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Background: Infectious diseases are a major cause of mortality in spite of existing public health, anti-microbial and vaccine interventions. We aimed to define plasma proteomic associates of infection mortality and then apply Mendelian randomisation (MR) to yield biomarkers that may be causally associated., Methods: We used UK Biobank plasma proteomic data to associate 2923 plasma proteins with infection mortality before 31st December 2019 (240 events in 52,520 participants). Since many plasma proteins also predict non-infection mortality, we focussed on those associated with >1.5-fold risk of infection mortality in an analysis excluding survivors. Protein quantitative trait scores (pQTS) were then used to identify whether genetically predicted protein levels also associated with infection mortality. To conduct Two Sample MR, we performed a genome-wide association study (GWAS) of infection mortality using UK Biobank participants without plasma proteomic data (n = 363,953 including 984 infection deaths)., Findings: After adjusting for clinical risk factors, 1142 plasma proteins were associated with risk of infection mortality (false discovery rate <0.05). 259 proteins were associated with >1.5-fold increased risk of infection versus non-infection mortality. Of these, we identified genetically predicted increasing MERTK concentration was associated with increased risk of infection mortality. MR supported a causal association between increasing plasma MERTK protein and infection mortality (odds ratio 1.46 per unit; 95% CI 1.15- 1.85; p = 0.002)., Conclusion: Plasma MERTK is causally associated with infection mortality and warrants exploration as a potential therapeutic target., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: RMC has received speaker’s fees from Janssen Oncology. AWM has received speaker’s fees from Vifor, consultancy fees from Vifor and AstraZenca on behalf of the University of Leeds and investigator-initiated project funding from Roche Products Limited in the last 3 years., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Infectious diseases (ID) physicians are increasingly faced with the challenge of caring for patients with terminal illnesses or incurable infections., Methods: This was a retrospective cohort of all patients with an ID consult within an academic health system from 1 January 2014 through 31 December 2023, including community, general, and transplant ID consult services., Results: There were 60 820 inpatient ID consults (17 235 community, 29 999 general, and 13 586 transplant) involving 37 848 unique patients. The number of consults increased by 94% and the rate rose from 5.0 to 9.9 consults per 100 inpatients (P < .001). In total, 7.5% of patients receiving an ID consult died during admission and 1006 (2.6%) of patients were discharged to hospice. In-hospital mortality was 5.2% for community ID, 7.8% for general ID, and 10.7% for transplant ID patients (P < .001). Six-month mortality was 9% for all nonobstetric admissions versus 19% for community ID, 20.9% for general ID, and 22.3% for transplant ID. In total 2866 (7.6%) of all patients receiving ID consultation also received palliative care consultation during the same hospitalization. The index ID consult preceded any palliative consult in the majority (69.5%) of cases. A total of 16.3% of patients had a do-not-resuscitate order during the index hospitalization; 12.2% of all patients with a do-not-resuscitate order had this placed on the same day as the ID consult., Conclusions: Patients receiving ID consultation were increasingly complex and more likely to die soon after consultation. These results provide a framework for ID clinicians to consider their role in end-of-life care., Competing Interests: Potential conflicts of interest. The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Objectives: Data supporting routine infectious diseases (ID) consultation in gram-negative bloodstream infection (GN-BSI) are limited. We evaluated the association between ID consultation and mortality in patients with GN-BSI in a retrospective population-wide cohort study in Ontario using linked health administrative databases., Methods: Hospitalized adult patients with GN-BSI between April 2017 and December 2021 were included. The primary outcome was time to all-cause mortality censored at 30 days, analyzed using a mixed effects Cox proportional hazards model with hospital as a random effect. ID consultation 1-10 days after the first positive blood culture was treated as a time-varying exposure., Results: Of 30 159 patients with GN-BSI across 53 hospitals, 11 013 (36.5%) received ID consultation. Median prevalence of ID consultation for patients with GN-BSI across hospitals was 35.0% with wide variability (range 2.7%-76.1%, interquartile range 19.6%-41.1%). In total, 1041 (9.5%) patients who received ID consultation died within 30 days, compared to 1797 (9.4%) patients without ID consultation. In the fully adjusted multivariable model, ID consultation was associated with mortality benefit (adjusted hazard ratio [HR] 0.82, 95% confidence interval [CI] .77-.88, P < .0001; translating to absolute risk reduction of -3.8% or number needed to treat [NNT] of 27). Exploratory subgroup analyses of the primary outcome showed that ID consultation could have greater benefit in patients with high-risk features (nosocomial infection, polymicrobial or non-Enterobacterales infection, antimicrobial resistance, or non-urinary tract source)., Conclusions: Early ID consultation was associated with reduced mortality in patients with GN-BSI. If resources permit, routine ID consultation for this patient population should be considered to improve patient outcomes., Competing Interests: Potential conflicts of interest . The authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Background: Infectious diseases remain a major global health concern, including in China, with an estimated >10 million cases of infectious disease in 2019. We describe the burden of site-specific infectious diseases among Chinese adults., Methods: From 2004 to 2008, the prospective China Kadoorie Biobank enrolled 512,726 adults aged 30-79 years from 10 diverse areas (5 rural, 5 urban) of China. During the 12 years of follow-up, 101,673 participants were hospitalized for any infectious disease. Descriptive analyses examined standardized incidence, mortality and case fatality of infections., Findings: The incidence of any infectious disease was 1856 per 100,000 person-years; respiratory tract infections (1069) were most common. The infectious disease mortality rate was 31.8 per 100,000 person-years (20.3 and 9.4 for respiratory and non-respiratory infections, respectively) and case fatality was 2.2% (2.6% and 1.6% for respiratory and non-respiratory infections, respectively). Infectious disease incidence and mortality rates were higher at older ages and in rural areas. There were no clear sex differences in infectious disease incidence rates, but mortality and case fatality rates were twice as high in men as in women., Interpretation: Infectious diseases were common in Chinese adults. The observed burden of, and disparities in, site-specific infections can inform targeted prevention efforts., Funding: Kadoorie Foundation, Wellcome Trust, MRC, BHF, CR-UK, MoST, NNSF., Competing Interests: Declarations of Competing Interest The authors declare no competing interests., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Population data on mortality and causes of death among 5-19-year-olds are limited., Objectives: To assess levels, trends, and risk factors of cause-specific mortality and place at death among 5-19-year-olds in Tanzania (1995-2022)., Methods: Using longitudinal data from the Magu Health and Demographic Surveillance System in northwest Tanzania, we identified leading causes of death among 5-19-year-olds from verbal autopsy interviews, using physician review and a Bayesian probabilistic model (InSilicoVA). We analyzed trends in cause and place of death using three periods: 1995-2004, 2005-2014 and 2015-2022, and assessed risk factors in a Cox-proportional hazards model. We compared the results with children aged 1-4 years and global estimates for Tanzania., Results: Between 1995 and 2022, communicable disease mortality decreased by 73%, similar to the 76% decline among 1-4-year-olds. This decline in communicable disease mortality drove all-cause mortality declines of 43% and 48% among 5-14- and 15-19-year-olds, respectively. Non-communicable diseases and injuries gained importance, with their relative share of all deaths increasing from 15% in 1995-2004 to 58% in 2015-2022. Mortality risks were significantly higher among boys (particularly for injuries), those residing in rural areas (for non-communicable diseases), and those from the poorest households (for communicable diseases). By 2015-2022, 48% of 5-14 and 42% of 15-19-year-olds died in health facilities, up from 25% in 1995-2002., Conclusions: Since 1995, the decline in communicable disease mortality drove a major all-cause mortality reduction among 5-19-year-olds. Further progress will depend on continued reduction in communicable disease mortality, particularly among the poorest, and effectively addressing non-communicable and injury mortality.

Cambodia has made progress in reducing the under-five mortality rate and burden of infectious diseases among children over the last decades. However the determinants of child mortality and morbidity in Cambodia is not well understood, and no recent analysis has been conducted to investigate possible determinants. We applied a multivariable logistical regression model and a conditional random forest to explore possible determinants of under-five mortality and under-five child morbidity from infectious diseases using the most recent Demographic Health Survey in 2021-2022. Our findings show that the majority (58%) of under-five deaths occurred during the neonatal period. Contraceptive use of the mother led to lower odds of under-five mortality (0.51 [95% CI 0.32-0.80], p-value 0.003), while being born fourth or later was associated with increased odds (3.25 [95% CI 1.09-9.66], p-value 0.034). Improved household water source and higher household wealth quintile was associated with lower odds of infectious disease while living in the Great Lake or Coastal region led to increased odds respectively. The odds ratios were consistent with the results from the conditional random forest. The study showcases how closely related child mortality and morbidity due to infectious disease are to broader social development in Cambodia and the importance of accelerating progress in many sectors to end preventable child mortality and morbidity., (© 2024. The Author(s).)

Objective: To describe presenting diagnoses and rates and causes of death by age category and sex among children with acute illness brought to a district headquarter hospital in Pakistan., Design: Prospective cohort study., Setting: Sanghar district headquarter hospital, Sindh, Pakistan between December 2019 and April 2020 and August 2020 and December 2020., Participants: 3850 children 0-14 years presenting with acute illness to the emergency and outpatient departments and 1286 children admitted to the inpatient department., Outcome Measures: The primary outcome was Global Burden of Disease diagnosis category. Secondary outcomes were 28-day mortality rate, cause of death and healthcare delays, defined as delay in care-seeking, delay in reaching the healthcare facility and delay in appropriate treatment., Results: Communicable diseases were the most common presenting diagnoses among outpatients and among inpatients aged 1 month to 9 years. Non-communicable diseases and nutritional disorders were more common with increasing age. Few children presented with injuries. Newborn period (age <28 days) was associated with increased odds of death (OR 4.34 [95% CI 2.38 to 8.18], p<0.001, reference age 28 days-14 years) and there was no significant difference in odds of death between female vs male children (OR 1.12, 95% CI 0.6 to 2.04, p=0.72). 47 children died in the hospital (3.6%) and three (0.2%) died within 28 days of admission. Most children who died were <28 days old (n=32/50, 64%); leading diagnoses included neonatal sepsis/meningitis (n=13/50, 26%), neonatal encephalopathy (n=7/50, 14%) and lower respiratory tract infections (n=6/50, 12%). Delays in care-seeking (n=15) and in receiving appropriate treatment (n=12) were common., Conclusion: This study adds to sparse literature surrounding the epidemiology of disease and hospital outcomes for children with acute illness seeking healthcare in rural Pakistan and, in particular, among children aged 5-14 years. Further studies should include public and private hospitals within a single region to comprehensively describe patterns of care-seeking and interfacility transfer in district health systems., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

Background: Despite a global epidemiological transition towards increased burden of non-communicable diseases, communicable diseases continue to cause substantial morbidity and mortality worldwide. Understanding the burden of a wide range of infectious diseases, and its variation by geography and age, is pivotal to research priority setting and resource mobilisation globally., Methods: We estimated disability-adjusted life-years (DALYs) associated with 85 pathogens in 2019, globally, regionally, and for 204 countries and territories. The term pathogen included causative agents, pathogen groups, infectious conditions, and aggregate categories. We applied a novel methodological approach to account for underlying, immediate, and intermediate causes of death, which counted every death for which a pathogen had a role in the pathway to death. We refer to this measure as the burden associated with infection, which was estimated by combining different sources of information. To compare the burden among all pathogens, we used pathogen-specific ratios to incorporate the burden of immediate and intermediate causes of death for pathogens modelled previously by the GBD. We created the ratios by using multiple cause of death data, hospital discharge data, linkage data, and minimally invasive tissue sampling data to estimate the fraction of deaths coming from the pathway to death chain. We multiplied the pathogen-specific ratios by age-specific years of life lost (YLLs), calculated with GBD 2019 methods, and then added the adjusted YLLs to age-specific years lived with disability (YLDs) from GBD 2019 to produce adjusted DALYs to account for deaths in the chain. We used standard GBD methods to calculate 95% uncertainty intervals (UIs) for final estimates of DALYs by taking the 2·5th and 97·5th percentiles across 1000 posterior draws for each quantity of interest. We provided burden estimates pertaining to all ages and specifically to the under 5 years age group., Findings: Globally in 2019, an estimated 704 million (95% UI 610-820) DALYs were associated with 85 different pathogens, including 309 million (250-377; 43·9% of the burden) in children younger than 5 years. This burden accounted for 27·7% (and 65·5% in those younger than 5 years) of the previously reported total DALYs from all causes in 2019. Comparing super-regions, considerable differences were observed in the estimated pathogen-associated burdens in relation to DALYs from all causes, with the highest burden observed in sub-Saharan Africa (314 million [270-368] DALYs; 61·5% of total regional burden) and the lowest in the high-income super-region (31·8 million [25·4-40·1] DALYs; 9·8%). Three leading pathogens were responsible for more than 50 million DALYs each in 2019: tuberculosis (65·1 million [59·0-71·2]), malaria (53·6 million [27·0-91·3]), and HIV or AIDS (52·1 million [46·6-60·9]). Malaria was the leading pathogen for DALYs in children younger than 5 years (37·2 million [17·8-64·2]). We also observed substantial burden associated with previously less recognised pathogens, including Staphylococcus aureus and specific Gram-negative bacterial species (ie, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Acinetobacter baumannii, and Helicobacter pylori). Conversely, some pathogens had a burden that was smaller than anticipated., Interpretation: Our detailed breakdown of DALYs associated with a comprehensive list of pathogens on a global, regional, and country level has revealed the magnitude of the problem and helps to indicate where research funding mismatch might exist. Given the disproportionate impact of infection on low-income and middle-income countries, an essential next step is for countries and relevant stakeholders to address these gaps by making targeted investments., Funding: Bill & Melinda Gates Foundation, Wellcome Trust, and Department of Health and Social Care using UK aid funding managed by the Fleming Fund., Competing Interests: Declaration of interests B S Cooper reports support to their institution (University of Oxford) for their contribution to this research from the Wellcome Trust, and from the Department of Health and Social Care using UK aid funding managed by the Fleming Fund. E Chung reports support from the US National Institutes of Health (training grant NICHD T32HD007233). S J Dunachie has received support from the UK Fleming Fund at the Department of Health and Social Care, the Bill & Melinda Gates Foundation, Wellcome Trust, the UK National Institute of Health and Care Research, and a Wellcome Drug Resistant Infections Discretionary Award; served as Scientific Advisor for the Scottish Parliament, for which a fee was received; served on funding committees for Wellcome Trust, for which fees were received; served as a Data Monitoring Committee member for the UK STABILISE study of BCG vaccine in COPD; is a member of the New and Emerging Respiratory Virus Threats Advisory Group; is Chair of the Wellcome SEDRIC subgroup on Data Standards and Harmonisation in Antimicrobial Resistance; is a member of the Variant Technical Group for SARS-CoV-2 (invited as a T-cell specialist) for the UK Health Security Agency; is an expert advisor to WHO's Global Antimicrobial Resistance Surveillance System; and is a member of the WHO Guidelines Development Group on Treatment of Ebola. C E Moore reports participation on an advisory board for an MRC grant (no payments received); participation in a WHO Advisory Group for the WHO Medically Important Antimicrobial List; participation in a REVIVE Advisory Group as a member of the Steering Group for the REVIVE study; and served as an unpaid Co-Chair of the Impact and Influence Group for the Microbiology Society. J F Mosser reports grant funding from the Bill & Melinda Gates Foundation and GAVI, and travel support for attending meetings from the Bill & Melinda Gates Foundation. A Stergachis reports being a member of the Executive Board for the Safety Platform for Emergency Vaccines, Brighton Collaboration, based at the Task Force for Global Health; Chair of the Data Safety Monitoring Board for the IMPROVE 1 and 2 trials in Malawi, Tanzania, and Kenya; member of the Data Safety Monitoring Board for the Improving Neonatal Health Through Rapid Malaria Testing in Early Pregnancy with High-Sensitivity Diagnostics study; and member of the Scientific Advisory Board for Vivli AMR Register., (Copyright © 2024 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Regardless of microbial virulence (i.e., the global infection-fatality ratio), age generally drives the prevalence of death from infection in unvaccinated humans. Four mortality patterns are recognized: the common U- and L-shaped curves of endemic infections and the unique W- and J-shaped curves of pandemic infections. We suggest that these patterns result from different sets of human genetic and immunological determinants. In this model, it is the interplay between (1) monogenic genotypes affecting immunity to primary infection that preferentially manifest early in life and related genotypes or their phenocopies, including auto-antibodies, which manifest later in life and (2) the occurrence and persistence of adaptive, acquired immunity to primary or cross-reactive infections, which shapes the age-dependent pattern of human deaths from infection., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Environmental factors greatly impact infectious disease-related mortality, yet there's a lack of comprehensive global studies on the contemporary burden and trends. This study aims to evaluate the global burden and trends of infectious disease mortality caused by air pollution, unsafe water, poor sanitation, and non-optimal temperature across Socio-Demographic Index (SDI) regions from 1990 to 2019., Methods: This observational study utilized data from the Global Burden of Diseases Study to examine mortality rates from infectious diseases attributed to environmental risk factors between 1990 and 2019, including air pollution, unsafe water, sanitation, handwashing facilities (UWSH), and non-optimal temperatures. Age-standardized mortality rates (ASMRs) and estimated annual percentage change (EAPC) were utilized to present infectious disease mortality, and its trajectory influenced by environmental risk factors over the years. Nonlinear regression was conducted to explore the association between the SDI and ASMRs across regions from 1990 to 2019., Results: In 2019, global infectious disease deaths linked to air pollution, UWSH, and non-optimal temperature reached a startling 2,556,992. Disease mortality varied widely across SDI regions, with the highest number of deaths due to air pollution and UWSH in Low SDI regions, and deaths from non-optimal temperature primarily in High SDI regions. Age disparities emerged, with children under five and the elderly most affected. However, an increasing mortality trend was observed among seniors (65-69, 75-79, and over 80) in High SDI regions due to enteric infections linked to UWSH. Globally, a consistent decrease in ASMR was seen from 1990 to 2019 for all diseases connected to these factors, except for respiratory infections linked to non-optimal temperature., Conclusions: Our study underscores the significant impact of air pollution, UWSH, and non-optimal temperatures on global infectious disease mortality, particularly among vulnerable groups such as children and the elderly. It's important to tackle these challenges with targeted interventions aiming to enhance environmental quality, improve water and sanitation systems, and control extreme temperatures. In addition, international cooperation is essential for bridging regional disparities and driving global public health initiatives forward, thereby helping achieve Sustainable Development Goals more effectively., (© 2024. The Author(s).)

Objectives: To quantify the burden of communicable diseases and characterize the most reported infections during public health emergency of floods in Pakistan., Methods: The study's design is a descriptive trend analysis. The study utilized the disease data reported to District Health Information System (DHIS2) for the 12 most frequently reported priority diseases under the Integrated Disease Surveillance and Response (IDSR) system in Pakistan., Results: In total, there were 1,532,963 suspected cases during August to December 2022 in flood-affected districts (n = 75) across Pakistan; Sindh Province reported the highest number of cases (n = 692,673) from 23 districts, followed by Khyber Pakhtunkhwa (KP) (n = 568,682) from 17 districts, Balochistan (n = 167,215) from 32 districts, and Punjab (n = 104,393) from 3 districts. High positivity was reported for malaria (79,622/201,901; 39.4%), followed by acute diarrhea (non-cholera) (23/62; 37.1%), hepatitis A and E (47/252; 18.7%), and dengue (603/3245; 18.6%). The crude mortality rate was 11.9 per 10 000 population (1824/1,532,963 [deaths/cases])., Conclusion: The study identified acute respiratory infection, acute diarrhea, malaria, and skin diseases as the most prevalent diseases. This suggests that preparedness efforts and interventions targeting these diseases should be prioritized in future flood response plans. The study highlights the importance of strengthening the IDSR as a Disease Early Warning System through the implementation of the DHIS2.

Aim: This study aimed to investigate the impact of communicable diseases with epidemic potential in complex emergency (CE) situations, focusing on the epidemiological profile of incidence and mortality and exploring underlying factors contributing to increased epidemic risks., Methods: Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses for Scoping Review (PRISMA-ScR) guidelines, we conducted a scoping review of articles published between 1990 and 2022. The search included terms related to complex emergencies, communicable diseases, outbreaks, and epidemics. We identified 92 epidemics related to CE occurring in 32 different countries., Results: Communicable diseases like Shigellosis, Cholera, Measles, Meningococcal meningitis, Yellow Fever, and Malaria caused significant morbidity and mortality. Diarrhoeal diseases, particularly Cholera and Shigellosis, had the highest incidence rates. Shigella specifically had an incidence of 241.0 per 1000 (people at risk), with a mortality rate of 11.7 per 1000, while Cholera's incidence was 13.0 per 1000, with a mortality rate of 0.22 per 1000. Measles followed, with an incidence of 25.0 per 1000 and a mortality rate of 0.76 per 1000. Meningococcal Meningitis had an incidence rate of 1.3 per 1000 and a mortality rate of 0.13 per 1000. Despite their lower incidences, yellow fever at 0.8 per 1000 and malaria at 0.4 per 1000, their high case fatality rates of 20.1% and 0.4% remained concerning in CE. The qualitative synthesis reveals that factors such as water, sanitation, and hygiene, shelter and settlements, food and nutrition, and public health and healthcare in complex emergencies affect the risk of epidemics., Conclusion: Epidemics during complex emergencies could potentially lead to a public health crisis. Between 1990 and 2022, there have been no statistically significant changes in the trend of incidence, mortality, or fatality rates of epidemic diseases in CE. It is crucial to understand that all epidemics identified in CE are fundamentally preventable., (© 2024 The Authors Tropical Medicine & International Health Published by John Wiley & Sons Ltd.)

Historical demographic research shows that the factors influencing mortality risk are labile across time and space. This is particularly true for datasets that span societal transitions. Here, we seek to understand how marriage, migration, and the local economy influenced mortality dynamics in a rapidly changing environment characterized by high in-migration and male-biased sex ratios. Mortality records were extracted from a compendium of historical vital records for the Baja California peninsula (Mexico). Our sample consists of 1,201 mortality records spanning AD 1835-1900. Findings from Cox proportional hazard models indicate that (1) marriage was associated with a protective effect for both sexes; (2) residing in a mining town was associated with higher mortality for men, but not women; (3) migration was associated with decreased mortality risk for women, but not men; and (4) the risk of mortality increased in the face of infectious disease, but decreased over time. Despite the early initiation of reproduction for women, marriage had a protective effect, likely because marriage linked women to resources. Although mining boomtowns were associated with elevated risk factors generally, only men experienced greater mortality risk, likely due to dangerous working conditions that women did not experience. Last, female, but not male, migrants experienced greater longevity, possibly because exposure to harsh labor conditions eroded the protective effect of selection bias for men. Together, these results shed light on an understudied historical population and broaden our understanding of demographic dynamics in preindustrial settings., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This study aimed to investigate the prevalence of antimicrobial de-escalation (ADE) strategy and assess its effect on 14-day mortality among intensive care unit patients., Methods: A single-center retrospective cohort study was conducted on patients admitted to the intensive care unit (ICU) with infectious diseases between January 2018 and December 2020. Patients were stratified into three groups based on the initial treatment regimen within 5 days of antimicrobial administration: ADE, No Change, and Other Change. Confounders between groups were screened using one-way ANOVA and Chi-square analysis. Univariate and multivariate analyses were performed to identify risk factors for 14-day mortality. Potential confounders were balanced using propensity score inverse probability of treatment weighting (IPTW), followed by multivariate logistic regression analysis to evaluate the effect of ADE strategy on 14-day mortality., Results: A total of 473 patients met the inclusion criteria, with 53 (11.2%) in the ADE group, 173 (36.6%) in the No Change group, and 247 (52.2%) in the Other Change group. The 14-day mortality rates in the three groups were 9.4%, 11.6%, and 21.9%, respectively. After IPTW, the adjusted odds ratio for 14-day mortality comparing No Change with ADE was 1.557 (95% CI 1.078-2.247, P = 0.0181) while comparing Other Change with ADE was 1.282(95% CI 0.884-1.873, P = 0.1874)., Conclusion: The prevalence of ADE strategy was low among intensive care unit patients. The ADE strategy demonstrated a protective effect or no adverse effect on 14-day mortality compared to the No Change or Other Change strategies, respectively. These findings provide evidence supporting the implementation of the ADE strategy in ICU patients., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Objective: To investigate if there were changes in mortality knowing that industrialization was a slow and late process in Portugal., Materials: The biographic information (1) of the individuals buried at the Coimbra Municipal Cemetery, considering three quinquennia: 1861-1865 (n = 1111, 18.3%), 1870-1974 (n = 2602, 42.7%), 1910-1914 (n = 2374, 39.0%), related to the periods before, during and at the end of the second industrialization and (2) of the Coimbra identified osteological collections (CIOC, N = 1796) composed of individuals who were born and died in the city., Methods: Excel databases with the biographic information were analyzed with SPSS., Results: Data from the cemetery show statistically significant differences between sexes and age-at-death mortalities. Non-adult mortality (higher in the age range from 1 to 7 years) has decreased over time which has increased mean age-at-death. The main adult occupations are domestic work (females) and craft activities (males). Child labor is common after the age of 14. The main causes of death (in both cemetery and CIOC records) were infections, respiratory diseases, heart disease, and malignant neoplasm. Among the communicable diseases, tuberculosis accounted for the highest number of deaths. The identified individuals have lesions compatible with tuberculosis and sinusitis while malignant neoplasms are more difficult to identify. The high prevalence of heart disease can overshadow other causes of death., Conclusions: In the absence of industrialization, tuberculosis, heart disease, and malignant neoplasms increased over time, while respiratory diseases decreased., Significance: Mortality profile changed between 1861-1864 and 1910-1914 in Coimbra., Limitations: The causes of death were studied, but not all diseases., Suggestions for Further Research: Study of other cemetery records for further comparison., (Copyright © 2022 Elsevier Inc. All rights reserved.)

A new theoretical model of epidemic kinetics is considered, which uses elements of the physical model of the kinetics of the atomic level populations of an active laser medium as follows: a description of states and their populations, transition rates between states, an integral operator, and a source of influence. It is shown that to describe a long-term epidemic, it is necessary to use the concept of the source of infection. With a model constant source of infection, the epidemic, in terms of the number of actively infected people, goes to a stationary regime, which does not depend on the population size and the characteristics of quarantine measures. Statistics for Moscow daily increase in infected is used to determine the real source of infection. An interpretation of the waves generated by the source is given. It is shown that more accurate statistics of excess mortality can only be used to clarify the frequency rate of mortality of the epidemic, but not to determine the source of infection., Competing Interests: The authors Andrey V Borovskiy and Andrey L Galkin declare that they have no conflict of interests., (Copyright © 2022 Andrey V. Borovsky and Andrey L. Galkin.)

Women have a longer life expectancy than men in the general population. However, it has remained unclear whether this advantage is maintained in patients undergoing maintenance hemodialysis. The aim of this study was to compare the risk of mortality, especially infection-related mortality, between male and female hemodialysis patients. A total of 3065 Japanese hemodialysis patients aged ≥ 18 years old were followed up for 10 years. The primary outcomes were all-cause and infection-related mortality. The associations between sex and these outcomes were examined using Cox proportional hazards models. During the median follow-up of 8.8 years, 1498 patients died of any cause, 387 of whom died of infection. Compared with men, the multivariable-adjusted hazard ratios (95% confidence interval) for all-cause and infection-related mortality in women were 0.51 (0.45-0.58, P < 0.05) and 0.36 (0.27-0.47, P < 0.05), respectively. These findings remained significant even when propensity score-matching or inverse probability of treatment weighting adjustment methods were employed. Furthermore, even when the non-infection-related mortality was considered a competing risk, the infection-related mortality rate in women was still significantly lower than that in men. Regarding all-cause and infection-related deaths, women have a survival advantage compared with men among Japanese patients undergoing maintenance hemodialysis., (© 2022. The Author(s).)

Background: Randomized controlled trials (RCTs) indicate that bacille Calmette-Guérin (BCG) vaccination provides broad beneficial "nonspecific" protection against infections. We investigated the effect on in-hospital mortality of providing BCG immediately upon admission to a neonatal intensive care unit (NICU), rather than BCG-at-discharge. The pretrial NICU mortality was 13% and we hypothesized that BCG would reduce mortality by 40%., Methods: Parallel-group, open-label RCT was initiated in 2013 in Guinea-Bissau. Neonatal intensive care unit-admitted neonates were randomized 1:1 to BCG + oral polio vaccine (OPV) immediately (intervention) versus BCG + OPV at hospital discharge (control; usual practice). The trial was discontinued due to decreasing in-hospital mortality and major NICU restructuring. We assessed overall and disease-specific mortality by randomization allocation in cox proportional hazards models providing mortality rate ratios (MRRs)., Results: We recruited 3353 neonates, and the overall mortality was 3.1% (52 of 1676) for BCG-vaccinated neonates versus 3.3% (55 of 1677) for controls (MRR = 0.94; 0.64-1.36). For noninfectious causes of death, the MRR was 1.20 (0.70-2.07), and there tended to be fewer deaths from infections in the BCG group (N = 14) than among controls (N = 21) (MRR = 0.65; 0.33-1.28)., Conclusions: Providing BCG + OPV to frail neonates was safe and might protect against fatal infection in the immediate newborn period. Deaths due to prematurity and perinatal complications were unaffected by BCG., (© The Author(s) 2021. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Introduction: A criterion for disseminated intravascular coagulation (DIC) that reflects the status of controlled coagulopathy would be useful for determining when to stop treatment. Use of the DIC criteria of the Japanese Society on Thrombosis and Hemostasis (JSTH) for predicting the outcome during recombinant soluble thrombomodulin (thrombomodulin alfa, TM-α) treatment was evaluated., Methods: A retrospective, multicenter survey was conducted in 798 medical facilities in Japan. Of the 4342 patients who underwent TM-α treatment, 193 with infection-associated DIC were investigated., Results: The 28-day mortality rate increased with the increase in JSTH DIC scores at the end of TM-α treatment, with a Cramer's coefficient of association of 0.431. A reduced platelet count (odds ratio [OR]: 0.847, P < .001), prolonged prothrombin time ratio (OR: 5.681, P < .001), decreased fibrinogen level (OR: 0.995, P < .001), higher level of fibrinogen and fibrin degradation products (OR: 1.009, P = .026), and lower antithrombin activity (OR: 0.973, P < .001) were correlated with 28-day mortality. On multivariate analysis, the JSTH DIC score at the completion of TM-α therapy was a predictor of mortality (OR: 1.591, 95% CI: 1.219-2.077)., Conclusion: The JSTH DIC score at the end of anticoagulation therapy may be a reliable tool for predicting the outcome in patients with infection-associated DIC., (© 2021 John Wiley & Sons Ltd.)

Human mobility is crucial to understand the transmission pattern of COVID-19 on spatially embedded geographic networks. This pattern seems unpredictable, and the propagation appears unstoppable, resulting in over 350,000 death tolls in the U.S. by the end of 2020. Here, we create the spatiotemporal inter-county mobility network using 10 TB (Terabytes) trajectory data of 30 million smart devices in the U.S. in the first six months of 2020. We investigate the bond percolation process by removing the weakly connected edges. As we increase the threshold, the mobility network nodes become less interconnected and thus experience surprisingly abrupt phase transitions. Despite the complex behaviors of the mobility network, we devised a novel approach to identify a small, manageable set of recurrent critical bridges, connecting the giant component and the second-largest component. These adaptive links, located across the United States, played a key role as valves connecting components in divisions and regions during the pandemic. Beyond, our numerical results unveil that network characteristics determine the critical thresholds and the bridge locations. The findings provide new insights into managing and controlling the connectivity of mobility networks during unprecedented disruptions. The work can also potentially offer practical future infectious diseases both globally and locally., Competing Interests: The authors have declared that no competing interests exist.

Abstract: This study was performed to verify whether lactate dehydrogenase to albumin (LDH/ALB) ratio could be used as an independent prognostic factor in patients with severe infection requiring intensive care.We reviewed electronic medical records of patients hospitalized to the intensive care unit via the emergency department with a diagnosis of infection between January 2014 and December 2019. From the collected data, ALB-based ratios (LDH/ALB, blood urea nitrogen to albumin, C-reactive protein to albumin, and lactate to albumin ratios) and some severity scores (modified early warning score, mortality in emergency department sepsis score [MEDS], and Acute Physiology And Chronic Health Evaluation II [APACHE II] score) were calculated. LDH/ALB ratio for predicting the in-hospital mortality was compared with other ALB-based ratios and severity scales by univariable and receiver-operating characteristics curve analysis. Modified severity scores by LDH/ALB ratio and multivariable logistic regression were used to verify the independence and usefulness of the LDH/ALB ratio.The median LDH/ALB ratio was higher in non-survivors than survivors (166.9 [interquartile range: 127.2-233.1] vs 214.7 [interquartile range: 160.2-309.7], P < .001). The area under the receiver-operating characteristics curve of the LDH/ALB ratio (0.642, 95% confidence interval: 0.602-0.681, P < .001) was not lower than that of other ALB-based ratios and severity scores. From multivariable logistic regression, LDH/ALB ratio was independently associated with in-hospital mortality (odds ratio = 1.001, 95% confidence interval: 1.000-1.002, P = .047). Area under the receiver-operating characteristics curves of MEDS and APACHE II scores were improved by modification with LDH/ALB ratio (MEDS: 0.643 vs 0.680, P < .001; APACHE II score: 0.675 vs 0.700, P = .003).LDH/ALB ratio may be useful as the prognostic factor in patients with severe infection requiring intensive care., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: To examine the epidemiology, time trends, and outcomes and types of serious infections in people with vasculitis in the US., Methods: We identified people with vasculitis who were hospitalized with a primary diagnosis of pneumonia, sepsis/bacteremia, urinary tract infection (UTI), skin and soft tissue infections, or opportunistic infections in the 1998-2016 US National Inpatient Sample. We used adjusted logistic regression to examine the predictors of a hospital stay >3 days, total hospital charges greater than the median, discharge to a non-home setting, and in-hospital mortality., Results: We noted 111,345 serious infections in patients with vasculitis (14% of all vasculitis hospitalizations). Among the patients, the mean age was 67.3 years, the Deyo-Charlson comorbidity index score was ≥2 in 54%, 37% were male, and 67% were White. The serious infection hospitalization rate per 100,000 US National Inpatient Sample claims in 1998-2000 versus 2015-2016 (and rates of increase) in patients with vasculitis was as follows: overall, 12.14 versus 25.15 (2.1-fold); opportunistic infections, 0.78 versus 0.83 (1.1-fold); skin and soft tissue infections, 1.38 versus 2.52 (1.8-fold); UTI, 0.35 versus 1.48 (4.2-fold); pneumonia, 7.10 versus 6.23 (0.9-fold); and sepsis, 2.53 versus 14.10 (5.6-fold). Pneumonia was the most common serious infection in 1998-2000 (58%) versus sepsis in 2015-2016 (56%). Sepsis, older age, Deyo-Charlson comorbidity index score of ≥2, urban hospital, or medium/large hospital (by number of beds) were associated with higher health care utilization and in-hospital mortality rates; Northeast region and Medicare and Medicaid payer type were associated with higher rates of health care utilization., Conclusion: Serious infection hospitalization rates are increasing in patients with vasculitis except among those with pneumonia. Sepsis was the most common serious infection in 2015-2016. Several patient and hospital factors are associated with health care utilization and mortality in serious infection hospitalization in vasculitis., (© 2020, American College of Rheumatology. This article has been contributed to by US Government employees and their work is in the public domain in the USA.)

Kidney transplant recipients (KTR) are at increased risk of mortality, particularly from infectious diseases, due to lifelong immunosuppression. Although very long chain saturated fatty acids (VLSFA) have been identified as crucial for phagocytosis and clearance of infections, their association with mortality in immunocompromised patient groups has not been studied. In this prospective cohort study we included 680 outpatient KTR with a functional graft ≥1 year and 193 healthy controls. Plasma VLSFA (arachidonic acid (C20:0), behenic acid (C22:0) and lignoceric acid (C24:0)) were measured by gas chromatography coupled with a flame ionization detector. Cox regression analyses was used to prospectively study the associations of VLSFA with all-cause and cause-specific mortality. All studied VLSFA were significantly lower in KTR compared to healthy controls (all p < 0.001). During a median (interquartile range) follow-up of 5.6 (5.2-6.3) years, 146 (21%) KTR died, of which 41 (28%) died due to infectious diseases. In KTR, C22:0 was inversely associated with risk of all-cause mortality, with a HR (95% CI) per 1-SD-increment of 0.79 (0.64-0.99), independent of adjustment for potential confounders. All studied VLSFA were particularly strongly associated with mortality from infectious causes, with respective HRs for C20:0, C22:0 and C24:0 of 0.53 (0.35-0.82), 0.48 (0.30-0.75), and 0.51 (0.33-0.80), independent of potential confounders. VLSFA are inversely associated with infectious disease mortality in KTR after adjustment, including HDL-cholesterol. Further studies are needed to assess the effect of VLSFA-containing foods on the risk of infectious diseases in immunocompromised patient groups.

Background: Mortality during and after incarceration is poorly understood in low- and middle-income countries (LMICs). The need to address this knowledge gap is especially urgent in South America, which has the fastest growing prison population in the world. In Brazil, insufficient data have precluded our understanding of all-cause and cause-specific mortality during and after incarceration., Methods and Findings: We linked incarceration and mortality databases for the Brazilian state of Mato Grosso do Sul to obtain a retrospective cohort of 114,751 individuals with recent incarceration. Between January 1, 2009 and December 31, 2018, we identified 3,127 deaths of individuals with recent incarceration (705 in detention and 2,422 following release). We analyzed age-standardized, all-cause, and cause-specific mortality rates among individuals detained in different facility types and following release, compared to non-incarcerated residents. We additionally modeled mortality rates over time during and after incarceration for all causes of death, violence, or suicide. Deaths in custody were 2.2 times the number reported by the national prison administration (n = 317). Incarcerated men and boys experienced elevated mortality, compared with the non-incarcerated population, due to increased risk of death from violence, suicide, and communicable diseases, with the highest standardized incidence rate ratio (IRR) in semi-open prisons (2.4; 95% confidence interval [CI]: 2.0 to 2.8), police stations (3.1; 95% CI: 2.5 to 3.9), and youth detention (8.1; 95% CI: 5.9 to 10.8). Incarcerated women experienced increased mortality from suicide (IRR = 6.0, 95% CI: 1.2 to 17.7) and communicable diseases (IRR = 2.5, 95% CI: 1.1 to 5.0). Following release from prison, mortality was markedly elevated for men (IRR = 3.0; 95% CI: 2.8 to 3.1) and women (IRR = 2.4; 95% CI: 2.1 to 2.9). The risk of violent death and suicide was highest immediately post-release and declined over time; however, all-cause mortality remained elevated 8 years post-release. The limitations of this study include inability to establish causality, uncertain reliability of data during incarceration, and underestimation of mortality rates due to imperfect database linkage., Conclusions: Incarcerated individuals in Brazil experienced increased mortality from violence, suicide, and communicable diseases. Mortality was heightened following release for all leading causes of death, with particularly high risk of early violent death and elevated all-cause mortality up to 8 years post-release. These disparities may have been underrecognized in Brazil due to underreporting and insufficient data., Competing Interests: The authors have declared that no competing interests exist.

Background: Receiving a cancer diagnosis may trigger immediate fatal non-cancer health outcomes in addition to dying of cancer itself. We aim to investigate the full pattern of non-cancer deaths in patients within a year of a cancer diagnosis., Methods: Patients diagnosed with cancer between 1990 and 2016 were identified from the SEER program. Standardized mortality ratios (SMRs) were calculated to characterize the relative risks of non-cancer deaths compared with the general population., Results: Among 7,366,229 patients, 241,575 non-cancer deaths (15.9%) were recorded in the first year following a cancer diagnosis. The relative risk of non-cancer deaths was 2.34-fold (95% confidence interval (CI): 2.33-2.35) that of the general population. The majority of non-cancer deaths were caused by cardiovascular diseases (21.8%), followed by infectious diseases (7.2%). Significant elevations in mortality risks were observed for nearly all non-cancer causes, particularly in infectious diseases (SMR: 5.08; 95% CI: 5.03-5.13). Patients with liver cancer (SMR: 12.29; 95% CI: 12.06-12.53) were at the highest risk of early non-cancer deaths. The risks of non-cancer deaths were highest within the first month after diagnosis, and decreased rapidly thereafter., Conclusions: Risks of non-cancer deaths vary by the types of causes and anatomic sites of cancer. Our data underscore the importance of close observation and early multidisciplinary care for noncancer conditions in patients who have recently received a cancer diagnosis., (© 2021. The Author(s).)

The African buffalo (Syncerus caffer) is an iconic species of South African megafauna. As the farmed buffalo population expands, the potential impacts on population health and disease transmission warrant investigation. A retrospective study of skin biopsy and necropsy samples from 429 animals was performed to assess the spectrum of conditions seen in buffaloes in South Africa. Determination of the cause of death (or euthanasia) could not be made in 33.1% (136/411) of the necropsy cases submitted due to autolysis or the absence of significant lesions in the samples submitted. Infectious and parasitic diseases accounted for 53.5% (147/275) of adult fatal cases and non-infectious conditions accounted for 34.9% (96/275). Abortions and neonatal deaths made up 11.6% (32/275) of necropsy cases. Rift Valley fever, bovine viral diarrhoea, malignant catarrhal fever, tuberculosis, bacterial pneumonia, anaesthetic deaths, cachexia and hepatotoxic lesions were the most common causes of death. The range of infectious, parasitic and non-infectious diseases to which African buffaloes were susceptible was largely similar to diseases in domestic cattle which supports concerns regarding disease transmission between the two species. The similarity between diseases experienced in both species will assist wildlife veterinarians in the diagnosis and treatment of diseases in captive African buffaloes. The present study likely does not represent accurate disease prevalence data within the source population of buffaloes, and diseases such as anthrax, brucellosis and foot and mouth disease are under-represented in this study. Hepatic ductal plate abnormalities and haemorrhagic septicaemia have not, to our knowledge, been previously reported in African buffaloes.

Background: Lymphopenia is associated with various pathologies such as sepsis, burns, trauma, general anesthesia and major surgeries. All these pathologies are clinically expressed by the so-called Systemic Inflammatory Response Syndrome which does not include lymphopenia into defining criteria. The main objective of this work was to analyze the diagnosis of patients admitted to a hospital related to lymphopenia during hospital stay. In addition, we investigated the relationship of lymphopenia with the four levels of the Severity of Illness (SOI) and the Risk of Mortality (ROM)., Method and Findings: Lymphopenia was defined as Absolute Lymphocyte Count (ALC) <1.0 x109/L. ALC were analyzed every day since admission. The four levels (minor, moderate, major and extreme risk) of both SOI and ROM were assessed. A total of 58,260 hospital admissions were analyzed. More than 41% of the patients had lymphopenia during hospital stay. The mean time to death was shorter among patients with lymphopenia on admission 65.6 days (CI95%, 57.3-73.8) vs 89.9 (CI95%, 82.4-97.4), P<0.001. Also, patients with lymphopenia during hospital stay had a shorter time to the mortality, 67.5 (CI95%, 61.1-73.9) vs 96.9 (CI95%, 92.6-101.2), P<0.001., Conclusions: Lymphopenia had a high prevalence in hospitalized patients with greater relevance in infectious pathologies. Lymphopenia was related and clearly predicts SOI and ROM at the time of admission, and should be considered as clinical diagnostic criteria to define SIRS., Competing Interests: The authors have declared that no competing interests exist.

Context.—: There is a paucity of literature about tissue granulomas in transplant patients., Objective.—: To characterize the clinicopathologic features of granulomas in this population and develop a clinically judicious approach to their evaluation., Design.—: We performed chart reviews of solid organ and allogeneic hematopoietic stem cell transplant recipients at Yale New Haven Hospital to identify patients with granulomas on biopsy obtained pathologic specimens. Pretransplant and posttransplant specimens were included. Data points included demographics, clinical presentation, epidemiologic risk factors, biopsy indication, location and timing, immunosuppression, histopathology, microbiology, and associated clinical diagnosis. Granuloma-related readmissions and mortality were recorded at 1, 3, and 12 months., Results.—: Biopsy proven granulomas were identified in 56 of 2139 (2.6%) patients. Of 56, 16 (29%) were infectious. Common infectious etiologies were bartonellosis (n = 3) and cytomegalovirus hepatitis (n = 3). Tuberculosis was not identified. Clinical symptoms prompted tissue biopsy in 27 of 56 (48.2%) cases while biopsies were obtained for evaluation of incidental findings or routine disease surveillance in 29 of 56 (51.8%). Presence of symptoms was significantly associated with infectious etiologies; 11 of 27 (40.7%) symptomatic patients compared with 5 of 29 (17.2%) asymptomatic patients had infectious causes. One death from granulomatous cryptogenic organizing pneumonia occurred. In pretransplant asymptomatic patients, no episodes of symptomatic disease occurred posttransplantation., Conclusions.—: Granulomas were uncommon in a large transplant population; most were noninfectious but presence of symptoms was associated with infectious etiologies. Granulomas discovered pretransplant without clear infectious etiology likely do not require prolonged surveillance after transplantation. Symptomatology and epidemiologic risks factors should guide extent of microbiologic evaluation., Competing Interests: The authors have no relevant financial interest in the products or companies described in this article.

The need for improved models that can accurately predict COVID-19 dynamics is vital to managing the pandemic and its consequences. We use machine learning techniques to design an adaptive learner that, based on epidemiological data available at any given time, produces a model that accurately forecasts the number of reported COVID-19 deaths and cases in the United States, up to 10 weeks into the future with a mean absolute percentage error of 9%. In addition to being the most accurate long-range COVID predictor so far developed, it captures the observed periodicity in daily reported numbers. Its effectiveness is based on three design features: (1) producing different model parameters to predict the number of COVID deaths (and cases) from each time and for a given number of weeks into the future, (2) systematically searching over the available covariates and their historical values to find an effective combination, and (3) training the model using "last-fold partitioning", where each proposed model is validated on only the last instance of the training dataset, rather than being cross-validated. Assessments against many other published COVID predictors show that this predictor is 19-48% more accurate.

Vascular graft or endograft Infections (VGEI) are rare but severe complications of vascular reconstructive surgery, and associated with significant mortality and morbidity risk. Positron emission tomography/computed tomography with 18 F-fluorodeoxyglucose (PET/CT) has been shown to have a high diagnostic accuracy in the detection of VGEI. In this single-center prospective cohort study, we assessed the rate and the impact on patient management of relevant unknown incidental findings in PET/CT of patients with proven or suspected VGEI, and clinical follow-up of all patients was performed. Our study results show a comparably high rate of relevant unknown incidental findings (181 in 502 examinations), with documented direct impact on patient management in 80 of 181 (44%) of all findings. PET/CT scan- and patient-based evaluation revealed impact on patient management in 76 of 502 (17%) of all PET/CT scans, and in 59 of 162 (36%) of all patients, respectively. Furthermore, PET/CT correctly identified the final diagnosis in 20 of 36 (56%) patients without VGEI. In conclusion, in proven and suspected VGEI, PET/CT detects a high rate of relevant unknown incidental findings with high impact on patient management.

Objective: To estimate the overall and infection-related neonatal mortality rate and the pathogens responsible using electronic death registrations., Design: Retrospective analysis of national electronic death registrations data., Setting: England and Wales., Patients: Neonates aged <28 days., Main Outcome Measures: Overall and infection-related mortality rate per 1000 live births in term, preterm (28-36 weeks) and extremely preterm (<28 weeks) neonates; the contribution of infections and specific pathogens; comparison with mortality rates in 2003-2005., Results: The neonatal mortality rate during 2013-2015 (2.4/1000 live births; 5095 deaths) was 31% lower than in 2003-2005 (3.5/1000; 6700 deaths). Infection-related neonatal mortality rate in 2013-2015 (0.32/1000; n=669) was 20% lower compared with 2003-2015 (0.40/1000; n=768), respectively. Infections were responsible for 13.1% (669/5095) of neonatal deaths during 2013-2015 and 11.5% (768/6700) during 2003-2005. Of the infection-related deaths, 44.2% (296/669) were in term, 19.9% (133/669) preterm and 35.9% (240/669) extremely preterm neonates. Compared with term infants (0.15/1000 live births), infection-related mortality rate was 5.9-fold (95% CI 4.7 to 7.2) higher in preterm (0.90/1000) and 188-fold (95% CI 157 to 223) higher in extremely preterm infants (28.7/1000) during 2013-2015. A pathogen was recorded in 448 (67%) registrations: 400 (89.3%) were bacterial, 37 (8.3%) viral and 11 (2.4%) fungal. Group B streptococcus (GBS) was reported in 30.4% (49/161) of records that specified a bacterial infection and 7.3% (49/669) of infection-related deaths., Conclusions: Overall and infection-related neonatal mortality rates have declined, but the contribution of infection and of specific pathogens has not changed. Further preventive measures, including antenatal GBS vaccine may be required to prevent the single most common cause of infection-related deaths in neonates., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Advance care planning (ACP) for medical decision-making at the end of life has developed around the expectation of death from long-term, progressive chronic illnesses. We reexamine advance care planning in light of the increased probability of death from COVID-19, an exemplar of death that occurs relatively quickly after disease onset. We draw several conclusions about ACP in the context of infectious diseases: interpersonal and sociostructural barriers to ACP are high; ACP is not well-oriented toward decision-making for treatment of an acute illness; and the U.S. health care system is not well positioned to fulfill patients' end of life preferences in a pandemic. Passing the peak of the crisis will reduce, but not eliminate, these problems.

The objective of this 20-yr retrospective study was to review and summarize causes of mortality in the North American (NA) snow leopard population to inform and enhance animal health and husbandry practices. Pathology reports were requested from all NA zoological institutions housing snow leopards that died between 01 January 1999 and 31 December 2019. Data were reviewed and cause of death (COD) and concurrent diseases were summarized and compared by age group, organ system, and disease process. The 241 snow leopards in this report include 109 males, 130 females, and two of undetermined sex. Among them were 116 geriatric snow leopards (>15 yr), 72 adults (15-3 yr), 16 juveniles (3 yr to 2 mo), 32 neonates (2 mo to 0 days), and five fetuses (<0 days). Overall, noninfectious diseases were the most common COD across all age groups (73%). In adult and geriatric snow leopards, chronic renal disease (CRD) (38.8%) and malignant neoplasia (19.7%), including oral squamous cell carcinoma (6.4%), were a common COD. In juveniles and neonates, perinatal death and congenital diseases, including ocular coloboma (15.6%), were a common COD. Individuals with CRD were 13.5 and 4.36 times more likely to have veno-occlusive disease and cardiac fibrosis, respectively. Snow leopards with urolithiasis were 5.27 times more likely to have CRD. Infectious (14.1%) and inflammatory diseases (8.7%) for which no specific etiology was identified were less common overall and more common in juveniles and neonates (25% and 21%, respectively). Neoplasms not previously reported in snow leopards or that are generally uncommon in the veterinary literature included transitional cell carcinoma of the urinary bladder ( n = 7) and mesothelioma ( n = 1).

The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Paediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 84.0% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. Twelve percent were transferred to the Vietnam National Children's Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time polymerase chain reaction assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use., Competing Interests: The authors declare they have no conflicts of interest., (© 2020 The Authors. Published by Atlantis Press International B.V.)

Objectives: The impact of contracting stroke-associate infection (SAI) that requires antibiotic treatment after an acute ischemic stroke (AIS) treated with alteplase remains unclear. We studied the profiles of SAI in patients with AIS treated with alteplase toward identifying predictive factors and prognostic implications at 90 days post-stroke., Methods: We analyzed 33 parameters readily available within 24 hours after AIS: demographics, risk factors, and several clinical and biochemical parameters. Outcome measures were mRS ≤ 2 and mortality 90 days post-stroke., Results: 83 (23.6%) of 352 patients developed SAI. Multivariate logistic regression analysis showed that atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS (the difference between NIHSS score measured upon admission and 24 hours after later), CRP≥10 mg/L, and elevated WBC count affected SAI risk (model including CRP levels and WBC count) and atrial fibrillation, mRS above 0 pre-stroke, lower delta NIHSS, HT, and elevated fibrinogen levels affected SAI risk (model excluding CRP levels and WBC count). 231 patients (74.1%) had mRS ≤ 2 at day 90. Multivariate logistic regression analysis showed that younger age, no hypertension, mRS=0 pre-stroke, higher delta NIHSS, no HT, no SAI, and CRP<10 mg/L, were associated with mRS≤2 at day 90. 54 (15.3%) patients died within 90 days. Multivariate logistic regression analysis showed that pre-stroke mRS>0, lower delta NIHSS, HT, CRP≥10 mg/L, lower triglyceride levels affected the risk of death within 90 days., Conclusions: Several markers available within 24 hours post-stroke were predictive of SAI that requires antibiotic treatment. SAI affects long-term outcome but not mortality., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The past two decades have seen expansion of childhood vaccination programmes in low-income and middle-income countries (LMICs). We quantify the health impact of these programmes by estimating the deaths and disability-adjusted life-years (DALYs) averted by vaccination against ten pathogens in 98 LMICs between 2000 and 2030., Methods: 16 independent research groups provided model-based disease burden estimates under a range of vaccination coverage scenarios for ten pathogens: hepatitis B virus, Haemophilus influenzae type B, human papillomavirus, Japanese encephalitis, measles, Neisseria meningitidis serogroup A, Streptococcus pneumoniae, rotavirus, rubella, and yellow fever. Using standardised demographic data and vaccine coverage, the impact of vaccination programmes was determined by comparing model estimates from a no-vaccination counterfactual scenario with those from a reported and projected vaccination scenario. We present deaths and DALYs averted between 2000 and 2030 by calendar year and by annual birth cohort., Findings: We estimate that vaccination of the ten selected pathogens will have averted 69 million (95% credible interval 52-88) deaths between 2000 and 2030, of which 37 million (30-48) were averted between 2000 and 2019. From 2000 to 2019, this represents a 45% (36-58) reduction in deaths compared with the counterfactual scenario of no vaccination. Most of this impact is concentrated in a reduction in mortality among children younger than 5 years (57% reduction [52-66]), most notably from measles. Over the lifetime of birth cohorts born between 2000 and 2030, we predict that 120 million (93-150) deaths will be averted by vaccination, of which 58 million (39-76) are due to measles vaccination and 38 million (25-52) are due to hepatitis B vaccination. We estimate that increases in vaccine coverage and introductions of additional vaccines will result in a 72% (59-81) reduction in lifetime mortality in the 2019 birth cohort., Interpretation: Increases in vaccine coverage and the introduction of new vaccines into LMICs have had a major impact in reducing mortality. These public health gains are predicted to increase in coming decades if progress in increasing coverage is sustained., Funding: Gavi, the Vaccine Alliance and the Bill & Melinda Gates Foundation., (Copyright © 2021 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY 4.0 license. Published by Elsevier Ltd.. All rights reserved.)

Background: Although traditional diagnostic techniques of infection are mature and price favorable at present, most of them are time-consuming and with a low positivity. Metagenomic next⁃generation sequencing (mNGS) was studied widely because of identification and typing of all pathogens not rely on culture and retrieving all DNA without bias. Based on this background, we aim to detect the difference between mNGS and traditional culture method, and to explore the relationship between mNGS results and the severity, prognosis of infectious patients., Methods: 109 adult patients were enrolled in our study in Shanghai Tenth People's Hospital from October 2018 to December 2019. The diagnostic results, negative predictive values, positive predictive values, false positive rate, false negative rate, pathogen and sample types were analyzed by using both traditional culture and mNGS methods. Then, the samples and clinical information of 93 patients in the infected group (ID) were collected. According to whether mNGS detected pathogens, the patients in ID group were divided into the positive group of 67 cases and the negative group of 26 cases. Peripheral blood leukocytes, C-reactive protein (CRP), procalcitonin (PCT) and neutrophil counts were measured, and the concentrations of IL-2, IL-4, IL-6, TNF-α, IL-17A, IL-10 and INF-γ in the serum were determined by ELISA. The correlation between the positive detection of pathogens by mNGS and the severity of illness, hospitalization days, and mortality were analyzed., Results: 109 samples were assigned into infected group (ID, 92/109, 84.4%), non-infected group (NID, 16/109, 14.7%), and unknown group (1/109, 0.9%). Blood was the most abundant type of samples with 37 cases, followed by bronchoalveolar lavage fluid in 36 cases, tissue, sputum, pleural effusion, cerebrospinal fluid (CSF), pus, bone marrow and nasal swab. In the ID group, the majority of patients were diagnosed with lower respiratory system infections (73/109, 67%), followed by bloodstream infections, pleural effusion and central nervous system infections. The sensitivity of mNGS was significantly higher than that of culture method (67.4% vs 23.6%; P < 0.001), especially in sample types of bronchoalveolar lavage fluid (P = 0.002), blood (P < 0.001) and sputum (P = 0.037), while the specificity of mNGS was not significantly different from culture method (68.8% vs 81.3%; P = 0.41). The number of hospitals stays and 28-day-motality in the positive mNGS group were significantly higher than those in the negative group, and the difference was statistically significant (P < 0.05). Age was significant in multivariate logistic analyses of positive results of mNGS., Conclusions: The study found that mNGS had a higher sensitivity than the traditional method, especially in blood, bronchoalveolar lavage fluid and sputum samples. And positive mNGS group had a higher hospital stay, 28-day-mortality, which means the positive of pathogen nucleic acid sequences detection may be a potential high-risk factor for poor prognosis of adult patients and has significant clinical value. MNGS should be used more in early pathogen diagnosis in the future.

Risk factors associated with 72-h mortality in patients with extremely high serum aspartate aminotransferase levels (AST; ≥ 3000 U/L) are unknown. This single-centre, retrospective, case-controlled, cross-sectional study obtained data from medical records of adult patients treated at Saitama Medical Center, Japan, from 2005 to 2019. We conducted a multivariate logistic after adjusting for age, sex, height, weight, body mass index, Brinkman Index, vital signs, biochemical values, updated Charlson Comorbidity Index (CCI) score, CCI components, and underlying causes. A logistic regression model with selected validity risks and higher C-statistic for predicting 72-h mortality was established. During the 15-year period, 428 patients (133 non-survivors and 295 survivors [cases and controls by survival < 72 and ≥ 72 h, respectively]) with AST levels ≥ 3000 U/L were identified. The 72-h mortality rate was 133/428 (31.1%). The model used for predicting 72-h mortality through the assessment of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus levels had a C-statistic value of 0.852 (sensitivity and specificity, 76.6%). The main independent risk factors associated with 72-h mortality among patients with AST levels ≥ 3000 U/L included higher serum values of alkaline phosphatase, creatine kinase, serum sodium, potassium, and phosphorus.

Introduction: Despite similar disease severity scores; we found a higher crude death rate in the group of immigrant children compared to the group of native children in a paediatric intensive care unit. Our study aimed to compare descriptive data and standardised mortality ratios (SMR) in order to analyse differences in mortality., Material and Methods: We conducted a retrospective study comparing demographic characteristics, diagnostic data, disease severity scores and mortality in immigrant children of Syrian descent and children of Turkish descent. We included data for the medical and surgical patients admitted in 1 year. The sample included 1283 patients., Results: We compared the age and sex distribution, presence of underlying disease, frequency of community-acquired infectious diseases, length of say, PRISM scores, SMR and crude death rates in the 2 groups. There were 1077 patients in the Turkish group and 206 patients in the immigrant group. The proportion of patients with underlying disease was greater in the Turkish group (42% vs. 37.4%). The proportion of patients with a community-acquired infectious disease as the presenting complaint was similar in both groups (52.9% vs. 47.4%). The mortality in patients with infectious disease was higher in the immigrant group (19.3% vs. 9.8%). There was not significant difference in the mean PRISM score between the 2 groups. We found a higher mortality in the immigrant group (16% vs. 11%). The standardised mortality ratio was 0.32 in the total sample group; 0.4 in the immigrant group and 0.24 in the Turkish group., Conclusions: In our study, we found an association between community-acquired infectious disease and increased mortality in the immigrant group. The underlying mechanism for this increase remains to be explained and further research is required to determine whether parameters related to infection should be added to this severity score for its use in this specific population., (Copyright © 2020. Publicado por Elsevier España, S.L.U.)

Background/aim: This study aims to serve as a unique consolidated source in Turkey’s vaccination history and as an example for other countries by objectively revealing the change in mortality and morbidity rates in Turkey following the beginning of vaccination without asserting any claim on the benefits or risks of vaccines. This unbiased research will also help health professionals identify the challenges more easily when they face with the people who hesitate to vaccinate their children., Materials and Methods: Descriptive research design is adopted in this study. The coverages of vaccinations, mortality, and morbidity rates were identified through a retrospective analysis of the data provided from the Ministry of Health of Turkey. The data provided by the Turkish Statistical Institute were used for the identification of the population by the year. Mortality and morbidity rates were calculated based on these data, Results: Morbidity rates, mortality rates, and vaccine coverages are all presented in years. Successful interventions have been observed in the eradication of polio, the elimination of maternal neonatal tetanus, and also in combating with other diseases. A decline in pertussis mortality from 0.59 to 0.06 along with a decline in diphtheria morbidity under to 0.0001 were recognized; additionally the last death due to poliomyelitis was observed in 1998. Only 4 deaths occurred in the measles epidemic in 2013. With the initiation of vaccination, both the morbidity of the rubella with the ratio of 3.12/100,000 and the mortality of pumps with the ratio of 25/100,000 fell to zero. Also, no death due to neonatal tetanus has been recorded since 2014., Conclusion: The present study demonstrates that many possible diseases and deaths have been prevented through vaccination studies. In this regard, this study demonstrating the importance of vaccination presents that all individuals in the society have a responsibility in this scope when the communicable diseases and wars are taken into consideration. The main responsibility is to ensure that they and their children are vaccinated against communicable diseases that are risky for society’s health., Competing Interests: none declared, (This work is licensed under a Creative Commons Attribution 4.0 International Licens)

Attributable mortality is an important metric that mirrors the public health effect of a potentially harmful infection by accounting not only for the effect of infection on mortality, but also for its prevalence within the target population. We did a systematic literature review to identify how attributable deaths were quantified and interpreted in core clinical infectious diseases journals between Jan 1, 2013, and April 6, 2020. Of the 1591 abstracts screened, 234 entered the primary analysis. Our summary of the epidemiological measures used in these articles reveals fundamental shortcomings in the conception of attributable mortality. Because of its importance as a basis for decision making on public health matters, it is essential to correctly quantify and report on attributable mortality. Our recommendation for quantification and reporting of attributable deaths aids clinical researchers in the correct statistical assessment of the burden of infections. Fictional as well as real data is used to illustrate these issues., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Background/aim: The aim of this study was to evaluate the impact of laparoscopic gastrectomy (LG) for gastric cancer on long-term survival in patients with postoperative infectious complications (PIC)., Patients and Methods: A total of 608 patients who underwent gastrectomy were classified into two groups based on the surgical approach: LG (385 patients) and open gastrectomy (OG: 211 patients). Long-term survival after gastrectomy was compared between patients with and without PIC in both LG and OG groups., Results: Although the patients with PIC in OG group tended to have worse overall survival (OS) than those without PIC, the OS was not significantly different between the patients with and without PIC in LG group. Although multivariate analysis demonstrated that nodal involvement and PIC were significantly associated with OS in OG group, age and tumor depth, and not PIC, were associated with OS in LG group., Conclusion: PIC were negative predictors of clinical outcomes in patients with gastric cancer, particularly those who underwent OG, and long-term prognosis may be impacted less by PIC in patients undergoing LG., (Copyright © 2020 International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Objectives: Cases of positive blood cultures were previously reported by a microbiological technologist (MT) to an attending physician (AP), and the Antimicrobial Stewardship team provided medical assistance by grasping the situation at the morning meeting the next day. Since April 2018, MTs have reported positive blood cultures to an infectious disease physician (IDP), who proposes the management approach to the AP and provides weekend support. This study assessed the effectiveness of blood culture reports provided by IDPs to APs on outcomes of bacteremia, including weekend-onset cases., Methods: Patient characteristics and prognoses before (October 2017 to March 2018) and after intervention (April to September 2018) were compared., Results: The pre-intervention and post-intervention groups comprised 134 and 161 patients, respectively. Patients were more likely to be older (>65 years) in the post-intervention group (p < 0.05). There were no significant between-group differences in infection severity. The rate of de-escalation significantly increased from 38.1%-57.8% (p = 0.001). The rates of 28-day and in-hospital mortality reduced following the intervention (21.3% vs. 8.2% and 32.8% vs. 10.6%; p = 0.004 and p < 0.001, respectively). In-hospital mortality for weekend-onset cases also reduced following the intervention (33.3% vs. 12.9%, p = 0.01). Sepsis was a poor prognostic factor (OR 8.070, 95% CI 3.320-19.600, p < 0.001) and intervention was a good prognostic factor (OR 0.311, 95% CI 0.142-0.680, p = 0.003) affecting 28-day mortality in multivariate analysis., Conclusions: Changes to blood culture result reporting protocols can improve outcomes of bacteremia, including weekend-onset cases., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Infection is the most common non-cardiovascular cause of re-hospitalizations for heart failure patients. We therefore investigated the predictors of infection-related re-hospitalization (IRRH) in heart failure patients and its impact on long-term survival., Methods and Results: We prospectively recruited 622 patients after the index hospitalization for decompensated heart fail with primary endpoints of IRRH and all-cause mortality. During follow-up of 3.9 ± 2.7 years, IRRHs occurred in 104 (16.7%) patients. Of the 104 patients who experienced IRRHs, the time from the index hospitalization to IRRH was 1.0 (interquartile range: 0.4-2.6) years. Independent predictors of IRRH were age (hazard ratio: 1.02, 95% confidence interval: 1.01-1.04), diabetes mellitus (2.12, 1.42-3.17), not taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers (1.67, 1.01-2.78), needing maintenance therapy with a loop diuretic (2.10, 1.36-3.26), hemoglobin levels (0.87, 0.79-0.96), and estimated glomerular filtration rates (eGFRs) (0.99, 0.98-0.99). IRRH independently predicted all-cause mortality (1.99, 1.32-2.98) after adjusting for age, body mass index, New York Heart Association functional class, chronic obstructive pulmonary disease, brain natriuretic peptide, hemoglobin, and eGFR. The increased risk of death associated with IRRHs was predominantly for lower respiratory tract infections (3.71, 2.28-6.04), urogenital tract infections (2.83, 1.32-6.10), and sepsis (3.26, 1.20-8.85)., Conclusion: IRRHs in patients discharged for acute decompensated heart fail independently predicted worse long-term survival. We further identified independent predictors of IRRHs. These findings warrant future studies for tackling IRRH.

The COVID-19 pandemic has ignited interest in age-specific manifestations of infection but surprisingly little is known about relative severity of infectious disease between the extremes of age. In a systematic analysis we identified 142 datasets with information on severity of disease by age for 32 different infectious diseases, 19 viral and 13 bacterial. For almost all infections, school-age children have the least severe disease, and severity starts to rise long before old age. Indeed, for many infections even young adults have more severe disease than children, and dengue was the only infection that was most severe in school-age children. Together with data on vaccine response in children and young adults, the findings suggest peak immune function is reached around 5-14 years of age. Relative immune senescence may begin much earlier than assumed, before accelerating in older age groups. This has major implications for understanding resilience to infection, optimal vaccine scheduling, and appropriate health protection policies across the life course.

Retrospective analysis of diagnostic findings from 30 marine-foraging river otter (Lontra canadensis) carcasses opportunistically acquired between 2003 and 2013 revealed trauma as the most common cause of mortality (47%). Within this focal population, causes of trauma included vehicular, gunshot, and one case of suspect intraspecific aggression. Other causes of death included idiopathic (20%), infectious (13%), metabolic (10%), nutritional (7%), and neoplasia (3%). One case of neoplasia, a pancreatic islet cell adenoma, was identified in a 12-yr-old female. In six animals, diffuse renal interstitial fibrosis and multifocal glomerulosclerosis of unknown clinical significance were noted., (© Wildlife Disease Association 2020.)