Development of a cross-sectoral antimicrobial resistance capability assessment framework.

Antimicrobial resistance (AMR) is an urgent and growing global health concern, and a clear understanding of existing capacities to address AMR, particularly in low-income and middle-income countries (LMICs), is needed to inform national priorities, investment targets and development activities. Across LMICs, there are limited data regarding existing mechanisms to address AMR, including national AMR policies, current infection prevention and antimicrobial prescribing practices, antimicrobial use in animals, and microbiological testing capacity for AMR. Despite the development of numerous individual tools designed to inform policy formulation and implementation or surveillance interventions to address AMR, there is an unmet need for easy-to-use instruments that together provide a detailed overview of AMR policy, practice and capacity. This paper describes the development of a framework comprising five assessment tools which provide a detailed assessment of country capacity to address AMR within both the human and animal health sectors. The framework is flexible to meet the needs of implementers, as tools can be used separately to assess the capacity of individual institutions or as a whole to align priority-setting and capacity-building with AMR National Action Plans (NAPs) or national policies. Development of the tools was conducted by a multidisciplinary team across three phases: (1) review of existing tools; (2) adaptation of existing tools; and (3) piloting, refinement and finalisation. The framework may be best used by projects which aim to build capacity and foster cross-sectoral collaborations towards the surveillance of AMR, and by LMICs wishing to conduct their own assessments to better understand capacity and capabilities to inform future investments or the implementation of NAPs for AMR.

Antimicrobial Consumption in the Livestock Sector in Bhutan: Volumes, Values, Rates, and Trends for the Period 2017-2021.

Data on the use of antimicrobials in humans and livestock may provide evidence to guide policy changes to mitigate the risk of antimicrobial resistance (AMR). However, there is limited information available about antimicrobial use in livestock in low- and middle-income countries, even though these nations are most vulnerable to the impact of AMR. This study aimed to assess the consumption of veterinary antimicrobials in Bhutan and identify areas for improvement to reduce the use of antimicrobials in livestock. National data on livestock numbers and annual procurement of veterinary antimicrobials over five years (2017-2021) were used to calculate rates of antimicrobial consumption and annual national expenditure on veterinary antimicrobials in Bhutan. The rate of antimicrobial consumption in Bhutan was 3.83 mg per population correction unit, which is lower than most countries in Europe, comparable with the rates of consumption in Iceland and Norway, and approximately 120-fold lower than published rates of antimicrobial consumption in South Asian countries, including Nepal and Pakistan. The low rates of antimicrobial consumption by the animal health sector in Bhutan could be attributable to stronger governance of antimicrobial use in Bhutan, higher levels of compliance with regulation, and better adherence to standard guidelines for antimicrobial treatment of livestock.

Patient-focused pathogen genetic counselling-has the time come?

Ensuring accordance with principles of healthcare ethics requires improved communication of pathogen genomic data. This could include educating healthcare professionals in communicating pathogen genomic information to individuals, developing ethical frameworks for reporting pathogen genomic results to individuals, responsible media reporting guidelines, and counselling for individuals ('pathogen genetic counselling').

An implementation science approach to evaluating pathogen whole genome sequencing in public health.

BACKGROUND: Pathogen whole genome sequencing (WGS) is being incorporated into public health surveillance and disease control systems worldwide and has the potential to make significant contributions to infectious disease surveillance, outbreak investigation and infection prevention and control. However, to date, there are limited data regarding (i) the optimal models for integration of genomic data into epidemiological investigations and (ii) how to quantify and evaluate public health impacts resulting from genomic epidemiological investigations. METHODS: We developed the Pathogen Genomics in Public HeAlth Surveillance Evaluation (PG-PHASE) Framework to guide examination of the use of WGS in public health surveillance and disease control. We illustrate the use of this framework with three pathogens as case studies: Listeria monocytogenes, Mycobacterium tuberculosis and SARS-CoV-2. RESULTS: The framework utilises an adaptable whole-of-system approach towards understanding how interconnected elements in the public health application of pathogen genomics contribute to public health processes and outcomes. The three phases of the PG-PHASE Framework are designed to support understanding of WGS laboratory processes, analysis, reporting and data sharing, and how genomic data are utilised in public health practice across all stages, from the decision to send an isolate or sample for sequencing to the use of sequence data in public health surveillance, investigation and decision-making. Importantly, the phases can be used separately or in conjunction, depending on the need of the evaluator. Subsequent to conducting evaluation underpinned by the framework, avenues may be developed for strategic investment or interventions to improve utilisation of whole genome sequencing. CONCLUSIONS: Comprehensive evaluation is critical to support health departments, public health laboratories and other stakeholders to successfully incorporate microbial genomics into public health practice. The PG-PHASE Framework aims to assist public health laboratories, health departments and authorities who are either considering transitioning to whole genome sequencing or intending to assess the integration of WGS in public health practice, including the capacity to detect and respond to outbreaks and associated costs, challenges and facilitators in the utilisation of microbial genomics and public health impacts.

Walking the talk: evaluating the alignment between Australian governments' stated principles for working in Aboriginal and Torres Strait Islander health contexts and health evaluation practice.

BACKGROUND: Stated principles in government policy documents serve as a set of values outlining how governments intend to work. As such, health planning principles should be reflected in health policy across the cycle of planning, implementation and evaluation. Such principles should be reflected in the process of governments commissioning and funding evaluation, and in the work of those commissioned to do evaluation on behalf of governments. METHODS: We reviewed health planning policy documents to identify principles Australian State and Territory and National governments stated as being important to the work they do within Aboriginal and Torres Strait Islander health contexts. Evaluation tenders and reports relating to Aboriginal and Torres Strait Islander health policy, programs and service for the period 1-Jan-2007 to 1-Jan-2017 were retrieved and assessed as to whether they embedded principles governments state as important. RESULTS: In Aboriginal and Torres Strait Islander health planning policy contexts, Australian governments outline shared responsibility, cultural competence, engagement, partnership, capacity building, equity, a holistic concept of health, accountability, and evidence-based as fundamental principles that will underpin the work they will do. In total, we identified 390 publicly advertised evaluation tenders, but were only able to retrieve 18 tenders and 97 reports. Despite strong rhetoric placing importance on the abovementioned principles, these were not consistently embedded in tenders released by government commissioners, nor in reports largely commissioned by governments. Principles most widely incorporated in documents were those corresponding to Closing the Gap - accountability, evidence-based and equity. Principles of holistic concept of health, capacity building, cultural competence and partnership do not appear well applied in evaluation practice. CONCLUSION: Notwithstanding the tensions and criticism of current practice that sees dominant governments policing Aboriginal and Torres Strait Islander populations and defining what principles should inform health policy and evaluation practice, this paper reveals shortcomings in current evaluation practice. Firstly, this paper reveals a lack of transparency about current practice, with only 2% of tenders and 25% of reports in the public domain. Secondly, this paper reveals that governments do not 'walk the talk', particularly when it comes to principles relating to Aboriginal participation in health.

Reflections on ethics in Indigenous health research in Chile / Reflexiones sobre la ética en la investigación de la salud de la población indígena en Chile / Reflexões sobre a ética na pesquisa em saúde indígena no Chile

Abstract The article aims to reflect on the creation of a more solid ethical research infrastructure in relation to Indigenous health research in Chile. It presents an ethical research framework that aims to support a more equitable and collaborative relationship between academics and Indigenous communities, which may lead to more relevant research and increased benefits for communities in accordance with bioethical research principles. We use international experiences to inform consideration of how ethical Indigenous health research infrastructure could be established in the Chilean context. We then present the development and adoption of guidelines for ethical Indigenous health research and orientation towards collaborative and community-led research as mechanisms that may assist in achieving these aims.

Resumen El objetivo de este artículo es reflexionar sobre la creación de una infraestructura de investigación ética más sólida en relación con la investigación de la salud de la población indígena en Chile. Se expone un marco de investigación ética que apunta a apoyar una relación más equitativa y colaborativa entre académicos y comunidades indígenas, lo que puede conducir a investigaciones más pertinentes y a mayores beneficios para las comunidades de conformidad con los principios de la investigación bioética. Se emplearon experiencias internacionales para informar sobre la forma en que se podría establecer una infraestructura de investigación de la salud de la población indígena en el contexto chileno. Luego, se presenta el desarrollo y la adopción de directrices para la investigación ética de la salud de la población indígena y la orientación hacia la investigación colaborativa y dirigida por la comunidad como mecanismos que pueden ayudar a lograr estos objetivos.

Resumo O artigo busca refletir sobre a criação de uma infraestrutura de pesquisa ética mais sólida em relação à pesquisa em saúde indígena no Chile. Apresenta-se um âmbito de pesquisa ética que visa corroborar um relacionamento mais justo e colaborativo entre a academia e as comunidades indígenas, o que pode resultar em estudos mais relevantes e no aumento dos benefícios para as comunidades, de acordo com os princípios bioéticos da pesquisa. Usamos experiências internacionais para indicar como a infraestrutura da pesquisa em saúde indígena poderia ser estabelecida no contexto chileno. Em seguida, apresentamos o desenvolvimento e adoção de diretrizes para a pesquisa ética em saúde indígena e a orientação em direção a uma pesquisa colaborativa e à comunidade como mecanismos que podem ajudar a alcançar esses objetivos.

Exploring the mental health benefits of participation in an Australian anti-racism intervention.

There is a vast body of research demonstrating the deleterious effects of racism on health. Despite this, there is limited research that considers the health benefits of anti-racism interventions. We assess the mental health effects for young people participating in an anti-racism intervention that was based on the principles of intergroup contact theory and delivered through five projects addressing specific issues and contexts. An evaluation of the intervention used a before-and-after design. The analyses reported here focus on data collected from participants who completed both pre- and post-intervention surveys (n = 246). Analyses examine the characteristics of participants, the environment for intergroup contact (equal status between ethnic groups, shared goals, co-operation and institutional support for intergroup relationships) and basic psychological needs (competence, relatedness and autonomy) as defined by Self-Determination Theory. The results suggest that the projects met the criteria for promoting positive intergroup contact. There was also evidence that participants' involvement in these projects had positive effects on their autonomy, with particular improvements among people with ethnicities other than 'Australian'. The findings suggest that anti-racism interventions can have positive mental health effects for participants. These benefits redress some of the individual-level effects of racism experiences by supporting young people to develop confidence and self-esteem.

Enhancing the use of research in health-promoting, anti-racism policy.

BACKGROUND: The Localities Embracing and Accepting Diversity (LEAD) programme was established to improve the health of ethnic minority communities through the reduction of racial discrimination. Local governments in the state of Victoria, Australia, were at the forefront of LEAD implementation in collaboration with leading state and national organisations. Key aims included expanding the available evidence regarding effective anti-racism interventions and facilitating the uptake of this evidence in organisational policies and practices. METHODS: One rural and one metropolitan local government areas were selected to participate in LEAD. Key informant interviews and discussions were conducted with individuals who had participated in LEAD implementation and members of LEAD governance structures. Data were also collected on programme processes and implementation, partnership formation and organisational assessments. RESULTS: The LEAD model demonstrated both strengths and weaknesses in terms of facilitating the use of evidence in a complex, community-based health promotion initiative. Representation of implementing, funding and advisory bodies at different levels of governance enabled the input of technical advice and guidance alongside design and implementation. The representation structure assisted in ensuring the development of a programme that was acceptable to all partners and informed by the best available evidence. Simultaneous evaluation also enhanced perceived validity of the intervention, allowed for strategy correction when necessary and supported the process of double-loop organisational learning. However, due to the model's demand for simultaneous and intensive effort by various organisations, when particular elements of the intervention were not functional, there was a considerable loss of time and resources across the partner organisations. The complexity of the model also presented a challenge in ensuring clarity regarding roles, functions and the direction of the programme. CONCLUSIONS: The example of LEAD provides guidance on mechanisms to strengthen the entry of evidence into complex community-based health promotion programmes. The paper highlights some of the strengths and weaknesses of the LEAD model and implications for practical collaboration between policymakers, implementers and researchers.

Mental health impacts of racial discrimination in Australian culturally and linguistically diverse communities: a cross-sectional survey.

BACKGROUND: Racial discrimination denies those from racial and ethnic minority backgrounds access to rights such as the ability to participate equally and freely in community and public life, equitable service provision and freedom from violence. Our study was designed to examine how people from racial and ethnic minority backgrounds in four Australian localities experience and respond to racial discrimination, as well as associated health impacts. METHODS: Data were collected from 1,139 Australians regarding types of racial discrimination experienced, settings for these incidents, response mechanisms and psychological distress as measured by the Kessler 6 (K6) Psychological Distress Scale. RESULTS: Age, education, religion, gender, visibility and rurality were all significantly associated with differences in the frequency of experiencing racial discrimination. Experiencing racial discrimination was associated with worse mental health. Mental health impacts were not associated with the type of discriminatory experience, but experiencing racial discrimination in shops and in employment and government settings was associated with being above the threshold for high or very high psychological distress. One out of twelve response mechanisms was found to be associated with lower stress following a discriminatory incident. CONCLUSIONS: Study results indicate that poorer mental health was associated with the volume of discrimination experienced, rather than the type of experience. However, the impact of experiencing discrimination in some settings was shown to be particularly associated with high or very high psychological distress. Our findings suggest that interventions designed to prevent the occurrence of racism have more potential to increase mental health in racial and ethnic minority communities than interventions that work with individuals in response to experiencing racism.

Aboriginal health promotion through addressing employment discrimination.

The Localities Embracing and Accepting Diversity (LEAD) program aimed to improve the mental health of Aboriginal Victorians by addressing racial discrimination and facilitating social and economic participation. As part of LEAD, Whittlesea Council adopted the Aboriginal Employment Pathways Strategy (AEPS) to increase Aboriginal employment and retention within the organisation. The Aboriginal Cultural Awareness Training Program was developed to build internal cultural competency and skills in recruiting and retaining Aboriginal staff. Analysis of surveys conducted before (pre; n=124) and after (post; n=107) the training program indicated a significant increase in participant understanding across all program objectives and in support of organisational policies to improve Aboriginal recruitment and retention. Participants ended the training with concrete ideas about intended changes, as well as how these changes could be supported by their supervisors and the wider organisation. Significant resources have since been allocated to implementing the AEPS over 5 years. In line with principles underpinning the National Aboriginal and Torres Strait Islander Health Plan 2013-23, particularly the focus on addressing racism as a determinant of health, this paper explores the AEPS and training program as promising approaches to health promotion through addressing barriers to Aboriginal employment. Possible implications for other large organisations are also considered.

Experiencing racism in health care: the mental health impacts for Victorian Aboriginal communities.

OBJECTIVES: To examine experiences of racism in health settings and their impact on mental health among Aboriginal Australians. DESIGN, SETTING AND PARTICIPANTS: A cross-sectional survey of experiences of racism and mental health was conducted in two metropolitan and two rural Victorian local government areas (LGAs) between 1 December 2010 and 31 October 2011. Participants included 755 Aboriginal Australians aged over 18 years who had resided in the relevant LGA for at least a year. The response rate across all LGAs was 99%. MAIN OUTCOME MEASURES: Being above or below the threshold for high or very high psychological distress on the Kessler Psychological Distress Scale. RESULTS: 221 participants reported experiences of racism in health settings in the past 12 months. The results suggested that people experiencing racism in health settings (OR, 4.49; 95% CI, 2.28-8.86) and non-health settings (OR, 2.66; 95% CI, 1.39-5.08) were more likely than people who did not experience racism to be above the threshold for high or very high psychological distress. CONCLUSIONS: Experiencing interpersonal racism in health settings is associated with increased psychological distress over and above what would be expected in other settings. This finding supports the rationale for improving cultural competency and reducing racism as a means of closing the health gap between Aboriginal and other Australians. Capitalising on this investment will require explicitly evaluating the impact of these initiatives on reducing patient experiences of racism.

The zinc finger protein ras-responsive element binding protein-1 is a coregulator of the androgen receptor: implications for the role of the Ras pathway in enhancing androgenic signaling in prostate cancer.

Androgen receptor (AR) plays an important role in normal prostate function as well as in the etiology of prostate cancer. Activation of AR is dictated by hormone binding and by interactions with coregulators. Several of these coregulators are known targets of Ras-related signals. Recent evidence suggests that Ras activation may play a causal role in the progression of prostate cancer toward a more malignant and hormone-insensitive phenotype. In the present study, we used a transcription factor-transcription factor interaction array method to identify the zinc finger protein Ras-responsive element binding protein (RREB-1) as a partner and coregulator of AR. In LNCaP prostate cancer cells, RREB-1 was found to be present in a complex with endogenous AR as determined by coimmunoprecipitation, glutathione S-transferase pull down, and immunofluorescence analyses. RREB-1 bound to the prostate-specific antigen (PSA) promoter as assessed by chromatin immunoprecipitation. Transient expression of RREB-1 down-regulated AR-mediated promoter activity and suppressed expression of PSA protein. The repressor activity of RREB-1 was significantly attenuated by cotransfection of activated Ras. Moreover, expression of the dominant-negative N-17-Ras or, alternatively, use of the MAPK kinase inhibitor PD98059 [2-(2-amino-3-methyoxyphenyl)-4H-1-benzopyran-4-one] abolished the effect of Ras in attenuating RREB-1-mediated repression. Furthermore, inhibition of RREB-1 expression by RNA interference enhanced the effect of Ras on PSA promoter activity and PSA expression. In addition, activation of the Ras pathway depleted AR from the RREB-1/AR complex. Collectively, our data for the first time identify RREB-1 as a repressor of AR and further implicate the Ras/MAPK kinase pathway as a likely antagonist of the inhibitory effects of RREB-1 on androgenic signaling.

Unraveling androgen receptor interactomes by an array-based method: discovery of proto-oncoprotein c-Rel as a negative regulator of androgen receptor.

The androgen receptor (AR) plays a key role in the development and function of male reproductive organs. Using a high-throughput transcription factor-transcription factor (TF-TF) interaction array method, we captured the AR interactomes in androgen-responsive LNCaP cells. Several known and unknown partners of AR, including AP-2, Pax 3/5 (BSAP), c-Rel, RREB-1, LIII BP, and NPAS2 were identified. We investigated one unreported AR-associated transcription factor, the proto-oncoprotein c-Rel, in detail. C-Rel belongs to the NF-kB/Rel families and is persistently active in a number of diseases, including cancer. The presence of c-Rel transcript, protein, and its in vitro and in vivo association with AR was determined. Co-localization of c-Rel with AR both in cytoplasm and nucleus was confirmed by indirect immunofluorescence analysis. Chromatin immunoprecipitation data indicated that c-Rel, like AR, is a part of the nucleoprotein complex regulating the androgen-responsive prostate-specific antigen (PSA) promoter. Overexpression of c-Rel downregulated the promoter activity of both PSA and GRE4-TATA-Luc plasmids in LNCaP and COS cells. Analysis of AR and c-Rel protein levels indicated that the promoter downregulation was not due to reciprocal decrease in the amounts of AR or c-Rel. In summary, we have identified several new partners of AR by using the TF-TF array method and have provided the first evidence of a functional role for c-Rel in androgen-responsive human prostate cancer cells.

Development of a "reverse capture" autoantibody microarray for studies of antigen-autoantibody profiling.

Diagnosing cancers based on serum profiling is a particularly attractive concept. However, the technical challenges to analysis of the serum proteome arise from the dynamic range of protein amounts. Cancer sera contain antibodies that react with a unique group of autologous cellular antigens, which affords a dramatic amplification of signal in the form of antibodies relative to the amount of the corresponding antigens. The serum autoantibody repertoire from cancer patients might, therefore, be exploited for antigen-antibody profiling. To date, studies of antigen-antibody reactivity using microarrays have relied on recombinant proteins or synthetic peptides as arrayed features. However, recombinant proteins and/or synthetic peptides may fail to accurately detect autoantibody binding due to the lack of proper PTMs. Here we describe the development and use of a "reverse capture" autoantibody microarray. Our "reverse capture" autoantibody microarray is based on the dual-antibody sandwich immunoassay platform of ELISA, which allows the antigens to be immobilized in their native configuration. As "proof-of-principle", we demonstrate its use for antigen-autoantibody profiling with sera from patients with prostate cancer and benign prostate hyperplasia.

Chromatofocusing fractionation and two-dimensional difference gel electrophoresis for low abundance serum proteins.

The technical challenge to analysis of the serum proteome is that the serum proteins are present at unequal concentrations. A few are so dominant, such as serum albumin and immunoglobulins, that they mask detection of other proteins. Because of these high abundance proteins, current technologies, while theoretically capable of analyzing protein amounts spanning four orders of magnitude, are only able to analyze proteins ranging over two orders of magnitude and cannot analyze the lower abundance proteins that may be the next biomarkers and drug targets. To facilitate the identification of low abundance proteins, we fractionated serum samples from patients with prostate cancer and patients with benign prostate hyperplasia using anion displacement liquid chromatofocusing chromatography, which separates proteins by a pH gradient and a positively charged column. Differential expression of proteins from fractions was then determined and identified by IEF gels and 2-D DIGE. Results demonstrate improved resolution of proteins within the chosen pH gradient when compared to the unfractionated samples. Several proteins that were differentially expressed in serum from patients with prostate cancer were identified in the fractionated serum. Three of these proteins, squamous cell carcinoma antigen 1 (SCCA1), calgranulin B, and haptoglobin-related protein, are present in the serum at levels below the classical protein level of mg/mL. SCCA1 is normally expressed in serum at ng/mL levels, and calgranulin B is an intracellular protein. Our results demonstrate that the use of anion displacement liquid chromatofocusing chromatography may reduce the complexity of the serum proteome by separating proteins into distinct pH ranges, and facilitate the identification of low abundance proteins.