A922 Sequential measurement of 1 hour creatinine clearance (1-CRCL) in critically ill patients at risk of acute kidney injury (AKI)

Meeting abstrac

A dexamethasone prodrug reduces the renal macrophage response and provides enhanced resolution of established murine lupus nephritis

We evaluated the ability of a macromolecular prodrug of dexamethasone (P-Dex) to treat lupus nephritis in (NZB × NZW)F1 mice. We also explored the mechanism underlying the anti-inflammatory effects of this prodrug. P-Dex eliminated albuminuria in most (NZB × NZW)F1 mice. Furthermore, P-Dex reduced the incidence of severe nephritis and extended lifespan in these mice. P-Dex treatment also prevented the development of lupus-associated hypertension and vasculitis. Although P-Dex did not reduce serum levels of anti-dsDNA antibodies or glomerular immune complexes, P-Dex reduced macrophage recruitment to the kidney and attenuated tubulointerstitial injury. In contrast to what was observed with free dexamethasone, P-Dex did not induce any deterioration of bone quality. However, P-Dex did lead to reduced peripheral white blood cell counts and adrenal gland atrophy. These results suggest that P-Dex is more effective and less toxic than free dexamethasone for the treatment of lupus nephritis in (NZB × NZW)F1 mice. Furthermore, the data suggest that P-Dex may treat nephritis by attenuating the renal inflammatory response to immune complexes, leading to decreased immune cell infiltration and diminished renal inflammation and injury

ICAR: endoscopic skull‐base surgery

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Measuring routine childhood vaccination coverage in 204 countries and territories, 1980-2019: a systematic analysis for the Global Burden of Disease Study 2020, Release 1

Background: Measuring routine childhood vaccination is crucial to inform global vaccine policies and programme implementation, and to track progress towards targets set by the Global Vaccine Action Plan (GVAP) and Immunization Agenda 2030. Robust estimates of routine vaccine coverage are needed to identify past successes and persistent vulnerabilities. Drawing from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2020, Release 1, we did a systematic analysis of global, regional, and national vaccine coverage trends using a statistical framework, by vaccine and over time. // Methods: For this analysis we collated 55 326 country-specific, cohort-specific, year-specific, vaccine-specific, and dose-specific observations of routine childhood vaccination coverage between 1980 and 2019. Using spatiotemporal Gaussian process regression, we produced location-specific and year-specific estimates of 11 routine childhood vaccine coverage indicators for 204 countries and territories from 1980 to 2019, adjusting for biases in country-reported data and reflecting reported stockouts and supply disruptions. We analysed global and regional trends in coverage and numbers of zero-dose children (defined as those who never received a diphtheria-tetanus-pertussis [DTP] vaccine dose), progress towards GVAP targets, and the relationship between vaccine coverage and sociodemographic development. // Findings: By 2019, global coverage of third-dose DTP (DTP3; 81·6% [95% uncertainty interval 80·4–82·7]) more than doubled from levels estimated in 1980 (39·9% [37·5–42·1]), as did global coverage of the first-dose measles-containing vaccine (MCV1; from 38·5% [35·4–41·3] in 1980 to 83·6% [82·3–84·8] in 2019). Third-dose polio vaccine (Pol3) coverage also increased, from 42·6% (41·4–44·1) in 1980 to 79·8% (78·4–81·1) in 2019, and global coverage of newer vaccines increased rapidly between 2000 and 2019. The global number of zero-dose children fell by nearly 75% between 1980 and 2019, from 56·8 million (52·6–60·9) to 14·5 million (13·4–15·9). However, over the past decade, global vaccine coverage broadly plateaued; 94 countries and territories recorded decreasing DTP3 coverage since 2010. Only 11 countries and territories were estimated to have reached the national GVAP target of at least 90% coverage for all assessed vaccines in 2019. // Interpretation: After achieving large gains in childhood vaccine coverage worldwide, in much of the world this progress was stalled or reversed from 2010 to 2019. These findings underscore the importance of revisiting routine immunisation strategies and programmatic approaches, recentring service delivery around equity and underserved populations. Strengthening vaccine data and monitoring systems is crucial to these pursuits, now and through to 2030, to ensure that all children have access to, and can benefit from, lifesaving vaccines

Efficacy of Major Plant Extracts/Molecules on Field Insect Pests

Insect pests are considered the major hurdle in enhancing the production and productivity of any farming system. The use of conventional synthetic pesticides has led to the emergence of pesticide-resistant insects, environmental pollution, and negative effects on natural enemies, which have caused an ecological imbalance of the predator-prey ratio and human health hazards; therefore, eco-friendly alternative strategies are required. The plant kingdom, a rich repertoire of secondary metabolites, can be tapped as an alternative for insect pest management strategies. A number of plants have been documented to have insecticidal properties against various orders of insects in vitro by acting as antifeedants, repellents, sterilant and oviposition deterrents, etc. However, only a few plant compounds are applicable at the field level or presently commercialised. Here, we have provided an overview of the broad-spectrum insecticidal activity of plant compounds from neem, Annona, Pongamia, and Jatropha. Additionally, the impact of medicinal plants, herbs, spices, and essential oils has been reviewed briefl

Global, regional, and national burden of rheumatoid arthritis, 1990–2020, and projections to 2050: a systematic analysis of the Global Burden of Disease Study 2021

Background Rheumatoid arthritis is a chronic autoimmune inflammatory disease associated with disability and premature death. Up-to-date estimates of the burden of rheumatoid arthritis are required for health-care planning, resource allocation, and prevention. As part of the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021, we provide updated estimates of the prevalence of rheumatoid arthritis and its associated deaths and disability-adjusted life-years (DALYs) by age, sex, year, and location, with forecasted prevalence to 2050. Methods Rheumatoid arthritis prevalence was estimated in 204 countries and territories from 1990 to 2020 using Bayesian meta-regression models and data from population-based studies and medical claims data (98 prevalence and 25 incidence studies). Mortality was estimated from vital registration data with the Cause of Death Ensemble model (CODEm). Years of life lost (YLL) were calculated with use of standard GBD lifetables, and years lived with disability (YLDs) were estimated from prevalence, a meta-analysed distribution of rheumatoid arthritis severity, and disability weights. DALYs were calculated by summing YLLs and YLDs. Smoking was the only risk factor analysed. Rheumatoid arthritis prevalence was forecast to 2050 by logistic regression with Socio-Demographic Index as a predictor, then multiplying by projected population estimates. Findings In 2020, an estimated 17·6 million (95% uncertainty interval 15·8–20·3) people had rheumatoid arthritis worldwide. The age-standardised global prevalence rate was 208·8 cases (186·8–241·1) per 100 000 population, representing a 14·1% (12·7–15·4) increase since 1990. Prevalence was higher in females (age-standardised female-to-male prevalence ratio 2·45 [2·40–2·47]). The age-standardised death rate was 0·47 (0·41–0·54) per 100 000 population (38 300 global deaths [33 500–44 000]), a 23·8% (17·5–29·3) decrease from 1990 to 2020. The 2020 DALY count was 3 060 000 (2 320 000–3 860 000), with an age-standardised DALY rate of 36·4 (27·6–45·9) per 100 000 population. YLDs accounted for 76·4% (68·3–81·0) of DALYs. Smoking risk attribution for rheumatoid arthritis DALYs was 7·1% (3·6–10·3). We forecast that 31·7 million (25·8–39·0) individuals will be living with rheumatoid arthritis worldwide by 2050. Interpretation Rheumatoid arthritis mortality has decreased globally over the past three decades. Global age-standardised prevalence rate and YLDs have increased over the same period, and the number of cases is projected to continue to increase to the year 2050. Improved access to early diagnosis and treatment of rheumatoid arthritis globally is required to reduce the future burden of the disease. Funding Bill & Melinda Gates Foundation, Institute of Bone and Joint Research, and Global Alliance for Musculoskeletal Health

Global, regional, and national sex-specific burden and control of the HIV epidemic, 1990-2019, for 204 countries and territories: the Global Burden of Diseases Study 2019.

BACKGROUND: The sustainable development goals (SDGs) aim to end HIV/AIDS as a public health threat by 2030. Understanding the current state of the HIV epidemic and its change over time is essential to this effort. This study assesses the current sex-specific HIV burden in 204 countries and territories and measures progress in the control of the epidemic. METHODS: To estimate age-specific and sex-specific trends in 48 of 204 countries, we extended the Estimation and Projection Package Age-Sex Model to also implement the spectrum paediatric model. We used this model in cases where age and sex specific HIV-seroprevalence surveys and antenatal care-clinic sentinel surveillance data were available. For the remaining 156 of 204 locations, we developed a cohort-incidence bias adjustment to derive incidence as a function of cause-of-death data from vital registration systems. The incidence was input to a custom Spectrum model. To assess progress, we measured the percentage change in incident cases and deaths between 2010 and 2019 (threshold >75% decline), the ratio of incident cases to number of people living with HIV (incidence-to-prevalence ratio threshold <0·03), and the ratio of incident cases to deaths (incidence-to-mortality ratio threshold <1·0). FINDINGS: In 2019, there were 36·8 million (95% uncertainty interval [UI] 35·1-38·9) people living with HIV worldwide. There were 0·84 males (95% UI 0·78-0·91) per female living with HIV in 2019, 0·99 male infections (0·91-1·10) for every female infection, and 1·02 male deaths (0·95-1·10) per female death. Global progress in incident cases and deaths between 2010 and 2019 was driven by sub-Saharan Africa (with a 28·52% decrease in incident cases, 95% UI 19·58-35·43, and a 39·66% decrease in deaths, 36·49-42·36). Elsewhere, the incidence remained stable or increased, whereas deaths generally decreased. In 2019, the global incidence-to-prevalence ratio was 0·05 (95% UI 0·05-0·06) and the global incidence-to-mortality ratio was 1·94 (1·76-2·12). No regions met suggested thresholds for progress. INTERPRETATION: Sub-Saharan Africa had both the highest HIV burden and the greatest progress between 1990 and 2019. The number of incident cases and deaths in males and females approached parity in 2019, although there remained more females with HIV than males with HIV. Globally, the HIV epidemic is far from the UNAIDS benchmarks on progress metrics. FUNDING: The Bill & Melinda Gates Foundation, the National Institute of Mental Health of the US National Institutes of Health (NIH), and the National Institute on Aging of the NIH

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

Prevalence, years lived with disability, and trends in anaemia burden by severity and cause, 1990-2021: findings from the Global Burden of Disease Study 2021

Background Anaemia is a major health problem worldwide. Global estimates of anaemia burden are crucial for developing appropriate interventions to meet current international targets for disease mitigation. We describe the prevalence, years lived with disability, and trends of anaemia and its underlying causes in 204 countries and territories. Methods We estimated population-level distributions of haemoglobin concentration by age and sex for each location from 1990 to 2021. We then calculated anaemia burden by severity and associated years lived with disability (YLDs). With data on prevalence of the causes of anaemia and associated cause-specific shifts in haemoglobin concentrations, we modelled the proportion of anaemia attributed to 37 underlying causes for all locations, years, and demographics in the Global Burden of Disease Study 2021. Findings In 2021, the global prevalence of anaemia across all ages was 24·3% (95% uncertainty interval [UI] 23·9–24·7), corresponding to 1·92 billion (1·89–1·95) prevalent cases, compared with a prevalence of 28·2% (27·8–28·5) and 1·50 billion (1·48–1·52) prevalent cases in 1990. Large variations were observed in anaemia burden by age, sex, and geography, with children younger than 5 years, women, and countries in sub-Saharan Africa and south Asia being particularly affected. Anaemia caused 52·0 million (35·1–75·1) YLDs in 2021, and the YLD rate due to anaemia declined with increasing Socio-demographic Index. The most common causes of anaemia YLDs in 2021 were dietary iron deficiency (cause-specific anaemia YLD rate per 100 000 population: 422·4 [95% UI 286·1–612·9]), haemoglobinopathies and haemolytic anaemias (89·0 [58·2–123·7]), and other neglected tropical diseases (36·3 [24·4–52·8]), collectively accounting for 84·7% (84·1–85·2) of anaemia YLDs. Interpretation Anaemia remains a substantial global health challenge, with persistent disparities according to age, sex, and geography. Estimates of cause-specific anaemia burden can be used to design locally relevant health interventions aimed at improving anaemia management and prevention. Funding Bill & Melinda Gates Foundation