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Placing patients who require mechanical ventilation in the prone rather than the supine position improves oxygenation. In this trial, the investigators found a benefit with respect to all-cause mortality with this change in body position in patients with severe ARDS. Prone positioning has been used for many years to improve oxygenation in patients who require mechanical ventilatory support for management of the acute respiratory distress syndrome (ARDS). Randomized, controlled trials have confirmed that oxygenation is significantly better when patients are in the prone position than when they are in the supine position. 1 , 2 Furthermore, several lines of evidence have shown that prone positioning could prevent ventilator-induced lung injury. 3 – 6 In several previous trials, these physiological benefits did not translate into better patient outcomes, since no significant improvement was observed in patient survival with prone positioning. 7 – 10 However, meta-analyses 2 , 11 have . . .

The global spread of epidemics, rumors, opinions, and innovations are complex, network-driven dynamic processes. The combined multiscale nature and intrinsic heterogeneity of the underlying networks make it difficult to develop an intuitive understanding of these processes, to distinguish relevant from peripheral factors, to predict their time course, and to locate their origin. However, we show that complex spatiotemporal patterns can be reduced to surprisingly simple, homogeneous wave propagation patterns, if conventional geographic distance is replaced by a probabilistically motivated effective distance. In the context of global, air-traffic-mediated epidemics, we show that effective distance reliably predicts disease arrival times. Even if epidemiological parameters are unknown, the method can still deliver relative arrival times. The approach can also identify the spatial origin of spreading processes and successfully be applied to data of the worldwide 2009 H1N1 influenza pandemic and 2003 SARS epidemic.

The first cases of human infection with the avian influenza A(H7N9) virus were identified in China in early 2013. This report describes findings for 139 persons with confirmed H7N9 virus infection through December 1, 2013. The first identified cases of human infection with a novel influenza A(H7N9) virus occurred in eastern China during February and March 2013 and were characterized by rapidly progressive pneumonia, respiratory failure, the acute respiratory distress syndrome (ARDS), and fatal outcomes. 1 We analyzed available data from field investigations to characterize the descriptive epidemiology of laboratory-confirmed cases of avian influenza A(H7N9) virus infection in humans that were reported to the Chinese Center for Disease Control and Prevention (China CDC) as of December 1, 2013. In this report, we summarize the epidemiologic findings of case investigations and follow-up monitoring of close contacts of . . .

Acute respiratory distress syndrome (ARDS) is a fatal complication of influenza infection. In this Review we provide an integrated model for its pathogenesis. ARDS involves damage to the epithelial–endothelial barrier, fluid leakage into the alveolar lumen, and respiratory insufficiency. The most important part of the epithelial–endothelial barrier is the alveolar epithelium, strengthened by tight junctions. Influenza virus targets these epithelial cells, reducing sodium pump activity, damaging tight junctions, and killing infected cells. Infected epithelial cells produce cytokines that attract leucocytes—neutrophils and macrophages—and activate adjacent endothelial cells. Activated endothelial cells and infiltrated leucocytes stimulate further infiltration, and leucocytes induce production of reactive oxygen species and nitric oxide that damage the barrier. Activated macrophages also cause direct apoptosis of epithelial cells. This model for influenza-induced ARDS differs from the classic model, which is centred on endothelial damage, and provides a rationale for therapeutic intervention to moderate host response in influenza-induced ARDS.

The emergence of a novel avian-origin influenza A virus strain (H7N9) causing severe human disease in China has raised serious concerns. In this report, key clinical and virologic features of this outbreak are presented. Sporadic human infections with avian influenza A viruses, which usually occur after recent exposure to poultry, have caused a wide spectrum of illness, ranging from conjunctivitis and upper respiratory tract disease to pneumonia and multiorgan failure. Low pathogenic avian influenza A (H7N2, H7N3, H9N2, or H10N7) 1 – 4 virus infections have caused lower respiratory tract illness that is mild (conjunctivitis or uncomplicated influenza-like illness) to moderate in severity. Most human infections with highly pathogenic avian influenza (HPAI) A (H7) viruses have resulted in conjunctivitis (H7N3) or uncomplicated influenza illness, but one case of fatal acute respiratory distress syndrome (ARDS) was reported . . .

18 500 laboratory-confirmed deaths caused by the 2009 pandemic influenza A H1N1 were reported worldwide for the period April, 2009, to August, 2010. This number is likely to be only a fraction of the true number of the deaths associated with 2009 pandemic influenza A H1N1. We aimed to estimate the global number of deaths during the first 12 months of virus circulation in each country. We calculated crude respiratory mortality rates associated with the 2009 pandemic influenza A H1N1 strain by age (0–17 years, 18–64 years, and >64 years) using the cumulative (12 months) virus-associated symptomatic attack rates from 12 countries and symptomatic case fatality ratios (sCFR) from five high-income countries. To adjust crude mortality rates for differences between countries in risk of death from influenza, we developed a respiratory mortality multiplier equal to the ratio of the median lower respiratory tract infection mortality rate in each WHO region mortality stratum to the median in countries with very low mortality. We calculated cardiovascular disease mortality rates associated with 2009 pandemic influenza A H1N1 infection with the ratio of excess deaths from cardiovascular and respiratory diseases during the pandemic in five countries and multiplied these values by the crude respiratory disease mortality rate associated with the virus. Respiratory and cardiovascular mortality rates associated with 2009 pandemic influenza A H1N1 were multiplied by age to calculate the number of associated deaths. We estimate that globally there were 201 200 respiratory deaths (range 105 700–395 600) with an additional 83 300 cardiovascular deaths (46 000–179 900) associated with 2009 pandemic influenza A H1N1. 80% of the respiratory and cardiovascular deaths were in people younger than 65 years and 51% occurred in southeast Asia and Africa. Our estimate of respiratory and cardiovascular mortality associated with the 2009 pandemic influenza A H1N1 was 15 times higher than reported laboratory-confirmed deaths. Although no estimates of sCFRs were available from Africa and southeast Asia, a disproportionate number of estimated pandemic deaths might have occurred in these regions. Therefore, efforts to prevent influenza need to effectively target these regions in future pandemics. None.

A new betacoronavirus—Middle East respiratory syndrome coronavirus (MERS-CoV)—has been identified in patients with severe acute respiratory infection. Although related viruses infect bats, molecular clock analyses have been unable to identify direct ancestors of MERS-CoV. Anecdotal exposure histories suggest that patients had been in contact with dromedary camels or goats. We investigated possible animal reservoirs of MERS-CoV by assessing specific serum antibodies in livestock. We took sera from animals in the Middle East (Oman) and from elsewhere (Spain, Netherlands, Chile). Cattle (n=80), sheep (n=40), goats (n=40), dromedary camels (n=155), and various other camelid species (n=34) were tested for specific serum IgG by protein microarray using the receptor-binding S1 subunits of spike proteins of MERS-CoV, severe acute respiratory syndrome coronavirus, and human coronavirus OC43. Results were confirmed by virus neutralisation tests for MERS-CoV and bovine coronavirus. 50 of 50 (100%) sera from Omani camels and 15 of 105 (14%) from Spanish camels had protein-specific antibodies against MERS-CoV spike. Sera from European sheep, goats, cattle, and other camelids had no such antibodies. MERS-CoV neutralising antibody titres varied between 1/320 and 1/2560 for the Omani camel sera and between 1/20 and 1/320 for the Spanish camel sera. There was no evidence for cross-neutralisation by bovine coronavirus antibodies. MERS-CoV or a related virus has infected camel populations. Both titres and seroprevalences in sera from different locations in Oman suggest widespread infection. European Union, European Centre For Disease Prevention and Control, Deutsche Forschungsgemeinschaft.

Improving the efficacy of influenza vaccination in older adults is a challenge. In this randomized clinical trial, a high-dose influenza vaccine was shown to be more effective than a standard-dose vaccine in the prevention of laboratory-confirmed influenza. Between 1990 and 1999, seasonal influenza caused an average of 36,000 deaths and 226,000 hospitalizations per year in the United States. 1 – 3 Adults 65 years of age or older are particularly vulnerable to complications associated with influenza and account for most seasonal influenza–related hospitalizations and deaths. 2 , 3 Although vaccination currently represents the most effective intervention against influenza and associated complications, 3 , 4 antibody response and protection elicited by the vaccine are lower among persons 65 years of age or older than among younger adults. 5 – 7 Strategies to improve antibody responses to influenza vaccine in the older population, such as increasing the . . .

About 200 million cases of viral community-acquired pneumonia occur every year—100 million in children and 100 million in adults. Molecular diagnostic tests have greatly increased our understanding of the role of viruses in pneumonia, and findings indicate that the incidence of viral pneumonia has been underestimated. In children, respiratory syncytial virus, rhinovirus, human metapneumovirus, human bocavirus, and parainfluenza viruses are the agents identified most frequently in both developed and developing countries. Dual viral infections are common, and a third of children have evidence of viral-bacterial co-infection. In adults, viruses are the putative causative agents in a third of cases of community-acquired pneumonia, in particular influenza viruses, rhinoviruses, and coronaviruses. Bacteria continue to have a predominant role in adults with pneumonia. Presence of viral epidemics in the community, patient's age, speed of onset of illness, symptoms, biomarkers, radiographic changes, and response to treatment can help differentiate viral from bacterial pneumonia. However, no clinical algorithm exists that will distinguish clearly the cause of pneumonia. No clear consensus has been reached about whether patients with obvious viral community-acquired pneumonia need to be treated with antibiotics. Apart from neuraminidase inhibitors for pneumonia caused by influenza viruses, there is no clear role for use of specific antivirals to treat viral community-acquired pneumonia. Influenza vaccines are the only available specific preventive measures. Further studies are needed to better understand the cause and pathogenesis of community-acquired pneumonia. Furthermore, regional differences in cause of pneumonia should be investigated, in particular to obtain more data from developing countries.

Defining transmission dynamics of the Middle East respiratory syndrome coronavirus (MERS-CoV) is important for public health measures. In this report, potential transmission to household contacts of 26 index patients with MERS-CoV infection is investigated. The Middle East respiratory syndrome coronavirus (MERS-CoV) was first isolated in 2012 from a patient with fatal pneumonia in Jeddah, Saudi Arabia. 1 From 2012 through July 2014, at least 834 laboratory-confirmed cases of MERS-CoV infection associated mostly with respiratory tract illness were reported to the World Health Organization; of these cases, 288 were fatal. Known cases have been directly or indirectly linked to countries in the Arabian peninsula. 2 The epidemiologic features of MERS remain poorly defined. Studies that have modeled the reproductive rate of MERS-CoV in humans have been based on notified, clinically apparent cases and auxiliary measurements, such as . . .