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      Impacts of age and gender at the risk of underlying medical conditions and death in patients with avian influenza A (H7N9): a meta-analysis study

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          Abstract

          Objective

          The objective of our study was to conduct a series of analyses that examined the impacts of age and gender at the risk of underlying medical conditions (UMCs) and death in patients with influenza A (H7N9).

          Methods

          We began by searching for potentially relevant articles in English or Chinese before February 28, 2018. Additionally, we reviewed our own files and reference lists of articles identified by this search.

          Results

          The association between death and UMCs was significant in H7N9 patients, with an OR of 1.49 (95% CI: 1.24–1.78). Subgroup analyses showed that having two or more UMCs of any type (OR: 2.24; P=0.044), chronic respiratory diseases (OR: 1.81; P=0.032), and chronic cardiovascular disease (OR: 1.63; P=0.013) had an association with increased fatality in H7N9 patients. Age (60 years or older) [adjusted OR (AOR): 1.86; P=0.032] and gender (male: AOR: 1.68, P=0.006; female: AOR: 1.88, P=0.044) were significantly associated with death in H7N9 patients with UMCs compared to H7N9 patients without any UMC. Stratification analyses found statistically significant increased death in H7N9 patients with UMCs who were 60 years of age and older (AOR: 2.72; P<0.001) and gender (male; AOR=1.64; P=0.033), compared to H7N9 patients without these respective conditions.

          Conclusion

          Impacts of age are substantial and significant at the risk of UMCs and death in H7N9 patients. This analysis did not find a significant difference in gender comparisons. Efforts should particularly focus on reducing fatality rates in patients with combined risks from UMCs and other significant impact factor such as age (60 years or older).

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          Most cited references 26

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          Clinical findings in 111 cases of influenza A (H7N9) virus infection.

          During the spring of 2013, a novel avian-origin influenza A (H7N9) virus emerged and spread among humans in China. Data were lacking on the clinical characteristics of the infections caused by this virus. Using medical charts, we collected data on 111 patients with laboratory-confirmed avian-origin influenza A (H7N9) infection through May 10, 2013. Of the 111 patients we studied, 76.6% were admitted to an intensive care unit (ICU), and 27.0% died. The median age was 61 years, and 42.3% were 65 years of age or older; 31.5% were female. A total of 61.3% of the patients had at least one underlying medical condition. Fever and cough were the most common presenting symptoms. On admission, 108 patients (97.3%) had findings consistent with pneumonia. Bilateral ground-glass opacities and consolidation were the typical radiologic findings. Lymphocytopenia was observed in 88.3% of patients, and thrombocytopenia in 73.0%. Treatment with antiviral drugs was initiated in 108 patients (97.3%) at a median of 7 days after the onset of illness. The median times from the onset of illness and from the initiation of antiviral therapy to a negative viral test result on real-time reverse-transcriptase-polymerase-chain-reaction assay were 11 days (interquartile range, 9 to 16) and 6 days (interquartile range, 4 to 7), respectively. Multivariate analysis revealed that the presence of a coexisting medical condition was the only independent risk factor for the acute respiratory distress syndrome (ARDS) (odds ratio, 3.42; 95% confidence interval, 1.21 to 9.70; P=0.02). During the evaluation period, the novel H7N9 virus caused severe illness, including pneumonia and ARDS, with high rates of ICU admission and death. (Funded by the National Natural Science Foundation of China and others.).
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            A major role for cardiovascular burden in age-related cognitive decline.

            The incidence of dementia and cardiovascular disease (CVD) increases with age. Current evidence supports the role for both atherosclerosis and arteriosclerosis as a common pathophysiological ground for the heart-brain connection in ageing. Cognitive decline and CVDs share many vascular risk factors (VRFs) such as smoking, hypertension, and diabetes mellitus; furthermore, CVDs can contribute to cognitive decline by causing cerebral hypoperfusion, hypoxia, emboli, or infarcts. Mixed dementia, resulting from both cerebrovascular lesions and neurodegeneration, accounts for the majority of dementia cases among very old individuals (≥75 years). An accumulation of multiple VRFs, especially in middle age (40-59 years of age), can substantially increase dementia risk. The suggested declining trend in dementia risk, occurring in parallel with the decreasing incidence of cardiovascular events in high-income countries, supports the role of cardiovascular burden in dementia. Accordingly, strategies to promote cardiovascular health, especially if implemented from early life, might help to delay the onset of dementia. In this Review, we discuss the literature investigating the association of cardiovascular burden with cognitive decline and dementia over the life-course.
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              Impact of Pneumococcal Conjugate Vaccination of Infants on Pneumonia and Influenza Hospitalization and Mortality in All Age Groups in the United States

              INTRODUCTION Pneumonia is not only the world’s leading cause of death among children (1), but it is also the leading infectious cause of death among adults (2). Immunization of infants using pneumococcal conjugate vaccines has reduced invasive pneumococcal disease (IPD) and hospitalization for pneumonia in children in randomized trials (3–5). Since its introduction in the United States in 2000, seven-valent conjugate pneumococcal vaccine (PCV7) has reduced IPD dramatically, including in unvaccinated age groups, through induction of herd immunity (6–10). Most of the burden of pneumococcal disease, however, is not from IPD but nonbacteremic pneumonia in adults 65 years old and older, that is, pneumococcal pneumonia without a positive culture from a sterile site. It is biologically plausible that interruption of transmission of vaccine-type Streptococcus pneumoniae can reduce this burden. A groundbreaking prospective observational study through 2004 on the Health Care Cost and Utilization Project (HCUP) Nationwide Inpatient Sample, a 20% sample of hospitalizations nationwide, found a significant reduction in ICD9-coded pneumococcal pneumonia in infants 1 year of age. We converted these annual coverage estimates to seasonal estimates for the 1999–2000 through 2005–2006 winter seasons by averaging coverage in each pair of years (e.g., we took the average of the 2002 and 2003 coverage to arrive at the coverage for the 2002–2003 season). ICD9-coded outcome definitions and rate comparisons. For each state and season, we extracted the numbers of hospitalizations for each outcome from among all of the listed diagnosis codes. We defined IPD as ICD9 code 320.1 or 038.2 or as codes 320.8, 790.7, or 038.9 and 041.2; pneumonia with diagnosed S. pneumoniae infection as ICD9 code 481; and all-cause pneumonia as ICD9 codes 480 to 486. Nonbacteremic pneumococcal pneumonia cases were defined as those with any mention of an ICD9 code 481 diagnosis but without mention of a diagnosis of IPD as defined above. We scanned across discharge diagnoses in each patient record for any mention of these disease codes. We used the disposition information at discharge to identify the subset of hospitalizations for each outcome that resulted in inpatient death. We constructed time series of each outcome for each state and for six age groups, <2 years old, 2 to 4 years old, 5 to 17 years old, 18 to 39 years old, 40 to 64 years old, and ≥65 years old. Baseline rates before introduction of PCV7 were defined as the average annualized rates during the 1996–1997 through 1998–1999 seasons; incidence RR estimates and 95% CIs were calculated using outcome-specific Poisson regression models. Attributing pneumococcal and influenza-associated pneumonia hospitalizations. Because influenza virus infection is rarely confirmed by laboratory testing and because a triggering influenza virus infection is often resolved by the time a patient presents with secondary complications such as bacterial pneumonia, it is not possible to directly assess the influenza disease burden. Modeling the pediatric burden of influenza is further complicated by the concurrent impact of RSV during winter months. Moreover, because most pneumonia hospitalizations are not linked to a specific pathogen, pneumonia due to infection with S. pneumoniae is frequently not recorded as such on hospital discharge forms. To overcome these limitations, we applied a Poisson regression modeling strategy to monthly time series of outcome incidences per 100,000 in order to estimate the seasonal influenza-related and pneumococcal pneumonia-associated burdens in our six age groups. Our strategy was similar to that used by Thompson et al. (16) to assess influenza-related pneumonia. However, instead of weekly laboratory virus surveillance data for influenza and RSV epidemic patterns, we used ICD9-coded counts of influenza (ICD9 487, any mention) and RSV infection (ICD9 480.1, any mention) as explanatory variables, similar to Pitman et al. (22); we also included S. pneumoniae pneumonia (ICD9 481, any mention) as a third explanatory respiratory pathogen variable. A linear trend and a sinusoidal wave component accounted for seasonality and secular trends not captured by the “pathogen” explanatory variables. The best-fitting model was of the form AC pneumonia = exp [β0 + β1(month) + β2(influenza) + β3(RSV) + β4(pneumococcus) + β5sin(2 Π t/12) + β6cos(2 Π t/12)]  where AC pneumonia is all-cause pneumonia, defined as ICD codes 480 to 486 as the primary cause (removing records with first-listed ICD9 codes of 480.1 and 481); influenza (ICD code 487), RSV (ICD code 480.1), and pneumococcus (ICD code 481) are the monthly rates of hospitalizations specifically associated with each outcome in each state (all ages, any mention); and month is the running month variable. The cyclical terms track additional seasonality in the pneumonia data. We computed fractions of all-cause pneumonia attributed to influenza virus, RSV, and S. pneumoniae for all available state/age group time series. For most state/age group combinations, all of the variables in the model were significant. However, we did not change the model form to accommodate states or age groups in cases where not all explanatory variables were significant at the P < 0.05 level. If any parameter value was less than zero, we set the number of attributed cases to zero. And finally, we summed the model attribution and the ICD9-coded attribution to generate the total attributed fraction of all-cause pneumonia to S. pneumoniae, RSV, and influenza virus, respectively. Figure S3 in the supplemental material shows a typical model fit, here for data from children 2 to 4 years of age in New Jersey. Modeling reductions in pneumococcal disease burden associated with PCV7 use. We first constructed Poisson regression models to assess the effect of PCV7 coverage on hospitalization and in-hospital mortality. We analyzed time series extracted from SID data from 10 states spanning the 1996–1997 through 2005–2006 seasons, with the exception of Utah, for which data were unavailable for the 1996–1997 season. We constructed time series for six age groups, younger than 2 years old, 2 through 4 years old, 5 through 17 years old, 18 through 39 years old, 40 through 64 years old, and 65 years old or older. RRs and accompanying 95% CIs were calculated to represent the association between 10 percentage point increments in PCV7 coverage and outcome rates. For hospitalization rates, we ran age-specific Poisson regressions on monthly time series for each state and age group. The model form that best fit the data was Y / N = exp { β 0 + β 1 [ sin ( 2 t π / 12 ) ] + β 2 [ cos ( 2 t π / 12 ) ] + β 3 ( PCV ) } ⁢ where Y is the number of hospitalizations during a particular month for a specific age group, N is the population offset, and t is the calendar month, β0 yielded the intercept while β1 and β2 accounted for seasonal changes in hospitalizations and β3 accounted for the effect of PCV7 coverage in children <5 years old. For in-hospital mortality rates, we applied the same model form to seasonal counts of cases in which a patient had both a diagnosis code associated with each outcome and a discharge status code indicating that the patient died in the hospital. We used the results of these analyses to estimate cumulative national reductions in disease and mortality burdens associated with PCV7 use in each age group. For each outcome, we first used U.S. census data and the aggregate seasonal rates for the 1996–1997 through the 1998–1999 seasons from 10 states to estimate the national burden. Then, for each season and age group, we used national PCV7 coverage, the RR per percentage point increment in coverage, and U.S. census data to estimate the PCV7-associated change in burden for each season and summed these reductions for the 1999–2000 through the 2005–2006 seasons. Single-season analysis of IPD and model-attributed influenza-related pneumonia. Using SID data from 10 states for each age group, we determined the ratio of the rates of IPD and model-attributed influenza-related pneumonia in each post-PCV7 season compared to a baseline determined by the average of rates in the 1996–1997 through the 1998–1999 seasons. We then used Poisson regression to model the relative rate reduction associated with a 10 percentage point increase in PCV7 coverage and calculated two-sided P values to test the hypothesis of no effect of vaccination. SUPPLEMENTAL MATERIAL FIG S1 Monthly rate of hospitalization with a pneumococcal pneumonia diagnosis (ICD9 code 481) in New Jersey among adults ≥65 years old, 1994–1995 through 2005–2006 seasons. Download FIG S2 Total PCV7 coverage estimates, including both normal-schedule and catch-up vaccinations, versus season for U.S. children less than 5 years of age in 10 states. Download FIG S3 Model fit for attribution of pneumococcal pneumonia, RSV, and influenza-related pneumonia attributions for infants <2 years old and adults ≥65 years old. Download FIG S4 Scatterplots of state hospitalization RRs (season/baseline) versus state PCV coverage for the 1999–2000 through the 2003–2004 seasons for (a) IPD among those <2 years old and (b) IPD among those ≥65 years old. The lines represent exponential fits to the data from each season, showing the trend. An asterisk next to the year in each panel indicates a significant trend. Download
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                Author and article information

                Journal
                Ther Clin Risk Manag
                Ther Clin Risk Manag
                Therapeutics and Clinical Risk Management
                Therapeutics and Clinical Risk Management
                Dove Medical Press
                1176-6336
                1178-203X
                2018
                06 September 2018
                : 14
                : 1615-1626
                Affiliations
                [1 ]Division of Infectious Diseases, Hangzhou Center for Disease Control and Prevention, Hangzhou 310021, China, wanghzcdc@ 123456sina.com
                [2 ]Department of Adolescents and Children Health, School of Public Health, Medical College of Soochow University, Suzhou 215123, China
                Author notes
                Correspondence: Xuchu Wang, Division of Infectious Diseases, Hangzhou Center for Disease Control and Prevention, 568 Mingshi Road, Hangzhou 310021, China, Tel/fax +86 571 8800 0505, Email wanghzcdc@ 123456sina.com
                [*]

                These authors contributed equally to this work

                Article
                tcrm-14-1615
                10.2147/TCRM.S173834
                6132488
                © 2018 Cheng et al. This work is published and licensed by Dove Medical Press Limited

                The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed.

                Categories
                Original Research

                Medicine

                meta-analysis, underlying medical conditions, fatality, h7n9, avian influenza virus

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