Assessment of a cellular host response test to risk-stratify suspected COVID-19 patients in the Emergency Department setting.

OBJECTIVE: Assess the IntelliSep Index (ISI) for risk stratification of patients presenting to the Emergency Department (ED) with respiratory symptoms suspected of COVID-19 during the pandemic. METHODS: An observational single-center study of prospective cohort of patients presenting to the ED during the early COVID-19 pandemic with respiratory symptoms and a CBC drawn within 4.5 hours of initial vital signs. A sample of this blood was aliquoted for performance of the ISI, and patients were followed for clinical outcomes. The study required no patient-centered activity beyond standard of care and treating clinicians were unaware of study enrollment and ISI test results. MAIN FINDINGS: 282 patients were included. The ISI ranges 0.1 to 10.0, with three interpretation bands indicating risk of adverse outcome: low (green), 0.1-4.9; intermediate (yellow), 5.0-6.2; and high (red), 6.3-10.0. Of 193 (68.4%) tested for SARS-CoV-2, 96 (49.7%) were positive. The ISI resulted in 182 (64.5%) green, 54 (18.1%) yellow, and 46 (15.6%) red band patients. Green band patients had a 1.1% (n = 2) 3-day mortality, while yellow and red band had 3.7% (n = 2, p > .05) and 10.9% (n = 5, p < .05) 3-day mortalities, respectively. Fewer green band patients required admission (96 [52.7%]) vs yellow (44 [81.5%]) and red (43 [93.5%]). Green band patients had more hospital free days (median 23 (Q1-Q3 20-25) than yellow (median 22 [Q1-Q3 0-23], p < 0.05) and red (median 21 [Q1-Q3 0-24], p < 0.01). SOFA increased with interpretation band: green (2, [Q1-Q3 0-4]) vs yellow (4, [Q1-Q3 2-5], p < 0.001) and red (5, [Q1-Q3 3-6]) p < 0.001). CONCLUSIONS: The ISI rapidly risk-stratifies patients presenting to the ED during the early COVID-19 pandemic with signs or suspicion of respiratory infection.

Temporal Trends, Management and Outcomes of Acute Myocardial Infarction with Concomitant Respiratory Infections.

There are limited contemporary data on the management and outcomes of acute myocardial infarction (AMI) in patients with concomitant acute respiratory infections. Hence, using the National Inpatient Sample from 2000-2017, adult AMI admissions with and without concomitant respiratory infections were identified. We evaluated in-hospital mortality, utilization of cardiac procedures, hospital length of stay, hospitalization costs, and discharge disposition. Among 10,880,856 AMI admissions, respiratory infections were identified in 745,536 (6.9%). Temporal trends revealed a relatively stable tr end with a peak during 2008-2009. Admissions with respiratory infections were on average older (74 vs. 67 years), female (45% vs 39%), with greater comorbidity (mean Charlson comorbidity index 5.9 ± 2.2 vs 4.4 ± 2.3), and had higher rates of non-ST-segment-elevation AMI presentation (71.8% vs. 62.2%) (all p < 0.001). Higher rates of cardiac arrest (8.2% vs 4.8%), cardiogenic shock (10.7% vs 4.4%), and acute organ failure (27.8% vs 8.1%) were seen in AMI admissions with respiratory infections. Coronary angiography (41.4% vs 65.6%, p < 0.001) and percutaneous coronary intervention (20.7% vs 43.5%, p < 0.001) were used less commonly in those with respiratory infections. Admissions with respiratory infections had higher in-hospital mortality (14.5% vs 5.5%; propensity matched analysis: 14.6% vs 12.5%; adjusted odds ratio 1.25 [95% confidence interval 1.24-1.26], p < 0.001), longer hospital stay, higher hospitalization costs, and less frequent discharges to home compared to those without respiratory infections. In conclusion, respiratory infections significantly impact AMI admissions with higher rates of complications, mortality and resource utilization.

Assessment of immunodeficiency scoring index performance in enterovirus/rhinovirus respiratory infection after allogeneic hematopoietic stem cell transplantation.

BACKGROUND: Enterovirus/rhinoviruses (EvRh) are the most common cause of respiratory virus infections in recipients of allogeneic stem cell transplantation (allo-HSCT). OBJECTIVE: We sought to analyze the value of the immunodeficiency scoring index (ISI) in predicting lower respiratory tract disease (LRTD) progression and mortality in a prospective cohort of consecutive adult (>16 years) allo-HSCT recipients with EvRh infection from December 1 2013 to December 1 2019 at two Spanish transplant centers. RESULTS: We included 234 allo-HSCT recipients with 383 EvRh episodes. Out of 383 EvRh episodes, 98 (25%) had LRTD. Multivariate logistic regression analysis identified three independent factors associated with LRTD progression: Ig G < 400 mg/dL, community-acquired respiratory virus (CARV) co-infection and high-risk ISI. Inclusion of Ig G levels and CARV co-infection in the ISI improved its performance by significantly increasing the area under the receiver operator characteristic curve (AUROC) from 0.643 to 0.734 (P = .03). Likewise, the two conditions identified by multivariate analyses as associated with higher probability of mortality were high-risk ISI and EvRh infection within 6 months after transplant. CONCLUSIONS: Our findings confirm the value of high-risk ISI in predicting both probability of EvRh LRTD and 3-month overall mortality. We also demonstrate that the original ISI could be adapted to other CARV types by including additional variables to improve its performance.

Deprivation and mortality related to pediatric respiratory tract infection: a cohort study in 3 high-income jurisdictions.

BACKGROUND: Deaths from respiratory tract infections (RTIs) in children are preventable through timely access to public health and medical interventions. We aimed to assess whether socioeconomic disparities in mortality related to pediatric RTI persisted after accounting for health status at birth. METHODS: We compared the prevalence of and risk factors for RTI-related death in singletons aged 28 days to 4 years across Ontario (Canada), Scotland and England (jurisdictions with universal health care) using linked administrative data for 2003-2013. We estimated rates of RTI-related mortality for children living in deprived areas and those born to teenage girls; we estimated both crude rates and those adjusted for health status at birth. RESULTS: A total of 1 299 240 (Ontario), 547 556 (Scotland) and 3 910 401 (England) children were included in the study. Across all jurisdictions, children born in the most deprived areas experienced the highest rates of RTI-related mortality. After adjustment for high-risk chronic conditions and prematurity, we observed differences in mortality according to area-level deprivation in Ontario and England but not in Scotland. In Ontario, teenage motherhood was also an independent risk factor for RTI-related mortality. INTERPRETATION: Socioeconomic disparities played a substantial role in child mortality related to RTI in all 3 jurisdictions. Context-specific investigations around the mechanisms of this increased risk and development of programs to address socioeconomic disparities are needed.

Attributable burden in patients with carbapenem-nonsusceptible gram-negative respiratory infections.

OBJECTIVE: We aimed to describe the clinical and economic burden attributable to carbapenem-nonsusceptible (C-NS) respiratory infections. METHODS: This retrospective matched cohort study assessed clinical and economic outcomes of adult patients (aged ≥18 years) who were admitted to one of 78 acute care hospitals in the United States with nonduplicate C-NS and carbapenem-susceptible (C-S) isolates from a respiratory source. A subset analysis of patients with principal diagnosis codes denoting bacterial pneumonia or other diagnoses was also conducted. Isolates were classified as community- or hospital-onset based on collection time. A generalized linear mixed model method was used to estimate the attributable burden for mortality, 30-day readmission, length of stay (LOS), cost, and net gain/loss (payment minus cost) using propensity score-matched C-NS versus C-S cohorts. RESULTS: For C-NS cases, mortality (25.7%), LOS (29.4 days), and costs ($81,574) were highest in the other principal diagnosis, hospital-onset subgroup; readmissions (19.4%) and net loss (-$9522) were greatest in the bacterial pneumonia, hospital-onset subgroup. Mortality and readmissions were not significantly higher for C-NS cases in any propensity score-matched subgroup. Significant C-NS-attributable burden was found for both other principal diagnosis subgroups for LOS (hospital-onset: 3.7 days, P = 0.006; community-onset: 1.5 days, P<0.001) and cost (hospital-onset: $12,777, P<0.01; community-onset: $2681, P<0.001). CONCLUSIONS: Increased LOS and cost burden were observed in propensity score-matched patients with C-NS compared with C-S respiratory infections; the C-NS-attributable burden was significant only for patients with other principal diagnoses.

Strong effect of Ecuador's conditional cash transfer program on childhood mortality from poverty-related diseases: a nationwide analysis.

BACKGROUND: The mortality rate in children under 5 years old (U5MR) has decreased considerably in Ecuador in the last decade; however, thousands of children continue to die from causes related to poverty. A social program known as Bono de Desarrollo Humano (BDH) was created to guarantee a minimum level of consumption for families and to reduce chronic malnutrition and preventable childhood diseases. We sought to evaluate the effect of the BDH program on mortality of children younger than 5 years, particularly from malnutrition, diarrheal diseases, and lower respiratory tract infections. METHODS: Mortality rates and BDH coverage from 2009 to 2014 were evaluated from the 144 (of 222) Ecuadorian counties with intermediate and high quality of vital information. A multivariable regression analyses for panel data was conducted by using a negative binomial regression model with fixed effects, adjusted for all relevant demographic and socioeconomic covariates. RESULTS: Our research shows that for each 1% increase in BDH county coverage there would be a decrease in U5MR from malnutrition of 3% (RR 0.971, 95% CI 0.953-0.989). An effect of BDH county coverage on mortality resulting from respiratory infections was also observed (RR 0.992, 95% CI 0.984-0.999). The BDH also reduced hospitalization rates in children younger than 5 years, overall and for diarrhea. CONCLUSIONS: A conditional cash transfer program such as BDH could contribute to the reduction of mortality due to causes related to poverty, such as malnutrition and respiratory infections. The coverage should be maintained -or increased in a period of economic crisis- and its implementation strengthened.

Incremental clinical and economic burden of suspected respiratory infections due to multi-drug-resistant Pseudomonas aeruginosa in the United States.

BACKGROUND: Multi-drug resistant (MDR) Pseudomonas aeruginosa can negatively affect patients and hospitals. AIM: To evaluate excess mortality and cost burden among patients hospitalized with suspected respiratory infections due to MDR P. aeruginosa vs patients with non-MDR P. aeruginosa in 78 United States (US) hospitals. METHODS: This study analyzed electronically captured microbiological and outcomes data of patients hospitalized with non-duplicate P. aeruginosa isolates from respiratory sources collected ≥3 days after admission to identify hospital-onset MDR or non-MDR P. aeruginosa per the Centers for Disease Control and Prevention definition. The risk of multi-drug resistance was estimated on mortality, length of stay (LOS), cost, operation gain/loss, and 30-day readmission. A sensitivity analysis was conducted utilizing a cohort with pharmacy data available. FINDINGS: Of 523 MDR and 1381 non-MDR P. aeruginosa cases, unadjusted mortality was 23.7% vs 18.0% and multi-variable-adjusted mortality was 20.0% (95% confidence interval (CI): 14.3-27.2%) vs 15.5% (95% CI: 11.2-20.9%; P=0.026), the average adjusted excess LOS was 6.7 days (P<0.001); excess cost per case was US$22,370 higher (P=0.002) and operational loss per case was US$10,661 (P=0.024) greater, and the multi-variable adjusted readmission rate was 16.2% (95% CI: 11.2-22.9%) vs 11.1% (95% CI: 7.8-15.6%; P=0.006). The sensitivity analysis yielded similar results. CONCLUSIONS: Compared with suspected infections due to non-MDR P. aeruginosa, patients with MDR P. aeruginosa had higher risk of mortality, readmission, and longer LOS, as well as US$20,000 incremental cost and >US$10,000 incremental net loss per case after controlling for patient and hospital characteristics.

Antibiotic use and associated factors in a large sample of hospitalised older people.

OBJECTIVES: The aims of this study were to assess (i) the prevalence of antibiotic use, (ii) factors associated with their use and (iii) the association with in-hospital mortality in a large sample of hospitalised older people in Italy. METHODS: Data were obtained from the 2010-2017 REPOSI register held in more than 100 internal medicine and geriatric wards in Italy. Patients aged ≥65 years with at least one antibiotic prescription during their hospitalisation were selected. Multivariable logistic regression models were used to determine factors associated with antibiotic use. RESULTS: A total of 5442 older patients were included in the analysis, of whom 2786 (51.2%) were prescribed antibiotics during their hospitalisation. The most frequently prescribed antibiotic class was ß- lactams, accounting for 50% of the total prescriptions. Poor physical independence, corticosteroid use and being hospitalised in Northern Italy were factors associated with a higher likelihood of being prescribed antibiotics. Antibiotic use was associated with an increased risk of in-hospital mortality (odds ratio=2.52, 95% confidence interval 1.82-3.48) also when accounting for factors associated with their use. CONCLUSION: Hospitalised older people are often prescribed antibiotics. Factors related to poor physical independence and corticosteroid use are associated with increased antibiotic use. Being prescribed antibiotics is also associated with an increased risk of in-hospital death. These results demand the implementation of specific stewardship programmes to improve the correct use of antibiotics in hospital settings and to reduce the risk of antimicrobial resistance.

Burden of Respiratory Syncytial Virus Disease and Mortality Risk Factors in Argentina: 18 Years of Active Surveillance in a Children's Hospital.

BACKGROUND: Respiratory syncytial virus is the leading cause of acute lower respiratory infection in children. We aimed to describe the clinical-epidemiologic pattern and risk factors for mortality associated with RSV infection. METHODS: This is a prospective, cross-sectional study of acute lower respiratory infection in children admitted to the Children's Hospital during 2000 to 2017. Viral diagnosis was made by fluorescent antibody techniques or real-time-polymerase chain reaction. We compared clinical-epidemiologic characteristics of RSV infection in nonfatal versus fatal cases. Multiple logistic regression was used to identify independent predictors of mortality. RESULTS: Of 15,451 patients with acute lower respiratory infection, 13,033 were tested for respiratory viruses and 5831 (45%) were positive: RSV 81.3% (4738), influenza 7.6% (440), parainfluenza 6.9% (402) and adenovirus 4.3% (251). RSV had a seasonal epidemic pattern coinciding with months of lowest average temperature. RSV cases show a case fatality rate of 1.7% (82/4687). Fatal cases had a higher proportion of prematurity (P < 0.01), perinatal respiratory history (P < 0.01), malnourishment (P < 0.01), congenital heart disease (P < 0.01), chronic neurologic disease (P < 0.01) and pneumonia at clinical presentation (P = 0.014). No significant difference between genders was observed. Most deaths occurred among children who had complications: respiratory distress (80.5%), nosocomial infections (45.7%), sepsis (31.7%) and atelectasis (13.4%). Independent predictors of RSV mortality were moderate-to-severe malnourishment, odds ratio (OR): 3.69 [95% confidence interval (CI): 1.98-6.87; P < 0.0001]; chronic neurologic disease, OR: 4.14 (95% CI: 2.12-8.08; P < 0.0001); congenital heart disease, OR: 4.18 (95% CI: 2.39-7.32; P< 0.0001); and the age less than 6 months, OR: 1.99 (95% CI: 1.24-3.18; P = 0.004). CONCLUSIONS: RSV showed an epidemic pattern affecting mostly young children. Malnourishment, chronic neurologic disease, congenital heart disease and the age less than 6 months were the independent risk factors for RSV mortality.

Free hospitalization for acute respiratory infections in children: what effect and how much does it cost for Armenia?

INTRODUCTION: The "Child Certificate" program, launched in Armenia in 2011, made hospitalization for children less than seven years free in order to improve access to hospitalization, reduce out-of-pocket expenses and ensure Universal Health Coverage. We aimed to estimate trends in the number of outpatient and hospitalized acute respiratory infection (ARI) cases and related under-five mortality. METHODOLOGY: Cross-sectional study using data from national databases before (2008-2011) and after (2012-2017) Program implementation. The diagnosis of ARI was based on the International Classification of Disease (ICD-10). RESULTS: The average hospitalization per 1000 children under 14 and infants increased by 85% and 75% respectively, compared with the period before the introduction of the Program, while the frequency of outpatient visits remained unchanged. The ARI-related mortality in children less than five years and in infants decreased by 11% and 19%, respectively. Financial allocations for ARI-associated hospitalizations amounted to 2.1 billion Armenian drams in 2011 and increased to 3.3 billion drams in 2016 (an increase of 57%). For pneumonia, this increase was 108% (from 0.35 to 0.72 billion). CONCLUSIONS: The introduction of free hospitalization for ARI led to an increase in the hospitalization rates. There was a favorable decline in under-five mortality and an exponential increase in financial allocations. The reasons for hospitalization should be investigated to ensure rational hospitalization with parallel improvement of primary care to reduce delayed presentations. It is necessary to find ways addressing the growing financial allocations for ARI-associated hospitalization.

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory infections in 195 countries, 1990-2016: a systematic analysis for the Global Burden of Disease Study 2016.

BACKGROUND: Lower respiratory infections are a leading cause of morbidity and mortality around the world. The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2016, provides an up-to-date analysis of the burden of lower respiratory infections in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 26 years and shows how the burden of lower respiratory infection has changed in people of all ages. METHODS: We used three separate modelling strategies for lower respiratory infections in GBD 2016: a Bayesian hierarchical ensemble modelling platform (Cause of Death Ensemble model), which uses vital registration, verbal autopsy data, and surveillance system data to predict mortality due to lower respiratory infections; a compartmental meta-regression tool (DisMod-MR), which uses scientific literature, population representative surveys, and health-care data to predict incidence, prevalence, and mortality; and modelling of counterfactual estimates of the population attributable fraction of lower respiratory infection episodes due to Streptococcus pneumoniae, Haemophilus influenzae type b, influenza, and respiratory syncytial virus. We calculated each modelled estimate for each age, sex, year, and location. We modelled the exposure level in a population for a given risk factor using DisMod-MR and a spatio-temporal Gaussian process regression, and assessed the effectiveness of targeted interventions for each risk factor in children younger than 5 years. We also did a decomposition analysis of the change in LRI deaths from 2000-16 using the risk factors associated with LRI in GBD 2016. FINDINGS: In 2016, lower respiratory infections caused 652 572 deaths (95% uncertainty interval [UI] 586 475-720 612) in children younger than 5 years (under-5s), 1 080 958 deaths (943 749-1 170 638) in adults older than 70 years, and 2 377 697 deaths (2 145 584-2 512 809) in people of all ages, worldwide. Streptococcus pneumoniae was the leading cause of lower respiratory infection morbidity and mortality globally, contributing to more deaths than all other aetiologies combined in 2016 (1 189 937 deaths, 95% UI 690 445-1 770 660). Childhood wasting remains the leading risk factor for lower respiratory infection mortality among children younger than 5 years, responsible for 61·4% of lower respiratory infection deaths in 2016 (95% UI 45·7-69·6). Interventions to improve wasting, household air pollution, ambient particulate matter pollution, and expanded antibiotic use could avert one under-5 death due to lower respiratory infection for every 4000 children treated in the countries with the highest lower respiratory infection burden. INTERPRETATION: Our findings show substantial progress in the reduction of lower respiratory infection burden, but this progress has not been equal across locations, has been driven by decreases in several primary risk factors, and might require more effort among elderly adults. By highlighting regions and populations with the highest burden, and the risk factors that could have the greatest effect, funders, policy makers, and programme implementers can more effectively reduce lower respiratory infections among the world's most susceptible populations. FUNDING: Bill & Melinda Gates Foundation.

Higher mortality and hospital charges in patients with cirrhosis and acute respiratory illness: a population-based study.

Both cirrhosis and acute respiratory illness (ARI) carry substantial disease and financial burden. To compare hospitalized patients with cirrhosis with ARI to cirrhotic patients without ARI, a retrospective cohort study was conducted using the California Office of Statewide Health Planning and Development database. To balance the groups, propensity score matching (PSM) was used. We identified a total of 46,192 cirrhotic patients during the three study periods (14,049, 15,699, and 16,444 patients, respectively). Among patients hospitalized with cirrhosis, the ARI prevalence was higher in older age groups (p < 0.001), the Asian population (p = 0.002), non-Hispanic population (p = 0.001), and among Medicare patients (p < 0.001). Compared to controls, patients with ARI had 53.8% higher adjusted hospital charge ($122,555 vs. $79,685 per patient per admission, p < 0.001) and 35.0% higher adjusted in-hospital mortality (p < 0.001). Older patients, patients with alcoholic liver disease or liver cancer were at particularly higher risk (adjusted hazard ratio = 2.94 (95% CI: 2.26-3.83), 1.22 (95% CI: 1.02-1.45), and 2.17 (95% CI: 1.76-2.68) respectively, p = 0.028 to <0.001). Mortality rates and hospital charges in hospitalized cirrhotic patients with ARI were higher than in cirrhotic controls without ARI. Preventive efforts such as influenza and pneumococcal vaccination, especially in older patients and those with liver cancer, or alcoholic liver disease, would be of value.

Inequalities on mortality due to acute respiratory infection in children: A Colombian analysis. / Desigualdades en la mortalidad por infección respiratoria aguda en niños: un análisis colombiano

INTRODUCTION: Acute respiratory infections (ARI) are a leading public health issue worldwide. OBJECTIVE: To explore the inequalities in ARI mortality rates in under-5, according to socioeconomic characteristics. MATERIALS AND METHODS: We conducted an ecological analysis to study inequalities at municipal level due to ARI mortality in children under 5 years. The data were obtained from official death records of the Departamento Administrativo Nacional de Estadística. The analysis of inequalities in the under-5 mortality rate (U5MR) included: 1) Classification of the population in different socio-economic strata, and 2) measurement of the degree of inequality. We used the ARI-U5MR as an outcome measurement.The mortality rates were estimated at national and municipal levels for the years 2000, 2005, 2010, and 2013. Rate ratios, rates differences, and concentration curves were calculated to observe the inequalities. RESULTS: A total of 18,012 children under 5 years died by ARI in Colombia from 2000 to 2013. ARIU5MR was greater in boys than in girls. During this period, an increase in the infant mortality relative gap in both boys and girls was observed. In 2013, the U5MR evidenced that for boys from municipalities with the highest poverty had a 1.6-fold risk to die than those in municipalities with the lowest poverty (low tercile). In girls, the ARI-U5MR for 2005 and 2013 in the poorest tercile was 1.5 and 2 times greater than in the first tercile, respectively. CONCLUSION: Colombian inequalities in the ARI mortality rate among the poorest municipalities compared to the richest ones continue to be a major challenge in public health.

Introducción. Las infecciones respiratorias agudas (IRA) son un importante problema de salud pública a nivel mundial. Objetivo. Explorar las desigualdades de la tasa de mortalidad debida a IRA (TM-IRA) en <5 años, de acuerdo a variables socioeconómicas. Materiales y métodos. Se realizó un análisis ecológico para estudiar las desigualdades a nivel municipal de las TM-IRA en <5 años. Los datos se obtuvieron a partir de registros de muertes del Departamento Administrativo Nacional de Estadística. En análisis de desigualdades en <5 incluyó: 1) Clasificación de la población por estatus socioeconómico y 2) Medición del grado de desigualdad. Como resultado en salud se utilizó la TM-IRA en <5 años. Se estimaron tasas a nivel nacional y municipal para 2000, 2005, 2010, 2013. Se calcularon razones y diferencias de tasas y curvas de concentración para observar las desigualdades. Resultados. Entre 2000-2013 murieron en Colombia por IRA 18.012 <5 años. La TM-ARI fue mayor en niños que en niñas. En el periodo, se observó un incremento en la brecha de mortalidad infantil en ambos sexos. En 2013, la tasa en niños que murieron en municipios con mayor pobreza fue 1,6 veces mayor que la de niños en aquellos con menor. En niñas, para 2015 y 2013, la tasa en el tercil más pobre fue 1,5 y 2 veces mayor que la del primer tercil, respectivamente. Conclusión. Las desigualdades en la TM-IRA entre los municipios más pobres en comparación con los más ricos continúan siendo un reto importante en salud pública.

Estimation of Burden of Influenza among under-Five Children in India: A Meta-Analysis.

BACKGROUND: We estimated the burden of influenza-related acute respiratory tract infection (ARI) among under-fives in India through meta-analysis. METHODOLOGY: We estimated pooled incidence and proportional positivity of laboratory-diagnosed influenza among under-fives using data from observational studies published from 1 January 1961 to 31 December 2016. Death due to influenza was estimated using a multiplier model. RESULTS: Influenza-associated ARI incidence was estimated as 132 per 1000 child-years (115-149). The patients positive for influenza among ARI in outpatients and inpatients were estimated to be 11.2% (8.8-13.6) and 7.1% (5.5-8.8), respectively. We estimated total influenza cases during 2016 as 16 009 207 (13 942 916-18 082 769) in India. Influenza accounted for 10 913 476 (9 504 666-12 362 310) outpatient visits and 109 431 (83 882-134 980) hospitalizations. A total of 27 825 (21 382-34 408) influenza-associated under-five deaths were estimated in India in 2016. CONCLUSION: Influenza imposes a substantial burden among under-fives in India. Public health approach for its prevention and control needs to be explored.

The risk of lower respiratory tract infection following influenza virus infection: A systematic and narrative review.

BACKGROUND: Lower respiratory tract infections (LRTI) are a major cause of morbidity and mortality worldwide, particularly in young children and older adults. Influenza is known to cause severe disease but the risk of developing LRTI following influenza virus infection in various populations has not been systematically reviewed. Such data are important for estimating the impact specific influenza vaccine programs would have on LRTI outcomes in a community. We sought to review the published literature to determine the risk of developing LRTI following an influenza virus infection in individuals of any age. METHODS AND FINDINGS: We conducted a systematic review to identify prospective studies that estimated the incidence of LRTI following laboratory-confirmed influenza virus infection. We searched PubMed, Medline, and Embase databases for relevant literature. We supplemented this search with a narrative review of influenza and LRTI. The systematic review identified two prospective studies that both followed children less than 5 years. We also identified one additional pediatric study from our narrative review meeting the study inclusion criteria. Finally, we summarized recent case-control studies on the etiology of pneumonia in both adults and children. CONCLUSIONS: There is a dearth of prospective studies evaluating the risk of developing LRTI following influenza virus infection. Determining the burden of severe LRTI that is attributable to influenza is necessary to estimate the benefits of influenza vaccine on this important public health outcome. Vaccine probe studies are an efficient way to evaluate these questions and should be encouraged going forward.

Children's Environmental Health Indicators for Low- and Middle-Income Countries in Asia.

BACKGROUND: Given that low- and middle-income countries (LMICs) in Asia still have high child mortality rates, improved monitoring using children's environmental health indicators (CEHI) may help reduce preventable deaths by creating healthy environments. OBJECTIVES: Thus, the aim of this study is to build a set of targeted CEHI that can be applied in LMICs in Asia through the CEHI initiative using a common conceptual framework. METHODS: A systematic review was conducted to identify the most frequently used framework for developing CEHI. Due to the limited number of eligible records, a hand search of the reference lists and an extended search of Google Scholar were also performed. Based on our findings, we designed a set of targeted CEHI to address the children's environmental health situation in LMICs in Asia. The Delphi method was then adopted to assess the relevance, appropriateness, and feasibility of the targeted CEHI. FINDINGS: The systematic review indicated that the Driving-Pressure-State-Exposure-Effect-Action framework and the Multiple-Exposures-Multiple-Effects model were the most common conceptual frameworks for developing CEHI. The Multiple-Exposures-Multiple-Effects model was adopted, given that its population of interest is children and its emphasis on the many-to-many relationship. Our review also showed that most of the previous studies covered upper-middle- or high-income countries. The Delphi results validated the targeted CEHI. The targeted CEHI were further specified by age group, gender, and place of residence (urban/rural) to enhance measurability. CONCLUSIONS: Improved monitoring systems of children's environmental health using the targeted CEHI may mitigate the data gap and enhance the quality of data in LMICs in Asia. Furthermore, critical information on the complex interaction between the environment and children's health using the CEHI will help establish a regional environmental children's health action plan, named "The Children's Environment and Health Action Plan for Asia."

Spatial modelling of contribution of individual level risk factors for mortality from Middle East respiratory syndrome coronavirus in the Arabian Peninsula.

BACKGROUND: Middle East respiratory syndrome coronavirus is a contagious respiratory pathogen that is contracted via close contact with an infected subject. Transmission of the pathogen has occurred through animal-to-human contact at first followed by human-to-human contact within families and health care facilities. DATA AND METHODS: This study is based on a retrospective analysis of the Middle East respiratory syndrome coronavirus outbreak in the Kingdom of Saudi Arabia between June 2012 and July 2015. A Geoadditive variable model for binary outcomes was applied to account for both individual level risk factors as well spatial variation via a fully Bayesian approach. RESULTS: Out of 959 confirmed cases, 642 (67%) were males and 317 (33%) had died. Three hundred and sixty four (38%) cases occurred in Ar Riyad province, while 325 (34%) cases occurred in Makkah. Individuals with some comorbidity had a significantly higher likelihood of dying from MERS-CoV compared with those who did not suffer comorbidity [Odds ratio (OR) = 2.071; 95% confidence interval (CI): 1.307, 3.263]. Health-care workers were significantly less likely to die from the disease compared with non-health workers [OR = 0.372, 95% CI: 0.151, 0.827]. Patients who had fatal clinical experience and those with clinical and subclinical experiences were equally less likely to die from the disease compared with patients who did not have fatal clinical experience and those without clinical and subclinical experiences respectively. The odds of dying from the disease was found to increase as age increased beyond 25 years and was much higher for individuals with any underlying comorbidities. CONCLUSION: Interventions to minimize mortality from the Middle East respiratory syndrome coronavirus should particularly focus individuals with comorbidity, non-health-care workers, patients with no clinical fatal experience, and patients without any clinical and subclinical experiences.

Estimates of the global, regional, and national morbidity, mortality, and aetiologies of lower respiratory tract infections in 195 countries: a systematic analysis for the Global Burden of Disease Study 2015.

BACKGROUND: The Global Burden of Diseases, Injuries, and Risk Factors (GBD) Study 2015 provides an up-to-date analysis of the burden of lower respiratory tract infections (LRIs) in 195 countries. This study assesses cases, deaths, and aetiologies spanning the past 25 years and shows how the burden of LRI has changed in people of all ages. METHODS: We estimated LRI mortality by age, sex, geography, and year using a modelling platform shared across most causes of death in the GBD 2015 study called the Cause of Death Ensemble model. We modelled LRI morbidity, including incidence and prevalence, using a meta-regression platform called DisMod-MR. We estimated aetiologies for LRI using two different counterfactual approaches, the first for viral pathogens, which incorporates the aetiology-specific risk of LRI and the prevalence of the aetiology in LRI episodes, and the second for bacterial pathogens, which uses a vaccine-probe approach. We used the Socio-demographic Index, which is a summary indicator derived from measures of income per capita, educational attainment, and fertility, to assess trends in LRI-related mortality. The two leading risk factors for LRI disability-adjusted life-years (DALYs), childhood undernutrition and air pollution, were used in a decomposition analysis to establish the relative contribution of changes in LRI DALYs. FINDINGS: In 2015, we estimated that LRIs caused 2·74 million deaths (95% uncertainty interval [UI] 2·50 million to 2·86 million) and 103·0 million DALYs (95% UI 96·1 million to 109·1 million). LRIs have a disproportionate effect on children younger than 5 years, responsible for 704 000 deaths (95% UI 651 000-763 000) and 60.6 million DALYs (95ÙI 56·0-65·6). Between 2005 and 2015, the number of deaths due to LRI decreased by 36·9% (95% UI 31·6 to 42·0) in children younger than 5 years, and by 3·2% (95% UI -0·4 to 6·9) in all ages. Pneumococcal pneumonia caused 55·4% of LRI deaths in all ages, totalling 1 517 388 deaths (95% UI 857 940-2 183 791). Between 2005 and 2015, improvements in air pollution exposure were responsible for a 4·3% reduction in LRI DALYs and improvements in childhood undernutrition were responsible for an 8·9% reduction. INTERPRETATION: LRIs are the leading infectious cause of death and the fifth-leading cause of death overall; they are the second-leading cause of DALYs. At the global level, the burden of LRIs has decreased dramatically in the last 10 years in children younger than 5 years, although the burden in people older than 70 years has increased in many regions. LRI remains a largely preventable disease and cause of death, and continued efforts to decrease indoor and ambient air pollution, improve childhood nutrition, and scale up the use of the pneumococcal conjugate vaccine in children and adults will be essential in reducing the global burden of LRI. FUNDING: Bill & Melinda Gates Foundation.

Burden of disease by lower respiratory tract infections in Brazil, 1990 to 2015: estimates of the Global Burden of Disease 2015 study. / Carga de doença por infecções do trato respiratório inferior no Brasil, 1990 a 2015: estimativas do estudo Global Burden of Disease 2015.

INTRODUCTION:: Lower respiratory tract infections (LRTIs) present significant incidence and mortality in the world. This article presents the impact of LRTIs in the burden of disease, according to the metrics used in the Global Burden of Disease study (GBD 2015) for Brazil in 1990 and 2015. METHODS:: Analysis of estimates from the GBD 2015: years of life lost due to premature death (YLLs), years lived with disability (YLDs), years of life lost due to death or disability (DALYs = YLLs + YLDs). RESULTS:: LRTIs were the third cause of mortality in Brazil in 1990 and 2015, with 63.5 and 47.0 deaths/100,000 people, respectively. Although the number of deaths increased 26.8%, there was a reduction of 25.5% in mortality rates standardized by age, with emphasis on children under 5 years of age. The disability indicators, as measured by the DALYs, demonstrate a progressive reduction of the disease burden by LRTIs. DISCUSSION:: Despite the reduction in mortality rates in the period, LRTIs were an important cause of disability and still the third cause of death in Brazil in 2015. The increase in the number of deaths occurred due to the increase in population and its aging. The reduction in mortality rates accompanied the improvement of socioeconomic conditions, broader access to health care, national availability of antibiotics, and vaccination policies adopted in the country. CONCLUSION:: Despite the current socioeconomic difficulties, there has been a progressive reduction of the LRTIs load effect in Brazil, mostly in mortality and disability, and among children under 5 years of age.

Carga de doença por infecções do trato respiratório inferior no Brasil, 1990 a 2015: estimativas do estudo Global Burden of Disease 2015 / Burden of disease by lower respiratory tract infections in Brazil, 1990 to 2015: estimates of the Global Burden of Disease 2015 study

RESUMO: Introdução: Infecções do trato respiratório inferior (ITRi) apresentam incidência e mortalidade significativas no mundo. Este artigo apresenta o impacto das ITRi na carga de doença, segundo as métricas utilizadas no estudo Global Burden of Disease 2015 (GBD 2015) para o Brasil, em 1990 e 2015. Métodos: Análise de estimativas do GBD 2015: anos de vida perdidos por morte prematura (YLLs), anos vividos com incapacidade (YLDs) e anos de vida perdidos por morte ou incapacidade (DALYs = YLLs + YLDs). Resultados: As ITRi foram a terceira causa de mortalidade no Brasil em 1990 e 2015, com 63,5 e 47,0 mortes/100 mil habitantes, respectivamente. Embora o número absoluto de óbitos tenha aumentado 26,8%, houve redução de 25,5% nas taxas de mortalidade padronizadas por idade, sendo a redução mais marcante em menores de 5 anos. Também houve redução progressiva da carga da doença, expressa em DALYs. Discussão: Apesar da redução da carga da doença no período, as ITRi foram importante causa de incapacidade e a terceira causa de mortes no Brasil em 2015. O aumento do número de óbitos ocorreu devido ao aumento e envelhecimento populacional. A redução das taxas de mortalidade acompanhou a melhora das condições socioeconômicas, do acesso mais amplo aos cuidados de saúde, da disponibilidade nacional de antibióticos e das políticas de vacinação adotadas no país. Conclusão: Apesar das dificuldades socioeconômicas vigentes, constatou-se uma redução progressiva da carga das ITRi, principalmente na mortalidade e na incapacidade, e entre os menores de cinco anos de idade.

ABSTRACT: Introduction: Lower respiratory tract infections (LRTIs) present significant incidence and mortality in the world. This article presents the impact of LRTIs in the burden of disease, according to the metrics used in the Global Burden of Disease study (GBD 2015) for Brazil in 1990 and 2015. Methods: Analysis of estimates from the GBD 2015: years of life lost due to premature death (YLLs), years lived with disability (YLDs), years of life lost due to death or disability (DALYs = YLLs + YLDs). Results: LRTIs were the third cause of mortality in Brazil in 1990 and 2015, with 63.5 and 47.0 deaths/100,000 people, respectively. Although the number of deaths increased 26.8%, there was a reduction of 25.5% in mortality rates standardized by age, with emphasis on children under 5 years of age. The disability indicators, as measured by the DALYs, demonstrate a progressive reduction of the disease burden by LRTIs. Discussion: Despite the reduction in mortality rates in the period, LRTIs were an important cause of disability and still the third cause of death in Brazil in 2015. The increase in the number of deaths occurred due to the increase in population and its aging. The reduction in mortality rates accompanied the improvement of socioeconomic conditions, broader access to health care, national availability of antibiotics, and vaccination policies adopted in the country. Conclusion: Despite the current socioeconomic difficulties, there has been a progressive reduction of the LRTIs load effect in Brazil, mostly in mortality and disability, and among children under 5 years of age.