Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (range) of 4·3 (1·9-9·7) months of panobinostat. In responders, T-lymphocyte histone acetylation increased after both three cycles (P < 0·05) and six cycles (P < 0·01) of panobinostat when compared to baseline, with no differences in non-responders. The reduction in the proportion of CD127+ CD8+ T cells and CD4:CD8 ratio was significantly greater, after three and six cycles of panobinostat compared to pre-transplant, in non-responders when compared to responders. Whole marrow RNA-seq revealed widespread transcriptional changes only in responders with baseline differences in genes involved in ribosome biogenesis, oxidative phosphorylation and metabolic pathways. This study confirmed the efficacy of panobinostat as a single agent in multiple myeloma and established acetylation of lymphocyte histones, modulation of immune subsets and transcriptional changes as pharmacodynamic biomarkers of clinical benefit.

Australia in 2030: what is our path to health for all?

CHAPTER 1: HOW AUSTRALIA IMPROVED HEALTH EQUITY THROUGH ACTION ON THE SOCIAL DETERMINANTS OF HEALTH: Do not think that the social determinants of health equity are old hat. In reality, Australia is very far away from addressing the societal level drivers of health inequity. There is little progressive policy that touches on the conditions of daily life that matter for health, and action to redress inequities in power, money and resources is almost non-existent. In this chapter we ask you to pause this reality and come on a fantastic journey where we envisage how COVID-19 was a great disruptor and accelerator of positive progressive action. We offer glimmers of what life could be like if there was committed and real policy action on the social determinants of health equity. It is vital that the health sector assists in convening the multisectoral stakeholders necessary to turn this fantasy into reality. CHAPTER 2: ABORIGINAL AND TORRES STRAIT ISLANDER CONNECTION TO CULTURE: BUILDING STRONGER INDIVIDUAL AND COLLECTIVE WELLBEING: Aboriginal and Torres Strait Islander peoples have long maintained that culture (ie, practising, maintaining and reclaiming it) is vital to good health and wellbeing. However, this knowledge and understanding has been dismissed or described as anecdotal or intangible by Western research methods and science. As a result, Aboriginal and Torres Strait Islander culture is a poorly acknowledged determinant of health and wellbeing, despite its significant role in shaping individuals, communities and societies. By extension, the cultural determinants of health have been poorly defined until recently. However, an increasing amount of scientific evidence supports what Aboriginal and Torres Strait Islander people have always said - that strong culture plays a significant and positive role in improved health and wellbeing. Owing to known gaps in knowledge, we aim to define the cultural determinants of health and describe their relationship with the social determinants of health, to provide a full understanding of Aboriginal and Torres Strait Islander wellbeing. We provide examples of evidence on cultural determinants of health and links to improved Aboriginal and Torres Strait Islander health and wellbeing. We also discuss future research directions that will enable a deeper understanding of the cultural determinants of health for Aboriginal and Torres Strait Islander people. CHAPTER 3: PHYSICAL DETERMINANTS OF HEALTH: HEALTHY, LIVEABLE AND SUSTAINABLE COMMUNITIES: Good city planning is essential for protecting and improving human and planetary health. Until recently, however, collaboration between city planners and the public health sector has languished. We review the evidence on the health benefits of good city planning and propose an agenda for public health advocacy relating to health-promoting city planning for all by 2030. Over the next 10 years, there is an urgent need for public health leaders to collaborate with city planners - to advocate for evidence-informed policy, and to evaluate the health effects of city planning efforts. Importantly, we need integrated planning across and between all levels of government and sectors, to create healthy, liveable and sustainable cities for all. CHAPTER 4: HEALTH PROMOTION IN THE ANTHROPOCENE: THE ECOLOGICAL DETERMINANTS OF HEALTH: Human health is inextricably linked to the health of the natural environment. In this chapter, we focus on ecological determinants of health, including the urgent and critical threats to the natural environment, and opportunities for health promotion arising from the human health co-benefits of actions to protect the health of the planet. We characterise ecological determinants in the Anthropocene and provide a sobering snapshot of planetary health science, particularly the momentous climate change health impacts in Australia. We highlight Australia's position as a major fossil fuel producer and exporter, and a country lacking cohesive and timely emissions reduction policy. We offer a roadmap for action, with four priority directions, and point to a scaffold of guiding approaches - planetary health, Indigenous people's knowledge systems, ecological economics, health co-benefits and climate-resilient development. Our situation requires a paradigm shift, and this demands a recalibration of health promotion education, research and practice in Australia over the coming decade. CHAPTER 5: DISRUPTING THE COMMERCIAL DETERMINANTS OF HEALTH: Our vision for 2030 is an Australian economy that promotes optimal human and planetary health for current and future generations. To achieve this, current patterns of corporate practice and consumption of harmful commodities and services need to change. In this chapter, we suggest ways forward for Australia, focusing on pragmatic actions that can be taken now to redress the power imbalances between corporations and Australian governments and citizens. We begin by exploring how the terms of health policy making must change to protect it from conflicted commercial interests. We also examine how marketing unhealthy products and services can be more effectively regulated, and how healthier business practices can be incentivised. Finally, we make recommendations on how various public health stakeholders can hold corporations to account, to ensure that people come before profits in a healthy and prosperous future Australia. CHAPTER 6: DIGITAL DETERMINANTS OF HEALTH: THE DIGITAL TRANSFORMATION: We live in an age of rapid and exponential technological change. Extraordinary digital advancements and the fusion of technologies, such as artificial intelligence, robotics, the Internet of Things and quantum computing constitute what is often referred to as the digital revolution or the Fourth Industrial Revolution (Industry 4.0). Reflections on the future of public health and health promotion require thorough consideration of the role of digital technologies and the systems they influence. Just how the digital revolution will unfold is unknown, but it is clear that advancements and integrations of technologies will fundamentally influence our health and wellbeing in the future. The public health response must be proactive, involving many stakeholders, and thoughtfully considered to ensure equitable and ethical applications and use. CHAPTER 7: GOVERNANCE FOR HEALTH AND EQUITY: A VISION FOR OUR FUTURE: Coronavirus disease 2019 has caused many people and communities to take stock on Australia's direction in relation to health, community, jobs, environmental sustainability, income and wealth. A desire for change is in the air. This chapter imagines how changes in the way we govern our lives and what we value as a society could solve many of the issues Australia is facing - most pressingly, the climate crisis and growing economic and health inequities. We present an imagined future for 2030 where governance structures are designed to ensure transparent and fair behaviour from those in power and to increase the involvement of citizens in these decisions, including a constitutional voice for Indigenous peoples. We imagine that these changes were made by measuring social progress in new ways, ensuring taxation for public good, enshrining human rights (including to health) in legislation, and protecting and encouraging an independent media. Measures to overcome the climate crisis were adopted and democratic processes introduced in the provision of housing, education and community development.

'Calibrating to scale: a framework for humanitarian health organizations to anticipate, prevent, prepare for and manage climate-related health risks'.

Climate Change is adversely affecting health by increasing human vulnerability and exposure to climate-related stresses. Climate change impacts human health both directly and indirectly, through extreme weather events, changing distribution of health risks, increased risks of undernutrition, population displacement, and greater risks of injuries, disease, and death (Ebi, K., Campbell-Lendrum, D., & Wyns, A. The 1. 5 health report. WHO. 2018). This risk amplification is likely to increase the need for humanitarian support. Recent projections indicate that under a business as usual scenario of sustained greenhouse gas emissions, climate change could double the demand for humanitarian assistance by 2050 (World Health Organization. Operational Framework for building climateresilient health systems. WHO. 2015). Humanitarian assistance is currently not meeting the existing needs, therefore, any additional burden is likely to be highly challenging.Global health advocates, researchers, and policymakers are calling for urgent action on climate change, yet there is little clarity on what that action practically entails for humanitarian organizations. While some humanitarian organizations may consider themselves well designed to respond, climate change as a transversal threat requires the incorporation of a resilience approach to humanitarian action and policy responses.By bringing together authors from two historically disparate fields - climate change and health, and humanitarian assistance - this paper aims to increase the capacity of humanitarian organizations to protect health in an unstable climate by presenting an adapted framework. We adapted the WHO operational framework for climate-resilient health systems for humanitarian organizations and present concrete case studies to demonstrate how the framework can be implemented. Rather than suggest a re-design of humanitarian operations we recommend the application of a climate-lens to humanitarian activities, or what is also referred to as mainstreaming climate and health concerns into policies and programs. The framework serves as a starting point to encourage further dialogue, and to strengthen collaboration within, between, and beyond humanitarian organizations.

The health impacts of climate-related migration.

BACKGROUND: Changes in climate, in conjunction with other drivers of mobility, shape human migration. While there is an increasing focus on the adaptive potential of migration, the health impacts of climate-related migration, including planned relocation and forced displacement, have not been thoroughly examined. The Intergovernmental Panel on Climate Change stated that migration is currently, and will increasingly be, influenced by environmental degradation and climate change, and that it needs to be addressed in a focused and coordinated manner. DISCUSSION: This paper examines the links between climate change, migration, and health, considering diverse migration responses, including immobility, forced displacement and planned migration, as well as the associated health risks and opportunities in different contexts. Using case studies, the paper illustrates strategies to reduce the health risks associated with climate change-related migration. CONCLUSION: While there is an increasing body of research examining the climate change-migration nexus, a dual approach is now required. This approach must include debate and further research regarding the health consequences and responses associated with climate migration as well as immediate strengthening of health systems to make them both climate resilient and migrant inclusive.

A 'Healthy Islands' framework for climate change in the Pacific.

Small Pacific Island countries (PICs) are among the most vulnerable countries in the world to the anticipated detrimental health effects of climate change. The assessment of health vulnerabilities and planning adaptation strategies to minimize the impacts of climate change on health tests traditional health governance structures and depends on strong linkages and partnerships between actors involved in these vital processes. This article reviews the actors, processes and contexts of the climate change and health vulnerability assessment and adaptation planning project carried out by the World Health Organization and health sector partners in three island countries in the Micronesian region of the Pacific throughout 2010 and 2011: Federated States of Micronesia, Marshall Islands and Palau. Despite their shared history and cultural characteristics, the findings and implications of this article are considered to have substantial relevance and potential application to other PICs. The modified 'Healthy Islands' framework for climate change and health adaptation presented in this article draws upon real-world experience and governance theory from both the health and climate change literature and, for the first time, places health systems adaptation within the vision for 'Healthy Islands' in the Pacific region.

Mental health impacts from repeated climate disasters: an australian longitudinal analysis.

Background: Extreme weather events are becoming more frequent and intense under changing climatic conditions. Whilst there is substantial evidence that exposure to a single weather related disaster is detrimental for mental health, few studies have explored how exposure to multiple disasters impacts mental health. Methods: We utilised 11 waves of data from the Household, Income and Labour Dynamics in Australia (HILDA) Survey, yielding a sample of 16,629 observations from 2003 individuals. Fixed effects linear regression analysis was used to estimate the impact of experiencing multiple disasters on mental health. We tested for effect modification on this association by sex, rurality, employment and presence of a long-term health condition. Findings: Exposure to multiple disasters was associated with a relative decrease in MHI-5 score compared to baseline by -1.8 points (95% CI -3.4, -0.3), whereas exposure to a single disaster was not associated with a decline in mental health scores. There was evidence of effect modification by employment status. Unemployed individuals had evidence of moderate reduction in MHI-5 scores when exposed to a single disaster (-4.3, 95% CI -7.0, -1.5). Interpretation: Findings suggest that repeat exposure to disasters is associated with worsening mental health outcomes. As extreme weather events increase, these findings highlight the need for greater attention on climate change action, and mental health interventions targeting impacted populations. Funding: Suicide Prevention Australia.

Using social capital to address youth sexual and reproductive health and rights in disaster preparedness and response: A qualitative study highlighting the strengths of Pacific community organisations and networks.

In the Pacific region, youth sexual and reproductive health and rights (SRHR) are strongly influenced by sociocultural and structural factors, which limit access to SRHR information and services for youth. As climate-related disasters intensify in the Pacific, existing challenges to youth SRHR may increase the risk of worse SRHR experiences and outcomes for youth before, during and after disasters. Community-based models of SRHR service provision models increase accessibility for youth in non-disaster times, but there is limited evidence of how community organisations address youth SRHR in disaster contexts. We conducted qualitative interviews with 16 participants from community organisations and networks in Fiji, Vanuatu, and Tonga following the 2020 Tropical Cyclone (TC) Harold. Guided by the Recovery Capitals Framework (natural, built, political, cultural, human, social, and financial capitals), we explored how community organisations addressed challenges to facilitate access to youth SRHR information and services. Social capital in the form of peer networks and virtual safe spaces was used to navigate challenges in political, financial, and natural capitals. Existing relationships and trusted collaborations were crucial to address cultural taboos related to youth SRHR. Previous experiences of disasters and knowledge of contexts enabled participants to provide sustainable solutions to identified SRHR needs. The work conducted by community organisations and networks pre-disaster made it easier to identify and address youth SRHR risks following disasters. Our research offers a unique perspective into how social capitals were used to mitigate challenges to youth SRHR across natural, human, financial, cultural, built, and political capitals. Findings offer important opportunities to invest in existing community strengths, for transformative action to advance the SRHR of Pacific youth.

Changing climates, compounding challenges: a participatory study on how disasters affect the sexual and reproductive health and rights of young people in Fiji.

Pacific youth are at the forefront of the climate crisis, which has important implications for their health and rights. Youth in Fiji currently bear a disproportionate burden of poor experiences and outcomes related to their sexual and reproductive health and rights (SRHR). There is limited information about how the increasing climate impacts may affect their SRHR, and what the implications may be for climate action and disaster risk reduction. We aimed to explore the experiences of 21 Fijian youth in fulfilling their SRHR when living through multiple natural hazards. We conducted 2 workshops and 18 individual semistructured interviews using visual and storytelling methods. Irrespective of the type of hazard or context of disasters, participants identified limited agency as the main challenge that increased SRHR risks. Through reflexive thematic analysis, we identified four themes centred around 'youth SRHR agency'; (1) information and knowledge, (2) community and belonging, (3) needs and resources, and (4) collective risks. These themes encompassed multiple factors that limited youth agency and increased their SRHR risks. Participants highlighted how existing challenges to their SRHR, such as access to SRHR information being controlled by community gatekeepers, and discrimination of sexual and gender diverse youth, were exacerbated in disasters. In disaster contexts, immediate priorities such as water, food and financial insecurity increased risks of transactional early marriage and transactional sex to access these resources. Daily SRHR risks related to normalisation of sexual and gender-based violence and taboos limited youth agency and influenced their perceptions of disasters and SRHR risks. Findings offer important insights into factors that limited youth SRHR agency before, during and after disasters. We underscore the urgency for addressing existing social and health inequities in climate and disaster governance. We highlight four key implications for reducing youth SRHR risks through whole-of-society approaches at multiple (sociocultural, institutional, governance) levels.

Climate change adaptation: where does global health fit in the agenda?

Human-induced climate change will affect the lives of most populations in the next decade and beyond. It will have greatest, and generally earliest, impact on the poorest and most disadvantaged populations on the planet. Changes in climatic conditions and increases in weather variability affect human wellbeing, safety, health and survival in many ways. Some impacts are direct-acting and immediate, such as impaired food yields and storm surges. Other health effects are less immediate and typically occur via more complex causal pathways that involve a range of underlying social conditions and sectors such as water and sanitation, agriculture and urban planning. Climate change adaptation is receiving much attention given the inevitability of climate change and its effects, particularly in developing contexts, where the effects of climate change will be experienced most strongly and the response mechanisms are weakest. Financial support towards adaptation activities from various actors including the World Bank, the European Union and the United Nations is increasing substantially. With this new global impetus and funding for adaptation action come challenges such as the importance of developing adaptation activities on a sound understanding of baseline community needs and vulnerabilities, and how these may alter with changes in climate. The global health community is paying heed to the strengthening focus on adaptation, albeit in a slow and unstructured manner. The aim of this paper is to provide an overview of adaptation and its relevance to global health, and highlight the opportunities to improve health and reduce health inequities via the new and additional funding that is available for climate change adaptation activities.

Taking globally consistent health impact projections to the next level.

Despite intensive research activity within the area of climate change, substantial knowledge gaps still remain regarding the potential future impacts of climate change on human health. A key shortcoming in the scientific understanding of these impacts is the lack of studies that are conducted in a coordinated and consistent fashion, producing directly comparable outputs. This Viewpoint discusses and exemplifies a bottom-up initiative generating new research evidence in a more coordinated and consistent way compared with previous efforts. It describes one of the largest model comparisons of projected health impacts due to climate change, so far. Yet, the included studies constitute only a selection of health impacts in a variety of geographical locations, and are therefore not a comprehensive assessment of all possible impact pathways and potential consequences. The new findings of these studies shed light on the complex and multidirectional impacts of climate change on health, where impacts can be both adverse or beneficial. However, the adverse impacts dominate overall, especially in the scenarios with more greenhouse gas forcing. Overall, the future population at risk of disease and incidence rates are predicted to increase substantially, but in a highly location-specific and disease-specific fashion. Greenhouse gas emission mitigation can substantially reduce risk and resultant morbidity and mortality. The potential positive impact of adaptation has not been included in the models applied, and thus remains a major source of uncertainty. This bottom-up initiative lays out a research strategy that brings more meaningful research outputs and calls for greater coordination of research initiatives across the health community.

Health Synergies across International Sustainability and Development Agendas: Pathways to Strengthen National Action.

Since 2015 there has been a surge of international agendas to address a range of global challenges: climate change (Paris Agreement), sustainable development (Agenda 2030), disaster risk reduction (Sendai Framework) and sustainable urban transformation (New Urban Agenda). Health is relevant to all of these agendas. Policymakers must now translate these global agendas into national level policies to implement the agreed goals in a coherent manner. However, approaches to synergise health activities within and across these agendas are needed, in order to achieve better coherence and maximise national level implementation. This research evaluated the framing of human health within these agendas. A content analysis of the agendas was conducted. Findings indicate (i) the importance of increased awareness of health systems strengthening as a helpful framework to guide the integration of health issues across the agendas, (ii) only two health themes had synergies across the agendas, (iii) the lack of a governance mechanism to support the integration of these four agendas to enable national (and sub-national) governments to more feasibly implement their ambitions, and (iv) the vital component of health leadership. Finally, planetary health is a relevant and timely concept that can support the urgent shift to a healthy planet and people.

Interactions between two existential threats: COVID-19 and climate change.

The COVID-19 pandemic and climate change are complex existential threats, unpredictable in many ways and unprecedented in modern times. There are parallels between the scale and scope of their impacts and responses. Understanding shared drivers, coupled vulnerabilities, and criteria for effective responses will help societies worldwide prepare for the simultaneous threats of climate change and future pandemics. We summarize some shared characteristics of COVID-19 and climate change impacts and interventions and discuss key policy implications and recommendations.

The effects on public health of climate change adaptation responses: a systematic review of evidence from low- and middle-income countries.

Climate change adaptation responses are being developed and delivered in many parts of the world in the absence of detailed knowledge of their effects on public health. Here we present the results of a systematic review of peer-reviewed literature reporting the effects on health of climate change adaptation responses in low- and middle-income countries (LMICs). The review used the 'Global Adaptation Mapping Initiative' database (comprising 1682 publications related to climate change adaptation responses) that was constructed through systematic literature searches in Scopus, Web of Science and Google Scholar (2013-2020). For this study, further screening was performed to identify studies from LMICs reporting the effects on human health of climate change adaptation responses. Studies were categorised by study design and data were extracted on geographic region, population under investigation, type of adaptation response and reported health effects. The review identified 99 studies (1117 reported outcomes), reporting evidence from 66 LMICs. Only two studies were ex ante formal evaluations of climate change adaptation responses. Papers reported adaptation responses related to flooding, rainfall, drought and extreme heat, predominantly through behaviour change, and infrastructural and technological improvements. Reported (direct and intermediate) health outcomes included reduction in infectious disease incidence, improved access to water/sanitation and improved food security. All-cause mortality was rarely reported, and no papers were identified reporting on maternal and child health. Reported maladaptations were predominantly related to widening of inequalities and unforeseen co-harms. Reporting and publication-bias seems likely with only 3.5% of all 1117 health outcomes reported to be negative. Our review identified some evidence that climate change adaptation responses may have benefits for human health but the overall paucity of evidence is concerning and represents a major missed opportunity for learning. There is an urgent need for greater focus on the funding, design, evaluation and standardised reporting of the effects on health of climate change adaptation responses to enable evidence-based policy action.

Pathways to sex-work in Nagaland, India: implications for HIV prevention and community mobilisation.

There are an estimated 1800-3500 sex-workers in Dimapur, the commercial capital of Nagaland, which is the second-highest HIV prevalence state in India. The HIV prevalence among these sex-workers has increased from 4.4% in 2004 to 16.4% in 2006, highlighting their vulnerability. The aim of this study was to contribute to understanding of the pathways to sex-work for women in Nagaland in order to inform the development of effective HIV prevention strategies. A convenient sample of 220 female sex-workers completed a cross-sectional survey, and 30 female sex-workers participated in semi-structured in-depth interviews during mid 2007. Participants were asked about their life situation at the time of initial engagement in sex-work and circumstances of the first occasion of sex-work. The four main pathways into sex-work were identified as: (1) to obtain money to meet basic needs for self and family (45% of survey and 43% of interview participants); (2) to obtain money to purchase drugs or alcohol (15% of survey and 27% of interview participants); (3) being coerced, tricked or forced into sex-work (13% of survey and 30% of interview participants); and (4) for pleasure (12% of survey and no interview participants). Women from each of these pathways were significantly different from each other in relation to a range of socio-cultural variables (e.g., ethnicity, marital status and education), and HIV risk factors (e.g., drug and alcohol use, age of sexual debut and HIV awareness). This diversity has implications for HIV prevention strategies, including the willingness and capacity of sex-workers to mobilise as a community and NGO capacity to ensure that the interests of all sex-workers are adequately captured and represented.

A Meta-Synthesis of Policy Recommendations Regarding Human Mobility in the Context of Climate Change.

Changing mobility patterns combined with changes in the climate present challenges and opportunities for global health, requiring effective, relevant, and humane policy responses. This study used data from a systematic literature review that examined the intersection between climate change, migration, and health. The study aimed to synthesize policy recommendations in the peer-reviewed literature, regarding this type of environmental migration with respect to health, to strengthen the evidence-base. Systematic searches were conducted in four academic databases (PubMed, Ovid Medline, Global Health and Scopus) and Google Scholar for empirical studies published between 1990-2020 that used any study design to investigate migration and health in the context of climate change. Studies underwent a two-stage protocol-based screening process and eligible studies were appraised for quality using a standardized mixed-methods tool. From the initial 2425 hits, 68 articles were appraised for quality and included in the synthesis. Among the policy recommendations, six themes were discernible: (1) avoid the universal promotion of migration as an adaptive response to climate risk; (2) preserve cultural and social ties of mobile populations; (3) enable the participation of migrants in decision-making in sites of relocation and resettlement; (4) strengthen health systems and reduce barriers for migrant access to health care; (5) support and promote optimization of social determinants of migrant health; (6) integrate health into loss and damage assessments related to climate change, and consider immobile and trapped populations. The results call for transformative policies that support the health and wellbeing of people engaging in or affected by mobility responses, including those whose migration decisions and experiences are influenced by climate change, and to establish and develop inclusive migrant healthcare.

Using Implementation Science For Health Adaptation: Opportunities For Pacific Island Countries.

The health risks of a changing climate are immediate and multifaceted. Policies, plans, and programs to reduce climate-related health impacts exist, but multiple barriers hinder the uptake of these strategies, and information remains limited on the factors affecting implementation. Implementation science-a discipline focused on systematically examining the gap between knowledge and action-can address questions related to implementation and help the health sector scale up successful adaptation measures in response to climate change. Implementation science, in the context of a changing climate, can guide decision makers in introducing and prioritizing potential health adaptation and disaster risk management solutions, advancing sustainability initiatives, and evaluating and improving intervention strategies. In this article we highlight examples from Pacific Island countries and outline approaches based on implementation science to enhance the capacity of health systems to anticipate, prepare for, respond to, and recover from climate-related exposures.