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Impact of inappropriate empirical antibiotic therapy on in-hospital mortality: a retrospective multicentre cohort study of patients with bloodstream infections in Chile, 2018-2022.

INTRODUCTION: Empirical antibiotic therapy is essential for treating bloodstream infections (BSI), yet there is limited evidence from resource-limited settings. We quantified the association of inappropriate empirical antibiotic therapy (IEAT) with in-hospital mortality and the associated burden on BSI patients in Chile. METHODS: We used a retrospective multicentre cohort study of BSI cases in three Chilean tertiary hospitals (2018-2022) to assess the impact of IEAT on 30-day and overall in-hospital mortality and quantify excess disease and economic burdens associated with IEAT. We determined the appropriateness of pathogen-antimicrobial pairings based on in vitro susceptibilities and pathogen-corresponding antibiotic treatment, allowing a 48-hour window after the initial blood culture. We addressed confounding using propensity scores and inverse probability weights (IPW). We used IPW-weighted logistic competing-risk survival models, including time-varying independent variables after blood tests as controls. RESULTS: Among 1323 BSI episodes, 432 (33%) received IEAT, with an average time to adequate therapy of 4.6 days. Compared with adequate treatment, IEAT was associated with 30-day and overall mortality risks that were 1.31 and 1.24 times higher, respectively. These risks were further inflated between twofold and fourfold when antibiotic-resistant bacteria (ARB) was included. Competing-risk models showed associations between IEAT and IEAT-ARB combinations with in-hospital mortality. Accounting for time-varying variables yielded similar results. The economic burden of IEAT resulted in an additional cost of ~US$9900 from premature mortality and 0.46 disability-adjusted life-years per patient with BSI. CONCLUSION: Approximately one in three patients received IEAT, often associated with ARB. IEAT was linked to increased mortality risk and higher economic costs. Timely appropriate treatment, early pathogen detection and resistance profiling are likely to improve health and financial outcomes at the population level.

Identification and Characterization of Salmonella Phages and Absence of Salmonella Strains from Three Different Study Areas of Cattle Livestock

Background: Salmonella represents a significant risk to both public and animal health. Although Salmonella strains have not been isolated from cattle livestock, Salmonella phages have been successfully identified. Materials and Methods: Our study was conducted through (i) investigating the presence of Salmonella strains and Salmonella phages in three study areas, (ii) phenotypic screening by lytic profile (LP); (iii) selecting nine phages for sequencing; and (iv) genomic comparison to evaluate their relative diversity. Results: A total of 307 samples were analyzed, resulting in a total of 162 virus-like particles (VLPs) analyzed. The LP was performed to identify Salmonella strains susceptible to phage infection, including the most frequent serovars: Dublin, Enteritidis, and Javiana. From the VLPs, nine phages were selected for genomic comparison. These phages represent three morphotypes: siphoviruses, myoviruses, and podoviruses, originating from different geographic and productive sites. Conclusions: This study enhances the understanding of the presence and diversity of Salmonella phages in cattle livestock, even in the absence of Salmonella strains.

Global burden of bacterial antimicrobial resistance 1990–2021: a systematic analysis with forecasts to 2050

Background: Antimicrobial resistance (AMR) poses an important global health challenge in the 21st century. A previous study has quantified the global and regional burden of AMR for 2019, followed with additional publications that provided more detailed estimates for several WHO regions by country. To date, there have been no studies that produce comprehensive estimates of AMR burden across locations that encompass historical trends and future forecasts. Methods: We estimated all-age and age-specific deaths and disability-adjusted life-years (DALYs) attributable to and associated with bacterial AMR for 22 pathogens, 84 pathogen–drug combinations, and 11 infectious syndromes in 204 countries and territories from 1990 to 2021. We collected and used multiple cause of death data, hospital discharge data, microbiology data, literature studies, single drug resistance profiles, pharmaceutical sales, antibiotic use surveys, mortality surveillance, linkage data, outpatient and inpatient insurance claims data, and previously published data, covering 520 million individual records or isolates and 19 513 study-location-years. We used statistical modelling to produce estimates of AMR burden for all locations, including those with no data. Our approach leverages the estimation of five broad component quantities: the number of deaths involving sepsis; the proportion of infectious deaths attributable to a given infectious syndrome; the proportion of infectious syndrome deaths attributable to a given pathogen; the percentage of a given pathogen resistant to an antibiotic of interest; and the excess risk of death or duration of an infection associated with this resistance. Using these components, we estimated disease burden attributable to and associated with AMR, which we define based on two counterfactuals; respectively, an alternative scenario in which all drug-resistant infections are replaced by drug-susceptible infections, and an alternative scenario in which all drug-resistant infections were replaced by no infection. Additionally, we produced global and regional forecasts of AMR burden until 2050 for three scenarios: a reference scenario that is a probabilistic forecast of the most likely future; a Gram-negative drug scenario that assumes future drug development that targets Gram-negative pathogens; and a better care scenario that assumes future improvements in health-care quality and access to appropriate antimicrobials. We present final estimates aggregated to the global, super-regional, and regional level. Findings: In 2021, we estimated 4·71 million (95% UI 4·23–5·19) deaths were associated with bacterial AMR, including 1·14 million (1·00–1·28) deaths attributable to bacterial AMR. Trends in AMR mortality over the past 31 years varied substantially by age and location. From 1990 to 2021, deaths from AMR decreased by more than 50% among children younger than 5 years yet increased by over 80% for adults 70 years and older. AMR mortality decreased for children younger than 5 years in all super-regions, whereas AMR mortality in people 5 years and older increased in all super-regions. For both deaths associated with and deaths attributable to AMR, meticillin-resistant Staphylococcus aureus increased the most globally (from 261 000 associated deaths [95% UI 150 000–372 000] and 57 200 attributable deaths [34 100–80 300] in 1990, to 550 000 associated deaths [500 000–600 000] and 130 000 attributable deaths [113 000–146 000] in 2021). Among Gram-negative bacteria, resistance to carbapenems increased more than any other antibiotic class, rising from 619 000 associated deaths (405 000–834 000) in 1990, to 1·03 million associated deaths (909 000–1·16 million) in 2021, and from 127 000 attributable deaths (82 100–171 000) in 1990, to 216 000 (168 000–264 000) attributable deaths in 2021. There was a notable decrease in non-COVID-related infectious disease in 2020 and 2021. Our forecasts show that an estimated 1·91 million (1·56–2·26) deaths attributable to AMR and 8·22 million (6·85–9·65) deaths associated with AMR could occur globally in 2050. Super-regions with the highest all-age AMR mortality rate in 2050 are forecasted to be south Asia and Latin America and the Caribbean. Increases in deaths attributable to AMR will be largest among those 70 years and older (65·9% [61·2–69·8] of all-age deaths attributable to AMR in 2050). In stark contrast to the strong increase in number of deaths due to AMR of 69·6% (51·5–89·2) from 2022 to 2050, the number of DALYs showed a much smaller increase of 9·4% (–6·9 to 29·0) to 46·5 million (37·7 to 57·3) in 2050. Under the better care scenario, across all age groups, 92·0 million deaths (82·8–102·0) could be cumulatively averted between 2025 and 2050, through better care of severe infections and improved access to antibiotics, and under the Gram-negative drug scenario, 11·1 million AMR deaths (9·08–13·2) could be averted through the development of a Gram-negative drug pipeline to prevent AMR deaths. Interpretation: This study presents the first comprehensive assessment of the global burden of AMR from 1990 to 2021, with results forecasted until 2050. Evaluating changing trends in AMR mortality across time and location is necessary to understand how this important global health threat is developing and prepares us to make informed decisions regarding interventions. Our findings show the importance of infection prevention, as shown by the reduction of AMR deaths in those younger than 5 years. Simultaneously, our results underscore the concerning trend of AMR burden among those older than 70 years, alongside a rapidly ageing global community. The opposing trends in the burden of AMR deaths between younger and older individuals explains the moderate future increase in global number of DALYs versus number of deaths. Given the high variability of AMR burden by location and age, it is important that interventions combine infection prevention, vaccination, minimisation of inappropriate antibiotic use in farming and humans, and research into new antibiotics to mitigate the number of AMR deaths that are forecasted for 2050. Funding: UK Department of Health and Social Care's Fleming Fund using UK aid, and the Wellcome Trust.

Global, regional, and national age-specific progress towards the 2020 milestones of the WHO End TB Strategy: a systematic analysis for the Global Burden of Disease Study 2021

Background: Global evaluations of the progress towards the WHO End TB Strategy 2020 interim milestones on mortality (35% reduction) and incidence (20% reduction) have not been age specific. We aimed to assess global, regional, and national-level burdens of and trends in tuberculosis and its risk factors across five separate age groups, from 1990 to 2021, and to report on age-specific progress between 2015 and 2020. Methods: We used the Global Burden of Diseases, Injuries, and Risk Factors Study 2021 (GBD 2021) analytical framework to compute age-specific tuberculosis mortality and incidence estimates for 204 countries and territories (1990–2021 inclusive). We quantified tuberculosis mortality among individuals without HIV co-infection using 22 603 site-years of vital registration data, 1718 site-years of verbal autopsy data, 825 site-years of sample-based vital registration data, 680 site-years of mortality surveillance data, and 9 site-years of minimally invasive tissue sample (MITS) diagnoses data as inputs into the Cause of Death Ensemble modelling platform. Age-specific HIV and tuberculosis deaths were established with a population attributable fraction approach. We analysed all available population-based data sources, including prevalence surveys, annual case notifications, tuberculin surveys, and tuberculosis mortality, in DisMod-MR 2.1 to produce internally consistent age-specific estimates of tuberculosis incidence, prevalence, and mortality. We also estimated age-specific tuberculosis mortality without HIV co-infection that is attributable to the independent and combined effects of three risk factors (smoking, alcohol use, and diabetes). As a secondary analysis, we examined the potential impact of the COVID-19 pandemic on tuberculosis mortality without HIV co-infection by comparing expected tuberculosis deaths, modelled with trends in tuberculosis deaths from 2015 to 2019 in vital registration data, with observed tuberculosis deaths in 2020 and 2021 for countries with available cause-specific mortality data. Findings: We estimated 9·40 million (95% uncertainty interval [UI] 8·36 to 10·5) tuberculosis incident cases and 1·35 million (1·23 to 1·52) deaths due to tuberculosis in 2021. At the global level, the all-age tuberculosis incidence rate declined by 6·26% (5·27 to 7·25) between 2015 and 2020 (the WHO End TB strategy evaluation period). 15 of 204 countries achieved a 20% decrease in all-age tuberculosis incidence between 2015 and 2020, eight of which were in western sub-Saharan Africa. When stratified by age, global tuberculosis incidence rates decreased by 16·5% (14·8 to 18·4) in children younger than 5 years, 16·2% (14·2 to 17·9) in those aged 5–14 years, 6·29% (5·05 to 7·70) in those aged 15–49 years, 5·72% (4·02 to 7·39) in those aged 50–69 years, and 8·48% (6·74 to 10·4) in those aged 70 years and older, from 2015 to 2020. Global tuberculosis deaths decreased by 11·9% (5·77 to 17·0) from 2015 to 2020. 17 countries attained a 35% reduction in deaths due to tuberculosis between 2015 and 2020, most of which were in eastern Europe (six countries) and central Europe (four countries). There was variable progress by age: a 35·3% (26·7 to 41·7) decrease in tuberculosis deaths in children younger than 5 years, a 29·5% (25·5 to 34·1) decrease in those aged 5–14 years, a 15·2% (10·0 to 20·2) decrease in those aged 15–49 years, a 7·97% (0·472 to 14·1) decrease in those aged 50–69 years, and a 3·29% (–5·56 to 9·07) decrease in those aged 70 years and older. Removing the combined effects of the three attributable risk factors would have reduced the number of all-age tuberculosis deaths from 1·39 million (1·28 to 1·54) to 1·00 million (0·703 to 1·23) in 2020, representing a 36·5% (21·5 to 54·8) reduction in tuberculosis deaths compared to those observed in 2015. 41 countries were included in our analysis of the impact of the COVID-19 pandemic on tuberculosis deaths without HIV co-infection in 2020, and 20 countries were included in the analysis for 2021. In 2020, 50 900 (95% CI 49 700 to 52 400) deaths were expected across all ages, compared to an observed 45 500 deaths, corresponding to 5340 (4070 to 6920) fewer deaths; in 2021, 39 600 (38 300 to 41 100) deaths were expected across all ages compared to an observed 39 000 deaths, corresponding to 657 (–713 to 2180) fewer deaths. Interpretation: Despite accelerated progress in reducing the global burden of tuberculosis in the past decade, the world did not attain the first interim milestones of the WHO End TB Strategy in 2020. The pace of decline has been unequal with respect to age, with older adults (ie, those aged >50 years) having the slowest progress. As countries refine their national tuberculosis programmes and recalibrate for achieving the 2035 targets, they could consider learning from the strategies of countries that achieved the 2020 milestones, as well as consider targeted interventions to improve outcomes in older age groups. Funding: Bill & Melinda Gates Foundation.

Opportunities and challenges in antimicrobial resistance policy including animal production systems and humans across stakeholders in Argentina: A context and qualitative analysis

Introduction Gaps in antimicrobial resistance (AMR) surveillance and control, including implementation of national action plans (NAPs), are evident internationally. Countries' capacity to translate political commitment into action is crucial to cope with AMR at the human-animal-environment interface. Methods We employed a two-stage process to understand opportunities and challenges related to AMR surveillance and control at the human-animal interface in Argentina. First, we compiled the central AMR policies locally and mapped vital stakeholders around the NAP and the national commission against bacterial resistance. Second, we conducted qualitative interviews using a semistructured questionnaire covering stakeholders' understanding and progress towards AMR and NAP. We employed a mixed deductive-inductive approach and used the constant comparative analysis method. We created categories and themes to cluster subthemes and determined crucial relationships among thematic groups. Results Crucial AMR policy developments have been made since 1969, including gradually banning colistin in food-producing animals. In 2023, a new government decree prioritised AMR following the 2015 NAP launch. Our qualitative analyses identified seven major themes for tackling AMR: (I) Cultural factors and sociopolitical country context hampering AMR progress, (II) Fragmented governance, (III) Antibiotic access and use, (IV) AMR knowledge and awareness throughout stakeholders, (V) AMR surveillance, (VI) NAP efforts and (VII) External drivers. We identified a fragmented structure of the food production chain, poor cross-coordination between stakeholders, limited surveillance and regulation among food-producing animals and geographical disparities over access, diagnosis and treatment. The country is moving to integrate animal and food production into its surveillance system, with most hospitals experienced in monitoring AMR through antimicrobial stewardship programmes. Conclusion AMR accountability should involve underpinning collaboration at different NAP implementation levels and providing adequate resources to safeguard long-term sustainability. Incorporating a multisectoral context-specific approach relying on different One Health domains is crucial to strengthening local AMR surveillance.

Extended-Spectrum β-Lactamase-Producing Escherichia coli and Klebsiella pneumoniae: Risk Factors and Economic Burden Among Patients with Bloodstream Infections

Introduction: Although Extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae (ESBL-EK) significantly contribute to bloodstream infections, their economic repercussions remain largely unquantified. Data Source and Methods: We performed a retrospective analysis of inpatients diagnosed with Escherichia coli or Klebsiella pneumoniae bacteremia in a tertiary hospital from January 2020 to December 2022 in Guangzhou, China. We employed the chi-square test to examine ESBL risk factors and utilized propensity score matching (PSM) to negate baseline confounding factors, assessing economic burden through disability-adjusted life years (DALYs), hospital costs and productivity losses. We employed mediation analysis to eliminate confounding factors and better identify ESBL sources of burden related. Results: We found 166 ESBL-EC/KP BSI patients (52.2% of the total examined 318 patients). Post-PSM analysis revealed that ESBL-producing EC/KP will reduce the effectiveness of empirical medication by 19.8%, extend the total length of hospitalization by an average of 3 days, and increase the patient’s financial burden by US$2047. No significant disparity was found in overall mortality and mean DALYs between the groups. Mediation analysis showed that the link between ESBL and hospital costs is predominantly, if not entirely, influenced by the appropriateness of empirical antibiotic treatment and length of hospital stay. Conclusion: Patients with BSI due to ESBL-producing ESBL-EK incur higher costs compared to those with non-ESBL-EK BSI. This cost disparity is rooted in varying rates of effective empirical antimicrobial therapy and differences in hospital stay durations. A nuanced approach, incorporating a thorough understanding of regional epidemiological trends and judicious antibiotic use, is crucial for mitigating the financial impact on patients.

A decision support tool for risk–benefit analysis of Japanese encephalitis vaccine in travellers

Background: During pre-travel consultations, clinicians and travellers face the challenge of weighing the risks verus benefits of Japanese encephalitis (JE) vaccination due to the high cost of the vaccine, low incidence in travellers (∼1 in 1 million), but potentially severe consequences (∼30% case-fatality rate). Personalised JE risk assessment based on the travellers’ demographics and travel itinerary is challenging using standard risk matrices. We developed an interactive digital tool to estimate risks of JE infection and severe health outcomes under different scenarios to facilitate shared decision-making between clinicians and travellers. Methods: A Bayesian network (conditional probability) model risk–benefit analysis of JE vaccine in travellers was developed. The model considers travellers’ characteristics (age, sex, co-morbidities), itinerary (destination, departure date, duration, setting of planned activities) and vaccination status to estimate the risks of JE infection, the development of symptomatic disease (meningitis, encephalitis), clinical outcomes (hospital admission, chronic neurological complications, death) and adverse events following immunization. Results: In low-risk travellers (e.g. to urban areas for <1 month), the risk of developing JE and dying is low (<1 per million) irrespective of the destination; thus, the potential impact of JE vaccination in reducing the risk of clinical outcomes is limited. In high-risk travellers (e.g. to rural areas in high JE incidence destinations for >2 months), the risk of developing symptomatic disease and mortality is estimated at 9.5 and 1.4 per million, respectively. JE vaccination in this group would significantly reduce the risk of symptomatic disease and mortality (by ∼80%) to 1.9 and 0.3 per million, respectively.

A country-wide health policy in Chile for deaf adults using cochlear implants: Analysis of health determinants and social impacts

Background Post-lingual deafness represents a critical challenge for adults’ well-being with substantial public health burdens. One treatment of choice has been cochlear implants (CI) for people with severe to profound hearing loss (HL). Since 2018, Chile has implemented a high-cost policy to cover CI treatment, the “Ley Ricarte Soto" (LRS) health policy. However, wide variability exists in the use of this device. To date, no related study has been published on policy evaluation in Chile or other Latin American countries. Objectives This study aimed to evaluate the impact of the LRS policy on the treatment success and labour market inclusion among deaf or hard of hearing (DHH) adults using CI. We examined and characterised outcomes based on self-reports about treatment success and occupation status between 2018 and 2020. Design We performed a prospective study using hospital clinical records and an online questionnaire with 76 DHH adults aged >15 who had received CIs since the introduction of the LRS policy in 2018. Using univariate and multivariate regression models, we investigated the relationship between demographic, audiological, and social determinants of health and outcomes, including treatment success for social inclusion (International Outcome inventory for Hearing Aids and CIs assessment: IOI-HA) and occupation status for labour market inclusion. Results Our study showed elevated levels of treatment success in most of the seven sub-scores of the IOI-HA assessment. Similarly, around 70% of participants maintained or improved their occupations after receiving their CI. We found a significant positive association between treatment success and market inclusion. Participants diagnosed at younger ages had better results than older participants in both outcomes. Regarding social determinants of health, findings suggested participants with high social health insurance and a shorter commute time to the clinic had better results in treatment success. For labour market inclusion, participants with high education levels and better pre- CI occupation had better post-CI occupation status. Conclusions In evaluating the LRS policy for providing CIs for DHH adults in Chile, we found positive effects relating to treatment success and occupation status. Our study supports the importance of age at diagnosis and social determinants of health, which should be assessed by integrating public services and bringing them geographically closer to each beneficiary. Although evidence-based guidelines for candidate selection given by the LRS policy might contribute to good results, these guidelines could limit the policy access to people who do not meet the requirements of the guidelines due to social inequalities.

Antibiotic Consumption During the Coronavirus Disease 2019 Pandemic and Emergence of Carbapenemase-Producing Klebsiella pneumoniae Lineages Among Inpatients in a Chilean Hospital: A Time-Series Study and Phylogenomic Analysis

Background: The impact of coronavirus disease 2019 (COVID-19) on antimicrobial use (AU) and resistance has not been well evaluated in South America. These data are critical to inform national policies and clinical care. Methods: At a tertiary hospital in Santiago, Chile, between 2018 and 2022, subdivided into pre- (3/2018-2/2020) and post-COVID-19 onset (3/2020-2/2022), we evaluated intravenous AU and frequency of carbapenem-resistant Enterobacterales (CRE). We grouped monthly AU (defined daily doses [DDD]/1000 patient-days) into broad-spectrum β-lactams, carbapenems, and colistin and used interrupted time-series analysis to compare AU during pre- and post-pandemic onset. We studied the frequency of carbapenemase-producing (CP) CRE and performed whole-genome sequencing analyses of all carbapenem-resistant (CR) Klebsiella pneumoniae (CRKpn) isolates collected during the study period. Results: Compared with pre-pandemic, AU (DDD/1000 patient-days) significantly increased after the pandemic onset, from 78.1 to 142.5 (P

Global Pain and Aging: A Cross-Sectional Study on Age Differences in the Intensity of Chronic Pain Among Middle-Aged and Older Adults in 20 Countries

OBJECTIVES: This study aims to examine age differences in the intensity of chronic pain among middle-aged and older adults, where intensity is measured on a scale differentiating between chronic pain that is often troubling and likely requires intervention versus more endurable sensations. We aim to explore whether individual health and national gross domestic product (GDP) explain these differences as well. METHODS: Cross-nationally harmonized data from 20 countries on self-reported intensity of chronic pain (0 = no, 1 = mild, 2 = moderate, 3 = severe) in 104,826 individuals aged 50+ observed in 2012-2013. Two-level hierarchical ordinal linear models with individuals nested within countries were used to isolate estimations from heterogeneity explained by methodological differences across single-country studies. RESULTS: Overall, mean participant age was 66.9 (SD = 9.9), 56.1% were women, and 41.9% of respondents reported any chronic pain. Chronic pain intensity rose sharply with age in some countries (e.g., Korea and Slovenia), but this association waned or reversed in other countries (e.g., the United States and Denmark). Cross-country variation and age differences in chronic pain were partly explained (85.5% and 35.8%, respectively) by individual-level health (especially arthritis), country-level wealth (as indicated by GDP per capita), and demographics. DISCUSSION: Chronic pain intensity is not an inevitable consequence of chronological age, but the consequence of potential selection effects and lower activity levels combined with individual-level health and country-level wealth. Our findings suggest further investigation of health conditions and country affluence settings as potential targets of medical and policy interventions aiming to prevent, reduce, or manage chronic pain among older patients and aging populations.

Global mortality associated with 33 bacterial pathogens in 2019: a systematic analysis for the Global Burden of Disease Study 2019

Background: Reducing the burden of death due to infection is an urgent global public health priority. Previous studies have estimated the number of deaths associated with drug-resistant infections and sepsis and found that infections remain a leading cause of death globally. Understanding the global burden of common bacterial pathogens (both susceptible and resistant to antimicrobials) is essential to identify the greatest threats to public health. To our knowledge, this is the first study to present global comprehensive estimates of deaths associated with 33 bacterial pathogens across 11 major infectious syndromes. Methods: We estimated deaths associated with 33 bacterial genera or species across 11 infectious syndromes in 2019 using methods from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, in addition to a subset of the input data described in the Global Burden of Antimicrobial Resistance 2019 study. This study included 343 million individual records or isolates covering 11 361 study-location-years. We used three modelling steps to estimate the number of deaths associated with each pathogen: deaths in which infection had a role, the fraction of deaths due to infection that are attributable to a given infectious syndrome, and the fraction of deaths due to an infectious syndrome that are attributable to a given pathogen. Estimates were produced for all ages and for males and females across 204 countries and territories in 2019. 95% uncertainty intervals (UIs) were calculated for final estimates of deaths and infections associated with the 33 bacterial pathogens following standard GBD methods by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. Findings: From an estimated 13·7 million (95% UI 10·9–17·1) infection-related deaths in 2019, there were 7·7 million deaths (5·7–10·2) associated with the 33 bacterial pathogens (both resistant and susceptible to antimicrobials) across the 11 infectious syndromes estimated in this study. We estimated deaths associated with the 33 bacterial pathogens to comprise 13·6% (10·2–18·1) of all global deaths and 56·2% (52·1–60·1) of all sepsis-related deaths in 2019. Five leading pathogens—Staphylococcus aureus, Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, and Pseudomonas aeruginosa—were responsible for 54·9% (52·9–56·9) of deaths among the investigated bacteria. The deadliest infectious syndromes and pathogens varied by location and age. The age-standardised mortality rate associated with these bacterial pathogens was highest in the sub-Saharan Africa super-region, with 230 deaths (185–285) per 100 000 population, and lowest in the high-income super-region, with 52·2 deaths (37·4–71·5) per 100 000 population. S aureus was the leading bacterial cause of death in 135 countries and was also associated with the most deaths in individuals older than 15 years, globally. Among children younger than 5 years, S pneumoniae was the pathogen associated with the most deaths. In 2019, more than 6 million deaths occurred as a result of three bacterial infectious syndromes, with lower respiratory infections and bloodstream infections each causing more than 2 million deaths and peritoneal and intra-abdominal infections causing more than 1 million deaths. Interpretation: The 33 bacterial pathogens that we investigated in this study are a substantial source of health loss globally, with considerable variation in their distribution across infectious syndromes and locations. Compared with GBD Level 3 underlying causes of death, deaths associated with these bacteria would rank as the second leading cause of death globally in 2019; hence, they should be considered an urgent priority for intervention within the global health community. Strategies to address the burden of bacterial infections include infection prevention, optimised use of antibiotics, improved capacity for microbiological analysis, vaccine development, and improved and more pervasive use of available vaccines. These estimates can be used to help set priorities for vaccine need, demand, and development. Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care, using UK aid funding managed by the Fleming Fund.

Transmission of gram-negative antibiotic-resistant bacteria following differing exposure to antibiotic-resistance reservoirs in a rural community: a modelling study for bloodstream infections

Exposure to community reservoirs of gram-negative antibiotic-resistant bacteria (GN-ARB) genes poses substantial health risks to individuals, complicating potential infections. Transmission networks and population dynamics remain unclear, particularly in resource-poor communities. We use a dynamic compartment model to assess GN-ARB transmission quantitatively, including the susceptible, colonised, infected, and removed populations at the community-hospital interface. We used two side streams to distinguish between individuals at high- and low-risk exposure to community ARB reservoirs. The model was calibrated using data from a cross-sectional cohort study (N = 357) in Chile and supplemented by existing literature. Most individuals acquired ARB from the community reservoirs (98%) rather than the hospital. High exposure to GN-ARB reservoirs was associated with 17% and 16% greater prevalence for GN-ARB carriage in the hospital and community settings, respectively. The higher exposure has led to 16% more infections and attributed mortality. Our results highlight the need for early-stage identification and testing capability of bloodstream infections caused by GN-ARB through a faster response at the community level, where most GN-ARB are likely to be acquired. Increasing treatment rates for individuals colonised or infected by GN-ARB and controlling the exposure to antibiotic consumption and GN-ARB reservoirs, is crucial to curve GN-ABR transmission.

The gap in life expectancy and lifespan inequality between Iran and neighbour countries: the contributions of avoidable causes of death

Background: Healthcare system and intersectoral public health policies play a crucial role in improving population health and reducing health inequalities. This study aimed to quantify their impact, operationalized as avoidable deaths, on the gap in life expectancy (LE) and lifespan inequality (LI) between Iran and three neighbour countries viz., Turkey, Qatar, and Kuwait in 2015–2016. Methods: Annual data on population and causes of deaths by age and sex for Iran and three neighbour countries were obtained from the World Health Organization mortality database for the period 2015–2016. A recently developed list by the OECD/Eurostat was used to identify avoidable causes of death (with an upper age limit of 75). The cross-country gaps in LE and LI (measured by standard deviation) were decomposed by age and cause of death using a continuous-change model. Results: Iranian males and females had the second lowest and lowest LE, respectively, compared with their counterparts in the neighbour countries. On the other hand, the highest LIs in both sexes (by 2.3 to 4.5 years in males and 1.1 to 3.3 years in females) were observed in Iran. Avoidable causes contributed substantially to the LE and LI gap in both sexes with injuries and maternal/infant mortality represented the greatest contributions to the disadvantages in Iranian males and females, respectively. Conclusions: Higher mortality rates in young Iranians led to a double burden of inequality –shorter LE and greater uncertainty at timing of death. Strengthening intersectoral public health policies and healthcare quality targeted at averting premature deaths, especially from injuries among younger people, can mitigate this double burden.

Population-level risks of alcohol consumption by amount, geography, age, sex, and year: a systematic analysis for the Global Burden of Disease Study 2020

Background: The health risks associated with moderate alcohol consumption continue to be debated. Small amounts of alcohol might lower the risk of some health outcomes but increase the risk of others, suggesting that the overall risk depends, in part, on background disease rates, which vary by region, age, sex, and year. Methods: For this analysis, we constructed burden-weighted dose–response relative risk curves across 22 health outcomes to estimate the theoretical minimum risk exposure level (TMREL) and non-drinker equivalence (NDE), the consumption level at which the health risk is equivalent to that of a non-drinker, using disease rates from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020 for 21 regions, including 204 countries and territories, by 5-year age group, sex, and year for individuals aged 15–95 years and older from 1990 to 2020. Based on the NDE, we quantified the population consuming harmful amounts of alcohol. Findings: The burden-weighted relative risk curves for alcohol use varied by region and age. Among individuals aged 15–39 years in 2020, the TMREL varied between 0 (95% uncertainty interval 0–0) and 0·603 (0·400–1·00) standard drinks per day, and the NDE varied between 0·002 (0–0) and 1·75 (0·698–4·30) standard drinks per day. Among individuals aged 40 years and older, the burden-weighted relative risk curve was J-shaped for all regions, with a 2020 TMREL that ranged from 0·114 (0–0·403) to 1·87 (0·500–3·30) standard drinks per day and an NDE that ranged between 0·193 (0–0·900) and 6·94 (3·40–8·30) standard drinks per day. Among individuals consuming harmful amounts of alcohol in 2020, 59·1% (54·3–65·4) were aged 15–39 years and 76·9% (73·0–81·3) were male. Interpretation: There is strong evidence to support recommendations on alcohol consumption varying by age and location. Stronger interventions, particularly those tailored towards younger individuals, are needed to reduce the substantial global health loss attributable to alcohol. Funding: Bill & Melinda Gates Foundation.

The impact of time of entrance to center-based care on children’s general, language, and behavioral development

There are contrasting results of the association between center-based care attendance and child development, mainly related to how the time of entry and permanence in the program relates to developmental outcomes. Using latent class analysis in a nationally representative sample of Chilean children between 6 and 35 months old (n = 3,992), and controlling for the child’s age, maternal education, mother’s marital status, and household income, we identify three different timings of entrance in center-based care programs. The three timings of entrance were defined as early-entry (16%), those children who are more likely to enter before they are 6 months old; middle-entry (16%), those who are more likely to enter when they are between 6 and 18 months old; and late-entry (68%), those children with a low probability of enrollment any time before they are 35 months old. We found that children from the early- and middle-entry classes had higher language development when compared with children from the late-entry class. Still, only those from the middle-entry class showed higher general development in the Battelle test. In contrast, children in the early- and middle-entry classes presented higher scores in the Child Behavior Checklist’s externalizing behavior scale than children in the late-entry class. Our findings highlight the existence of a likely linkage between the timing of entry to center-based care and child development. It is essential to understand the potential advantages of center-based care in younger children, especially in enhancing their vocabulary and general development, and the potential negative association of early-entry with problematic behavior.

Impact of COVID-19 pandemic on the mental health of healthcare workers

Background: Healthcare workers' mental health was affected by SARS-CoV-2 pandemic. Aim: To evaluate healthcare workers' mental health and its associated factors during the pandemic in Chile. Material and Methods: An online self-reported questionnaire was designed including the Goldberg Health Questionnaire, the Patient Health Questionnaire, (PHQ-9), and the Columbia-Suicide Severity Rating Scale among other questions. It was sent to 28,038 healthcare workers. Results: The questionnaire was answered by 1,934 participants, with a median age of 38 years (74% women). Seventy five percent were professionals, and 48% worked at a hospital. Fifty nine percent of respondents had a risk of having a mental health disorder, and 73% had depressive symptoms. Significant associations were found with sex, workplace, and some of the relevant experiences during the pandemic. Fifty one percent reported the need for mental health support, and 38% of them received it. Conclusions: There is a high percentage of health workers with symptoms of psychological distress, depression, and suicidal ideas. The gender approach is essential to understand the important differences found. Many health workers who required mental health care did not seek or received it.

Exploring the Relationship between Climate Change and Antimicrobial-resistant Bacteria: To What Extent Does This Present a Current and Long-term Threat to Population Health?

Climate change and antimicrobial-resistant bacteria (AMR) have been studied as two separate problems affecting population health. Mortality attributable to AMR could reach up to 10 million people by 2050, becoming the most important challenge for global health. However, little is known about the changing environmental factors that could facilitate the spread of AMR infections. The article explores the linkage between climate change and AMR, in particular through the role of temperature, humidity, and the presence of metals in the environment. The PRISMA method was used for the systematic review based on the PubMed database. Previous research shows that warmer, more humid, and more highly polluted environments have a direct positive impact on the growth of microorganisms and most resistant bacteria. Global warming and structural changes in bacterial habitat, because of climate change, might result in new environmental conditions that facilitate the dissemination of AMR from a biological and reproductive perspective. This would have an impact on population health in the short- and long term because simple infections are becoming more aggressive as bacteria mutate constantly owing to the higher concentration of elements boosting their resistant capacity in their habitats. As a result, the morbidity and mortality of AMR could become more widespread as climate changes continue. Finally, the linkage between AMR and climate change is consistent and clear across different types of microorganisms and classes of antibiotics, and therefore the burden of AMR could be catastrophic if regulations on the environment, in the form of prevention policies, are not instituted in the future.

The impact of weight loss interventions on disordered eating symptoms in people with overweight and obesity: a systematic review & meta-analysis

Background: It is unclear whether weight loss interventions worsen disordered eating in people living with overweight/obesity. We aimed to systematically evaluate the association between weight loss interventions and disordered eating. Methods: Six databases were searched from inception until September 2024. Trials of weight loss interventions in people with overweight/obesity were included if they reported a validated score for disordered eating on either the Eating Disorder Examination Interview or the Eating Disorder Examination Questionnaire pre- and post-intervention. Interventions included behavioural weight loss programmes (BWL) and pharmacotherapy licenced for weight loss, with or without concurrent psychological support, provided for at least 4 weeks. Pooled standardised mean differences (SMD) in scores of disordered eating were calculated using random effects meta-analyses. Risk of bias (RoB) was assessed using the Cochrane RoB 2 tool and the Newcastle–Ottawa scale for randomised and single-arm trials, respectively (PROSPERO ID: CRD42023404792). Findings: Thirty-eight studies with 66 eligible arms (61 interventions: 29 BWL, 11 BWL + pharmacotherapy, 20 BWL + psychological intervention, 1 pharmacotherapy + psychological intervention) and 3364 participants in total were included. The mean weight change was −4.7 kg (95% CI: −5.7, −3.7). Compared with baseline, disordered eating scores improved by −1.47 SMD units (95% CI: −1.67, −1.27, p < 0.001, I2 = 94%) at intervention completion (median of 4 months). Seven randomised trials that directly compared a weight loss intervention to no/minimal intervention reported an improvement of −0.49 SMD units (95% CI, −0.93, −0.04, p = 0.0035, I2 = 73%). Sub-group analyses showed: (a) disordered eating scores improved more in people with an eating disorder at baseline compared with people without high scores, (b) no clear evidence that the association depended upon intervention type, and (c) disordered eating scores improved more in trials rated at low overall RoB. Interpretation: Despite heterogeneity in effect size, weight loss interventions consistently improved disordered eating scores. These findings provide reassurance that weight loss interventions might not worsen disordered eating and may improve it. Funding: Novo Nordisk UK Research Foundation Doctoral Fellowship in Clinical Diabetes.

Accelerating access to diagnostic tools: perspectives from the joint international tropical medicine meeting 2023.

The relative toxicity of medicines detected after poisoning suicide deaths in Australia, 2013–19: a data linkage case series study

AbstractObjectiveTo compare the toxicity (relative to population use) and lethality (relative to poisoning events) of medicines involved in poisoning suicides in Australia; to determine the proportions of cases in which the medicines had recently been dispensed to the deceased person.Study designCase series study; analysis of linked National Coronial Information System (NCIS) and Pharmaceutical Benefits Scheme (PBS) data.Setting, participantsClosed coronial cases for deaths of people aged ten years or older deemed to have been medicine poisoning suicides (including multiple cause deaths), Australia, 1 July 2013 – 10 October 2019, with recorded post mortem toxicology findings.Main outcome measuresFatal toxicity index (FTI): deaths per million years of use at the defined daily dose in Australia (2013–2015); proportion of FTI attributable to medicines dispensed to the deceased person during the twelve months preceding their death; estimated case fatality: deaths per number of calls to poisons information centres regarding the medicine (based on the number of calls to the NSW Poisons Information Centre, 2013–2017).ResultsDuring 2013–19, 2132 deaths were classified as medicine poisoning suicide deaths (median age, 51 years [interquartile range, 39–64 years]; 1036 girls or women [49%]). The 5703 detected substances deemed to have contributed to death included 140 medicines. The overall FTI was 32.0 (95% confidence interval [CI], 30.6–33.3) deaths per million years of use; overall estimated case fatality was 1.28% (95% CI, 1.23–1.34%) of poisoning events. FTI and estimated case fatality (each log10 transformed) were moderately correlated (R2 = 0.66). Both values were relatively high for most opioids, sedative psychotropics, and tricyclic antidepressants. Specific medicines with high values were phenobarbitone, oxycodone, morphine, clonazepam, nortriptyline, and propranolol; they were relatively low for risperidone and lithium. The proportions of opioids and hypnosedatives that had been recently dispensed to the deceased persons were smaller than for antidepressant, antipsychotic, and antiepileptic medicines.ConclusionsTo reduce the risk of suicide, access to medicines of greater toxicity and lethality should be restricted, including by staged supply (regular supply of medicines in limited quantities), and limiting pack sizes; real‐time prescription monitoring could detect and minimise stockpiling.