Search

Background: In patients with allogenic hematopoietic stem cell transplantation (allo-HSCT), immune-checkpoint inhibitors (ICI) are used to treat malignancy recurrence. However, ICI are also associated with graft vs. host disease (GVHD). In this pharmacovigilance analysis, we aimed to characterize cases of GVHD associated with ICI, drawn from the World Health Organization pharmacovigilance database, VigiBase®, and from literature.Methods: We performed VigiBase® query of cases of GVHD associated with ICI. These cases were combined with those of literature, not reported in VigiBase®. The Bayesian estimate of disproportionality analysis, the information component, was considered significant if its 95% credibility interval lower bound was positive; denoting a significant association between GVHD and the suspected ICI. Time to onset between ICI and GVHD onset and subsequent mortality were assessed.Results: Disproportionality analysis yielded 93 cases of GVHD associated with ICI (61.8% men, median age 38 [interquartile range = 27; 50] years). Cases were mostly associated with nivolumab (53/93, 57.0%), pembrolizumab (23/93, 24.7%) and ipilimumab (12/93, 12.9%) monotherapies. GVHD events occurred after 1 [1; 5.5] injection of ICI, with a time to onset of 35 [IQR = 14; 176] days. Immediate subsequent mortality after GVHD was 24/93, 25.8%. There was no significant difference in mortality depending on the molecule (p = 0.41) or the combination regimen (combined vs. monotherapy, p = 0.60). Previous history of GVHD was present in 11/18, 61.1% in cases reported in literature.Conclusion: In this worldwide pharmacovigilance study, disproportionality yielded significant association between GVHD and ICI, with subsequent mortality of 25.8%. Previous history of GVHD was reported in more than half of cases.Clinicaltrials.gov identifier:NCT03492242

Background: Takotsubo cardiomyopathy is triggered by emotional or physical stress. It is defined as a reversible myocardial dysfunction, usually with apical ballooning aspect due to apical akinesia associated with hyperkinetic basal left ventricular contraction. Described in cases of viral infections such as influenza, only few have been reported associated with novel coronavirus disease 2019 (COVID-19) in the recent pandemic.Case summary: A 79-years-old man, with cardiovascular risk factors (type 2 diabetes and hypertension) and chronic kidney disease, presented to the emergency room for severe dyspnea after 8 days of presenting respiratory symptoms and fever. Baseline electrocardiogram (ECG) was normal, but he presented marked inflammatory syndrome. He was transferred to an intensive care unit to receive mechanical ventilation within 6 h, due to acute respiratory distress syndrome. He presented circulatory failure 2 days after, requiring norepinephrine support (up to up to 1.04 μg/kg/min). Troponin T was elevated (637 ng/l). ECG showed diffuse T wave inversion. Echocardiography showed reduced left ventricular ejection fraction (LVEF 40%), with visual signs of Takotsubo cardiomyopathy. Cardiac failure resolved after 24 h with troponin T decrease (433 ng/l) and restoration of cardiac function (LVEF 60% with regression of Takotsubo features). Patient died after 15 days of ICU admission, due to septic shock from ventilator-acquired pneumonia. Cardiac function was then normal.Conclusion: Mechanisms of Takotsubo cardiomyopathy in viral infections include catecholamine-induced myocardial toxicity and inflammation related to sepsis. Differential diagnoses include myocarditis and myocardial infarction. Evidence of the benefit of immunomodulatory drugs and dexamethasone are growing to support this hypothesis in COVID-19.

BackgroundHydroxychloroquine combined with azithromycin (HCQ/AZI) has initially been used against coronavirus disease-2019 (COVID-19). In this retrospective study, we assessed the clinical effects of HCQ/AZI, with a 28-days follow-up.MethodsIn a registry-study which included patients hospitalized for COVID-19 between March 15 and April 2, 2020, we compared patients who received HCQ/AZI to those who did not, regarding a composite outcome of mortality and mechanical ventilation with a 28-days follow-up. QT was monitored for patients treated with HCQ/AZI. Were excluded patients in intensive care units, palliative care and ventilated within 24 hours of admission. Three analyses were performed to adjust for selection bias: propensity score matching, multivariable survival, and inverse probability score weighting (IPSW) analyses.ResultsOverall, 203 patients were included: 60 patients treated by HCQ/AZI and 143 control patients. During the 28-days follow-up, 32 (16.3%) patients presented the primary outcome and 23 (12.3%) patients died. Propensity-score matching identified 52 unique pairs of patients with similar characteristics. In the matched cohort (n = 104), HCQ/AZI was not associated with the primary composite outcome (log-rank p-value = 0.16). In the overall cohort (n = 203), survival and IPSW analyses also found no benefit from HCQ/AZI. In the HCQ/AZI group, 11 (18.3%) patients prolonged QT interval duration, requiring treatment cessation.ConclusionsHCQ/AZI combination therapy was not associated with lower in-hospital mortality and mechanical ventilation rate, with a 28-days follow-up. In the HCQ/AZI group, 18.3% of patients presented a prolonged QT interval requiring treatment cessation, however, control group was not monitored for this adverse event, making comparison impossible.

The paper presents results of completed conservation assessment of the strict Laos-Vietnamese endemic, Pinus cernua, based on survey of all previous publications and data obtained from extensive fieldworks during September–October 2016, supported by Mohamed bin Zayed Species Conservation Fund, Komarov Botanical Institute of the Russian Academy of Sciences, Russian Foundation for Fundamental Investigations (RFFI) and the Center for Plant Conservation of the Vietnam Union of Science and Technology Associations. Present review verified 23 locations of the species in Pha Luong Mountains situated on the state boundary of Laos (Houaphan province) and Vietnam (Son La province). Among available localities, 6 were found at first, the species extinction was detected in 1 locality. The area of the species distribution (EOO) decreased during last 3–5 years on 25–30 % from about 20 to 15 km2, with total occupancy area (AOO) becoming less than 3 km2, therefore species conservation status is assessed as globally critically endangered (CR) following to accepted IUCN Red List Categories and Criteria: B1a, b (i-v), B2a, b (i-v). Report also provides basic data on geography, geomorphology and climate of Pha Luong Mountains, as well as detailed descriptions of P. cernua ecology, habitats, vegetation, biology, population structure and taxonomy. All field data and descriptions are based on collected voucher herbaria, which belong to 99 families, 180 genera and 550 species. Among collected plants, 6 species are new for the flora of Laos and Vietnam, 30 species are local threatened endemics needed protection and 12 species are new for science. The main factors of P. cernua extinction are formulated and the recommendations for its effective protection are proposed.

In this investigation, we consider wireless powered relaying systems, where energy is scavenged by a relay via radio frequency (RF) signals. We explore hybrid time switching-based and power splitting-based relaying protocol (HTPSR) and compare performance of Amplify-and-Forward (AF) with Decode-and-Forward (DF) scheme under imperfect channel state information (CSI). Most importantly, the instantaneous rate, achievable bit error rate (BER) are determined in the closed-form expressions under the impact of imperfect CSI. Through numerical analysis, we evaluate system insights via different parameters such as power splitting (PS) and time switching (TS) ratio of the considered HTPSR which affect outage performance and BER. It is noted that DF relaying networks outperform AF relaying networks. Besides that, the numerical results are given to prove the optimization problems of PS and TS ratio to obtain optimal instantaneous rate.

Acute respiratory distress syndrome (ARDS) related to Coronavirus disease (COVID-19) is associated with high mortality. It has been suggested that venovenous extracorporeal membrane oxygenation (ECMO) was suitable in this indication, albeit the effects of ECMO on the mechanical respiratory parameters have been scarcely described. In this case-series, we prospectively described the use of venovenous ECMO and its effects on mechanical respiratory parameters in eleven COVID-19 patients with severe ARDS. Implantation of ECMO occurred 6 [3–11] days after the onset of mechanical ventilation. At the time of ECMO implantation, all patients received neuromuscular blocking agents, three (27%) received inhaled nitric oxide and prone positioning was performed in all patients with 4 [3−5] sessions of PP per patient. Under ECMO, the tidal volume was significantly decreased from 6.1 [4.0–6.3] to 3.4 [2.5–3.6] mL/kg of predicted body weight and the positive end-expiratory pressure level was increased by 25 ± 27% whereas the driving pressure and the mechanical power decreased by 33 ± 25% and 71 ± 27%, respectively. The PaO2/FiO2 ratio significantly increased from 68 [58–89] to 168 [137–218] and the oxygenation index significantly decreased from 28 [26–35] to 13 [10–15]. The duration of ECMO was 12 [8–25] days. Nine (82%) patients experienced ECMO-related complications and the main complication was major bleeding requiring blood transfusions. Intensive care unit mortality rate was 55% but no patient died from ECMO-related complications. In COVID-19 patients with severe ARDS, venovenous ECMO allowed ultra-protective ventilation, improved oxygenation and should be considered in highly selected patients with the most severe ARDS.

Uncertainty about the importance of influenza transmission by airborne droplet nuclei generates controversy for infection control. Human challenge-transmission studies have been supported as the most promising approach to fill this knowledge gap. Healthy, seronegative volunteer 'Donors' (n = 52) were randomly selected for intranasal challenge with influenza A/Wisconsin/67/2005 (H3N2). 'Recipients' randomized to Intervention (IR, n = 40) or Control (CR, n = 35) groups were exposed to Donors for four days. IRs wore face shields and hand sanitized frequently to limit large droplet and contact transmission. One transmitted infection was confirmed by serology in a CR, yielding a secondary attack rate of 2.9% among CR, 0% in IR (p = 0.47 for group difference), and 1.3% overall, significantly less than 16% (p

Cytokinesis is the step of the cell cycle in which the cell must faithfully separate the chromosomes and cytoplasm, yielding two daughter cells. The assembly and contraction of the contractile network is spatially and temporally coupled with the formation of the mitotic spindle to ensure the successful completion of cytokinesis. While decades of studies have elucidated the components of this machinery, the so-called usual suspects, and their functions, many lines of evidence are pointing to other unexpected proteins and sub-cellular systems as also being involved in cytokinesis. These we term the unusual suspects. In this review, we introduce recent discoveries on some of these new unusual suspects and begin to consider how these subcellular systems snap together to help complete the puzzle of cytokinesis.

This work aims to study the optimal conditions to synthesize hydroxyapatite-multiwalled carbon nanotube (HAp-MWCNT) coatings on Ti6Al4V by electrodeposition technique. The structural behaviors, morphology, and mechanical properties of the coatings were characterized by various advanced methods. The analyzed results showed that the obtained coatings were composed of hydroxyapatite (HAp) and multiwalled carbon nanotube (MWCNT) phases. The presence of MWCNTs in the HAp-MWCNT composite, which improved adhesion between the coatings and the substrate about 2.3 times, increased 20% of hardness and decreased about 40% the solubility of HAp-MWCNTs/Ti6Al4V in comparison with pure HAp coating on Ti6Al4V.

In cardiac surgery, patients are at risk of phrenic nerve injury, which leads to diaphragm dysfunction and acute respiratory failure. Diaphragm dysfunction (DD) is relatively frequent in cardiac surgery and particularly affects patients after coronary artery bypass graft. The onset of DD affects patients’ prognosis in term of weaning from mechanical ventilation and hospital length of stay. The authors present a narrative review about diaphragm physiology, techniques used to assess diaphragm function, and the clinical application of diaphragm ultrasound in patients undergoing cardiac surgery.

Purpose – The purpose of this paper is to investigate the simultaneous relationship among ownership concentration, innovation and firm performance of the small- and medium-sized enterprises (SMEs) in Vietnam during the 2011–2015. By employing a Conditional Mixed Process (CMP) model, the findings show that: there is no impact of ownership concentration on innovation, but it has a positive impact on sales growth; innovation positively affects firm performance; and there exists a positively reverse causality from sales growth to innovation. Design/methodology/approach – In this study, the authors propose the adaption of CMP model (Roodman, 2011). The nature of the first stage dependent variable – Innovation – is a binary one while the dependent variable Performance is continuous. Therefore, a model that can adapt the binary nature of the dependent variable and perform the estimation of a system of equations such as CMP model is preferred. The CMP framework is substantially that of seemingly unrelated regression, but with application in a larger scope. This approach is based on a “simulated maximum likelihood method” suggested by Geweke–Hajivassiliou–Keane algorithm. Findings – By applying CMP method, this study examines the simultaneous relationship among ownership concentration, innovation and firm performance of the SMEs in Vietnam from 2011 to 2015. The findings indicate that: there is no impact of ownership concentration on innovation, but it has a positive impact on sales growth; innovation positively affects firm performance; and there exists a positively reverse causality from sales growth to innovation. Research limitations/implications – In spite of the efforts to explore the simultaneous relationship among ownership concentration, innovation and firm performance of the SMEs in Vietnam, the study still has some limitations which are promising further research directions. First, the SME surveys by Central Institute for Economic Management do not have much information about other types of ownership including state-owned and foreign ownership. Therefore, possible further studies with richer data sets may explore the impacts of different types of ownership on firm innovation and performance. Second, other types of innovation such as organizational innovation, marketing innovation can also be investigated in further studies in a richer data set for the case of Vietnam SMEs. Originality/value – The findings show that: there is no impact of ownership concentration on innovation, but it has a positive impact on sales growth; innovation positively affects firm performance; and there exists a positively reverse causality from sales growth to innovation. The policy implications insist on facilitating SMEs with easier access to capital via loans with preferred interest or trust loans without collateral, training programs for the labor force and SME leaders, and reduction of unnecessary administrative procedure.

Abstract Background Low cardiac output syndrome (LCOS) is a severe condition which can occur after cardiac surgery, especially among patients with pre-existing left ventricular dysfunction. Dobutamine, its first-line treatment, is associated with sinus tachycardia. This study aims to assess the ability of intravenous ivabradine to decrease sinus tachycardia associated with dobutamine infused for LCOS after coronary artery bypass graft (CABG) surgery. Methods In a phase 2, multi-center, single-blind, randomized controlled trial, patients with left ventricular ejection fraction below 40% presenting sinus tachycardia of at least 100 beats per minute (bpm) following dobutamine infusion for LCOS after CABG surgery received either intravenous ivabradine or placebo (three ivabradine for one placebo). Treatment lasted until dobutamine weaning or up to 48 h. The primary endpoint was the proportion of patients achieving a heart rate (HR) in the 80- to 90-bpm range. Secondary endpoints were invasive and non-invasive hemodynamic parameters and arrhythmia events. Results Nineteen patients were included. More patients reached the primary endpoint in the ivabradine than in the placebo group (13 (93%) versus 2 (40%); P = 0.04). Median times to reach target HR were 1.0 h in the ivabradine group and 5.7 h in the placebo group. Ivabradine decreased HR (112 to 86 bpm, P

Abstract Background International and national travelling has made the rapid spread of infectious diseases possible. Little information is available on the role of major traffic hubs, such as airports, in the transmission of respiratory infections, including seasonal influenza and a pandemic threat. We investigated the presence of respiratory viruses in the passenger environment of a major airport in order to identify risk points and guide measures to minimize transmission. Methods Surface and air samples were collected weekly at three different time points during the peak period of seasonal influenza in 2015–16 in Finland. Swabs from surface samples, and air samples were tested by real-time PCR for influenza A and B viruses, respiratory syncytial virus, adenovirus, rhinovirus and coronaviruses (229E, HKU1, NL63 and OC43). Results Nucleic acid of at least one respiratory virus was detected in 9 out of 90 (10%) surface samples, including: a plastic toy dog in the children’s playground (2/3 swabs, 67%); hand-carried luggage trays at the security check area (4/8, 50%); the buttons of the payment terminal at the pharmacy (1/2, 50%); the handrails of stairs (1/7, 14%); and the passenger side desk and divider glass at a passport control point (1/3, 33%). Among the 10 respiratory virus findings at various sites, the viruses identified were: rhinovirus (4/10, 40%, from surfaces); coronavirus (3/10, 30%, from surfaces); adenovirus (2/10, 20%, 1 air sample, 1 surface sample); influenza A (1/10, 10%, surface sample). Conclusions Detection of pathogen viral nucleic acids indicates respiratory viral surface contamination at multiple sites associated with high touch rates, and suggests a potential risk in the identified airport sites. Of the surfaces tested, plastic security screening trays appeared to pose the highest potential risk, and handling these is almost inevitable for all embarking passengers.

Previous studies have made vital contributions to the theory and practice of engaging and managing project stakeholders. A literature review plays a critical role in supporting researchers to better understand the research topic, helping researchers identify the boundaries of the current body of knowledge and research trends, and shaping future research. Thus, this paper analyses the latest research developments in stakeholder management within the context of complex projects. It examines articles published between 2005 and 2016, and discusses the relevant trends under four themes: stakeholder analysis, stakeholder influence, stakeholder management strategies and stakeholder engagement. The paper reveals that social network analysis strongly emerges to be a valuable tool for analyzing the complexity of stakeholder interrelationships in the context of CPs. Stakeholder analysis and stakeholder engagement strategies are powerful in addressing environmental complexity (including multiple stakeholders, an environment of changing policy and regulation, and an environment with a changing nature) projects. The paper draws conclusions regarding the findings of the review, and provides some recommendations for future research.

The renin–angiotensin system (RAS) has long been described in the field of cardiovascular physiology as the main player in blood pressure homeostasis. However, other effects have since been described, and include proliferation, fibrosis, and inflammation. To illustrate the immunomodulatory properties of the RAS, we chose three distinct fields in which RAS may play a critical role and be the subject of specific treatments. In oncology, RAS hyperactivation has been associated with tumor migration, survival, cell proliferation, and angiogenesis; preliminary data showed promise of the benefit of RAS blockers in patients treated for certain types of cancer. In intensive care medicine, vasoplegic shock has been associated with severe macro- and microcirculatory imbalance. A relative insufficiency in angiotensin II (AngII) was associated to lethal outcomes and synthetic AngII has been suggested as a specific treatment in these cases. Finally, in solid organ transplantation, both AngI and AngII have been associated with increased rejection events, with a regional specificity in the RAS activity. These elements emphasize the complexity of the direct and indirect interactions of RAS with immunomodulatory pathways and warrant further research in the field.

Abstract Background Postoperative pulmonary complications are a leading cause of morbidity and mortality after cardiac surgery. There are no recommendations on mechanical ventilation associated with cardiopulmonary bypass (CPB) during surgery and anesthesiologists perform either no ventilation (noV) at all during CPB or maintain low tidal volume (LTV) ventilation. Indirect evidence points towards better pulmonary outcomes when LTV is performed but no large-scale prospective trial has yet been published in cardiac surgery. Design The MECANO trial is a single-center, double-blind, randomized, controlled trial comparing two mechanical ventilation strategies, noV and LTV, during cardiac surgery with CPB. In total, 1500 patients are expected to be included, without any restrictions. They will be randomized between noV and LTV on a 1:1 ratio. The noV group will receive no ventilation during CPB. The LTV group will receive 5 breaths/minute with a tidal volume of 3 mL/kg and positive end-expiratory pressure of 5 cmH2O. The primary endpoint will be a composite of all-cause mortality, early respiratory failure defined as a ratio of partial pressure of oxygen/fraction of inspired oxygen

This paper studies the outage performance and system throughput of a bidirectional wireless information and power transfer system with a helping relay. The relay helps forward wireless power from the access point (AP) to the user, and also the information from the user to the AP in the reverse direction. We assume that the relay uses time switching based energy harvesting protocol. The analytical results provide theoretical insights into the effect of various system parameters, such as time switching factor, source transmission rate, transmitting-power-to-noise ratio to system performance for both amplify-and-forward and decode-and-forward relaying protocols. The optimal time switching ratio is determined in each case to maximize the information throughput from the user to the AP subject to the energy harvesting and consumption balance constraints at both the relay and the user. All of the above analyses are confirmed by Monte-Carlo simulation.

Introduction: The World Health Organization recommends vaccination of health workers (HWs) against influenza, but low uptake is intransigent.We conducted a Rapid Evidence Appraisal on: the risk of influenza in HWs, transmission risk from HWs to patients, the benefit of HW vaccination, and strategies for improving uptake. We aimed to capture a ‘whole-of-system’ perspective to consider possible benefits for HWs, employers and patients. Methods: We executed a comprehensive search of the available literature published from 2006 to 2018 in the English language. We developed search terms for seven separate questions following the PICO framework (population, intervention, comparators, outcomes) and queried nine databases. Results: Of 3784 publications identified, 52 met inclusion criteria. Seven addressed HW influenza risk, of which four found increased risk; 15 addressed influenza vaccine benefit to HWs or their employers, of which 10 found benefit; 11 addressed influenza transmission from HWs to patients, of which 6 found evidence for transmission; 12 unique studies addressed whether vaccinating HWs produced patient benefit, of which 9 concluded benefits accrued. Regarding the number of HWs needed to vaccinate (NNV) to deliver patient benefit, NNV estimates ranged from 3 to 36,000 but were in significant disagreement. Fourteen studies provided insights on strategies to improve uptake; the strongest evidence was for mandatory vaccination. Conclusions: The evidence on most questions related to influenza vaccination in HWs is mixed and often of low-quality. Substantial heterogeneity exists in terms of study designs and settings, making comparison between studies difficult. Notwithstanding these limitations, a majority of studies suggests that influenza vaccination benefit HWs and their employers; and HWs are implicated in transmission events. The effects of vaccinating HWs on patient morbidity and mortality may include reductions in all-cause mortality and influenza-like illness (ILI). Taken together, the evidence suggests that HW vaccination is an important policy for HWs themselves, their employers, and their patients. Keywords: Influenza, Vaccine, Health worker, Healthcare, Policy, Transmission

The importance of accounting for social and behavioural processes when studying public health emergencies has been well-recognised. For infectious disease outbreaks in particular, several methods of incorporating individual behaviour have been put forward, but very few are based on established psychological frameworks. In this paper, we develop a decision framework based on the COM-B model of behaviour change to investigate the impact of individual decision-making on public health outcomes. We demonstrate the application of our decision framework in a proof-of-concept case study based on the 2009 A(H1N1) influenza pandemic in the UK. The National Pandemic Flu Service (NPFS) was set up in England during the pandemic as a means to provide antiviral (AV) treatment to clinically ill patients with influenza-like illness, via telephone calls or internet screening, thereby averting the need to see a doctor. The evaluated patients based on a clinical algorithm and authorised AV drugs for collection via community collection points. We applied our behavioural framework to evaluate the influence of human behaviour on AV collection rates, and subsequently to identify interventions that could help improve AV collection rates. Our model was validated against empirically collected pandemic data from 2009 in the UK. We also performed a sensitivity analysis to identify potentially effective interventions by varying model parameters. Using our behavioural framework in a proof-of-concept case study, we found that interventions geared towards increasing people's 'Capability' and 'Opportunity' are likely to result in increased AV collection, potentially resulting in fewer influenza-related hospitalisations and deaths. We note that important behavioural data from public health emergencies are largely scarce. Insights obtained from models such as ours can, not only be very useful in designing healthcare interventions, but also inform future data collection.

BackgroundIn patients with neuromuscular disorders, assessment of respiratory function relies on forced vital capacity (FVC) measurements. Providing complementary respiratory outcomes may be useful for clinical trials. Diaphragm sniff ultrasound (US) is a noninvasive technique that can assess diaphragm function that may be affected in patients with neuromuscular disorders.PurposeWe aimed to provide normal values of sniff diaphragm ultrasound, to assess the relationship between sniff diaphragm US, vital capacity (VC) and sniff nasal pressure. Additionally, we aimed to evaluate the diagnostic accuracy of sniff diaphragm US for predicting restrictive pulmonary insufficiency.Materials and methodsWe included patients with neuromuscular disorders that had been tested with a sniff diaphragm US and functional respiratory tests. Healthy subjects were also included to obtain normal diaphragm sniff ultrasound. We performed diaphragm tissue Doppler imaging (TDI) and time movement (TM) diaphragm echography combined with sniff maneuver.ResultsA total of 89 patients with neuromuscular diseases and 27 healthy subjects were included in our study. In patients, the median age was 32 years [25; 50] and the median FVC was 34% of predicted [18; 55]. Sniff diaphragm motion using TM ultrasound was significantly associated with sniff nasal pressure, both for the right hemidiaphragm (r = 0.6 p ConclusionSniff diaphragm TM and TDI measures were significantly associated with sniff nasal pressure. Sniff diaphragm TM and TDI had a high level of accuracy to reveal respiratory involvement in patients with neuromuscular disorders. This technique is useful to assess and follow up diaphragm function in patients with neuromuscular disorders. It may be used as a respiratory outcome for clinical trials.

Acquired hemophilia A (AHA) is a rare autoimmune disorder caused by autoantibodies against Factor VIII (FVIII). It has a high mortality due to bleeding complications. FVIIa-based bypassing agents are the first line of treatment but not always effective. Recombinant porcine (rp) FVIII (Obizur®) was recently approved for rescue treatment but with little evidence-based information regarding efficacy. We report a case of papillary thyroid cancer associated with AHA malignancy that responded to a single dose of rpFVIII after failure to achieve hemostasis with FVIIa-based bypassing products.

Two key factors bear on reaction rates for the conjugate addition of alkenyl boronic acids to heteroaryl-appended enones: the proximity of inductively electron-withdrawing heteroatoms to the site of bond formation and the resonance contribution of available heteroatom lone pairs to stabilize the developing positive charge at the enone β-position. For the former, the closer the heteroatom is to the enone β-carbon, the faster the reaction. For the latter, greater resonance stabilization of the benzylic cationic charge accelerates the reaction. Thus, reaction rates are increased by the closer proximity of inductive electron-withdrawing elements, but if resonance effects are involved, then increased rates are observed with electron-donating ability. Evidence for these trends in isomeric substrates is presented, and the application of these insights has allowed for reaction conditions that provide improved reactivity with previously problematic substrates.

Summary: In a multi-center, prospective, observational study over two influenza seasons, we sought to quantify and correlate the amount of virus recovered from the nares of infected subjects with that recovered from their immediate environment in community and hospital settings. We recorded the symptoms of adults and children with A(H1N1)pdm09 infection, took nasal swabs, and sampled touched surfaces and room air. Forty-two infected subjects were followed up. The mean duration of virus shedding was 6.2 days by PCR (Polymerase Chain Reaction) and 4.2 days by culture. Surface swabs were collected from 39 settings; 16 (41%) subject locations were contaminated with virus. Overall, 33 of the 671 (4.9%) surface swabs were PCR positive for influenza, of which two (0.3%) yielded viable virus. On illness Day 3, subjects yielding positive surface samples had significantly higher nasal viral loads (geometric mean ratio 25.7; 95% CI 1.75, 376.0, p = 0.021) and a positive correlation (r = 0.47, p = 0.006) was observed between subject nasal viral loads and viral loads recovered from the surfaces around them. Room air was sampled in the vicinity of 12 subjects, and PCR positive samples were obtained for five (42%) samples. Influenza virus shed by infected subjects did not detectably contaminate the vast majority of surfaces sampled. We question the relative importance of the indirect contact transmission of influenza via surfaces, though our data support the existence of super-spreaders via this route. The air sampling results add to the accumulating evidence that supports the potential for droplet nuclei (aerosol) transmission of influenza. Keywords: Influenza, Environmental, Deposition, Infection, Control

Background: Gemcitabine is a nucleoside analog, widely used either alone or in combination, for the treatment of multiple cancers. However, gemcitabine may also be associated with cardiovascular adverse-drug-reactions (CV-ADR). Methods: First, we searched for all cases of cardiotoxicity associated with gemcitabine, published in MEDLINE on 30 May 2019. Then, we used VigiBase, the World Health Organization’s global database of individual case safety reports, to compare CV-ADR reporting associated with gemcitabine against the full database between inception and 1 April 2019. We used the information component (IC), an indicator value for disproportionate Bayesian reporting. A positive lower end of the 95% credibility interval for the IC (IC025) ≥ 0, is deemed significant. Results: In VigiBase, 46,898 reports were associated with gemcitabine on a total of 18,908,940 in the full database. Gemcitabine was associated with higher reporting for myocardial ischemia (MI, n: 119), pericardial diseases (n: 164), supraventricular arrhythmias (SVA, n: 308) and heart failure (HF, n: 484) versus full database with IC025 ranging between 0.40 and 2.81. CV-ADR were associated with cardiovascular death in up to 17% of cases. Conclusion: Treatment with gemcitabine is associated with potentially lethal CV-ADRs, including MI, pericardial diseases, SVA and HF. These events should be considered in patient care and clinical trial design.

Tocilizumab, an anti-interleukin-6 receptor, administrated during the right timeframe may be beneficial against coronavirus-disease-2019 (COVID-19) pneumonia. All patients admitted for severe COVID-19 pneumonia (SpO2 ≤ 96% despite O2-support ≥ 6 L/min) without invasive mechanical ventilation were included in a retrospective cohort study in a primary care hospital. The treatment effect of a single-dose, 400 mg, of tocilizumab was assessed by comparing those who received tocilizumab to those who did not. Selection bias was mitigated using three statistical methods. Primary outcome measure was a composite of mortality and ventilation at day 28. A total of 246 patients were included (106 were treated with tocilizumab). Overall, 105 (42.7%) patients presented the primary outcome, with 71 (28.9%) deaths during the 28-day follow-up. Propensity-score-matched 84 pairs of comparable patients. In the matched cohort (n = 168), tocilizumab was associated with fewer primary outcomes than the control group (hazard ratio (HR) = 0.49 (95% confidence interval (95%CI) = 0.3–0.81), p-value = 0.005). These results were similar in the overall cohort (n = 246), with Cox multivariable analysis yielding a protective association between tocilizumab and primary outcome (adjusted HR = 0.26 (95%CI = 0.135–0.51, p = 0.0001), confirmed by inverse probability score weighting (IPSW) analysis (p < 0.0001). Analyses on mortality only, with 28 days of follow-up, yielded similar results. In this study, tocilizumab 400 mg in a single-dose was associated with improved survival without mechanical ventilation in patients with severe COVID-19.

Heart failure and restrictive respiratory insufficiency are complications in muscular dystrophies. We aimed to assess the accuracy of the B-natriuretic peptide (BNP) for the diagnosis of decompensated heart failure in muscular dystrophy. We included patients with muscular dystrophy and chronic respiratory insufficiency admitted in the Intensive Care Unit of the Raymond Poincare hospital (Garches, France) for suspected decompensated heart failure. Thirtyseven patients were included, among them, 23 Duchenne muscular dystrophy (DMD) (62%), 10 myotonic dystrophy type 1(DM1) (27%). Median age was 35 years [27.5; 48.5]. 86.5% of patients were on home mechanical ventilation (HMV). Median left ventricular ejection fraction (LVEF) was 47% [35.0; 59.5]. Median BNP blood level was 104 pg/mL [50; 399]. The BNP level was significantly inversely associated with LVEF (r= –0.37, p 0.03) and positively associated with the LVEDD (left ventricular end diastolic diameter) (r=0.59, P

BACKGROUND:Maternal nutrition during pregnancy and breastfeeding is important for the healthy growth and development of the fetus and infant. PURPOSE:This study aimed to evaluate the long-term effects of a maternal milk supplementation (MMS) in conjunction with a breastfeeding support program on breastfeeding practices including duration of any breastfeeding and exclusive breastfeeding and child neurodevelopment outcomes at 30 months old. METHODS:We followed up the offspring of 204 Vietnamese women who completed a randomized controlled trial where the intervention group received MMS with a breastfeeding support program from the last trimester to 12 weeks postpartum while the control group received standard care. At 30 months postpartum, information on child feeding practices was collected and child neurodevelopment was assessed by the Bayley Scales of Infant and Toddler Development (Bayley-III). RESULTS:There was no significant difference in the duration of any breastfeeding (ABF) from birth between the groups. However, the intervention group had longer exclusive breastfeeding (EBF) duration (p = 0.0172), higher EBF rate at 6 months (p = 0.0093) and lower risk of discontinuing EBF (p = 0.0071) than the control. Children in the intervention group had significantly higher Bayley-III composite scores in the domains of cognitive (p = 0.0498) and motor (p = 0.0422) functions, as well as a tendency toward better social-emotional behavior (p = 0.0513) than children in the control group. The association between maternal intervention and child development was attenuated after further adjustment for birth weight but not EBF duration, suggesting that improvements in child development may be partially attributed to the benefits of prenatal nutrition supplementation on birth outcomes. CONCLUSIONS:MMS with breastfeeding support during late pregnancy and early postpartum significantly improved EBF practices. The intervention was also associated with improvements in neurodevelopment in children at 30 months old.

Critically ill patients require close hemodynamic monitoring to titrate treatment on a regular basis. It allows administering fluid with parsimony and adjusting inotropes and vasoactive drugs when necessary. Although invasive monitoring is considered as the reference method, non-invasive monitoring presents the obvious advantage of being associated with fewer complications, at the expanse of accuracy, precision, and step-response change. A great many methods and devices are now used over the world, and this article focuses on several of them, providing with a brief review of related underlying physical principles and validation articles analysis. Reviewed methods include electrical bioimpedance and bioreactance, respiratory-derived cardiac output (CO) monitoring technique, pulse wave transit time, ultrasound CO monitoring, multimodal algorithmic estimation, and inductance thoracocardiography. Quality criteria with which devices were reviewed included: accuracy (closeness of agreement between a measurement value and a true value of the measured), precision (closeness of agreement between replicate measurements on the same or similar objects under specified conditions), and step response change (delay between physiological change and its indication). Our conclusion is that the offer of non-invasive monitoring has improved in the past few years, even though further developments are needed to provide clinicians with sufficiently accurate devices for routine use, as alternative to invasive monitoring devices.

Objectives: The stockpiling of neuraminidase inhibitor (NAI) antivirals as a defence against pandemic influenza is a significant public health policy decision that must be made despite a lack of conclusive evidence from randomised controlled trials regarding the effectiveness of NAIs on important clinical end points such as mortality. The objective of this study was to determine whether NAIs should be stockpiled for treatment of pandemic influenza on the basis of current evidence. Methods: A decision model for stockpiling was designed. Data on previous pandemic influenza epidemiology was combined with data on the effectiveness of NAIs in reducing mortality obtained from a recent individual participant meta-analysis using observational data. Evidence synthesis techniques and a bias modelling method for observational data were used to incorporate the evidence into the model. The stockpiling decision was modelled for adults (≥16 years old) and the United Kingdom was used as an example. The main outcome was the expected net benefits of stockpiling in monetary terms. Health benefits were estimated from deaths averted through stockpiling. Results: After adjusting for biases in the estimated effectiveness of NAIs, the expected net benefit of stockpiling in the baseline analysis was £444 million, assuming a willingness to pay of £20,000/QALY ($31,000/QALY). The decision would therefore be to stockpile NAIs. There was a greater probability that the stockpile would not be utilised than utilised. However, the rare but catastrophic losses from a severe pandemic justified the decision to stockpile. Conclusions: Taking into account the available epidemiological data and evidence of effectiveness of NAIs in reducing mortality, including potential biases, a decision maker should stockpile anti-influenza medication in keeping with the postulated decision rule.

Health care workers (HCWs) may transmit respiratory infection to patients. We assessed evidence for the effectiveness of vaccinating HCWs to provide indirect protection for patients at risk for severe or complicated disease after acute respiratory infection. We searched electronic health care databases and sources of gray literature by using a predefined strategy. Risk for bias was assessed by using validated tools, and results were synthesized by using a narrative approach. Seventeen of the 12,352 identified citations met the full inclusion criteria, and 3 additional articles were identified from reference or citation tracking. All considered influenza vaccination of HCWs, and most were conducted in long-term residential care settings. Consistency in the direction of effect was observed across several different outcome measures, suggesting a likely protective effect for patients in residential care settings. However, evidence was insufficient for us to confidently extrapolate this to other at-risk patient groups.

PROBLEM: Improving pandemic planning and preparedness is a challenge in Europe, a diverse region whose regional bodies (the Regional Office for Europe of the World Health Organization [WHO], the European Commission and the European Centre for Disease Prevention and Control) have overlapping roles and responsibilities. APPROACH: European pandemic preparedness indicators were used to develop an assessment tool and procedure based on the 2005 global WHO checklist for pandemic preparedness. These were then applied to Member States of WHO's European Region, initially as part of structured national assessments conducted during short visits by external teams. LOCAL SETTING: Countries in WHO's European Region. RELEVANT CHANGES: From 2005 to 2008, 43 countries underwent a pandemic preparedness assessment that included a short external assessment visit by an expert team. These short visits developed into a longer self-assessment procedure involving an external team but "owned" by the countries, which identified gaps and developed plans for improving preparedness. The assessment tool and procedure became more sophisticated as national and local pandemic preparedness became more complex. The 2009 pandemic revealed new gaps in planning, surveillance communications and immunization. LESSONS LEARNT: Structured national self-assessments with support from external teams allow individual countries to identify gaps in their pandemic preparedness plans and enable regional bodies to assess the regional and global resources that such plans require. The 2009 pandemic revealed additional problems with surveillance, pandemic severity estimates, the flexibility of the response, vaccination, involvement of health-care workers and communication. European national plans are being upgraded and global leadership is required to ensure that these plans are uniformly applied across the region.

The United Kingdom implemented a containment strategy for pandemic (H1N1) 2009 through administering antiviral agents (AVs) to patients and their close contacts. This observational household cohort study describes the effect of AVs on household transmission. We followed 285 confirmed primary cases in 259 households with 761 contacts. At 2 weeks, the confirmed secondary attack rate (SAR) was 8.1% (62/761) and significantly higher in persons 50 years of age (18.9% vs. 1.2%, p

To determine clinical characteristics of patients hospitalized in the United Kingdom with pandemic (H1N1) 2009, we studied 1,520 patients in 75 National Health Service hospitals. We characterized patients who acquired influenza nosocomially during the pandemic (H1N1) 2009 outbreak. Of 30 patients, 12 (80%) of 15 adults and 14 (93%) of 15 children had serious underlying illnesses. Only 12 (57%) of 21 patients who received antiviral therapy did so within 48 hours after symptom onset, but 53% needed escalated care or mechanical ventilation; 8 (27%) of 30 died. Despite national guidelines and standardized infection control procedures, nosocomial transmission remains a problem when influenza is prevalent. Health care workers should be routinely offered influenza vaccine, and vaccination should be prioritized for all patients at high risk. Staff should remain alert to the possibility of influenza in patients with complex clinical problems and be ready to institute antiviral therapy while awaiting diagnosis during influenza outbreaks.

Summary: We evaluated the effectiveness of inactivated influenza vaccine in persons aged ≥45 years with co-morbidities (including essential hypertension) likely to have prompted consideration of prophylactic statin therapy. Using case–control analyses, we measured the impact of vaccination on General Practitioner (GP) reported new episodes of illness for clinically diagnosed influenza-like illness (ILI) and total acute respiratory infection (TARI) during eight consecutive winters, adjusting for potential confounders using multivariable techniques. Although the study failed to demonstrate the effectiveness of influenza vaccine, we identified important potential confounding related to a greater likelihood of vaccinees than non-vaccinees to consult with a GP for respiratory infections. Future researchers should consider and account for this phenomenon. Keywords: Influenza, Inter-pandemic, Vaccine, Effectiveness, Cardiovascular risk

Glioblastoma is the most common, malignant primary tumor of the central nervous system. The average prognosis for life expectancy after diagnosis, with the triad of surgery, chemotherapy, and radiation therapy, is less than 1.5 years. Chemotherapy treatment is mostly limited to temozolomide. In this paper, the authors review an emerging, novel drug called acid ceramidase, which targets glioblastoma. Its role in cancer treatment in general, and more specifically, in the treatment of glioblastoma, are discussed. In addition, the authors provide insights on acid ceramidase as a potential druggable target for glioblastoma.

Pandemic influenza planning is well under way across the globe. Antiviral drugs and vaccines have dominated the therapeutic agenda. Far less work has been conducted on stockpiling and planning for deployment of antimicrobial drugs against secondary bacterial pneumonia, a cause of substantial illness and death in previous pandemics and epidemics. In the event of a pandemic, effective antimicrobial drug measures are expected to substantially benefit public health. We address issues regarding use of antimicrobial drugs as stocks of individual agents are diminished and the role of resistance surveillance in informing such policy. Furthermore, vaccination with polysaccharide and conjugate pneumococcal vaccines is considered as part of a pandemic strategy. Most illness and death from influenza are likely to occur in developing countries, where neuraminidase inhibitors and vaccines may be neither affordable nor available; thus, compared with industrialized countries, the benefits of treating bacterial complications in developing countries may be substantially greater.

Background: During pandemics of novel influenza and outbreaks of emerging infections, surge in health-care demand can exceed capacity to provide normal standards of care. In such exceptional circumstances, triage tools may aid decisions in identifying people who are most likely to benefit from higher levels of care. Rapid research during the early phase of an outbreak should allow refinement and validation of triage tools so that in the event of surge a valid tool is available. The overarching study aim is to conduct a prospective near real-time analysis of structured clinical assessments of influenza-like illness (ILI) using primary care electronic health records (EHRs) during a pandemic. This abstract summarises the preparatory work, infrastructure development, user testing and proof-of-concept study. Objectives: (1) In preparation for conducting rapid research in the early phase of a future outbreak, to develop processes that allow near real-time analysis of general practitioner (GP) assessments of people presenting with ILI, management decisions and patient outcomes. (2) As proof of concept: conduct a pilot study evaluating the performance of the triage tools ‘Community Assessment Tools’ and ‘Pandemic Medical Early Warning Score’ to predict hospital admission and death in patients presenting with ILI to GPs during inter-pandemic winter seasons. Design: Prospective near real-time analysis of structured clinical assessments and anonymised linkage to data from EHRs. User experience was evaluated by semistructured interviews with participating GPs. Setting: Thirty GPs in England, Wales and Scotland, participating in the Clinical Practice Research Datalink. Participants: All people presenting with ILI. Interventions: None. Main outcome measures: Study outcome is proof of concept through demonstration of data capture and near real-time analysis. Primary patient outcomes were hospital admission within 24 hours and death (all causes) within 30 days of GP assessment. Secondary patient outcomes included GP decision to prescribe antibiotics and/or influenza-specific antiviral drugs and/or refer to hospital – if admitted, the need for higher levels of care and length of hospital stay. Data sources: Linked anonymised data from a web-based structured clinical assessment and primary care EHRs. Results: In the 24 months to April 2015, data from 704 adult and 159 child consultations by 30 GPs were captured. GPs referred 11 (1.6%) adults and six (3.8%) children to hospital. There were 13 (1.8%) deaths of adults and two (1.3%) of children. There were too few outcome events to draw any conclusions regarding the performance of the triage tools. GP interviews showed that although there were some difficulties with installation, the web-based data collection tool was quick and easy to use. Some GPs felt that a minimal monetary incentive would promote participation. Conclusions: We have developed processes that allow capture and near real-time automated analysis of GP’s clinical assessments and management decisions of people presenting with ILI. Future work: We will develop processes to include other EHR systems, attempt linkage to data on influenza surveillance and maintain processes in readiness for a future outbreak. Study registration: This study is registered as ISRCTN87130712 and UK Clinical Research Network 12827. Funding: The National Institute for Health Research Health Technology Assessment programme. MGS is supported by the UK NIHR Health Protection Research Unit in Emerging and Zoonotic Infections.

The assessment of a recently discovered Laotian-Vietnamese endemic pine – Pinus cernua (Pinaceae) is presented including new information about species morphology, taxonomy, ecology, distribution, as well as a proposed identification of conservation status according to the IUCN Red List criteria. An annotated list of related pine species known from eastern Indochina also needed updated conservation assessments is provided as well. Four nomenclature combinations – Pinus dalatensis var. anemophila (Businský) Aver., P. dalatensis var. procera (Businský) Aver., P. wangii var. varifolia (Nan Li et Y.C. Zhang) Aver. and P. wangii var. eremitana (Businský) Aver. are proposed.

Abstract Objective To assess the effectiveness of internal and international travel restrictions in the rapid containment of influenza. Methods We conducted a systematic review according to the requirements of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Health-care databases and grey literature were searched and screened for records published before May 2014. Data extraction and assessments of risk of bias were undertaken by two researchers independently. Results were synthesized in a narrative form. Findings The overall risk of bias in the 23 included studies was low to moderate. Internal travel restrictions and international border restrictions delayed the spread of influenza epidemics by one week and two months, respectively. International travel restrictions delayed the spread and peak of epidemics by periods varying between a few days and four months. Travel restrictions reduced the incidence of new cases by less than 3%. Impact was reduced when restrictions were implemented more than six weeks after the notification of epidemics or when the level of transmissibility was high. Travel restrictions would have minimal impact in urban centres with dense populations and travel networks. We found no evidence that travel restrictions would contain influenza within a defined geographical area. Conclusion Extensive travel restrictions may delay the dissemination of influenza but cannot prevent it. The evidence does not support travel restrictions as an isolated intervention for the rapid containment of influenza. Travel restrictions would make an extremely limited contribution to any policy for rapid containment of influenza at source during the first emergence of a pandemic virus.

ObjectivesTo assess the effectiveness of neuraminidase inhibitors for use in rapid containment of influenza.MethodWe conducted a systematic review and meta-analysis in accordance with the PRISMA statement. Healthcare databases and sources of grey literature were searched up to 2012 and records screened against protocol eligibility criteria. Data extraction and risk of bias assessments were performed using a piloted form. Results were synthesised narratively and we undertook meta-analyses to calculate pooled estimates of effect, statistical heterogeneity and assessed publication bias.FindingsNine randomised controlled trials (RCTs) and eight observational studies met the inclusion criteria. Neuraminidase inhibitors provided 67 to 89% protection for individuals following prophylaxis. Meta-analysis of individual protection showed a significantly lower pooled odds of laboratory confirmed seasonal or influenza A(H1N1)pdm09 infection following oseltamivir usage compared to placebo or no therapy (n = 8 studies; odds ratio (OR) = 0.11; 95% confidence interval (CI) = 0.06 to 0.20; pConclusionOseltamivir and zanamivir are effective for prophylaxis of individuals and households irrespective of treatment of the index case. There are no data which directly support an effect on wider community transmission.Protocol registryPROSPERO registration number: CRD42013003880.

We report exploratory gene-expression profiling data from a single-arm Phase-II-study in patients with non-squamous (ns)NSCLC treated with pemetrexed and cisplatin. Previously disclosed results indicated a significant association of low thymidylate-synthase (TS)-expression with longer progression-free and overall survival (PFS/OS).Treatment-naïve nsNSCLC patients (IIIB/IV) received 4 cycles of pemetrexed/cisplatin; non-progressing patients continued on pemetrexed-maintenance. Diagnostic tissue-samples were used to assess TS-expression by immunohistochemistry (IHC) and mRNA-expression array-profiling (1,030 lung cancer-specific genes). Cox proportional-hazard models were applied to explore the association between each gene and PFS/OS. Genes significantly correlated with PFS/OS were further correlated with TS-protein expression (Spearman-rank). Unsupervised clustering was applied to all evaluable samples (n = 51) for all 1,030 genes and an overlapping 870-gene subset associated with adenocarcinoma (ADC, n = 47).51/70 tissue-samples (72.9%) were evaluable; 9 of 1,030 genes were significantly associated with PFS/OS (unadjusted p < 0.01, genes: Chromosome 16 open reading frame 89, napsin A, surfactant protein B, aquaporin 4, TRAF2- and Nck-interacting kinase, Lysophosphatidylcholine acyltransferase 1, Interleukin 1 receptor type II, NK2 homeobox 1, ABO glycosyl-transferase); expression for all except IL1R2 correlated negatively with nuclear TS-expression (statistically significant for 5/8 genes, unadjusted p

During severe influenza pandemics healthcare demand can exceed clinical capacity to provide normal standards of care. Community Assessment Tools (CATs) could provide a framework for triage decisions for hospital referral and admission. CATs have been developed based on evidence that supports the recognition of severe influenza and pneumonia in the community (including resource limited settings) for adults, children and infants, and serious feverish illness in children. CATs use six objective criteria and one subjective criterion, any one or more of which should prompt urgent referral and admission to hospital. A retrospective evaluation of the ability of CATs to predict use of hospital-based interventions and patient outcomes in a pandemic was made using the first recorded routine clinical assessment on or shortly after admission from 1520 unselected patients (800 female, 480 children

Nosocomial infection of health-care workers (HCWs) during outbreaks of respiratory infections (e.g. Influenza A H1N1 (2009)) is a significant concern for public health policy makers. World Health Organization (WHO)-defined 'aerosol generating procedures' (AGPs) are thought to increase the risk of aerosol transmission to HCWs, but there are presently insufficient data to quantify risk accurately or establish a hierarchy of risk-prone procedures.This study measured the amount of H1N1 (2009) RNA in aerosols in the vicinity of H1N1 positive patients undergoing AGPs to help quantify the potential risk of transmission to HCWs. There were 99 sampling occasions (windows) producing a total of 198 May stages for analysis in the size ranges 0.86-7.3 µm. Considering stages 2 (4-7.3 µm) and 3 (0.86-4 µm) as comprising one sample, viral RNA was detected in 14 (14.1%) air samples from 10 (25.6%) patients. Twenty three air samples were collected while potential AGPs were being performed of which 6 (26.1%) contained viral RNA; in contrast, 76 May samples were collected when no WHO 2009 defined AGP was being performed of which 8 (10.5%) contained viral RNA (unadjusted OR = 2.84 (95% CI 1.11-7.24) adjusted OR = 4.31 (0.83-22.5)).With our small sample size we found that AGPs do not significantly increase the probability of sampling an H1N1 (2009) positive aerosol (OR (95% CI) = 4.31 (0.83-22.5). Although the probability of detecting positive H1N1 (2009) positive aerosols when performing various AGPs on intensive care patients above the baseline rate (i.e. in the absence of AGPs) did not reach significance, there was a trend towards hierarchy of AGPs, placing bronchoscopy and respiratory and airway suctioning above baseline (background) values. Further, larger studies are required but these preliminary findings may be of benefit to infection control teams.

The Influenza Clinical Information Network (FLU-CIN) was established to gather detailed clinical and epidemiological information about patients with laboratory confirmed A(H1N1)pdm09 infection in UK hospitals. This report focuses on the clinical course and outcomes of infection in pregnancy.A standardised data extraction form was used to obtain detailed clinical information from hospital case notes and electronic records, for patients with PCR-confirmed A(H1N1)pdm09 infection admitted to 13 sentinel hospitals in five clinical 'hubs' and a further 62 non-sentinel hospitals, between 11th May 2009 and 31st January 2010.Outcomes were compared for pregnant and non-pregnant women aged 15-44 years, using univariate and multivariable techniques.Of the 395 women aged 15-44 years, 82 (21%) were pregnant; 73 (89%) in the second or third trimester. Pregnant women were significantly less likely to exhibit severe respiratory distress at initial assessment (OR = 0.49 (95% CI: 0.30-0.82)), require supplemental oxygen on admission (OR = 0.40 (95% CI: 0.20-0.80)), or have underlying co-morbidities (p-trend

Triage tools have an important role in pandemics to identify those most likely to benefit from higher levels of care. We compared Community Assessment Tools (CATs), the CURB-65 score, and the Pandemic Medical Early Warning Score (PMEWS); to predict higher levels of care (high dependency--Level 2 or intensive care--Level 3) and/or death in patients at or shortly after admission to hospital with A/H1N1 2009 pandemic influenza. This was a case-control analysis using retrospectively collected data from the FLU-CIN cohort (1040 adults, 480 children) with PCR-confirmed A/H1N1 2009 influenza. Area under receiver operator curves (AUROC), sensitivity, specificity, positive predictive values and negative predictive values were calculated. CATs best predicted Level 2/3 admissions in both adults [AUROC (95% CI): CATs 0.77 (0.73, 0.80); CURB-65 0.68 (0.64, 0.72); PMEWS 0.68 (0.64, 0.73), p

BACKGROUND: The World Health Organization and European Centre for Disease Prevention and Control have highlighted the importance of establishing systems to monitor severe influenza. Following the H1N1 (2009) influenza pandemic, a sentinel network of 23 Trusts, the UK Severe Influenza Surveillance System (USISS), was established to monitor hospitalisations due to confirmed seasonal influenza in England. This article presents the results of the first season of operation of USISS in 2010/11. METHODOLOGY/PRINCIPAL FINDINGS: A case was defined as a person hospitalised with confirmed influenza of any type. Weekly aggregate numbers of hospitalised influenza cases, broken down by flu type and level of care, were submitted by participating Trusts. Cases in 2010/11 were compared to cases during the 2009 pandemic in hospitals with available surveillance data for both time periods (n = 19). An unexpected resurgence in seasonal A/H1N1 (2009) influenza activity in England was observed in December 2010 with reports of severe disease. Reported cases over the period of 4 October 2010 to 13 February 2011 were mostly due to influenza A/H1N1 (2009). One thousand and seventy-one cases of influenza A/H1N1 (2009) occurred over this period compared to 409 at the same Trusts over the 2009/10 pandemic period (1 April 2009 to 6 January 2010). Median age of influenza A/H1N1 (2009) cases in 2010/11 was 35 years, compared with 20 years during the pandemic (p =

BackgroundStatins are drugs that are used to lower plasma cholesterol levels. Recently, contradictory claims have been made about possible additional effects of statins on progression of a variety of inflammatory disorders, including infections. We therefore examined the clinical course of patients admitted to hospital with 2009 pandemic influenza A(H1N1), who were or weren't taking statins at time of admission.MethodsA retrospective case-control study was performed using the United Kingdom Influenza Clinical Information Network (FLU-CIN) database, containing detailed information on 1,520 patients admitted to participating hospitals with confirmed 2009 pandemic influenza A(H1N1) infection between April 2009 and January 2010. We confined our analysis to those aged over 34 years. Univariate analysis was used to calculate unadjusted odds ratios (OR) and 95 percent confidence intervals (95%CI) for factors affecting progression to severe outcome (high dependency or intensive care unit level support) or death (cases); two multivariable logistic regression models were then established for age and sex, and for age, sex, obesity and "indication for statin" (e.g., heart disease or hypercholesterolaemia).ResultsWe found no statistically significant association between pre-admission statin use and severity of outcome after adjustment for age and sex [adjusted OR: 0.81 (95% CI: 0.46-1.38); n = 571]. After adjustment for age, sex, obesity and indication for statin, the association between pre-admission statin use and severe outcome was not statistically significant; point estimates are compatible with a small but clinically significant protective effect of statin use [adjusted OR: 0.72 (95% CI: 0.38-1.33)].ConclusionsIn this group of patients hospitalized with pandemic influenza, a significant beneficial effect of pre-admission statin use on the in-hospital course of illness was not identified. Although the database from which these observations are derived represents the largest available suitable UK hospital cohort, a larger study would be needed to confirm whether there is any benefit in this setting.

BackgroundImmunocompromised patients are vulnerable to severe or complicated influenza infection. Vaccination is widely recommended for this group. This systematic review and meta-analysis assesses influenza vaccination for immunocompromised patients in terms of preventing influenza-like illness and laboratory confirmed influenza, serological response and adverse events.Methodology/principal findingsElectronic databases and grey literature were searched and records were screened against eligibility criteria. Data extraction and risk of bias assessments were performed in duplicate. Results were synthesised narratively and meta-analyses were conducted where feasible. Heterogeneity was assessed using I(2) and publication bias was assessed using Begg's funnel plot and Egger's regression test. Many of the 209 eligible studies included an unclear or high risk of bias. Meta-analyses showed a significant effect of preventing influenza-like illness (odds ratio [OR]=0.23; 95% confidence interval [CI]=0.16-0.34; pConclusions/significanceInfection prevention and control strategies should recommend vaccinating immunocompromised patients. Potential for bias and confounding and the presence of heterogeneity mean the evidence reviewed is generally weak, although the directions of effects are consistent. Areas for further research are identified.

BackgroundThe majority of influenza transmission occurs in homes, schools and workplaces, where many frequently touched communal items are situated. However the importance of transmission via fomites is unclear since few data exist on the survival of virus on commonly touched surfaces. We therefore measured the viability over time of two H1N1 influenza strains applied to a variety of materials commonly found in households and workplaces.Methodology and principal findingsInfluenza A/PuertoRico/8/34 (PR8) or A/Cambridge/AHO4/2009 (pandemic H1N1) viruses were inoculated onto a wide range of surfaces used in home and work environments, then sampled at set times following incubation at stabilised temperature and humidity. Virus genome was measured by RT-PCR; plaque assay (for PR8) or fluorescent focus formation (for pandemic H1N1) was used to assess the survival of viable virus.Conclusions/significanceThe genome of either virus could be detected on most surfaces 24 h after application with relatively little drop in copy number, with the exception of unsealed wood surfaces. In contrast, virus viability dropped much more rapidly. Live virus was recovered from most surfaces tested four hours after application and from some non-porous materials after nine hours, but had fallen below the level of detection from all surfaces at 24 h. We conclude that influenza A transmission via fomites is possible but unlikely to occur for long periods after surface contamination (unless re-inoculation occurs). In situations involving a high probability of influenza transmission, our data suggest a hierarchy of priorities for surface decontamination in the multi-surface environments of home and hospitals.