Mpox vaccination routes: prevalence, correlates and adverse effects of subcutaneous versus intradermal vaccination at a mass vaccination clinic in Sydney, Australia.

The Royal Prince Alfred Hospital Mpox Vaccination Clinic opened in response to the 2022 multicountry mpox outbreak. A total of 9500 vaccinations were administered intradermally and subcutaneously during the first 16 weeks of clinic operation. The rate of adverse events was 0.1%. Compared to people who received the vaccine intradermally, those who received it subcutaneously were more likely to be aged 30-39 years (P = 0.047), sexual partners of gay and bisexual men (P < 0.001), eligible for Medicare (P < 0.001) and born in the Philippines (P = 0.01) or Malaysia (P = 0.04).

Strengthening learning and research in health equity - opportunities for university departments of primary health care and general practice.

This paper explores the roles of university departments of primary health care (PHC) and general practice in promoting health equity. The coronavirus disease 2019 (COVID-19) pandemic has exposed long-standing health and workforce inequities in Australia, as elsewhere. Addressing these inequities will require wide-ranging responses particularly focussed on PHC and the PHC workforce. Well-resourced university departments of PHC and general practice have potential to lead research informing PHC transformation and strategies to reduce health inequity, as well as to train and inspire a future PHC workforce. Examples from such academic departments in Australia and internationally are briefly described, and the experience of a recently established department of general practice is considered, in order to recommend enablers including institutional support, curriculum design, and partnerships with communities and between institutions. Support for community-based clinical schools, practice-based research networks and strengthening PHC research capacity will enable the PHC and general practice academy to engage more effectively in addressing health inequity.

One medical school's experience of sustaining general practice teaching in the time of COVID-19.

Challenges have been encountered in maintaining the Western Sydney University general practice program but effective strategies have been adopted to manage the impact of COVID-19.

Medicine in Context: ten years' experience in diversity education for medical students in Greater Western Sydney, Australia.

Objective: This paper describes the Western Sydney University School of Medicine (WSUSoM) diversity education program, Medicine in Context (MiC). MiC implements community-engaged learning and partnership pedagogy in teaching diverse social determinants of health to first clinical year medical students. Central to MiC content and delivery methods is the local region's diversity which is also reflected in the student population and MiC staff. Methodology: This is a descriptive report about how the WSUSoM staff with community and General Practice (GP) partners have co-designed, co-delivered, co-assessed and co-evaluated the MiC program in 2009-2018. In keeping with the community-engaged learning and partnership pedagogy, the report is co-authored by a cross section of MiC stakeholders: the WSUSoM staff members, community partners and an alumna. Results: Ten weeks' immersion in community-based services, with debriefing and scaffolding in tutorials and workshops, exposes students to the complex interplay between social determinants of health and clinical practice. Sharing of experiences, insights and reflections in safe environments enables students to overcome the uneasiness of diversity education. Quality assurance reviews identified positive trends in students' quality of learning and satisfaction in the program following evidence-based continuous improvements of the program design and delivery. Conclusion: Implementation of community-engaged learning and partnership pedagogy in the MiC program, supported by ongoing commitment from the WSUSoM and its community and GP partners, has been successful in engaging students in diversity education. The synthesis of diversity education and clinical learning throughout the MiC program is an important step toward building competency in patient-centred care.

Advance care planning in rural New South Wales from the perspective of general practice registrars and recently fellowed general practitioners.

OBJECTIVE: This study examined advance care planning as delivered by general practice registrars and recently fellowed GPs in New South Wales rural settings. The facilitators and barriers to advance care planning uptake in these areas were investigated, as well as the state of general practice training on advance care planning. DESIGN: Qualitative descriptive methodology, involving semi-structured face-to-face and telephone interviews. SETTING: Primary care. PARTICIPANTS: General practice registrars and recently fellowed GPs in New South Wales rural settings. Definition of rural using the Australian Standard Geographical Classification - Remoteness Area. Thirteen participants were included in the study. MAIN OUTCOME MEASURES: Thematic analysis of interview transcripts elucidated key issues emerging from participants' accounts. RESULTS: Key barriers included doctor-dependent uptake, demands on doctor's time and the limited relevant resources available. Facilitators recognised were patient control in end-of-life care and long-standing relationships between GPs and their patients. Uptake among patients was low, and minimal training on advance care planning reported. CONCLUSION: The lack of training opportunities in advance care planning during vocational training, especially when combined with the essential role played by rural GPs in initiating advance care planning and providing end-of-life care, appears to be a major problem that might contribute to poor uptake among patients in rural areas. This study demonstrated, however, the significant benefits that advance care planning could bring in patients living in rural communities if delivered effectively. Given that rural GPs face a number of barriers to providing routine health care, these results highlight an important need to provide GPs and rural communities with support, education, incentive, better administrative tools, options and greater awareness of advance care planning.

Factors influencing self-management in patients with type 2 diabetes in general practice: a qualitative study.

Many Australian adults with type 2 diabetes mellitus (T2DM) do not follow recommended self-management behaviours that could prevent or delay complications. This exploratory study aimed to investigate the factors influencing self-management of T2DM in general practice. Semi-structured qualitative interviews were conducted with patients with T2DM (n = 10) and their GPs (n = 4) and practice nurses (n = 3) in a low socioeconomic area of Sydney, New South Wales, Australia. The interviews were analysed thematically using the socio-ecological model as a framework for coding. Additional themes were derived inductively based on the explicitly stated meaning of the text. Factors influencing self-management occurred on four levels of the socio-ecological model: individual (e-health literacy, motivation, time constraints); interpersonal (family and friends, T2DM education, patient-provider relationship); organisational (affordability, multidisciplinary care); and community levels (culture, self-management resources). Multi-level strategies are needed to address this wide range of factors that are beyond the scope of single services or organisations. These could include tailoring health education and resources to e-health literacy and culture; attention to social networks and the patient-provider relationship; and facilitating access to affordable on-site allied health services.

Overcoming barriers to use of child car seats in an urban Aboriginal community-formative evaluation of a program for Aboriginal Community Controlled Health Services.

BACKGROUND: Little is known about the barriers to use of child car seats in Australian Aboriginal communities, or the acceptability of programs to increase appropriate car seat use. This formative evaluation sought to consult and partner with Aboriginal Community Controlled Health Services (ACCHS) to develop and evaluate the feasibility and acceptability of a program intended to improve optimal use of child car seats. METHODS: Focus groups were conducted with parents and carers of Aboriginal children to identify the barriers and facilitating factors for child car seat use, and staff of two ACCHS were interviewed to inform program development. Following the implementation of the resulting multi-faceted program, consisting of staff training, education, hands-on demonstrations and a subsidised car seat distribution scheme, interviews were conducted to assess process issues and acceptability with 13 staff members. RESULTS: Parents and carers in the focus groups reported a lack of awareness of child car seat use, confusion about the right car seats for different aged children but agreed about the importance of safety and community responsibility to keep children safe in cars. Interviews with service staff informed an approach to deliver relevant information. Information and resources were delivered to families, while the car seat distribution scheme supplied 33 families with child car seats. Following the conclusion of the program, staff reported that the program was relevant to their role. They also valued the car seat distribution scheme. Staff training in selection and installation of car seats increased confidence in staff knowledge. CONCLUSIONS: We developed a program to promote child car seat use in ACCHS, which focused on developing capacity, made use of existing infrastructure and developed resources for use in this setting. The program shows promise as a means to promote child car seat use in Aboriginal communities; however, the impact on child car seat use will need to be evaluated in a larger scale prospective trial.

Dynamic regulation of the Trypanosoma brucei transferrin receptor in response to iron starvation is mediated via the 3'UTR.

The bloodstream form of the parasite Trypanosoma brucei obtains iron from its mammalian host by receptor-mediated endocytosis of host transferrin through its own unique transferrin receptor (TbTfR). Expression of TbTfR rapidly increases upon iron starvation by post-transcriptional regulation through a currently undefined mechanism that is distinct from the mammalian iron response system. We have created reporter cell lines by fusing the TbTfR 3'UTR or a control Aldolase 3'UTR to reporter genes encoding GFP or firefly Luciferase, and inserted the fusions into a bloodstream form cell line at a tagged ribosomal RNA locus. Fusion of the TbTfR 3'UTR is sufficient to significantly repress the expression of the reporter proteins under normal growth conditions. Under iron starvation conditions we observed upregulation of the mRNA and protein level of the TbTfR 3'UTR fusions only, with a magnitude and timing consistent with that reported for upregulation of the TbTfR. We conclude that the dynamic regulation of the T. brucei transferrin receptor in response to iron starvation is mediated via its 3'UTR, and that the effect is independent of genomic location.

A Comprehensive Analysis of Replicative Lifespan in 4,698 Single-Gene Deletion Strains Uncovers Conserved Mechanisms of Aging.

Many genes that affect replicative lifespan (RLS) in the budding yeast Saccharomyces cerevisiae also affect aging in other organisms such as C. elegans and M. musculus. We performed a systematic analysis of yeast RLS in a set of 4,698 viable single-gene deletion strains. Multiple functional gene clusters were identified, and full genome-to-genome comparison demonstrated a significant conservation in longevity pathways between yeast and C. elegans. Among the mechanisms of aging identified, deletion of tRNA exporter LOS1 robustly extended lifespan. Dietary restriction (DR) and inhibition of mechanistic Target of Rapamycin (mTOR) exclude Los1 from the nucleus in a Rad53-dependent manner. Moreover, lifespan extension from deletion of LOS1 is nonadditive with DR or mTOR inhibition, and results in Gcn4 transcription factor activation. Thus, the DNA damage response and mTOR converge on Los1-mediated nuclear tRNA export to regulate Gcn4 activity and aging.

A narrative synthesis of the impact of primary health care delivery models for refugees in resettlement countries on access, quality and coordination.

INTRODUCTION: Refugees have many complex health care needs which should be addressed by the primary health care services, both on their arrival in resettlement countries and in their transition to long-term care. The aim of this narrative synthesis is to identify the components of primary health care service delivery models for such populations which have been effective in improving access, quality and coordination of care. METHODS: A systematic review of the literature, including published systematic reviews, was undertaken. Studies between 1990 and 2011 were identified by searching Medline, CINAHL, EMBASE, Cochrane Library, Scopus, Australian Public Affairs Information Service - Health, Health and Society Database, Multicultural Australian and Immigration Studies and Google Scholar. A limited snowballing search of the reference lists of all included studies was also undertaken. A stakeholder advisory committee and international advisers provided papers from grey literature. Only English language studies of evaluated primary health care models of care for refugees in developed countries of resettlement were included. RESULTS: Twenty-five studies met the inclusion criteria for this review of which 15 were Australian and 10 overseas models. These could be categorised into six themes: service context, clinical model, workforce capacity, cost to clients, health and non-health services. Access was improved by multidisciplinary staff, use of interpreters and bilingual staff, no-cost or low-cost services, outreach services, free transport to and from appointments, longer clinic opening hours, patient advocacy, and use of gender-concordant providers. These services were affordable, appropriate and acceptable to the target groups. Coordination between the different health care services and services responding to the social needs of clients was improved through case management by specialist workers. Quality of care was improved by training in cultural sensitivity and appropriate use of interpreters. CONCLUSION: The elements of models most frequently associated with improved access, coordination and quality of care were case management, use of specialist refugee health workers, interpreters and bilingual staff. These findings have implications for workforce planning and training.

Molecular mechanisms underlying genotype-dependent responses to dietary restriction.

Dietary restriction (DR) increases lifespan and attenuates age-related phenotypes in many organisms; however, the effect of DR on longevity of individuals in genetically heterogeneous populations is not well characterized. Here, we describe a large-scale effort to define molecular mechanisms that underlie genotype-specific responses to DR. The effect of DR on lifespan was determined for 166 single gene deletion strains in Saccharomyces cerevisiae. Resulting changes in mean lifespan ranged from a reduction of 79% to an increase of 103%. Vacuolar pH homeostasis, superoxide dismutase activity, and mitochondrial proteostasis were found to be strong determinants of the response to DR. Proteomic analysis of cells deficient in prohibitins revealed induction of a mitochondrial unfolded protein response (mtUPR), which has not previously been described in yeast. Mitochondrial proteotoxic stress in prohibitin mutants was suppressed by DR via reduced cytoplasmic mRNA translation. A similar relationship between prohibitins, the mtUPR, and longevity was also observed in Caenorhabditis elegans. These observations define conserved molecular processes that underlie genotype-dependent effects of DR that may be important modulators of DR in higher organisms.

End-of-life cell cycle arrest contributes to stochasticity of yeast replicative aging.

There is growing evidence that stochastic events play an important role in determining individual longevity. Studies in model organisms have demonstrated that genetically identical populations maintained under apparently equivalent environmental conditions display individual variation in life span that can be modeled by the Gompertz-Makeham law of mortality. Here, we report that within genetically identical haploid and diploid wild-type populations, shorter-lived cells tend to arrest in a budded state, while cells that arrest in an unbudded state are significantly longer-lived. This relationship is particularly notable in diploid BY4743 cells, where mother cells that arrest in a budded state have a shorter mean life span (25.6 vs. 35.6) and larger coefficient of variance with respect to individual life span (0.42 vs. 0.32) than cells that arrest in an unbudded state. Mutations that cause genomic instability tend to shorten life span and increase the proportion of the population that arrest in a budded state. These observations suggest that randomly occurring damage may contribute to stochasticity during replicative aging by causing a subset of the population to terminally arrest prematurely in the S or G2 phase of the cell cycle.

Dietary restriction and mitochondrial function link replicative and chronological aging in Saccharomyces cerevisiae.

Chronological aging of budding yeast cells results in a reduction in subsequent replicative life span through unknown mechanisms. Here we show that dietary restriction during chronological aging delays the reduction in subsequent replicative life span up to at least 23days of chronological age. We further show that among the viable portion of the control population aged 26days, individual cells with the lowest mitochondrial membrane potential have the longest subsequent replicative lifespan. These observations demonstrate that dietary restriction modulates a common molecular mechanism linking chronological and replicative aging in yeast and indicate a critical role for mitochondrial function in this process.

pH neutralization protects against reduction in replicative lifespan following chronological aging in yeast.

Chronological and replicative aging have been studied in yeast as alternative paradigms for post-mitotic and mitotic aging, respectively. It has been known for more than a decade that cells of the S288C background aged chronologically in rich medium have reduced replicative lifespan relative to chronologically young cells. Here we report replication of this observation in the diploid BY4743 strain background. We further show that the reduction in replicative lifespan from chronological aging is accelerated when cells are chronologically aged under standard conditions in synthetic complete medium rather than rich medium. The loss of replicative potential with chronological age is attenuated by buffering the pH of the chronological aging medium to 6.0, an intervention that we have previously shown can extend chronological lifespan. These data demonstrate that extracellular acidification of the culture medium can cause intracellular damage in the chronologically aging population that is asymmetrically segregated by the mother cell to limit subsequent replicative lifespan.