METHODS: In this analysis, we obtained data from individuals in 25 high-income, middle-income, and low-income countries from the Prospective Urban Rural Epidemiological (PURE) study (175 660 participants). In the PURE study, individuals aged 35-70 years who intended to continue living in their current home for a further 4 years were invited to complete a questionnaire on activity limitations. Participant follow-up was planned once every 3 years either by telephone or in person. The activity limitation screen consisted of questions on self-reported difficulty with walking, grasping, bending, seeing close, seeing far, speaking, hearing, and use of assistive devices (gait, vision, and hearing aids). We estimated crude prevalence of self-reported activity limitations and use of assistive devices, and prevalence standardised by age and sex. We used logistic regression to additionally adjust prevalence for education and socioeconomic factors and to estimate the probability of activity limitations and assistive devices by age, sex, and country income. We used Cox frailty models to evaluate the association between each activity limitation with mortality and clinical events (cardiovascular disease, heart failure, pneumonia, falls, and cancer). The PURE study is registered with ClinicalTrials.gov, NCT03225586.

FINDINGS: Between Jan 12, 2001, and May 6, 2019, 175 584 individuals completed at least one question on the activity limitation questionnaire (mean age 50·6 years [SD 9·8]; 103 625 [59%] women). Of the individuals who completed all questions, mean follow-up was 10·7 years (SD 4·4). The most common self-reported activity limitations were difficulty with bending (23 921 [13·6%] of 175 515 participants), seeing close (22 532 [13·4%] of 167 801 participants), and walking (22 805 [13·0%] of 175 554 participants); prevalence of limitations was higher with older age and among women. The prevalence of all limitations standardised by age and sex, with the exception of hearing, was highest in low-income countries and middle-income countries, and this remained consistent after adjustment for socioeconomic factors. The use of gait, visual, and hearing aids was lowest in low-income countries and middle-income countries, particularly among women. The prevalence of seeing close limitation was four times higher (6257 [16·5%] of 37 926 participants vs 717 [4·0%] of 18 039 participants) and the prevalence of seeing far limitation was five times higher (4003 [10·6%] of 37 923 participants vs 391 [2·2%] of 18 038 participants) in low-income countries than in high-income countries, but the prevalence of glasses use in low-income countries was half that in high-income countries. Walking limitation was most strongly associated with mortality (adjusted hazard ratio 1·32 [95% CI 1·25-1·39]) and most consistently associated with other clinical events, with other notable associations observed between seeing far limitation and mortality, grasping limitation and cardiovascular disease, bending limitation and falls, and between speaking limitation and stroke.

INTERPRETATION: The global prevalence of activity limitations is substantially higher in women than men and in low-income countries and middle-income countries compared with high-income countries, coupled with a much lower use of gait, visual, and hearing aids. Strategies are needed to prevent and mitigate activity limitations globally, with particular emphasis on low-income countries and women.

THE RISING HEALTH TOLL OF A CHANGING CLIMATE: In 2023, the world saw the highest global temperatures in over 100 000 years, and heat records were broken in all continents through 2022. Adults older than 65 years and infants younger than 1 year, for whom extreme heat can be particularly life-threatening, are now exposed to twice as many heatwave days as they would have experienced in 1986–2005 (indicator 1.1.2). Harnessing the rapidly advancing science of detection and attribution, new analysis shows that over 60% of the days that reached health-threatening high temperatures in 2020 were made more than twice as likely to occur due to anthropogenic climate change (indicator 1.1.5); and heat-related deaths of people older than 65 years increased by 85% compared with 1990–2000, substantially higher than the 38% increase that would have been expected had temperatures not changed (indicator 1.1.5). Simultaneously, climate change is damaging the natural and human systems on which people rely for good health. The global land area affected by extreme drought increased from 18% in 1951–60 to 47% in 2013–22 (indicator 1.2.2), jeopardising water security, sanitation, and food production. A higher frequency of heatwaves and droughts in 2021 was associated with 127 million more people experiencing moderate or severe food insecurity compared with 1981–2010 (indicator 1.4), putting millions of people at risk of malnutrition and potentially irreversible health effects. The changing climatic conditions are also putting more populations at risk of life-threatening infectious diseases, such as dengue, malaria, vibriosis, and West Nile virus (indicator 1.3). Compounding these direct health impacts, the economic losses associated with global heating increasingly harm livelihoods, limit resilience, and restrict the funds available to tackle climate change. Economic losses from extreme weather events increased by 23% between 2010–14 and 2018–22, amounting to US$264 billion in 2022 alone (indicator 4.1.1), whereas heat exposure led to global potential income losses worth $863 billion (indicators 1.1.4 and 4.1.3). Labour capacity loss resulting from heat exposure affected low and medium Human Development Index (HDI) countries the most, exacerbating global inequities, with potential income losses equivalent to 6·1% and 3·8% of their gross domestic product (GDP), respectively (indicator 4.1.3). The multiple and simultaneously rising risks of climate change are amplifying global health inequities and threatening the very foundations of human health. Health systems are increasingly strained, and 27% of surveyed cities declared concerns over their health systems being overwhelmed by the impacts of climate change (indicator 2.1.3). Often due to scarce financial resources and low technical and human capacity, the countries most vulnerable to climate impacts also face the most challenges in achieving adaptation progress, reflecting the human risks of an unjust transition. Only 44% of low HDI countries and 54% of medium HDI countries reported high implementation of health emergency management capacities in 2022, compared with 85% of very high HDI countries (indicator 2.2.5). Additionally, low and medium HDI countries had the highest proportion of cities not intending to undertake a climate change risk assessment in 2021 (12%; indicator 2.1.3). These inequalities are aggravated by the persistent failure of the wealthiest countries to deliver the promised modest annual sum of $100 billion to support climate action in those countries defined as developing within the UN Framework Convention on Climate Change. Consequently, those countries that have historically contributed the least to climate change are bearing the brunt of its health impacts—both a reflection and a direct consequence of the structural inequities that lie within the root causes of climate change.

THE HUMAN COSTS OF PERSISTENT INACTION: The growing threats experienced to date are early signs and symptoms of what a rapidly changing climate could mean for the health of the world’s populations. With 1337 tonnes of CO2 emitted each second, each moment of delay worsens the risks to people’s health and survival. In this year’s report, new projections reveal the dangers of further delays in action, with every tracked health dimension worsening as the climate changes. If global mean temperature continues to rise to just under 2°C, annual heat-related deaths are projected to increase by 370% by midcentury, assuming no substantial progress on adaptation (indicator 1.1.5). Under such a scenario, heat-related labour loss is projected to increase by 50% (indicator 1.1.4), and heatwaves alone could lead to 524·9 million additional people experiencing moderate-to-severe food insecurity by 2041–60, aggravating the global risk of malnutrition. Life-threatening infectious diseases are also projected to spread further, with the length of coastline suitable for Vibrio pathogens expanding by 17–25%, and the transmission potential for dengue increasing by 36–37% by midcentury. As risks rise, so will the costs and challenges of adaptation. These estimates provide some indication of what the future could hold. However, poor accounting for non-linear responses, tipping points, and cascading and synergistic interactions could render these projections conservative, disproportionately increasing the threat to the health of populations worldwide.

A WORLD ACCELERATING IN THE WRONG DIRECTION: The health risks of a 2°C hotter world underscore the health imperative of accelerating climate change action. With limits to adaptation drawing closer, ambitious mitigation is paramount to keep the magnitude of health hazards within the limits of the capacity of health systems to adapt. Yet years of scientific warnings of the threat to people’s lives have been met with grossly insufficient action, and policies to date have put the world on track to almost 3°C of heating. The 2022 Lancet Countdown report highlighted the opportunity to accelerate the transition away from health-harming fossil fuels in response to the global energy crisis. However, data this year show a world that is often moving in the wrong direction. Energy-related CO2 emissions increased by 0·9% to a record 36·8 Gt in 2022 (indicator 3.1.1), and still only 9·5% of global electricity comes from modern renewables (mainly solar and wind energy), despite their costs falling below that of fossil fuels. Concerningly, driven partly by record profits, oil and gas companies are further reducing their compliance with the Paris Agreement: the strategies of the world’s 20 largest oil and gas companies as of early 2023 will result in emissions surpassing levels consistent with the Paris Agreement goals by 173% in 2040—an increase of 61% from 2022 (indicator 4.2.6). Rather than pursuing accelerated development of renewable energy, fossil fuel companies allocated only 4% of their capital investment to renewables in 2022. Meanwhile, global fossil fuel investment increased by 10% in 2022, reaching over $1 trillion (indicator 4.2.1). The expansion of oil and gas extractive activities has been supported through both private and public financial flows. Across 2017–21, the 40 banks that lend most to the fossil fuel sector collectively invested $489 billion annually in fossil fuels (annual average), with 52% increasing their lending from 2010–16. Simultaneously, in 2020, 78% of the countries assessed, responsible for 93% of all global CO2 emissions, still provided net direct fossil fuels subsidies totalling $305 billion, further hindering fossil fuel phase-out (indicator 4.2.4). Without a rapid response to course correct, the persistent use and expansion of fossil fuels will ensure an increasingly inequitable future that threatens the lives of billions of people alive today.

THE OPPORTUNITY TO DELIVER A HEALTHY FUTURE FOR ALL: Despite the challenges, data also expose the transformative health benefits that could come from the transition to a zero-carbon future, with health professionals playing a crucial role in ensuring these gains are maximised. Globally, 775 million people still live without electricity, and close to 1 billion people are still served by health-care facilities without reliable energy. With structural global inequities in the development of, access to, and use of clean energy, only 2·3% of electricity in low HDI countries comes from modern renewables (against 11% in very high HDI countries), and 92% of households in low HDI countries still rely on biomass fuels to meet their energy needs (against 7·5% in very high HDI countries; indicators 3.1.1 and 3.1.2). In this context, the transition to renewables can enable access to decentralised clean energy and, coupled with interventions to increase energy efficiency, can reduce energy poverty and power high quality health-supportive services. By reducing the burning of dirty fuels (including fossil fuels and biomass), such interventions could help avoid a large proportion of the 1·9 million deaths that occur annually from dirty-fuel-derived, outdoor, airborne, fine particulate matter pollution (PM2·5; indicator 3.2.1), and a large proportion of the 78 deaths per 100 000 people associated with exposure to indoor air pollution (indicator 3.2.2). Additionally, the just development of renewable energy markets can generate net employment opportunities with safer, more locally available jobs. Ensuring countries, particularly those facing high levels of energy poverty, are supported in the safe development, deployment, and adoption of renewable energy is key to maximising health gains and preventing unjust extractive industrial practices that can harm the health and livelihoods of local populations and widen health inequities. With fossil fuels accounting for 95% of road transport energy (indicator 3.1.3), interventions to enable and promote safe active travel and zero-emission public transport can further deliver emissions reduction, promote health through physical activity, and avert many of the 460 000 deaths caused annually by transport-derived PM2·5 pollution (indicator 3.2.1), and some of the 3·2 million annual deaths related to physical inactivity. People-centred, climate-resilient urban redesign to improve building energy efficiency, increase green and blue spaces, and promote sustainable cooling, can additionally prevent heat-related health harms, avoid air-conditioning-derived emissions (indicator 2.2.2), and provide direct physical and mental health benefits. Additionally, food systems are responsible for 30% of global greenhouse gas (GHG) emissions, with 57% of agricultural emissions in 2020 being derived from the production of red meat and milk (indicator 3.3.1). Promoting and enabling equitable access to affordable, healthy, low-carbon diets that meet local nutritional and cultural requirements can contribute to mitigation, while preventing many of the 12·2 million deaths attributable to suboptimal diets (indicator 3.3.2). The health community could play a central role in securing these benefits, by delivering public health interventions to reduce air pollution, enabling and supporting active travel and healthier diets, and promoting improvements in the environmental conditions and commercial activities that define health outcomes. Importantly, the health sector can lead by example and transition to sustainable, resource-efficient, net-zero emission health systems, thereby preventing its 4·6% contribution to global GHG emissions, with cascading impacts ultimately affecting the broader economy (indicator 3.4). Some encouraging signs of progress offer a glimpse of the enormous human benefits that health-centred action could render. Deaths attributable to fossil-fuel-derived air pollution have decreased by 15·7% since 2005, with 80% of this reduction being the result of reduced coal-derived pollution. Meanwhile the renewable energy sector expanded to a historical high of 12·7 million employees in 2021 (indicator 4.2.2); and renewable energy accounted for 90% of the growth in electricity capacity in 2022 (indicator 3.1.1). Supporting this, global clean energy investment increased by 15% in 2022, to $1·6 trillion, exceeding fossil fuel investment by 61% (indicator 4.2.1); and lending to the green energy sector rose to $498 billion in 2021, approaching fossil fuel lending (indicator 4.2.7). Scientific understanding of the links between health and climate change is rapidly growing, and although coverage lags in some of the most affected regions, over 3000 scientific articles covered this topic in 2022 (indicators 5.3.1 and 5.3.2). Meanwhile, the health dimensions of climate change are increasingly acknowledged in the public discourse, with 24% of all climate change newspaper articles in 2022 referring to health, just short of the 26% in 2020 (indicator 5.1). Importantly, international organisations are increasingly engaging with the health co-benefits of climate change mitigation (indicator 5.4.2), and governments increasingly acknowledge this link, with 95% of updated Nationally Determined Contributions (NDCs) under the Paris Agreement now referring to health—up from 73% in 2020 (indicator 5.4.1). These trends signal what could be the start of a life-saving transition.

DEEPENING INEQUITIES IN A WARMING WORLD: Record temperatures in 2020 resulted in a new high of 3·1 billion more person-days of heatwave exposure among people older than 65 years and 626 million more person-days affecting children younger than 1 year, compared with the annual average for the 1986–2005 baseline (indicator 1.1.2). Looking to 2021, people older than 65 years or younger than 1 year, along with people facing social disadvantages, were the most affected by the record-breaking temperatures of over 40°C in the Pacific Northwest areas of the USA and Canada in June, 2021—an event that would have been almost impossible without human-caused climate change. Although the exact number will not be known for several months, hundreds of people have died prematurely from the heat. Furthermore, populations in countries with low and medium levels of UN-defined human development index (HDI) have had the biggest increase in heat vulnerability during the past 30 years, with risks to their health further exacerbated by the low availability of cooling mechanisms and urban green space (indicators 1.1.1, 2.3.2, and 2.3.3). Agricultural workers in countries with low and medium HDI were among the worst affected by exposure to extreme temperatures, bearing almost half of the 295 billion potential work hours lost due to heat in 2020 (indicator 1.1.4). These lost work hours could have devastating economic consequences to these already vulnerable workers—data in this year’s report shows that the average potential earnings lost in countries in the low HDI group were equivalent to 4–8% of the national gross domestic product (indicator 4.1.3). Through these effects, rising average temperatures, and altered rainfall patterns, climate change is beginning to reverse years of progress in tackling the food and water insecurity that still affects the most underserved populations around the world, denying them an essential aspect of good health. During any given month in 2020, up to 19% of the global land surface was affected by extreme drought; a value that had not exceeded 13% between 1950 and 1999 (indicator 1.2.2). In parallel with drought, warm temperatures are affecting the yield potential of the world’s major staple crops—a 6·0% reduction for maize; 3·0% for winter wheat; 5·4% for soybean; and 1·8% for rice in 2020, relative to 1981–2010 (indicator 1.4.1)—exposing the rising risk of food insecurity. Adding to these health hazards, the changing environmental conditions are also increasing the suitability for the transmission of many water-borne, air-borne, food-borne, and vector-borne pathogens. Although socioeconomic development, public health interventions, and advances in medicine have reduced the global burden of infectious disease transmission, climate change could undermine eradication efforts. The number of months with environmentally suitable conditions for the transmission of malaria (Plasmodium falciparum) rose by 39% from 1950–59 to 2010–19 in densely populated highland areas in the low HDI group, threatening highly disadvantaged populations who were comparatively safer from this disease than those in the lowland areas (indicator 1.3.1). The epidemic potential for dengue virus, Zika virus, and chikungunya virus, which currently primarily affect populations in central America, South America, the Caribbean, Africa, and south Asia, increased globally, with a basic reproductive rate increase of 13% for transmission by Aedes aegypti and 7% for transmission by Aedes albopictus compared with the 1950s. The biggest relative increase in basic reproductive rate of these arboviruses was seen in countries in the very high HDI group (indicator 1.3.1); however, people in the low HDI group are confronted with the highest vulnerability to these arboviruses (indicator 1.3.2). Similar findings are observed in the environmental suitability for Vibrio cholerae, a pathogen estimated to cause almost 100 000 deaths annually, particularly among populations with poor access to safe water and sanitation. Between 2003 and 2019, the coastal areas suitable for V cholerae transmission increased substantially across all HDI country groups—although, with 98% of their coastline suitable to the transmission of V cholerae in 2020, it is people in the low HDI country group that have the highest environmental suitability for this disease (indicator 1.3.1). The concurrent and interconnecting risks posed by extreme weather events, infectious disease transmission, and food, water, and financial insecurity are over-burdening the most vulnerable populations. Through multiple simultaneous and interacting health risks, climate change is threatening to reverse years of progress in public health and sustainable development. Even with overwhelming evidence on the health impacts of climate change, countries are not delivering an adaptation response proportionate to the rising risks their populations face. In 2020, 104 (63%) of 166 countries did not have a high level of implementation of national health emergency frameworks, leaving them unprepared to respond to pandemics and climate-related health emergencies (indicator 2.3.1). Importantly, only 18 (55%) of 33 countries with a low HDI had reported at least a medium level of implementation of national health emergency frameworks, compared with 47 (89%) of 53 countries with a very high HDI. In addition, only 47 (52%) of 91 countries reported having a national adaptation plan for health, with insufficient human and financial resources identified as the main barrier for their implementation (indicator 2.1.1). With a world facing an unavoidable temperature rise, even with the most ambitious climate change mitigation, accelerated adaptation is essential to reduce the vulnerabilities of populations to climate change and protect the health of people around the world.

AN INEQUITABLE RESPONSE FAILS EVERYONE: 10 months into 2021, global and equitable access to the COVID-19 vaccine had not been delivered—more than 60% of people in high-income countries have received at least one dose of a COVID-19 vaccine compared with just 3·5% of people in low-income countries. Data in this report exposes similar inequities in the global climate change mitigation response. To meet the Paris Agreement goals and prevent catastrophic levels of global warming, global greenhouse gas emissions must reduce by half within a decade. However, at the current pace of reduction, it would take more than 150 years for the energy system to fully decarbonise (indicator 3.1), and the unequal response between countries is resulting in an uneven realisation of the health benefits of a low-carbon transition. The use of public funds to subsidise fossil fuels is partly responsible for the slow decarbonisation rate. Of the 84 countries reviewed, 65 were still providing an overall subsidy to fossil fuels in 2018 and, in many cases, subsidies were equivalent to substantial proportions of the national health budget and could have been redirected to deliver net benefits to health and wellbeing. Furthermore, all the 19 countries whose carbon pricing policies outweighed the effect of any fossil fuels subsidies came from the very high HDI group (indicator 4.2.4). Although countries in the very high HDI group have collectively made the most progress in the decarbonisation of the energy system, they are still the main contributors to CO2 emissions through the local production of goods and services, accounting for 45% of the global total (indicator 4.2.5). With a slower pace of decarbonisation and poorer air quality regulations than countries in the very high HDI group, the medium and high HDI country groups produce the most fine particle matter (PM2·5) emissions and have the highest rates of air pollution-related deaths, which are about 50% higher than the total deaths in the very high HDI group (indicator 3.3). The low HDI group, with comparatively lower amounts of industrial activity than in the other groups, has a local production that contributes to only 0·7% of global CO2 emissions, and has the lowest mortality rate from ambient air pollution. However, with only 12% of its inhabitants relying on clean fuels and technologies for cooking, the health of these populations is still at risk from dangerously high concentrations of household air pollution (indicator 3.2). Even in the most affluent countries, people in the most deprived areas over-whelmingly bear the burden of health effects from exposure to air pollution. These findings expose the health costs of the delayed and unequal mitigation response and underscore the millions of deaths to be prevented annually through a low-carbon transition that prioritises the health of all populations. However, the world is not on track to realising the health gains of the transition to a low-carbon economy. Current global decarbonisation commitments are insufficient to meet Paris Agreement ambitions and would lead to a roughly 2·4°C average global temperature increase by the end of the century. The current direction of post-COVID-19 spending is threatening to make this situation worse, with just 18% of all the funds committed for economic recovery from the COVID-19 pandemic by the end of 2020 expected to lead to a reduction of greenhouse gas emissions. Indeed, the economic recovery from the pandemic is already predicted to lead to an unprecedented 5% increase in greenhouse gas emissions in 2021, which will bring global anthropogenic emissions back to their peak amounts. In addition, the current economic recession is threatening to undermine the target of mobilising US$100 billion per year from 2020 onwards to promote low-carbon shifts and adaptation responses in the most underserved countries, even though this quantity is minute compared with the trillions allocated to COVID-19 recovery. The high amounts of borrowing that countries have had to resort to during the pandemic could erase their ability to deliver a green recovery and maximise the health gains to their population of a low-carbon transition.

A DEBILITATED FIRST LINE OF DEFENCE: With the worsening health impacts of climate change compounding other coexisting crises, populations worldwide increasingly rely on health systems as their first line of defence. However, just as the need for healthcare rises, health systems worldwide are debilitated by the effects of the COVID-19 pandemic and the energy and cost-of-living crises. Urgent action is therefore needed to strengthen health-system resilience and to prevent a rapidly escalating loss of lives and to prevent suffering in a changing climate. However, only 48 (51%) of 95 countries reported having assessed their climate change adaptation needs (indicator 2.1.1) and, even after the profound impacts of COVID-19, only 60 (63%) countries reported a high to very high implementation status for health emergency management in 2021 (indicator 2.2.4). The scarcity of proactive adaptation is shown in the response to extreme heat. Despite the local cooling and overall health benefits of urban greenspaces, only 277 (27%) of 1038 global urban centres were at least moderately green in 2021 (indicator 2.2.3), and the number of households with air conditioning increased by 66% from 2000 to 2020, a maladaptive response that worsens the energy crisis and further increases urban heat, air pollution, and greenhouse gas emissions. As converging crises further threaten the world’s life-supporting systems, rapid, decisive, and coherent intersectoral action is essential to protect human health from the hazards of the rapidly changing climate.

HEALTH AT THE MERCY OF FOSSIL FUELS: The year 2022 marks the 30th anniversary of the signing of the UN Framework Convention on Climate Change, in which countries agreed to prevent dangerous anthropogenic climate change and its deleterious effects on human health and welfare. However, little meaningful action has since followed. The carbon intensity of the global energy system has decreased by less than 1% since the UNFCCC was established, and global electricity generation is still dominated by fossil fuels, with renewable energy contributing to only 8·2% of the global total (indicator 3.1). Simultaneously, the total energy demand has risen by 59%, increasing energy-related emissions to a historical high in 2021. Current policies put the world on track to a catastrophic 2·7°C increase by the end of the century. Even with the commitments that countries set in the Nationally Determined Contributions (NDCs) updated up until November 2021, global emissions could be 13·7% above 2010 levels by 2030—far from the 43% decrease from current levels required to meet Paris Agreement goals and keep temperatures within the limits of adaptation. Fossil fuel dependence is not only undermining global health through increased climate change impacts, but also affects human health and wellbeing directly, through volatile and unpredictable fossil fuel markets, frail supply chains, and geopolitical conflicts. As a result, millions of people do not have access to the energy needed to keep their homes at healthy temperatures, preserve food and medication, and meet the seventh Sustainable Development Goal (to ensure access to affordable, reliable, sustainable, and modern energy for all). Without sufficient support, access to clean energy has been particularly slow in low HDI countries, and only 1·4% of their electricity came from modern renewables (mostly wind and solar power) in 2020 (indicator 3.1). An estimated 59% of healthcare facilities in low and middle-income countries still do not have access to the reliable electricity needed to provide basic care. Meanwhile, biomass accounts for as much as 31% of the energy consumed in the domestic sector globally, mostly from traditional sources—a proportion that increases to 96% in low HDI countries (indicator 3.2). The associated burden of disease is substantial, with the air in people’s homes exceeding WHO guidelines for safe concentrations of small particulate air pollution (PM2·5) in 2020 by 30-fold on average in the 62 countries assessed (indicator 3.2). After 6 years of improvement, the number of people without access to electricity increased in 2020 as a result of the socioeconomic pressures of the COVID-19 pandemic. The current energy and cost-of-living crises now threaten to reverse progress toward affordable, reliable, and sustainable energy, further undermining the socioeconomic determinants of health. Simultaneously, oil and gas companies are registering record profits, while their production strategies continue to undermine people’s lives and wellbeing. An analysis of the production strategies of 15 of the world’s largest oil and gas companies, as of February 2022, revealed they exceed their share of emissions consistent with 1·5°C of global heating (indicator 4.2.6) by 37% in 2030 and 103% in 2040, continuing to undermine efforts to deliver a low carbon, healthy, liveable future. Aggravating this situation even further, governments continue to incentivise fossil fuel production and consumption: 69 (80%) of 86 countries reviewed had net-negative carbon prices (ie, provided a net subsidy to fossil fuels) for a net total of US$400 billion in 2019, allocating amounts often comparable with or even exceeding their total health budgets (indicator 4.2.4). Simultaneously, wealthier countries failed to meet their commitment of mobilising the considerably lower sum of $100 billion annually by 2020 as agreed at the 2009 Copenhagen Accord to support climate action in “developing countries”, and climate efforts are being undercut by a profound scarcity of funding (indicator 2.1.1). The impacts of climate change on global economies, together with the recession triggered by COVID-19 and worsened by geopolitical instability, could paradoxically further reduce the willingness of countries to allocate the funds needed to enable a just climate transition.

A HEALTH-CENTRED RESPONSE FOR A THRIVING FUTURE: The world is at a critical juncture. With countries facing concurrent crises, the implementation of long-term emissions-reduction policies risks being deflected or defeated by challenges wrongly perceived as more immediate. Addressing each of the concurrent crises in isolation risks alleviating one, while worsening another. Such a situation is emerging from the response to COVID-19, which has so far has not delivered the green recovery that the health community proposed, and, on the contrary, is aggravating climate change-related health risks. Less than one third of $3·11 trillion allocated to COVID-19 economic recovery is likely to reduce greenhouse gas emissions or air pollution, with the net effect likely to increase emissions. The COVID-19 pandemic affected climate action at the city level, and 239 (30%) of 798 cities reported that COVID-19 reduced financing available for climate action (indicator 2.1.3). As countries search for alternatives to Russian oil and gas, many continue to favour the burning of fossil fuels, with some even turning back to coal. Shifts in global energy supplies threaten to increase fossil fuel production. Even if implemented as a temporary transition, these responses could reverse progress on air quality improvement, irreversibly push the world off track from meeting the commitments set out in the Paris Agreement, and guarantee a future of accelerated climate change that threatens human survival. On the contrary, in this pivotal moment, a health-centred response to the current crises would still provide the opportunity for a low-carbon, resilient future, which not only avoids the health harms of accelerated climate change, but also delivers improved health and wellbeing through the associated co-benefits of climate action. Such response would see countries promptly shifting away from fossil fuels, reducing their dependence on fragile international oil and gas markets, and accelerating a just transition to clean energy sources. A health-centred response would reduce the likelihood of the most catastrophic climate change impacts, while improving energy security, creating an opportunity for economic recovery, and offering immediate health benefits. Improvements in air quality would help to prevent the 1·2 million deaths resulting from exposure to fossil fuel-derived ambient PM2·5 in 2020 alone (indicator 3.3), and a health-centred energy transition would enhance low-carbon travel and increase urban green spaces, promoting physical activity, and improving physical and mental health. In the food sector, an accelerated transition to balanced and more plant-based diets would not only help reduce the 55% of agricultural sector emissions coming from red meat and milk production (indicator 3.5.1), but also prevent up to 11·5 million diet-related deaths annually (indicator 3.5.2), and substantially reduce the risk of zoonotic diseases. These health-focused shifts would reduce the burden of communicable and non-communicable diseases, reducing the strain on overwhelmed health-care providers. Importantly, accelerating climate change adaptation would lead to more robust health systems, minimising the negative impacts of future infectious disease outbreaks and geopolitical conflicts, and restoring the first line of defence of global populations.

EMERGING GLIMMERS OF HOPE: Despite decades of insufficient action, emerging, albeit few, signs of change provide some hope that a health-centred response might be starting to emerge. Individual engagement with the health dimensions of climate change, essential to drive and enable an accelerated response, increased from 2020 to 2021 (indicator 5.2), and coverage of health and climate change in the media reached a new record high in 2021, with a 27% increase from 2020 (indicator 5.1). This engagement is also reflected by country leaders, with a record 60% of 194 countries focusing their attention on the links between climate change and health in the 2021 UN General Debate, and with 86% of national updated or new NDCs making references to health (indicator 5.4). At the city level, local authorities are progressively identifying risks of climate change on the health of their populations (indicator 2.1.3), a first step to delivering a tailored response that strengthens local health systems. Although the health sector is responsible for 5·2% of all global emissions (indicator 3.6), it has shown impressive climate leadership, and 60 countries had committed to transitioning to climate-resilient and/or low-carbon or net-zero carbon health systems as part of the COP26 Health Programme, as of July, 2022. Signs of change are also emerging in the energy sector. Although total clean energy generation remains grossly insufficient, record high levels were reached in 2020 (indicator 3.1). Zero-carbon sources accounted for 80% of investment in electricity generation in 2021 (indicator 4.2.1), and renewable energies have reached cost parity with fossil fuel energies. As some of the highest emitting countries attempt to cut their dependence on oil and gas in response to the war in Ukraine and soaring energy prices, many are focusing on increasing renewable energy generation, raising hopes for a health-centred response. However, increased awareness and commitments should be urgently translated into action for hope to turn into reality.

METHODS: This international, investigator-initiated, pragmatic, registry-based, single-blinded, randomised trial was undertaken in 85 intensive care units (ICUs) across 16 countries. We enrolled nutritionally high-risk adults (≥18 years) undergoing mechanical ventilation to compare prescribing high-dose protein (≥2·2 g/kg per day) with usual dose protein (≤1·2 g/kg per day) started within 96 h of ICU admission and continued for up to 28 days or death or transition to oral feeding. Participants were randomly allocated (1:1) to high-dose protein or usual dose protein, stratified by site. As site personnel were involved in both prescribing and delivering protein dose, it was not possible to blind clinicians, but patients were not made aware of the treatment assignment. The primary efficacy outcome was time-to-discharge-alive from hospital up to 60 days after ICU admission and the secondary outcome was 60-day morality. Patients were analysed in the group to which they were randomly assigned regardless of study compliance, although patients who dropped out of the study before receiving the study intervention were excluded. This study is registered with ClinicalTrials.gov, NCT03160547.

FINDINGS: Between Jan 17, 2018, and Dec 3, 2021, 1329 patients were randomised and 1301 (97·9%) were included in the analysis (645 in the high-dose protein group and 656 in usual dose group). By 60 days after randomisation, the cumulative incidence of alive hospital discharge was 46·1% (95 CI 42·0%-50·1%) in the high-dose compared with 50·2% (46·0%-54·3%) in the usual dose protein group (hazard ratio 0·91, 95% CI 0·77-1·07; p=0·27). The 60-day mortality rate was 34·6% (222 of 642) in the high dose protein group compared with 32·1% (208 of 648) in the usual dose protein group (relative risk 1·08, 95% CI 0·92-1·26). There appeared to be a subgroup effect with higher protein provision being particularly harmful in patients with acute kidney injury and higher organ failure scores at baseline.

INTERPRETATION: Delivery of higher doses of protein to mechanically ventilated critically ill patients did not improve the time-to-discharge-alive from hospital and might have worsened outcomes for patients with acute kidney injury and high organ failure scores.

METHODS: To estimate incidence and mortality for HIV, we used the UNAIDS Spectrum model appropriately modified based on a systematic review of available studies of mortality with and without antiretroviral therapy (ART). For concentrated epidemics, we calibrated Spectrum models to fit vital registration data corrected for misclassification of HIV deaths. In generalised epidemics, we minimised a loss function to select epidemic curves most consistent with prevalence data and demographic data for all-cause mortality. We analysed counterfactual scenarios for HIV to assess years of life saved through prevention of mother-to-child transmission (PMTCT) and ART. For tuberculosis, we analysed vital registration and verbal autopsy data to estimate mortality using cause of death ensemble modelling. We analysed data for corrected case-notifications, expert opinions on the case-detection rate, prevalence surveys, and estimated cause-specific mortality using Bayesian meta-regression to generate consistent trends in all parameters. We analysed malaria mortality and incidence using an updated cause of death database, a systematic analysis of verbal autopsy validation studies for malaria, and recent studies (2010-13) of incidence, drug resistance, and coverage of insecticide-treated bednets.

FINDINGS: Globally in 2013, there were 1·8 million new HIV infections (95% uncertainty interval 1·7 million to 2·1 million), 29·2 million prevalent HIV cases (28·1 to 31·7), and 1·3 million HIV deaths (1·3 to 1·5). At the peak of the epidemic in 2005, HIV caused 1·7 million deaths (1·6 million to 1·9 million). Concentrated epidemics in Latin America and eastern Europe are substantially smaller than previously estimated. Through interventions including PMTCT and ART, 19·1 million life-years (16·6 million to 21·5 million) have been saved, 70·3% (65·4 to 76·1) in developing countries. From 2000 to 2011, the ratio of development assistance for health for HIV to years of life saved through intervention was US$4498 in developing countries. Including in HIV-positive individuals, all-form tuberculosis incidence was 7·5 million (7·4 million to 7·7 million), prevalence was 11·9 million (11·6 million to 12·2 million), and number of deaths was 1·4 million (1·3 million to 1·5 million) in 2013. In the same year and in only individuals who were HIV-negative, all-form tuberculosis incidence was 7·1 million (6·9 million to 7·3 million), prevalence was 11·2 million (10·8 million to 11·6 million), and number of deaths was 1·3 million (1·2 million to 1·4 million). Annualised rates of change (ARC) for incidence, prevalence, and death became negative after 2000. Tuberculosis in HIV-negative individuals disproportionately occurs in men and boys (versus women and girls); 64·0% of cases (63·6 to 64·3) and 64·7% of deaths (60·8 to 70·3). Globally, malaria cases and deaths grew rapidly from 1990 reaching a peak of 232 million cases (143 million to 387 million) in 2003 and 1·2 million deaths (1·1 million to 1·4 million) in 2004. Since 2004, child deaths from malaria in sub-Saharan Africa have decreased by 31·5% (15·7 to 44·1). Outside of Africa, malaria mortality has been steadily decreasing since 1990.

INTERPRETATION: Our estimates of the number of people living with HIV are 18·7% smaller than UNAIDS's estimates in 2012. The number of people living with malaria is larger than estimated by WHO. The number of people living with HIV, tuberculosis, or malaria have all decreased since 2000. At the global level, upward trends for malaria and HIV deaths have been reversed and declines in tuberculosis deaths have accelerated. 101 countries (74 of which are developing) still have increasing HIV incidence. Substantial progress since the Millennium Declaration is an encouraging sign of the effect of global action.

METHODS: We generated updated estimates of child mortality in early neonatal (age 0-6 days), late neonatal (7-28 days), postneonatal (29-364 days), childhood (1-4 years), and under-5 (0-4 years) age groups for 188 countries from 1970 to 2013, with more than 29,000 survey, census, vital registration, and sample registration datapoints. We used Gaussian process regression with adjustments for bias and non-sampling error to synthesise the data for under-5 mortality for each country, and a separate model to estimate mortality for more detailed age groups. We used explanatory mixed effects regression models to assess the association between under-5 mortality and income per person, maternal education, HIV child death rates, secular shifts, and other factors. To quantify the contribution of these different factors and birth numbers to the change in numbers of deaths in under-5 age groups from 1990 to 2013, we used Shapley decomposition. We used estimated rates of change between 2000 and 2013 to construct under-5 mortality rate scenarios out to 2030.

FINDINGS: We estimated that 6·3 million (95% UI 6·0-6·6) children under-5 died in 2013, a 64% reduction from 17·6 million (17·1-18·1) in 1970. In 2013, child mortality rates ranged from 152·5 per 1000 livebirths (130·6-177·4) in Guinea-Bissau to 2·3 (1·8-2·9) per 1000 in Singapore. The annualised rates of change from 1990 to 2013 ranged from -6·8% to 0·1%. 99 of 188 countries, including 43 of 48 countries in sub-Saharan Africa, had faster decreases in child mortality during 2000-13 than during 1990-2000. In 2013, neonatal deaths accounted for 41·6% of under-5 deaths compared with 37·4% in 1990. Compared with 1990, in 2013, rising numbers of births, especially in sub-Saharan Africa, led to 1·4 million more child deaths, and rising income per person and maternal education led to 0·9 million and 2·2 million fewer deaths, respectively. Changes in secular trends led to 4·2 million fewer deaths. Unexplained factors accounted for only -1% of the change in child deaths. In 30 developing countries, decreases since 2000 have been faster than predicted attributable to income, education, and secular shift alone.

INTERPRETATION: Only 27 developing countries are expected to achieve MDG 4. Decreases since 2000 in under-5 mortality rates are accelerating in many developing countries, especially in sub-Saharan Africa. The Millennium Declaration and increased development assistance for health might have been a factor in faster decreases in some developing countries. Without further accelerated progress, many countries in west and central Africa will still have high levels of under-5 mortality in 2030.

METHODS: In the global, open-label, phase 3 IMbrave050 study, adult patients with high-risk surgically resected or ablated hepatocellular carcinoma were recruited from 134 hospitals and medical centres in 26 countries in four WHO regions (European region, region of the Americas, South-East Asia region, and Western Pacific region). Patients were randomly assigned in a 1:1 ratio via an interactive voice-web response system using permuted blocks, using a block size of 4, to receive intravenous 1200 mg atezolizumab plus 15 mg/kg bevacizumab every 3 weeks for 17 cycles (12 months) or to active surveillance. The primary endpoint was recurrence-free survival by independent review facility assessment in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT04102098.

FINDINGS: The intention-to-treat population included 668 patients randomly assigned between Dec 31, 2019, and Nov 25, 2021, to either atezolizumab plus bevacizumab (n=334) or to active surveillance (n=334). At the prespecified interim analysis (Oct 21, 2022), median duration of follow-up was 17·4 months (IQR 13·9-22·1). Adjuvant atezolizumab plus bevacizumab was associated with significantly improved recurrence-free survival (median, not evaluable [NE]; [95% CI 22·1-NE]) compared with active surveillance (median, NE [21·4-NE]; hazard ratio, 0·72 [adjusted 95% CI 0·53-0·98]; p=0·012). Grade 3 or 4 adverse events occurred in 136 (41%) of 332 patients who received atezolizumab plus bevacizumab and 44 (13%) of 330 patients in the active surveillance group. Grade 5 adverse events occurred in six patients (2%, two of which were treatment related) in the atezolizumab plus bevacizumab group, and one patient (<1%) in the active surveillance group. Both atezolizumab and bevacizumab were discontinued because of adverse events in 29 patients (9%) who received atezolizumab plus bevacizumab.

INTERPRETATION: Among patients at high risk of hepatocellular carcinoma recurrence following curative-intent resection or ablation, recurrence-free survival was improved in those who received atezolizumab plus bevacizumab versus active surveillance. To our knowledge, IMbrave050 is the first phase 3 study of adjuvant treatment for hepatocellular carcinoma to report positive results. However, longer follow-up for both recurrence-free and overall survival is needed to assess the benefit-risk profile more fully.

METHODS: The GBD 2019 comparative risk assessment framework was used to estimate cancer burden attributable to behavioural, environmental and occupational, and metabolic risk factors. A total of 82 risk-outcome pairs were included on the basis of the World Cancer Research Fund criteria. Estimated cancer deaths and disability-adjusted life-years (DALYs) in 2019 and change in these measures between 2010 and 2019 are presented.

FINDINGS: Globally, in 2019, the risk factors included in this analysis accounted for 4·45 million (95% uncertainty interval 4·01-4·94) deaths and 105 million (95·0-116) DALYs for both sexes combined, representing 44·4% (41·3-48·4) of all cancer deaths and 42·0% (39·1-45·6) of all DALYs. There were 2·88 million (2·60-3·18) risk-attributable cancer deaths in males (50·6% [47·8-54·1] of all male cancer deaths) and 1·58 million (1·36-1·84) risk-attributable cancer deaths in females (36·3% [32·5-41·3] of all female cancer deaths). The leading risk factors at the most detailed level globally for risk-attributable cancer deaths and DALYs in 2019 for both sexes combined were smoking, followed by alcohol use and high BMI. Risk-attributable cancer burden varied by world region and Socio-demographic Index (SDI), with smoking, unsafe sex, and alcohol use being the three leading risk factors for risk-attributable cancer DALYs in low SDI locations in 2019, whereas DALYs in high SDI locations mirrored the top three global risk factor rankings. From 2010 to 2019, global risk-attributable cancer deaths increased by 20·4% (12·6-28·4) and DALYs by 16·8% (8·8-25·0), with the greatest percentage increase in metabolic risks (34·7% [27·9-42·8] and 33·3% [25·8-42·0]).

INTERPRETATION: The leading risk factors contributing to global cancer burden in 2019 were behavioural, whereas metabolic risk factors saw the largest increases between 2010 and 2019. Reducing exposure to these modifiable risk factors would decrease cancer mortality and DALY rates worldwide, and policies should be tailored appropriately to local cancer risk factor burden.