualitative Analysis of How Thought Leaders Celebrate the Present and Envision the Future of Chiropractic.

Objective: This study aimed to (1) collect and analyze statements about how to celebrate chiropractic in the present and roles that chiropractors may fulfill in the future, (2) identify if there was congruence among the themes between present and future statements, and (3) offer a model about the chiropractic profession that captures its complex relationships that encompass its interactions within microsystem, mesosystem, exosystem, and macrosystem levels. Methods: For this qualitative analysis, we used pattern and grounded theory approaches. A purposive sample of thought leaders in the chiropractic profession were invited to answer the following 2 open-ended questions: (1) envision the chiropractor of the future, and (2) recommendations on how to celebrate chiropractic. Information was collected during April 2023 using Survey Monkey. The information was entered into a spreadsheet and analyzed for topic clusters, which resulted in matching concepts with social-ecological themes. The themes between the responses to the 2 questions were analyzed for congruence. We used the Standards for Reporting Qualitative Research to report our findings. Results: Of the 54 experts invited, 32 (59%) participated. Authors represented 7 countries and have a median of 32 years of chiropractic experience, with a range of 5 to 51 years. Nineteen major topics in the future statements and 23 major topics in statements about celebrating chiropractic were combined in a model. The topics were presented using the 4 levels of the social-ecological framework. Individual (microsystem): chiropractors are competent, well-educated experts in spine and musculoskeletal care who apply evidence-based practices, which is a combination of the best available evidence, clinical expertise, and patient values. Interpersonal relationships (mesosystem): chiropractors serve the best interests of their patients, provide person-centered care, embrace diversity, equity, and inclusion, consider specific health needs and the health of the whole person. Community (exosystem): chiropractors provide care within integrated health care environments and in private practices, serve the best interests of the public through participation in their communities, participate through multidisciplinary collaboration with and within the health care system, and work together as a profession with a strong professional identity. Societal (macrosystem): chiropractors contribute to the greater good of society and participate on a global level in policy, leadership, and research. There was concordance between both the future envisioning statements and the present celebration recommendations, which suggest logical validity based on the congruence of these concepts. Conclusion: A sample of independent views, including the perceptions from a broad range of chiropractic thought leaders from various backgrounds, philosophies, diversity characteristics, and world regions, were assembled to create a comprehensive model of the chiropractic profession. The resulting model shows an array of intrinsic values and provides the roles that chiropractors may provide to serve patients and the public. This study offers insights into the roles that future chiropractors may fulfill and how these are congruent with present-day values. These core concepts and this novel model may have utility during dialogs about identity, applications regarding chiropractic in policy, practice, education, and research, and building positive relationships and collaborations.

Peer review chair report: Association of Chiropractic Colleges Educational Conference and Research Agenda Conference 2023 peer review process.

OBJECTIVE: The purpose of this report is to provide a summary of the methods used and feedback from reviewers about the peer review process for the 2023 Association of Chiropractic Colleges Educational Conference and Research Agenda Conference (ACC-RAC). METHODS: After the peer review process was complete, the 2023 ACC-RAC peer review committee members were invited to provide feedback through an anonymous electronic form. The survey included a Likert scale to rate items about the peer review process and an option for open-ended comments. RESULTS: Of the 166 peer reviewers, 77 (46%) completed the survey. The reviewers represented 9 countries, with the greatest number from North America. The majority (95%) of respondents rated the process of peer review in topic groups as good to excellent, and the majority (92%) of respondents rated the overall 2023 peer review process as good to excellent. The critical comments that were submitted are addressed in this report. CONCLUSION: Overall, peer reviewer satisfaction with the process used for the 2023 ACC-RAC was high. We will include information from this report as part of the continuous quality improvement of peer review process, an important part of improving chiropractic education, research, and scholarly activities.

Family Carers' Experiences of Goals of Care Conversations in Acute Hospital Settings.

End-of-life Goals of Care (GoC) discussions aim to support care that is consistent with patients' preferences and values. This study uses an exploratory qualitative design drawing upon a social constructivist epistemology to examine family carers' perspectives on GoC within acute Australian hospital settings. Twenty-five family carers of aging inpatients were recruited from six Australian hospitals to participate in recorded, semi-structured interviews. Data were transcribed and analyzed using reflexive thematic analysis. Three main themes were developed. Theme 1 explored carers' experiences of GoC discussions-identifying varying levels of preparedness and carers' hopes for open, two-way discussions initiated by empathic Health Care Professionals (HCPs). Theme 2 examined carers' unmet needs for time, space, consistency, and support to make careful decisions. Theme 3 identified carers advocating for patients' needs when they could not do it themselves. Preparing carers and normalizing GoC discussions relating to end-of-life care maximizes benefits for patients, carers, and HCPs involved.

Review of current 2SLGBTQIA+ inequities in the Canadian health care system.

Gender identity and sexual orientation are determinants of health that can contribute to health inequities. In the 2SLGBTQIA+ community, belonging to a sexual and/or gender minority group leads to a higher risk of negative health outcomes such as depression, anxiety, and cancer, as well as maladaptive behaviors leading to poorer health outcomes such as substance abuse and risky sexual behavior. Empirical evidence suggests that inequities in terms of accessibility to health care, quality of care, inclusivity, and satisfaction of care, are pervasive and entrenched in the health care system. A better understanding of the current Canadian health care context for individuals of the 2SLGBTQIA+ community is imperative to inform public policy and develop sensitive public health interventions to make meaningful headway in reducing inequity. Our search strategy was Canadian-centric and aimed at highlighting the current state of 2SLGBTQIA+ health inequities in Canada. Discrimination, patient care and access to care, education and training of health care professionals, and crucial changes at the systemic and infrastructure levels have been identified as main themes in the literature. Furthermore, we describe health care-related disparities in the 2SLGBTQIA+ community, and present available resources and guidelines that can guide healthcare providers in narrowing the gap in inequities. Herein, the lack of training for both clinical and non-clinical staff has been identified as the most critical issue influencing health care systems. Researchers, educators, and practitioners should invest in health care professional training and future research should evaluate the effectiveness of interventions on staff attitudinal changes toward the 2SLGBTQIA+ community and the impact on patient outcomes.

Reframing the contribution of pelagic Sargassum epiphytic N2 fixation.

Though nitrogen fixation by epiphytic diazotrophs on pelagic Sargassum has been recognized for decades, it has been assumed to contribute insignificantly to the overall marine nitrogen budget. This six-year study reframes this concept through long-term measurements of Sargassum community nitrogen fixation rates, and by extrapolating mass-specific rates to a theoretical square meter portion of Sargassum mat allowing for comparison of these rates to those of other marine and coastal diazotrophs. On 24 occasions from 2015 to 2021, rates of nitrogen fixation were measured using whole fronds of Sargassum collected from the western edge of the Gulf Stream off Cape Hatteras, North Carolina. Across all dates, mass-specific rates ranged from 0 to 37.77 µmol N g-1 h-1 with a mean of 4.156 µmol N g-1 h-1. Extrapolating using a mat-specific density of Sargassum, these rates scale to a range of 0 to 30,916 µmol N m-2 d-1 and a mean of 3,697 µmol N m-2 d-1. Quantifying this community's rates of nitrogen fixation over several years captured the sometimes-extreme variability in rates, characteristic of marine diazotrophs, which has not been reported in the literature to date. When these measurements are considered alongside estimates of the density of pelagic Sargassum, rates of nitrogen fixation by Sargassum's epiphytic diazotrophs rival that of their coastal macrophyte and planktonic counterparts. Given Sargassum's wide and expanding geographic range, the results of this study suggest this community may contribute reactive nitrogen on a meaningful, basin-wide scale, which merits further study.

Palliative care needs and specialist services post stroke: national population-based study.

OBJECTIVES: (1) To compare palliative care needs of patients admitted primarily with stroke and (2) to determine how the care needs of these patients affect their use of different types of specialist palliative care services. METHODS: Observational study based on point-of-care data from the Australian Palliative Care Outcomes Collaboration. Multivariate logistic regression models were used to explore the association between patients' palliative care needs and use of community versus inpatient specialist palliative care services. RESULTS: The majority of patients who had a stroke in this study population had mild or no symptom distress, but experienced a high degree of functional impairment and needed substantial help with basic tasks of daily living. A lower Australia-modified Karnofsky Performance Status score (OR=1.82, 95% CI 1.06 to 3.13) and occurrence of an 'unstable' palliative care phase (OR=28.34, 95% CI 9.03 to 88.94) were associated with use of inpatient versus community palliative care, but otherwise, no clear association was observed between the majority of symptoms and use of different care services. CONCLUSIONS: Many people with stroke could potentially have been cared for and could have experienced the terminal phases of their condition in a community setting if more community support services were available for their families.

Antidepressant use and hyperactive delirium at the end of life: retrospective study.

OBJECTIVES: Little is known about the adverse effects associated with antidepressant use in palliative care inpatients imminently approaching death. This study investigates the relationship between antidepressant use and hyperactive delirium in this population. METHODS: This is a retrospective medical record review of patients who died in a metropolitan palliative care unit in Victoria, Australia, during 2019. Generalised estimating equations were used to estimate the association between antidepressant use and presence of hyperactive delirium in the final 2 weeks of life. RESULTS: Of the 501 adult patients who died in the 12-month period, 113 (22.55%) were on at least one antidepressant at the time of admission. Any antidepressant use in the last 14 days of life was significantly associated with the diagnosis of hyperactive delirium (OR 1.48; 95% CI 1.30, 1.68). Patients prescribed antidepressants also experienced longer durations of delirium (3.89 days; SD 4.23) compared with those not taking any antidepressant (2.99 days; SD 3.70) in the final 2 weeks of life. CONCLUSION: Antidepressant use or discontinuation is significantly associated with hyperactive delirium within 14 days of death. Although the causes of delirium are multifactorial and complex, antidepressant use is a potentially modifiable risk factor.

EFdA efficiently suppresses HIV replication in the male genital tract and prevents penile HIV acquisition.

Sexually transmitted HIV infections in heterosexual men are acquired through the penis. Low adherence to condom usage and the fact that 40% of circumcised men are not protected indicate the need for additional prevention strategies. Here, we describe a new approach to evaluate the prevention of penile HIV transmission. We demonstrated that the entire male genital tract (MGT) of bone marrow/liver/thymus (BLT) humanized mice is repopulated with human T and myeloid cells. The majority of the human T cells in the MGT express CD4 and CCR5. Direct penile exposure to HIV leads to systemic infection including all tissues of the MGT. HIV replication throughout the MGT was reduced 100-1,000-fold by treatment with 4'-ethynyl-2-fluoro-2'-deoxyadenosine (EFdA), resulting in the restoration of CD4+ T cell levels. Importantly, systemic preexposure prophylaxis with EFdA effectively protects from penile HIV acquisition. IMPORTANCE Over 84.2 million people have been infected by the human immunodeficiency virus type 1 (HIV-1) during the past 40 years, most through sexual transmission. Men comprise approximately half of the HIV-infected population worldwide. Sexually transmitted HIV infections in exclusively heterosexual men are acquired through the penis. However, direct evaluation of HIV infection throughout the human male genital tract (MGT) is not possible. Here, we developed a new in vivo model that permits, for the first time, the detail analysis of HIV infection. Using BLT humanized mice, we showed that productive HIV infection occurs throughout the entire MGT and induces a dramatic reduction in human CD4 T cells compromising immune responses in this organ. Antiretroviral treatment with novel drug EFdA suppresses HIV replication in all tissues of the MGT, restores normal levels of CD4 T cells and is highly efficient at preventing penile transmission.

MEPicides: α,ß-unsaturated Fosmidomycin N-Acyl Analogs as Efficient Inhibitors of Plasmodium falciparum 1-Deoxy-d-xylulose-5-phosphate reductoisomerase.

Malaria, a mosquito-borne disease caused by several parasites of the Plasmodium genus, remains a huge threat to global public health. There are an estimated 0.5 million malaria deaths each year, mostly among African children. Unlike humans, Plasmodium parasites and a number of important pathogenic bacteria employ the methyl erythritol phosphate (MEP) pathway for isoprenoid synthesis. Thus, the MEP pathway represents a promising set of drug targets for antimalarial and antibacterial compounds. Here, we present new unsaturated MEPicide inhibitors of 1-deoxy-d-xylulose-5-phosphate reductoisomerase (DXR), the second enzyme of the MEP pathway. A number of these compounds have demonstrated robust inhibition of Plasmodium falciparum DXR, potent antiparasitic activity, and low cytotoxicity against HepG2 cells. Parasites treated with active compounds are rescued by isopentenyl pyrophosphate, the product of the MEP pathway. With higher levels of DXR substrate, parasites acquire resistance to active compounds. These results further confirm the on-target inhibition of DXR in parasites by the inhibitors. Stability in mouse liver microsomes is high for the phosphonate salts, but remains a challenge for the prodrugs. Taken together, the potent activity and on-target mechanism of action of this series further validate DXR as an antimalarial drug target and the α,ß-unsaturation moiety as an important structural component.

Addressing the Shortage of Health Professionals in Official Language Minority Communities to Strengthen Retention Strategies for the Benefit of New Brunswick Francophone and Acadian Communities: Protocol for a Mixed Methods Design.

BACKGROUND: COVID-19 has highlighted already existing human resource gaps in health care systems. New Brunswick health care services are significantly weakened by a shortage of nurses and physicians, affecting regions where Official Language Minority Communities (OLMCs) reside. Since 2008, Vitalité Health Network (the "Network"), whose work language is French (with services delivered in both official languages, English and French), has provided health care to OLMCs in New Brunswick. The Network currently needs to fill hundreds of vacant physician and nurse positions. It is imperative to strengthen the network's retention strategies to ensure its viability and maintain adequate health care services for OLMCs. The study is a collaborative effort between the Network (our partner) and the research team to identify and implement organizational and structural strategies to upscale retention. OBJECTIVE: The aim of this study is to support one of New Brunswick health networks in identifying and implementing strategies to promote physician and registered nurse retention. More precisely, it wishes to make 4 important contributions to identify (and enhance our understanding of) the factors related to the retention of physicians and nurses within the Network; determine, based on the "Magnet Hospital" model and the "Making it Work" framework, on which aspects of the Network's environment (internal or external) it should focus for its retention strategy; define clear and actionable practices to help the Network replenish its strength and vitality; and improve the quality of health care services to OLMCs. METHODS: The sequential methodology combines quantitative and qualitative approaches based on a mixed methods design. For the quantitative part, data collected through the years by the Network will be used to take stock of vacant positions and examine turnover rates. These data will also help determine which areas have the most critical challenges and which ones have more successful approaches regarding retention. Recruitment will be made in those areas for the qualitative part of the study to conduct interviews and focus groups with different respondents, either currently employed or who have left it in the last 5 years. RESULTS: This study was funded in February 2022. Active enrollment and data collection started in the spring of 2022. A total of 56 semistructured interviews were conducted with physicians and nurses. As of manuscript submission, qualitative data analysis is in progress and quantitative data collection is intended to end by February 2023. Summer and fall 2023 is the anticipated period to disseminate the results. CONCLUSIONS: Applying the "Magnet Hospital" model and the "Making it Work" framework outside urban settings will offer a novel outlook to the knowledge of professional resource shortages within OLMCs. Furthermore, this study will generate recommendations that could contribute to a more robust retention plan for physicians and registered nurses. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/41485.