title: Predicting host taxonomic information from viral genomes: A comparison of feature representations

text: The rise in metagenomics has led to an exponential growth in virus discovery. However, the majority of these new virus sequences have no assigned host. Current machine learning approaches to predicting virus host interactions have a tendency to focus on nucleotide features, ignoring other representations of genomic information. Here we investigate the predictive potential of features generated from four different ‘levels’ of viral genome representation: nucleotide, amino acid, amino acid properties and protein domains. This more fully exploits the biological information present in the virus genomes. Over a hundred and eighty binary datasets for infecting versus non-infecting viruses at all taxonomic ranks of both eukaryote and prokaryote hosts were compiled. The viral genomes were converted into the four different levels of genome representation and twenty feature sets were generated by extracting k-mer compositions and predicted protein domains. We trained and tested Support Vector Machine, SVM, classifiers to compare the predictive capacity of each of these feature sets for each dataset. Our results show that all levels of genome representation are consistently predictive of host taxonomy and that prediction k-mer composition improves with increasing k-mer length for all k-mer based features. Using a phylogenetically aware holdout method, we demonstrate that the predictive feature sets contain signals reflecting both the evolutionary relationship between the viruses infecting related hosts, and host-mimicry. Our results demonstrate that incorporating a range of complementary features, generated purely from virus genome sequences, leads to improved accuracy for a range of virus host prediction tasks enabling computational assignment of host taxonomic information.


title: Estimation of Heart Rate and Respiratory Rate from PPG Signal Using Complementary Ensemble Empirical Mode Decomposition with both Independent Component Analysis and Non-Negative Matrix Factorization

text: This paper proposes a framework combining the complementary ensemble empirical mode decomposition with both the independent component analysis and the non-negative matrix factorization for estimating both the heart rate and the respiratory rate from the photoplethysmography (PPG) signal. After performing the complementary ensemble empirical mode decomposition on the PPG signal, a finite number of intrinsic mode functions are obtained. Then, these intrinsic mode functions are divided into two groups to perform the further analysis via both the independent component analysis and the non-negative matrix factorization. The surrogate cardiac signal related to the heart activity and another surrogate respiratory signal related to the respiratory activity are reconstructed to estimate the heart rate and the respiratory rate, respectively. Finally, different records of signals acquired from the Medical Information Mart for Intensive Care database downloaded from the Physionet Automated Teller Machine (ATM) data bank are employed for demonstrating the outperformance of our proposed method. The results show that our proposed method outperforms both the digital filtering approach and the conventional empirical mode decomposition based methods in terms of reconstructing both the surrogate cardiac signal and the respiratory signal from the PPG signal as well as both achieving the higher accuracy and the higher reliability for estimating both the heart rate and the respiratory rate.


title: Fiber Optic Particle Plasmon Resonance Biosensor for Label-Free Detection of Nucleic Acids and Its Application to HLA-B27 mRNA Detection in Patients with Ankylosing Spondylitis

text: We developed a label-free, real-time, and highly sensitive nucleic acid biosensor based on fiber optic particle plasmon resonance (FOPPR). The biosensor employs a single-strand deoxyoligonucleotides (ssDNA) probe, conjugated to immobilized gold nanoparticles on the core surface of an optical fiber. We explore the steric effects on hybridization affinity and limit of detection (LOD), by using different ssDNA probe designs and surface chemistries, including diluent molecules of different lengths in mixed self-assembled monolayers, ssDNA probes of different oligonucleotide lengths, ssDNA probes in different orientations to accommodate target oligonucleotides with a hybridization region located unevenly in the strand. Based on the optimized ssDNA probe design and surface chemistry, we achieved LOD at sub-nM level, which makes detection of target oligonucleotides as low as 1 fmol possible in the 10-μL sensor chip. Additionally, the FOPPR biosensor shows a good correlation in determining HLA-B27 mRNA, in extracted blood samples from patients with ankylosing spondylitis (AS), with the clinically accepted real-time reverse transcription-polymerase chain reaction (RT-PCR) method. The results from this fundamental study should guide the design of ssDNA probe for anti-sense sensing. Further results through application to HLA-B27 mRNA detection illustrate the feasibility in detecting various nucleic acids of chemical and biological relevance.


title: Level-Set Segmentation-Based Respiratory Volume Estimation Using a Depth Camera

text: In this paper, a method is proposed to measure human respiratory volume using a depth camera. The level-set segmentation method, combined with spatial and temporal information, was used to measure respiratory volume accurately. The shape of the human chest wall was used as spatial information. As temporal information, the segmentation result from the previous frame in the time-aligned depth image was used. The results of the proposed method were verified using a ventilator. The proposed method was also compared with other level-set methods. The result showed that the mean tidal volume error of the proposed method was 8.41% compared to the actual tidal volume. This was calculated to have less error than with two other methods: the level-set method with spatial information (14.34%) and the level-set method with temporal information (10.93%). The difference between these methods of tidal volume error was statistically significant [Formula: see text]. The intra-class correlation coefficient (ICC) of the respiratory volume waveform measured by a ventilator and by the proposed method was 0.893 on an average, while the ICC between the ventilator and the other methods were 0.837 and 0.879 on an average.


title: Evaluating Physiological Dynamics via Synchrosqueezing: Prediction of Ventilator Weaning

text: Oscillatory phenomena abound in many types of signals. Identifying the individual oscillatory components that constitute an observed biological signal leads to profound understanding about the biological system. The instantaneous frequency (IF), the amplitude modulation (AM), and their temporal variability are widely used to describe these oscillatory phenomena. In addition, the shape of the oscillatory pattern, repeated in time for an oscillatory component, is also an important characteristic that can be parametrized appropriately. These parameters can be viewed as phenomenological surrogates for the hidden dynamics of the biological system. To estimate jointly the IF, AM, and shape, this paper applies a novel and robust time-frequency analysis tool, referred to as the synchrosqueezing transform (SST). The usefulness of the model and SST are shown directly in predicting the clinical outcome of ventilator weaning. Compared with traditional respiration parameters, the breath-to-breath variability has been reported to be a better predictor of the outcome of the weaning procedure. So far, however, all these indices normally require at least [Formula: see text] min of data acquisition to ensure predictive power. Moreover, the robustness of these indices to the inevitable noise is rarely discussed. We find that based on the proposed model, SST and only [Formula: see text] min of respiration data, the ROC area under curve of the prediction accuracy is [Formula: see text]. The high predictive power that is achieved in the weaning problem, despite a shorter evaluation period, and the stability to noise suggest that other similar kinds of signal may likewise benefit from the proposed model and SST.


title: Multiple Vital-Sign-Based Infection Screening Outperforms Thermography Independent of the Classification Algorithm

text: Goal: Thermography-based infection screening at international airports plays an important role in the prevention of pandemics. However, studies show that thermography suffers from low sensitivity and specificity. To achieve higher screening accuracy, we developed a screening system based on the acquisition of multiple vital-signs. This multimodal approach increases accuracy, but introduces the need for sophisticated classification methods. This paper presents a comprehensive analysis of the multimodal approach to infection screening from a machine learning perspective. Methods: We conduct an empirical study applying six classification algorithms to measurements from the multimodal screening system and comparing their performance among each other, as well as to the performance of thermography. In addition, we provide an information theoretic view on the use of multiple vital-signs for infection screening. The classification methods are tested using the same clinical data, which has been analyzed in our previous study using linear discriminant analysis. A total of 92 subjects were recruited for influenza screening using the system, consisting of 57 inpatients diagnosed to have seasonal influenza and 35 healthy controls. Results: Our study revealed that the multimodal screening system reduces the misclassification rate by more than 50% compared to thermography. At the same time, none of the multimodal classifiers needed more than 6 ms for classification, which is negligible for practical purposes. Conclusion: Among the tested classifiers k-nearest neighbors, support vector machine and quadratic discriminant analysis achieved the highest cross-validated sensitivity score of 93%. Significance: Multimodal infection screening might be able to address the shortcomings of thermography.


title: The Association between Utilization of Media Information and Current Health Anxiety Among the Fukushima Daiichi Nuclear Disaster Evacuees

text: The 2011 nuclear disaster in Fukushima was not only a health disaster, but also an information disaster. Although media can promote health communication following disasters, studies have revealed associations between media information and negative psychological reactions. To clarify the relationship between media utilization and current health anxiety due to radiation exposure, a cross-sectional questionnaire survey was conducted in Fukushima. We selected 2000 subjects from evacuation (i.e., 500) and non-evacuation (i.e., 1500) areas by two-stage stratified random sampling. As the independent variable, participants were asked about current health anxiety due to radiation exposure at the time of answering the questionnaire. For utilization of media about radiation exposure, local media, national media, Internet media, public broadcasts, and public relations information from local government were set as the dependent variables. Questionnaire data were analyzed by evacuation type (i.e., forced/voluntary). In a multivariate logistic regression analysis, the use of public relations information was significantly associated with lower anxiety for the forced evacuees (odds ratio: 0.72; 95% confidence interval: 0.56–0.93). Our findings highlight the importance of public relations information from local government in terms of it being associated with lower current health anxiety, and this could potentially aid in preparing for future disasters.


title: Perinatal risk factors for pulmonary hemorrhage in extremely low-birth-weight infants

text: BACKGROUND: Pulmonary hemorrhage (PH) is a life-threatening respiratory complication of extremely low-birth-weight infants (ELBWIs). However, the risk factors for PH are controversial. Therefore, the purpose of this study was to analyze the perinatal risk factors and short-term outcomes of PH in ELBWIs. METHODS: This was a retrospective cohort study of live born infants who had birth weights that were less than 1000 g, lived for at least 12 hours, and did not have major congenital anomalies. A logistic regression model was established to analyze the risk factors associated with PH. RESULTS: There were 168 ELBWIs born during this period. A total of 160 infants were included, and 30 infants were diagnosed with PH. Risk factors including gestational age, small for gestational age, intubation in the delivery room, surfactant in the delivery room, repeated use of surfactant, higher FiO(2) during the first day, invasive ventilation during the first day and early onset sepsis (EOS) were associated with the occurrence of PH by univariate analysis. In the logistic regression model, EOS was found to be an independent risk factor for PH. The mortality and intraventricular hemorrhage rate of the group of ELBWIs with PH were significantly higher than those of the group of ELBWIs without PH. The rates of periventricular leukomalacia, moderate-to-severe bronchopulmonary dysplasia and severe retinopathy of prematurity, and the duration of the hospital stay were not significantly different between the PH and no-PH groups. CONCLUSIONS: Although PH did not extend hospital stay or increase the risk of bronchopulmonary dysplasia, it increased the mortality and intraventricular hemorrhage rate in ELBWIs. EOS was the independent risk factor for PH in ELBWIs.


title: Identification of cardiovascular and molecular prognostic factors for the medium-term and long-term outcomes of sepsis (ICROS): protocol for a prospective monocentric cohort study

text: INTRODUCTION: Sepsis is one of the most prevalent life-threatening conditions in the intensive care unit. Patients suffer from impaired organ function, reduced physical functional capacity and decreased quality of life even after surviving sepsis. The identification of prognostic factors for the medium-term and long-term outcomes of this condition is necessary to develop personalised theragnostic approaches. Sepsis can cause cardiac impairment. The impact of this septic cardiomyopathy on patient’s long-term outcome remains unclear. This study aims to evaluate cardiovascular risk factors, particularly the occurrence of septic cardiomyopathy, regarding their suitability as prognostic factors for the short-term and long-term outcomes of septic patients. Additionally, the study seeks to validate preclinical pathophysiological findings of septic cardiomyopathy in the clinical setting. METHODS AND ANALYSIS: In this prospective monocentric cohort study, patients will be clinically assessed during the acute and postacute phase of sepsis and two follow-ups after 6 and 12 months. To determine the effect of septic cardiomyopathy and concomitant cellular and molecular changes on patient mortality and morbidity, a comprehensive cardiovascular and molecular deep phenotyping of patients will be performed. This includes an echocardiographic and electrocardiographic assessment, and the evaluation of heart rate variability, body composition, mitochondrial oxygen metabolism, macrocirculation and microcirculation, and endothelial barrier function. These analyses are complemented by routine immunological, haematological and biochemical laboratory tests and analyses of the serum metabolome and lipidome, microbiome and epigenetic modifications of immune cells. The reversibility of patients’ organ dysfunction, their quality of life and physical functional capacity will be investigated in the follow-ups. Patients with cardiomyopathy without infection and healthy subjects will serve as control groups. ETHICS AND DISSEMINATION: Approval was obtained from the Ethics Committee of the Friedrich Schiller University Jena (5276-09/17). The results will be published in peer-reviewed journals and presented at appropriate conferences. TRIAL REGISTRATION NUMBERS: DRKS00013347; NCT03620409.


title: The MNK1/2-eIF4E Axis as a Potential Therapeutic Target in Melanoma

text: Melanoma is a type of skin cancer that originates in the pigment-producing cells of the body known as melanocytes. Most genetic aberrations in melanoma result in hyperactivation of the mitogen activated protein kinase (MAPK) and phosphoinositide 3-kinase (PI3K) pathways. We and others have shown that a specific protein synthesis pathway known as the MNK1/2-eIF4E axis is often dysregulated in cancer. The MNK1/2-eIF4E axis is a point of convergence for these signaling pathways that are commonly constitutively activated in melanoma. In this review we consider the functional implications of aberrant mRNA translation in melanoma and other malignancies. Moreover, we discuss the consequences of inhibiting the MNK1/2-eIF4E axis on the tumor and tumor-associated cells, and we provide important avenues for the utilization of this treatment modality in combination with other targeted and immune-based therapies. The past decade has seen the increased development of selective inhibitors to block the action of the MNK1/2-eIF4E pathway, which are predicted to be an effective therapy regardless of the melanoma subtype (e.g., cutaneous, acral, and mucosal).


title: A Neuroprotective Dose of Isatin Causes Multilevel Changes Involving the Brain Proteome: Prospects for Further Research

text: Isatin (indole-2,3-dione) is an endogenous regulator, exhibiting a wide range of biological and pharmacological activities. At doses of 100 mg/kg and above, isatin is neuroprotective in different experimental models of neurodegeneration. Good evidence exists that its effects are realized via interaction with numerous isatin-binding proteins identified in the brain and peripheral tissues studied. In this study, we investigated the effect of a single dose administration of isatin to mice (100 mg/kg, 24 h) on differentially expressed proteins and a profile of the isatin-binding proteins in brain hemispheres. Isatin administration to mice caused downregulation of 31 proteins. However, these changes cannot be attributed to altered expression of corresponding genes. Although at this time point isatin influenced the expression of more than 850 genes in brain hemispheres (including 433 upregulated and 418 downregulated genes), none of them could account for the changes in the differentially expressed proteins. Comparative proteomic analysis of brain isatin-binding proteins of control and isatin-treated mice revealed representative groups of proteins sensitive to isatin administration. Control-specific proteins (n = 55) represent specific targets that interact directly with isatin. Appearance of brain isatin-binding proteins specific to isatin-treated mice (n = 94) may be attributed to the formation of new clusters of protein–protein interactions and/or novel binding sites induced by a high concentration of this regulator (ligand-induced binding sites). Thus, isatin administration produces multiple effects in the brain, which include changes in gene expression and also profiles of isatin-binding proteins and their interactomes. Further studies are needed for deeper insight into the mechanisms of the multilevel changes in the brain proteome induced by isatin. In the context of the neuroprotective action, these changes may be aimed at interruption of pathological links that begin to form after initiation of pathological processes.


title: A Clinical Study of Hospitalized H1N1 Infected Children in Western Rajasthan

text: Objective: To study the cases of H1N1 influenza admitted in our hospital. Method: Hospital records of all the admitted patients diagnosed as H1N1 positive by throat swab rt-PCR (real time polymerase chain reaction) were retrospectively studied. Results: Between November 2009 and February 2010 total 62 children were hospitalized with 2009 H1N1 influenza virus infection. Of the admitted children, 19 (30.6%) were admitted in ICU and 4 (6.4%) expired. Consolidation was observed in 25 (40%) cases while 4 (6%) patients had pleural effusion and 1 patient each developed pneumothorax and pulmonary edema. Conclusions: Pandemic 2009 H1N1 influenza caused serious respiratory complications in children not usually seen with seasonal influenza.


title: Clinical and Epidemiological Characteristics of Pandemic Influenza A/(H1N1) in Hospitalized Pediatric Patients at a University Hospital, Istanbul, Turkey

text: Background: The aim of this study was to describe the clinical and epidemiological characteristics of pandemic influenza in hospitalized children. Methods: A total of 114 patients with suspected H1N1 virus infection were hospitalized, and nasal swabs were sent to National Influenza Reference Laboratory for confirmation of pandemic influenza A (H1N1) virus infection by rRT–PCR assay. Results: Forty-six female and 68 male patients were included in the study. Age of the patients ranged from 40 days to 16 years. Clinical and/or radiological pneumonia were detected in 96% of all. Sixteen patients required mechanical ventilation due to hypoxemia. Previously healthy children required mechanical ventilation and oxygen therapy more than patients with chronic diseases. Elevated levels of CRP and LDH in patients with respiratory distress and patients who required mechanical ventilation were statistically significant. Conclusion: Our study showed that progress of pandemic influenza infection in previously healthy children is as severe as their counterparts with chronic underlying diseases.


title: The Influenza Pandemic of 1918–1919 in the British Caribbean

text: The influenza pandemic swept through the Caribbean during the period October 1918 to March 1919 and resulted in c. 100 000 deaths. This article focuses on the British possessions and is based principally on official reports and the local press. It looks at how the virus entered and spread through the region, the possible reasons for variations in levels of morbidity and mortality between islands, popular responses to the infection, and the mainly fruitless official attempts to arrest and deal with the disease. Jamaica was the first island to be affected, and along with Belize and Guyana, suffered most severely. A number of islands, particularly those in the eastern Caribbean, appear to have escaped relatively lightly. Although all sections of the population were vulnerable, the heaviest mortality rates were among the very poor, East Indian immigrant labourers, and native Americans. There was also a high toll among males aged 15–40. Altogether the death rate from influenza in the British Caribbean was c. 30 000. In London influenza was added to the official list of British ‘imperial diseases’, and although it was recognized that poverty provided the conditions for the spread of disease, the resources in the Caribbean were barely used to improve standards of living and nutrition.


title: Pandemic non-adjuvanted influenza A H1N1 vaccine in a cohort of patients with systemic sclerosis

text: OBJECTIVE: To assess the possible effect of therapy, disease subtype and severity on H1N1 immunogenicity in patients with SSc. METHODS: Ninety-two patients and 92 age- and gender-matched healthy controls received adjuvant-free influenza A/California/7/2009 (pH1N1) vaccine. Blood samples were collected immediately before and 3 weeks after vaccination to evaluate antibody responses to the H1N1 virus. Efficacy was assessed by seroprotection (SP) and seroconversion (SC) rates and the factor increase in geometric mean antibody titre. Participants received a 21-day symptom diary card and were instructed to report local and systemic adverse events. RESULTS: SSc patients were predominantly females (91%) and 61% had limited SSc, 12% had severe skin involvement and 57.6% were on immunosuppressive (IS) therapy. SSc patients and controls presented comparable overall SP (P = 0.20) and SC (P = 0.61) rates. Further evaluation of the possible effect of disease and therapy revealed similar rates of SP and SC in patients with dcSSc vs lcSSc (SP P = 0.62 and SC P = 0.66), severe vs mild/moderate skin involvement (SP P = 1 and SC P = 0.45) and with vs without IS (SP P = 0.26 and SC P = 0.10). The frequency of mild local and minor systemic reactions was similar in patients with dcSSC vs lcSSc (P = 0.70 vs 0.32) and in those with and without severe skin involvement (P = 0.59 vs 0.28). CONCLUSION: The non-adjuvanted influenza H1N1 virus vaccine proved to be safe and effective, independent of SSc clinical subtype, disease severity or therapy. These latter factors do not seem to contribute to mild adverse events observed in SSc. Our data support the annual influenza vaccination recommendation for these patients. TRIAL REGISTRATION: ClinicalTrials.gov (http://clinicaltrials.gov), NCT01151644


title: Preparedness of Residential and Nursing Homes for Pandemic Flu

text: BACKGROUND: Work is being undertaken across a wide range of agencies to ensure a high level of preparedness for pandemic influenza. In England, the Department of Health has published a range of guidance to support this. The impact of pandemic flu on care homes, especially if unprepared may have a major knock on effect on the rest of the health and social care system. OBJECTIVE AND METHODS: A rapid survey was undertaken of a small number of care homes in West Yorkshire to assess preparedness. The homes were both local authority and privately owned. RESULTS: It was apparent that little preparation had been done at the time of the survey. A range of readily implementable ideas that may help this sector prepare was identified. CONCLUSION: Planning for pandemic flu in this sector will require effort and coordination across a range of sectors; it might best be coordinated through Local Resilience Forums.


title: TNF blockers show distinct patterns of immune response to the pandemic influenza A H1N1 vaccine in inflammatory arthritis patients

text: Objective. To evaluate the immunogenicity of the anti-influenza A H1N1/2009 vaccine in RA and spondyloarthritis (SpA) patients receiving distinct classes of anti-TNF agents compared with patients receiving DMARDs and healthy controls. Methods. One hundred and twenty patients (RA, n = 41; AS, n = 57; PsA, n = 22) on anti-TNF agents (monoclonal, n = 94; soluble receptor, n = 26) were compared with 116 inflammatory arthritis patients under DMARDs and 117 healthy controls. Seroprotection, seroconversion (SC), geometric mean titre, factor increase in geometric mean titre and adverse events were evaluated 21 days after vaccination. Results. After immunization, SC rates (58.2% vs 74.3%, P = 0.017) were significantly lower in SpA patients receiving anti-TNF therapy, whereas no difference was observed in RA patients receiving this therapy compared with healthy controls (P = 0.067). SpA patients receiving mAbs (infliximab/adalimumab) had a significantly lower SC rate compared with healthy controls (51.6% vs 74.3%, P = 0.002) or those on DMARDs (51.6% vs 74.7%, P = 0.005), whereas no difference was observed for patients on etanercept (86.7% vs 74.3%, P = 0.091). Further analysis of non-seroconverting and seroconverting SpA patients revealed that the former group had a higher mean age (P = 0.003), a higher frequency of anti-TNF (P = 0.031) and mAbs (P = 0.001) and a lower frequency of MTX (P = 0.028). In multivariate logistic regression, only older age (P = 0.015) and mAb treatment (P = 0.023) remained significant factors for non-SC in SpA patients. Conclusion. This study revealed a distinct disease pattern of immune response to the pandemic influenza vaccine in inflammatory arthritis patients receiving anti-TNF agents, illustrated by a reduced immunogenicity solely in SpA patients using mAbs. Trial Registration: ClinicalTrials.gov, www.clinicaltrials.gov, NCT01151644.


title: Immunogenicity of an adjuvanted 2009 pandemic influenza A (H1N1) vaccine in haemodialysed patients

text: Background. The 2009 pandemic of influenza A (H1N1) prompted an urgent worldwide vaccination campaign, especially of high-risk subjects, such as maintenance haemodialysis (HD) patients. Still the immunogenicity of the pandemic A (H1N1) vaccine in HD patients is unknown. Methods. We prospectively studied the immunogenicity of a monovalent adjuvanted influenza A/California/2009 (H1N1) vaccine (Pandemrix®, GSK Biologicals, Rixensart, Belgium) in HD patients and controls. Antibody level was measured using a seroneutralization assay before (D(0)) and 30 days after (D(30)) a single 3.75 μg vaccine dose. Specimens were tested in quadruplicates. Geometric mean (GM) antibody titers were determined in each subject at D(0) and D(30). Seroconversion was defined as an increase in GM titers by a factor 4 or more. Results. Fifty-three adult HD patients [aged 71 ± 10, 58.5% males, on HD for a median of 38 (3 − 146) months] and 32 control subjects (aged 47.3 ± 14, 31.3% males) were analyzed. Baseline GM titers were similar in HD patients and controls [7.9 (6.6 − 9.6) vs 10 (6 − 17); p = 0.69]. Seroconversion was observed in 30 (93.8%) controls and 34 (64.2%) HD patients (p = 0.002). In addition, GM titers at D(30) were significantly higher in controls than in HD patients [373 (217 − 640) vs 75.5 (42.5 − 134); p = 0.001]. HD patients were significantly older than controls (p < 0.001) and more likely to be males (p = 0.02). However, by multivariate analysis, HD status [OR 0.13 (0.02-0.78), p = 0.03], but neither age [OR 0.99 (0.96 − 1.03); p = 0.7] nor male gender [OR 1.31 (0.45 − 3.85); p = 0.63] was independently associated with seroconversion. The vaccine was generally well tolerated by HD patients. Conclusions. Only 64% of chronic HD patients developed seroconversion after a single dose of adjuvanted influenza A (H1N1) vaccine, a much lower rate than in controls (94%). These results underscore the substantial immunodeficiency associated with End-Stage Renal Disease. The persistence of protective antibodies as well as the effect of a booster dose remain to be investigated in HD patients.


title: The epidemiology of influenza

text: Influenza remains a globally important cause of febrile respiratory illness. Influenza virus activity in the community results in significant mortality, morbidity and economic disruption, particularly in those at high risk of developing complications, such as the elderly and those with underlying chronic medical conditions, including pulmonary disease and diabetes mellitus. The occurrence in Hong Kong in 1997 of avian influenza H5N1 in man, which resulted in six deaths, served to remind us of the importance of continuing surveillance and preparation for the next pandemic.


title: Antiviral treatment for outpatient use during an influenza pandemic: a decision tree model of outcomes averted and cost-effectiveness

text: BACKGROUND: Many countries have acquired antiviral stockpiles for pandemic influenza mitigation and a significant part of the stockpile may be focussed towards community-based treatment. METHODS: We developed a spreadsheet-based, decision tree model to assess outcomes averted and cost-effectiveness of antiviral treatment for outpatient use from the perspective of the healthcare payer in the UK. We defined five pandemic scenarios—one based on the 2009 A(H1N1) pandemic and four hypothetical scenarios varying in measures of transmissibility and severity. RESULTS: Community-based antiviral treatment was estimated to avert 14–23% of hospitalizations in an overall population of 62.28 million. Higher proportions of averted outcomes were seen in patients with high-risk conditions, when compared to non-high-risk patients. We found that antiviral treatment was cost-saving across pandemic scenarios for high-risk population groups, and cost-saving for the overall population in higher severity influenza pandemics. Antiviral effectiveness had the greatest influence on both the number of hospitalizations averted and on cost-effectiveness. CONCLUSIONS: This analysis shows that across pandemic scenarios, antiviral treatment can be cost-saving for population groups at high risk of influenza-related complications.


Is there really good news about pandemic diabetic nephropathy?


title: The determinants of health-seeking behaviour during the A/H1N1 influenza pandemic: an ecological study

text: BACKGROUND: This is an ecological study that examines the relationship between antiviral drug collection during the 2009/2010 A/H1N1 influenza pandemic, and area-level ethnicity, socioeconomic deprivation and distance from an antiviral collection point (ACP). METHODS: Age-standardized antiviral collection rates (ACR) were calculated for each super output area (geographic areas representing a population of ∼1500) in Sandwell, UK for all residents who received an antiviral drug for influenza-like illness between 23 July 2009 and 7 February 2010. Multivariable regression was used to examine the relationship between ACR and ethnicity (percentage population non-white), socioeconomic deprivation (index of multiple deprivation, IMD) and distance from an ACP. RESULTS: Socioeconomic deprivation, ethnicity and distance from an ACP were independently associated with a reduction in ACR. Each one-point increase in the IMD score was associated with a drop in the ACR of 15.7 prescriptions per 100 000 population (P= 0.013). CONCLUSIONS: Socioeconomic deprivation, ethnicity and distance from an ACP may have influenced health-seeking behaviour during the 2009/2010 influenza pandemic. This suggests possible inequalities in access to antivirals during the most recent influenza pandemic. Qualitative research is needed to examine the reasons for this. Individual-level data on ethnicity should be routinely collected in the event of a future pandemic.


docid: fjyaiqdo

title: An open-label, randomized clinical trial assessing immunogenicity, safety and tolerability of pandemic influenza A/H1N1 MF59-adjuvanted vaccine administered sequentially or simultaneously with seasonal virosomal-adjuvanted influenza vaccine to paediatric kidney transplant recipients

text: Background. The aim of this study was to investigate the immunogenicity, safety and tolerability of the 2009 A/H1N1 MF59-adjuvanted influenza vaccine, administered sequentially or simultaneously with the seasonal 2009–10 virosomal-adjuvanted influenza vaccine, to paediatric kidney transplant recipients. Methods. Thirty-two children and adolescents with transplanted kidneys and 32 age- and gender-matched healthy controls were randomized 1:1 to receive the pandemic vaccine upon enrolment and the seasonal vaccine 1 month later (16 transplant recipients and 16 healthy controls), or to receive the two vaccines simultaneously upon enrolment (16 transplant recipients and 16 healthy controls). Results. When the pandemic vaccine was administered sequentially to the seasonal vaccine, it was significantly less immunogenic in the patients than in the controls (P < 0.05); when it was administered together with the seasonal vaccine, the immune response of both patients (P < 0.05) and controls (P < 0.05) was significantly greater than when it was administered sequentially. Seroconversion rates and the geometric mean titres of all of the seasonal antigens were significantly lower in the patients, regardless of the type of vaccine administration (P < 0.05). Simultaneous administration was associated with a better immune response against A/H1N1 and A/H3N2 antigens in both patients and controls, and did not increase the mild local and systemic reactions. No impact on renal function was observed. Conclusions. Paediatric kidney transplant recipients have a lower immune response to the pandemic influenza A/H1N1 MF59-adjuvanted and seasonal virosomal-adjuvanted influenza vaccines than healthy controls. The simultaneous administration of the two vaccines seems to increase immune response to both pandemic and seasonal A/H1N1 and A/H3N2 antigens, and has the same safety profile as that of the pandemic vaccine administered sequentially to the seasonal vaccine.


title: Influenza Virus Research and Eu Export Regulations: Publication, Proliferation, and Pandemic Risks

text: An influenza pandemic would be a global health emergency, and laboratory-based research on influenza viruses is an important component of worldwide efforts to prevent and prepare for this. There are concerns, however, that publishing the findings of such research might sometimes increase the risk of a pandemic caused by a laboratory accident or the deliberate release of a deadly virus. This article addresses the challenge of governing scientific information sharing, with regard to public health benefits and risks, from an export-control perspective. The discussion focuses on research findings produced in 2011 by a team of influenza virologists in the Netherlands, and on the Dutch Government’s unprecedented decision to regard the intended publication of these findings as being subject to European Union regulations on the export of ‘dual-use’ items. I argue that, when a government is uncertain about whether the benefits of publishing particular research findings in a scientific journal outweigh the risks, a process of selectively disseminating those findings should be available as an alternative to official censorship.


title: The Global Threat of Animal Influenza Viruses of Zoonotic Concern: Then and Now

text: Animal influenza viruses can reassort or mutate to infect and spread sustainably among people and cause a devastating worldwide pandemic. Since the first evidence of human infection with an animal influenza virus, in 1958, 16 different novel, zoonotic influenza A virus subtype groups in 29 countries, Taiwan, and Hong Kong have caused human infections, with differing severity and frequency. The frequency of novel influenza virus detection is increasing, and human infections with influenza A(H5N1) and A(H7N9) viruses are now annual seasonal occurrences in Asia. The study of the epidemiology and virology of animal influenza viruses is key to understanding pandemic risk and informing preparedness. This supplement brings together select recent articles that look at the risk of emergence and transmission of and approaches to prevent novel influenza virus infections.


title: Serum Samples From Middle-aged Adults Vaccinated Annually with Seasonal Influenza Vaccines Cross-neutralize Some Potential Pandemic Influenza Viruses

text: We examined serum samples from adults ages 48–64 who received multiple seasonal influenza vaccines from 2004 to 2009 for cross-neutralizing antibodies to potential pandemic strains. Using pseudoviruses bearing various hemagglutinins (HA-pseudoviruses), we found serum neutralization titers (≥160) in 100% against A/Japan/305/1957 (H2N2), 53% against A/Hong Kong/1073/99 (H9N2), 56% against the H3N2 variant A/Indiana/08/11 (H3N2v), 11% against A/Hong Kong/G9/97 (H9N2), and 36% A/chicken/Hong Kong/SF4/01 (H6N1). None had titers >160 to A/Shanghai/2/13 (H7N9) or A/Netherlands/219/03 (H7N7). Thirty-six percent to 0% had neutralization titers to various H5N1 strains. Titers to H9, H6, and H5 HA-pseudoviruses correlated with each other, but not with H3N2v, suggesting group-specific cross-neutralization.


docid: naezfola

title: Infectious Diseases Society of America and Gain-of-Function Experiments With Pathogens Having Pandemic Potential


Response to Malkovsky


The Beneficial Effects of Neuraminidase Inhibitor Drug Therapy on Severe Patient Outcomes During the 2009–2010 Influenza A Virus Subtype H1N1 Pandemic


title: Neuraminidase Inhibitors and Hospital Length of Stay: A Meta-analysis of Individual Participant Data to Determine Treatment Effectiveness Among Patients Hospitalized With Nonfatal 2009 Pandemic Influenza A(H1N1) Virus Infection

text: BACKGROUND: The effect of neuraminidase inhibitor (NAI) treatment on length of stay (LoS) in patients hospitalized with influenza is unclear. METHODS: We conducted a one-stage individual participant data (IPD) meta-analysis exploring the association between NAI treatment and LoS in patients hospitalized with 2009 influenza A(H1N1) virus (A[H1N1]pdm09) infection. Using mixed-effects negative binomial regression and adjusting for the propensity to receive NAI, antibiotic, and corticosteroid treatment, we calculated incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Patients with a LoS of <1 day and those who died while hospitalized were excluded. RESULTS: We analyzed data on 18 309 patients from 70 clinical centers. After adjustment, NAI treatment initiated at hospitalization was associated with a 19% reduction in the LoS among patients with clinically suspected or laboratory-confirmed influenza A(H1N1)pdm09 infection (IRR, 0.81; 95% CI, .78–.85), compared with later or no initiation of NAI treatment. Similar statistically significant associations were seen in all clinical subgroups. NAI treatment (at any time), compared with no NAI treatment, and NAI treatment initiated <2 days after symptom onset, compared with later or no initiation of NAI treatment, showed mixed patterns of association with the LoS. CONCLUSIONS: When patients hospitalized with influenza are treated with NAIs, treatment initiated on admission, regardless of time since symptom onset, is associated with a reduced LoS, compared with later or no initiation of treatment.


title: Waiting for the Flu: Cognitive Inertia and the Spanish Influenza Pandemic of 1918–19

text: This study looks at public awareness and understanding of the Spanish flu in the United States between June 1918, when the flu became “Spanish,” and the end of September when the deadly second wave reached the majority of the country. Based on an extensive reading of local newspapers, it finds a near universal lack of preparation or panic or other signs of personal concern among those in the unaffected areas, despite extensive and potentially worrying coverage of the flu's progress. The normal reaction to news of the inexorable approach of a pandemic of uncertain virulence is anxiety and action. The Spanish flu produced neither in the uninfected areas for a month. The most likely reason appears to be cognitive inertia—the tendency of existing beliefs or habits of thought to blind people to changed realities. This inertia grew out of the widespread understanding of flu as a seasonal visitor that while frequently unpleasant almost never killed the strong and otherwise healthy. This view of the flu was powerful enough that it blinded many in the unaffected regions to the threat for weeks even in the face of daily or near daily coverage of the pandemic's spread.


Priming for Pandemic Influenza: Thanks for the Memories


title: WHO Knows Best? National and International Responses to Pandemic Threats and the “Lessons” of 1976

text: The discovery of a novel influenza strain at Fort Dix, New Jersey, in 1976—dubbed Swine Flu—prompted differing responses from national and international health organizations. The United States crafted a vaccination campaign to inoculate every citizen; conversely, the World Health Organization (WHO) recommended a ‘wait and see’ policy. An examination of the WHO conference that issued the influenza policy reveals the decision was driven by the limits of its member states' ability to produce inactivated vaccine and concern over the premature use of unstable live-virus vaccines. The WHO recommendation's reliance upon an uneven surveillance system would have replicated the 1957 and 1968 vaccination failures if a pandemic had appeared.


Survey of Human Antibody Responses to Influenza Virus Matrix Protein 2 by Use of a Sensitive Flow Cytometric Method


title: Perceived usefulness of syndromic surveillance in Ontario during the H1N1 pandemic

text: BACKGROUND: Despite the growing popularity of syndromic surveillance, little is known about if or how these systems are accepted, utilized and valued by end users. This study seeks to describe the use of syndromic surveillance systems in Ontario and users' perceptions of the value of these systems within the context of other surveillance systems. METHODS: Ontario's 36 public health units, the provincial ministry of health and federal public health agency completed a web survey to identify traditional and syndromic surveillance systems used routinely and during the pandemic and to describe system attributes and utility in monitoring pandemic activity and informing decision-making. RESULTS: Syndromic surveillance systems are used by 20/38 (53%) organizations. For routine surveillance, laboratory, integrated Public Health Information System and school absenteeism data are the most frequently used sources. Laboratory data received the highest ratings for reliability, timeliness and accuracy (‘very acceptable’ by 92, 51 and 89%). Hospital/clinic screening data were rated as the most reliable and timely syndromic data source (50 and 43%) and ED visit data the most accurate (48%). During the pandemic, laboratory data were considered the most useful for monitoring the epidemiology and informing decision-making while ED screening and visit data were considered the most useful syndromic sources. CONCLUSIONS: End user perceptions are valuable for identifying opportunities for improvement and guiding further investments in public health surveillance.


docid: hcyluzkx

title: Antibody Response to Influenza A(H1N1)pdm09 Among Healthcare Personnel Receiving Trivalent Inactivated Vaccine: Effect of Prior Monovalent Inactivated Vaccine

text: Background. Few data are available on the immunogenicity of repeated annual doses of influenza A(H1N1)pdm09-containing vaccines. Methods. We enrolled healthcare personnel (HCP) in direct patient care during the autumn of 2010 at 2 centers with voluntary immunization. We verified the receipt of A(H1N1)pdm09-containing monovalent inactivated influenza vaccine (MIIV) and 2010–2011 trivalent inactivated vaccine (TIV). We performed hemagglutination inhibition antibody (HI) assays on preseason, post-TIV, and end-of-season serum samples. We compared the proportion of HCPs with HI titer ≥40 against A(H1N1)pdm09 per receipt of prior-season MIIV, current-season TIV, both, or neither. Results. At preseason (n = 1417), HI ≥ 40 was significantly higher among those who received MIIV (34%) vs those who did not (14%) (adjusted relative risk [ARR], 3.26; 95% confidence interval [CI], 2.72–3.81). At post-TIV (n = 865), HI ≥ 40 was lower among HCP who received MIIV and TIV (66%) than among those receiving only TIV (85%) (ARR, 0.93 [95% CI, .84–.997]). At end-of-season (n = 1254), HI ≥ 40 was 40% among those who received both MIIV and TIV and 67% among those receiving only TIV (ARR, 0.76 [95% CI, .65–.88]), 52% among those who received MIIV only, and 12% among those receiving neither. Conclusions. HCP immunization programs should consider effects of host immune response and vaccine antigenic distance on immunogenicity of repeated annual doses of influenza vaccines.


title: Pandemic controllability: a concept to guide a proportionate and flexible operational response to future influenza pandemics

text: The 2009 H1N1 influenza pandemic posed challenges for governments worldwide. Strategies designed to limit community transmission, such as antiviral deployment, were largely ineffective due to both feasibility constraints and the generally mild nature of disease, resulting in incomplete case ascertainment. Reviews of national pandemic plans have identified pandemic impact, primarily linked to measures of transmissibility and severity, as a key concept to incorporate into the next generation of plans. While an assessment of impact provides the rationale under which interventions may be warranted, it does not directly provide an assessment on whether particular interventions may be effective. Such considerations motivate our introduction of the concept of pandemic controllability. For case-targeted interventions, such as antiviral treatment and post-exposure prophylaxis, we identify the visibility and transmissibility of a pandemic as the key drivers of controllability. Taking a case-study approach, we suggest that high-impact pandemics, for which control is most desirable, are likely uncontrollable with case-targeted interventions. Strategies that do not rely on the identification of cases may prove relatively more effective. By introducing a pragmatic framework for relating the assessment of impact to the ability to mitigate an epidemic (controllability), we hope to address a present omission identified in pandemic response plans.


How Live Attenuated Vaccines Can Inform the Development of Broadly Cross-Protective Influenza Vaccines


Influenza A(H5N1) Vaccines: Are We Better Prepared for the Next Pandemic?


title: Virological self-sampling to monitor influenza antiviral susceptibility in a community cohort

text: OBJECTIVE: To perform antiviral susceptibility monitoring of treated individuals in the community during the 2009 influenza A(H1N1) pandemic in England. PATIENTS AND METHODS: Between 200 and 400 patients were enrolled daily through the National Pandemic Flu Service (NPFS) and issued with a self-sampling kit. Initially, only persons aged 16 and over were eligible, but from 12 November (week 45), self-sampling was extended to include school-age children (5 years and older). All samples received were screened for influenza A(H1N1)pdm09 as well as seasonal influenza [A(H1N1), A(H3N2) and influenza B] by a combination of RT–PCR and virus isolation methods. Influenza A(H1N1)pdm09 RT–PCR-positive samples were screened for the oseltamivir resistance-inducing H275Y substitution, and a subset of samples also underwent phenotypic antiviral susceptibility testing by enzyme inhibition assay. RESULTS: We were able to detect virus by RT–PCR in self-taken samples and recovered infectious virus enabling further virological characterization. The majority of influenza A(H1N1)pdm09 RT–PCR-positive NPFS samples (n = 1273) were taken after oseltamivir treatment had begun. No reduction in phenotypic susceptibility to neuraminidase inhibitors was detected, but five cases with minority quasi-species of oseltamivir-resistant virus (an H275Y amino acid substitution in neuraminidase) were detected. CONCLUSIONS: Self-sampling is a useful tool for community surveillance, particularly for the follow-up of drug-treated patients. The virological study of self-taken samples from the NPFS provided a unique opportunity to evaluate the emergence of oseltamivir resistance in treated individuals with mild illness in the community, a target population that may not be captured by traditional sentinel surveillance schemes.


title: Pandemic influenza preparedness in Latin America: analysis of national strategic plans

text: The threat of a human pandemic of influenza has prompted the development of national influenza pandemic preparedness plans over the last 4 years. Analyses have been carried out to assess preparedness in Europe, Asia and Africa. We assessed plans to evaluate the national strategic pandemic influenza preparedness in the countries of Latin America. Published national pandemic influenza preparedness plans from Latin American countries were evaluated against criteria drawn from the World Health Organization checklist. Plans were eligible for inclusion if formally published before 16 November 2007. Fifteen national plans were identified and retrieved from the 17 Latin American countries surveyed. Latin American countries demonstrated different degrees of preparedness, and that a high level of completeness of plans was correlated to a country's wealth to a certain extent. Plans were judged strong in addressing surveillance requirements, and provided appropriate communication strategies directed to the general public and health care personnel. However, gaps remained, including the organization of health care services’ response; planning and maintenance of essential services; and the provision of containment measures such as the stockpiling of necessary medical supplies including vaccines and antiviral medications. In addition, some inconsistencies and variations which may be important, such as in border control measures and the capacity to contain outbreaks, exist between country plans—issues that could result in confusion in the event of a pandemic. A number of plans remain developmental in nature and, as elsewhere, more emphasis should be placed on strengthening the operability of plans, and in testing them. Whilst taking account of resources constraints, plans should be further developed in a coherent manner with both regional and international imperatives.


HRS/EHRA/APHRS/LAHRS/ACC/AHA worldwide practice update for telehealth and arrhythmia monitoring during and after a pandemic


title: Encephalitis after influenza and vaccination: a nationwide population-based registry study from Norway

text: BACKGROUND: Influenza is known to be associated with various neurological complications, including encephalitis. We conducted a registry-based study to assess the risk of encephalitis after influenza and A(H1N1)pdm09 vaccine. METHODS: Data from Norwegian national health registries during 2008–14 were linked using the unique personal identifiers given to all Norwegian residents (N = 5 210 519). Cox proportional-hazard models with time-varying variables were fitted to estimate hazard ratios (HRs) of encephalitis after influenza and A(H1N1)pdm09 vaccine, using the risk windows 0–7, 0–14, 0–30, 0–60, 0–90 and 0–180 days. RESULTS: In Norway, 684 172 individuals received an influenza diagnosis and 2793 patients were hospitalized with encephalitis during 2008–14. The risk of encephalitis increased after influenza: HR, 7-day risk window: 47.8 (95% confidence interval (CI): 35.8–63.8), and the HR decreased for longer risk windows; HR, 180-day risk window: 3.8 (95% CI: 3.1–4.7). HR of encephalitis after influenza during the 2009 main pandemic wave using a 7-day risk window was 30.0 (95% CI: 10.8–83.2). We found no differences in the risk of encephalitis after the seasonal influenza compared with influenza during the 2009 main pandemic wave; HR, 7-day risk window: 1.3 (95% CI: 0.4–4.3). A(H1N1)pdm09 vaccine was not associated with the risk of encephalitis: HR, 14-day risk window: 0.6 (95% CI: 0.2–2.1). CONCLUSIONS: There was an increased risk of encephalitis following influenza but not after A(H1N1)pdm09 vaccine. The risk of encephalitis was highest in the first few weeks after influenza.


title: Pandemic influenza preparedness in Africa is a profound challenge for an already distressed region: analysis of national preparedness plans

text: A new highly pathogenic strain of influenza virus, H5N1, has emerged causing severe outbreaks in poultry and high mortality rates when humans are infected. The threat of a new influenza pandemic has prompted countries to draft national strategic preparedness plans to prevent, contain and mitigate the next human influenza pandemic. To evaluate preparedness for an influenza pandemic in the African region we analysed African national preparedness plans available in the public domain. A data extraction tool, based on a World Health Organization checklist for influenza epidemic preparedness, was designed in consultation with pandemic influenza planning experts and experts on the region's public health challenges. Thirty-five plans were identified and available from 53 African countries. Most plans are relatively robust in addressing detection and containment of influenza in animals but strategic preparedness to respond to pandemic human influenza is weak. In most plans communication strategies have been developed with the aim to raise awareness of transmission factors and promote hygiene measures. By contrast, the human health care sector is ill-prepared. Case management, triage procedures, identification of health care facilities for patient treatment (including home care and provisions for the distribution and administration of pharmaceuticals) are poorly addressed by most plans. The maintenance of essential services in the event of a pandemic is absent from most plans. Whilst many African countries have strategic pandemic influenza preparedness plans, most are developmental in nature and lack operational clarity, or focus principally on the containment of avian influenza rather than pandemic human influenza. Clear strategies, that are operational, need to be developed that reflect the realities of national context and resource constraints and that meet national objectives. These objectives need also to be coherent with international imperatives such that the global threat of pandemic influenza can be met effectively and efficiently.


title: Avian and pandemic human influenza policy in South-East Asia: the interface between economic and public health imperatives

text: The aim of this study was to analyse the contemporary policies regarding avian and human pandemic influenza control in three South-East Asia countries: Thailand, Indonesia and Vietnam. An analysis of poultry vaccination policy was used to explore the broader policy of influenza A H5N1 control in the region. The policy of antiviral stockpiling with oseltamivir, a scarce regional resource, was used to explore human pandemic influenza preparedness policy. Several policy analysis theories were applied to analyse the debate on the use of vaccination for poultry and stockpiling of antiviral drugs in each country case study. We conducted a comparative analysis across emergent themes. The study found that whilst Indonesia and Vietnam introduced poultry vaccination programmes, Thailand rejected this policy approach. By contrast, all three countries adopted similar strategic policies for antiviral stockpiling in preparation. In relation to highly pathogenic avian influenza, economic imperatives are of critical importance. Whilst Thailand's poultry industry is large and principally an export economy, Vietnam's and Indonesia's are for domestic consumption. The introduction of a poultry vaccination policy in Thailand would have threatened its potential to trade and had a major impact on its economy. Powerful domestic stakeholders in Vietnam and Indonesia, by contrast, were concerned less about international trade and more about maintaining a healthy domestic poultry population. Evidence on vaccination was drawn upon differently depending upon strategic economic positioning either to support or oppose the policy. With influenza A H5N1 endemic in some countries of the region, these policy differences raise questions around regional coherence of policies and the pursuit of an agreed overarching goal, be that eradication or mitigation. Moreover, whilst economic imperatives have been critically important in guiding policy formulation in the agriculture sector, questions arise regarding whether agriculture sectoral policy is coherent with public health sectoral policy across the region.


Influenza: interspecies transmission and emergence of new pandemics


Detection of VIM-34, a novel VIM-1 variant identified in the intercontinental ST15 Klebsiella pneumoniae clone


title: Bacteriophage Therapy of a Vibrio parahaemolyticus Infection Caused by a Multiple-Antibiotic–Resistant O3:K6 Pandemic Clinical Strain

text: Background. Recently isolated Vibrio parahaemolyticus strains have displayed multiple antibiotic resistance. Alternatives to conventional antibiotics are needed, especially for the multiple-antibiotic–resistant V. parahaemolyticus pandemic strain. Methods. A bacteriophage, designated pVp-1, showed effective infectivity for multiple-antibiotic–resistant V. parahaemolyticus and V. vulnificus, including V. parahaemolyticus pandemic strains. The therapeutic potential of the phage was studied in a mouse model of experimental infection using a multiple-antibiotic–resistant V. parahaemolyticus pandemic strain. We monitored the survivability and histopathological changes, quantified the bacterial and phage titers during phage therapy, and observed the immune response induced by phage induction. Results. Phage-treated mice displayed protection from a V. parahaemolyticus infection and survived lethal oral and intraperitoneal bacterial challenges. Conclusions. To the best of our knowledge, this is the first report of phage therapy in a mouse model against a multiple-antibiotic–resistant V. parahaemolyticus pandemic strain infection.


title: Influenza-like illness in Norway: clinical course, attitudes towards vaccination and preventive measures during the 2009 pandemic

text: Objectives. To document clinical characteristics of influenza-like illness, reported use of health preventive measures and attitudes towards vaccination among patients with influenza-like illness in general practice during the influenza pandemic in 2009. Methods. Cross-sectional survey in general practice. Patients, who were identified as having influenza-like illness during the peak of the influenza pandemic activity in Norway, were eligible for inclusion in the study. A questionnaire was sent 2–4 weeks after the patients visit to the GP with influenza-like illness diagnosis during October to December 2009, from general practices in Norway. A sample of responders >18 years also had a blood test to check for serological response to the pandemic H1N1 virus. Results. Questionnaires were sent to 1324 patients, and 357 (27%) were returned. Fever (91% versus 49%, P < 0.01), cough (85% versus 73%, P = 0.016) and gastrointestinal symptoms (58% versus 38%, P < 0.01) were more frequent in the age group <18 years compared to older patients. Serological H1N1 responses were analysed in 72 patients; 34 (47%) were positive (haemagglutination inhibition assay titres ≥40). There were no statistically significant differences in symptoms between seropositive and seronegative patients. Women reported better adherence to personal protective measures, such as hand washing and cough etiquette than men. Women were also more concerned about possible adverse effects of the pandemic influenza vaccine than men. Conclusions. Discrimination between influenza and other viral upper respiratory tract infections is difficult in daily clinical practice, even during an influenza pandemic. A gender difference was found in reported precautions to prevent influenza.


title: Lessons from Pandemic H1N1 2009 to Improve Prevention, Detection, and Response to Influenza Pandemics from a One Health Perspective

text: In April 2009, a novel influenza A subtype H1N1 triple reassortant virus (novel H1N1 2009), composed of genes from swine, avian, and human influenza A viruses, emerged in humans in the United States and Mexico and spread person-to-person around the world to become the first influenza pandemic of the 21(st) century. The virus is believed to have emerged from a reassortment event involving a swine virus some time in the past 10 to 20 years, but pigs, pork, and pork products have not been involved with infection or spread of the virus to or among people. Because countries quickly implemented recently developed pandemic influenza plans, the disease was detected and reported and public health authorities instituted control measures in a timely fashion. But the news media's unfortunate and inappropriate naming of the disease as the “swine flu” led to a drop in the demand for pork and several countries banned pork imports from affected countries, resulting in serious negative economic impacts on the pork industry. With the continual circulation and interspecies transmission of human, swine, and avian influenza viruses in countries around the world, there are calls for strengthening influenza surveillance in pigs, birds, and other animals to aid in monitoring and assessing the risk of future pandemic virus emergence involving different species. We identify and discuss several lessons to be learned from pandemic H1N1 2009 from a One Health perspective, as stronger collaboration among human, animal, and environmental health sectors is necessary to more effectively prevent or detect and respond to influenza pandemics and thus improve human, animal, and environmental health and well-being.


title: Why did many more diamond miners than gold miners die in South Africa during the 1918 influenza pandemic?

text: The very large difference in mortality rates between Kimberley diamond miners and Witwatersrand gold miners during the 1918 influenza pandemic has never been explained. We examined extant epidemiological records from South African mining operations and other related activities to determine if mortality risk factors could be measured. During October 1918 when pandemic influenza struck in South Africa, the mortality rates in Kimberley diamond miners (22.4%, n = 11 445) were >35 times that of Rand gold miners (0.6%, n = 200 000). There were no differences discernable between diamond and gold miners regarding their recruitment, working conditions, housing or medical care that would explain the great variance in mortality rates. Reports of influenza-like illness in Natal Province some weeks prior to the main pandemic suggest infection from a mild version of influenza and thus protection of the gold miners from mortality whereas the more isolated diamond miners only experienced the second, more lethal, wave. The huge mortality difference between South African diamond and gold miners in 1918 is most likely explained by the circulation of a related but not identical virus to the A/H1N1 pandemic strain which reached Johannesburg prior to October 1918 because of its better transportation connections.


title: Five years of non-prescription oseltamivir: effects on resistance, immunization and stockpiling

text: OBJECTIVES: In 2007 New Zealand (NZ) became the first country to make oseltamivir (Tamiflu®) available off-prescription. This study investigated the extent of pharmacist supply of oseltamivir over 5 years, including during the influenza A(H1N1) pandemic, and the impact of pharmacist supply of oseltamivir on influenza virus oseltamivir susceptibility, personal stockpiling and influenza vaccine uptake. METHODS: Randomly selected community pharmacies in NZ reported oseltamivir provision by prescription and through pharmacist supply from 1 January 2007 to 15 September 2011. Oseltamivir resistance data on influenza viruses isolated during influenza surveillance from 2008 to 2011 were obtained, along with influenza vaccine uptake data from 2005 to 2011 and influenza detection data. RESULTS: Seventy of 85 eligible pharmacies completed the study (82% response rate). Most supplies of oseltamivir throughout the 5 years were dispensed against a prescription rather than pharmacist supplied, with pharmacist supply responsible for 11% of supplies during the pandemic years (2009–10) versus 27% and 31% during 2007 and 2008, respectively. Pharmacist-supplied oseltamivir did not appear to be associated with the development of resistance, with identified likely stockpiling or with a decline in influenza immunization. Pharmacist supplies largely matched the timing of influenza in the community and peaked in June 2009, as did prescription supplies. CONCLUSIONS: Five years of non-prescription oseltamivir in NZ has resulted in no significant change in the development of resistance or rates of influenza immunization. Supplies remained modest and significant consumer stockpiling through pharmacist supply has not occurred, even during the influenza A(H1N1)pdm09 pandemic in 2009 and 2010. Pharmacists could be better utilized in ensuring fast distribution of antivirals to influenza sufferers during a pandemic.


title: Factors in vaccination intention against the pandemic influenza A/H1N1

text: Background: Vaccination against pandemic influenza A/H1N1 is an effective strategy to mitigate the spread of the disease. While the vaccine is now available, social acceptance remains relatively uncertain in many societies. The purpose of this study was to examine the beliefs, attitudes and practices associated with the intention to get vaccinated against the A/H1N1 virus among the general population in France. Methods: A representative sample of 1001 individuals (stratified random recruitment procedure, ages 16–90 years) was interviewed by telephone. The questionnaire included a variety of items associated with socio-demographic characteristics, risk perceptions, illness perceptions, political attitudes and worldviews as well as intention to get vaccinated. Results: More than 6 out of 10 of the respondents indicated that they planned to get vaccinated when the vaccine becomes available. The same proportion of parents also reported the intention to vaccinate their children against the disease. In multiple regression analyses, socio-cognitive factors consistently predicting influenza A/H1N1 vaccination were: level of worry, risk perception and previous experience of vaccine against seasonal flu. Conclusions: The factors found to predict vaccination intention and their distribution are assumed to be a consequence of the fact that people perceive the risk of swine flu to be similar to that of seasonal flu. As a result, in the absence of an increase of the risk perception of pandemic influenza A/H1N1, a very low level of actual vaccination is forecasted. Behavioural change would require that the risks and consequences of pandemic influenza A/H1N1 be perceived as highly different from seasonal flu.


docid: vqwstvek

title: Evaluating the effectiveness of antiviral treatment in models for influenza pandemic

text: We study the effectiveness of antiviral treatment in simple susceptible–exposed–infectious–removed models that are at the base of models used for influenza pandemic. The strategy is assessed in terms of the value of the reproductive ratio R(0). We consider a general framework and analyse six different specific cases. The same antiviral strategy is simulated in all models, but they slightly differ in the compartmental structure. These differences correspond to different underlying assumptions concerning the timing of the intervention and the selection of individuals who receive treatment. It is shown that these details can have a strong influence on the predicted effectiveness of the strategy: for instance, with R(0) = 1.8 in absence of treatment, different models predict that with treatment R(0) can become as low as 0.4 or as high as 1.3; still, in all models 70% of infected individuals are treated and the infectiousness of treated individuals is reduced by 80%. A particular assumption that can be included when modelling influenza is time-varying infectivity. We consider a specific model to verify if the predicted effectiveness of antiviral treatment is influenced by the inclusion of this assumption. We compare the results obtained with constant and variable infectivity, in relation also to the time of intervention. It is likely that existing differences in the predictions of the effect of control measures depend on such modelling details. This finding stresses the need for carefully defining the structure of models in order to obtain results useful for policymakers in pandemic planning.


Thoracic surgeons’ insights: Improving thoracic surgery outcomes during the Coronavirus Disease 2019 pandemic


Editorial Commentary: Flying Under the Radar: The Stealth Pandemic of Escherichia coli Sequence Type 131


Tuberculosis Healthcare Workers: There Goes My Hero


title: Using Results From Infectious Disease Modeling to Improve the Response to a Potential H7N9 Influenza Pandemic

text: As the Centers for Disease Control and Prevention (CDC) and other government agencies prepared for a possible H7N9 pandemic, many questions arose about the virus's expected burden and the effectiveness of key interventions. Public health decision makers need information to compare interventions so that efforts can be focused on interventions most likely to have the greatest impact on morbidity and mortality. To guide decision making, CDC's pandemic response leadership turned to experts in modeling for assistance. H7N9 modeling results provided a quantitative estimate of the impact of different interventions and emphasized the importance of key assumptions. In addition, these H7N9 modeling efforts highlighted the need for modelers to work closely with investigators collecting data so that model assumptions can be adjusted as new information becomes available and with decision makers to ensure that the results of modeling impact policy decisions.


title: Seasonal Influenza Vaccine Impact on Pandemic H1N1 Vaccine Efficacy

text: BACKGROUND: In 2009, a novel influenza A (pH1N1) was identified, resulting in a pandemic with significant morbidity and mortality. A monovalent pH1N1 vaccine was separately produced in addition to the seasonal trivalent influenza vaccine. Formulation of the seasonal influenza vaccine (injectable trivalent inactivated influenza vaccine [TIV] vs. intranasal live, attenuated influenza vaccine [LAIV]) was postulated to have impacted the efficacy of the pH1N1 vaccination. METHODS: We reviewed electronic health and databases, which included vaccination records, and healthcare encounters for influenza-like illness (ILI), influenza, and pneumonia among US military members. We examined rates by vaccination type to identify factors associated with the risk for study outcomes. RESULTS: Compared with those receiving the seasonal influenza vaccine alone, subjects receiving the pH1N1 vaccine, either alone (RR, 0.49) or in addition to the seasonal vaccine (RR, 0.51), had an approximately 50% reduction in ILI, 88% reduction in influenza (RR, 0.11 and 0.12, respectively), and 63% reduction in pneumonia (RR, 0.37 and 0.35, respectively). There was no clinically significant difference in ILI, influenza, or pneumonia attack rates among those receiving the pH1N1 vaccine with or without presence of the seasonal vaccine. Similarly, there was no clinically relevant difference in pH1N1 effectiveness between seasonal TIV and LAIV recipients. CONCLUSIONS: During the 2009–2010 pandemic, the pH1N1 vaccination was effective in reducing rates of ILI, influenza, and pneumonia. Administration of the seasonal vaccine should continue without concern of potential interference with a novel pandemic vaccine, though more studies are needed to determine if this is applicable to other influenza seasons.


title: How Will Physicians Respond to the Next Influenza Pandemic?

text: The emergence of the H7N9 virus in China is another reminder of the threat of a global influenza pandemic. Many believe we could confront a pandemic by expanding our capacity to provide timely supplies of affordable pandemic vaccines and antiviral agents. Experience in 2009 demonstrated that this cannot and will not be done. Consequently, physicians may have little more to offer their patients than they had in the 1918 pandemic. Fortunately, several modern drugs (eg, statins, angiotensin II receptor blockers, angiotensin-converting enzyme inhibitors) can modify the host response to inflammatory illness, and laboratory and clinical studies suggest they might be used to treat pandemic patients. Unfortunately, little attention has been given to the research needed to support their use in patient care. There is no guarantee these drugs will work, but physicians will never know unless those responsible for pandemic preparedness recognize and act on the extraordinary possibility that they might save lives.


title: Ebola in Antiquity?

text: This article addresses whether Ebola may have been present in an urban setting in Athens in 430 bce and explores the historical importance of the ancient outbreak. New knowledge from today's West African epidemic allows a more accurate assessment of whether Ebola may have caused the Athenian outbreak than was once possible. The Athenian disease, whose etiology remains unknown, developed abruptly with fevers, abdominal pain, vomiting, diarrhea, dehydration, and hemorrhage. It originated in sub-Saharan Africa and was especially contagious to doctors and caregivers. No remedies were effective. But the few survivors who were reexposed to diseased patients were not attacked a second time, suggesting protective immunity. What lessons can we learn from the ancient outbreak that bears a clinical and epidemiologic resemblance to Ebola? The historian Thucydides, an eyewitness and disease sufferer, described how the unsuspecting city panicked as it struggled to handle the rapidly spreading, devastating disease. Moreover, he stressed a theme that has relevance today—namely, that fear and panic intensified the disruption of society and damage to the individual that was directly caused by the disease. Moreover, fear amplified the spread of disease. The destructive nature of fear has remained a signature feature of pestilences that have subsequently caught ill-prepared societies off-guard—Bubonic plague in medieval times, AIDS in the 1980s, and Ebola today. The ancient Athenian epidemic is relevant for today's West African Ebola outbreak because it shows how fear and panic can endanger the individual, our society, and our efforts to handle the disease.


docid: dbdtpojs

title: Effectiveness of Nonadjuvanted Monovalent Influenza A(H1N1)pdm09 Vaccines for Preventing Reverse Transcription Polymerase Chain Reaction–Confirmed Pandemic Influenza Hospitalizations: Case-Control Study of Children and Adults at 10 US Influenza Surveillance Network Sites

text: During 2009–2010, we examined 217 patients hospitalized with laboratory-confirmed pandemic influenza in 9 Influenza Hospitalization Surveillance Network sites and 413 age- and community-matched controls and found that a single dose of monovalent nonadjuvanted influenza A(H1N1)pdm09 vaccine was 50% (95% confidence interval, 13%–71%) effective in preventing hospitalization associated with A(H1N1)pdm09 virus infection.


title: Readiness for Responding to a Severe Pandemic 100 Years After 1918

text: The 1918 H1N1 pandemic caused an unprecedented number of deaths worldwide. The tools to deal with the global emergency were limited; there were insufficient surveillance systems and a dearth of diagnostic, treatment, and prevention options. With continuing focus on pandemic planning, technologic advances in surveillance, vaccine capabilities, and 21st century medical care and countermeasures, we are more prepared for a severe pandemic than people were 100 years ago; however, notable gaps remain.


Editorial Commentary: Is Prepandemic Vaccination a Wise Investment?


title: Investing in Immunity: Prepandemic Immunization to Combat Future Influenza Pandemics

text: We are unlikely, with current technologies, to have sufficient pandemic influenza vaccine ready in time to impact the first wave of the next pandemic. Emerging data show that prior immunization with an immunologically distinct hemagglutinin of the same subtype offers the potential to “prime” recipients for rapid protection with a booster dose, years later, of a vaccine then manufactured to match the pandemic strain. This article proposes making prepandemic priming vaccine(s) available for voluntary use, particularly to those at high risk of early occupational exposure, such as first responders and healthcare workers, and to others maintaining critical infrastructure. In addition to providing faster protection and potentially reducing social disruption, being able, early in a pandemic, to immunize those who had received prepandemic vaccine with one dose of the pandemic vaccine, rather than the 2 doses typically required, would reduce the total doses of pandemic vaccine then needed, extending vaccine supplies.


title: Reassessing the Global Mortality Burden of the 1918 Influenza Pandemic

text: Mortality estimates of the 1918 influenza pandemic vary considerably, and recent estimates have suggested that there were 50 million to 100 million deaths worldwide. We investigated the global mortality burden using an indirect estimation approach and 2 publicly available data sets: the Human Mortality Database (13 countries) and data extracted from the records of the Statistical Abstract for British India. The all-cause Human Mortality Database was used to estimate mortality annually for 1916–1921 for detailed age groups. Three different calculation methods were applied to the data (low, medium, and high scenarios), and we used a multilevel regression model to control for distorting factors (e.g., war and the underlying time trend in mortality). Total pandemic mortality was an estimated 15 million deaths worldwide in 1918 (n = 2.5 million in 1919) after including the rates for British India and controlling for wars and the underlying mortality trend. According to our validity analysis, simulations of total number of deaths being greater than 25 million are not realistic based on the underlying mortality rates included in Human Mortality Database and in British India. Our results suggest the global death impact of the 1918 pandemic was important (n = 17.4 million) but not as severe as most frequently cited estimates.


docid: jolhivgh

title: Accelerating Education During COVID-19 Through Virtual Learning


docid: mdewdbqs

title: Potential Demand for Respirators and Surgical Masks During a Hypothetical Influenza Pandemic in the United States

text: Background. To inform planning for an influenza pandemic, we estimated US demand for N95 filtering facepiece respirators (respirators) by healthcare and emergency services personnel and need for surgical masks by pandemic patients seeking care. Methods. We used a spreadsheet-based model to estimate demand for 3 scenarios of respirator use: base case (usage approximately follows epidemic curve), intermediate demand (usage rises to epidemic peak and then remains constant), and maximum demand (all healthcare workers use respirators from pandemic onset). We assumed that in the base case scenario, up to 16 respirators would be required per day per intensive care unit patient and 8 per day per general ward patient. Outpatient healthcare workers and emergency services personnel would require 4 respirators per day. Patients would require 1.2 surgical masks per day. Results and Conclusions. Assuming that 20% to 30% of the population would become ill, 1.7 to 3.5 billion respirators would be needed in the base case scenario, 2.6 to 4.3 billion in the intermediate demand scenario, and up to 7.3 billion in the maximum demand scenario (for all scenarios, between 0.1 and 0.4 billion surgical masks would be required for patients). For pandemics with a lower attack rate and fewer cases (eg, 2009-like pandemic), the number of respirators needed would be higher because the pandemic would have longer duration. Providing these numbers of respirators and surgical masks represents a logistic challenge for US public health agencies. Public health officials must urgently consider alternative use strategies for respirators and surgical masks during a pandemic that may vary from current practices.


title: Short-Term Birth Sequelae of the 1918–1920 Influenza Pandemic in the United States: State-Level Analysis

text: This paper examines short-term birth sequelae of the influenza pandemic of 1918–1920 in the United States using monthly data on births and all-cause deaths for 19 US states in conjunction with data on maternal deaths, stillbirths, and premature births. The data on births and all-cause deaths are adjusted for seasonal and trend effects, and the residual components of the 2 time series coinciding with the timing of peak influenza mortality are examined for these sequelae. Notable findings include: 1) a drop in births in the 3 months following peak mortality; 2) a reversion in births to normal levels occurring 5–7 months after peak mortality; and 3) a steep drop in births occurring 9–10 months after peak mortality. Interpreted in the context of parallel data showing elevated premature births, stillbirths, and maternal mortality during times of peak influenza mortality, these findings suggest that the main impacts of the 1918–1920 influenza on reproduction occurred through: 1) impaired conceptions, possibly due to effects on fertility and behavioral changes; 2) an increase in the preterm delivery rate during the peak of the pandemic; and 3) elevated maternal and fetal mortality, resulting in late-term losses in pregnancy.


title: Complications Among Adults Hospitalized With Influenza: A Comparison of Seasonal Influenza and the 2009 H1N1 Pandemic

text: Background. Persons with influenza can develop complications that result in hospitalization and death. These are most commonly respiratory related, but cardiovascular or neurologic complications or exacerbations of underlying chronic medical conditions may also occur. Patterns of complications observed during pandemics may differ from typical influenza seasons, and characterizing variations in influenza-related complications can provide a better understanding of the impact of pandemics and guide appropriate clinical management and planning for the future. Methods. Using a population-based surveillance system, we compared clinical complications using International Classification of Diseases, Ninth Revision (ICD-9) discharge diagnosis codes in adults hospitalized with seasonal influenza (n = 5270) or 2009 pandemic influenza A(H1N1) (H1N1pdm09; n = 4962). Results. Adults hospitalized with H1N1pdm09 were younger (median age, 47 years) than those with seasonal influenza (median age, 68 years; P < .01), and differed in the frequency of certain underlying medical conditions. Whereas there was similar risk for many influenza-associated complications, after controlling for age and type of underlying medical condition, adults hospitalized with H1N1pdm09 were more likely to have lower respiratory tract complications, shock/sepsis, and organ failure than those with seasonal influenza. They were also more likely to be admitted to the intensive care unit, require mechanical ventilation, or die. Young adults, in particular, had 2–4 times the risk of severe outcomes from H1N1pdm09 than persons of the same ages with seasonal influenza. Conclusions. Although H1N1pdm09 was thought of as a relatively mild pandemic, these data highlight the impact of the 2009 pandemic on the risk of severe influenza, especially among younger adults, and the impact this virus may continue to have.


title: The Rise of the Current Mortality Pattern of the United States, 1890–1930

text: This article examines how the epidemiologic transition and the reduction of the urban mortality penalty gave rise to the current mortality regime of the United States and demonstrates how the 1918 influenza pandemic signaled its advent. This article approaches those issues through the analysis of urban-rural mortality differentials from 1890 to 1930. Until 1910, infectious diseases dwarfed degenerative diseases in leading causes of death, and generally, the more urban the location was, the higher infectious disease and overall death rates were—a direct relationship. But by 1930, degenerative diseases had eclipsed infectious diseases, and infectious disease mortality had ceased to differ between cities and rural areas. The 1918 influenza pandemic broke out toward the end of these changes, and the larger the city was, the lower influenza and overall death rates were in that year—an inverse relationship. Such gradations characterized a new mortality regime emerging in the late 1910s and foreshadowed urban-rural mortality differentials in 1930 among persons aged 45 years or older, the group whose high rates of degenerative disease death would symbolize that regime. Thus, intertwined changes in the late 19th and early 20th centuries—a shift in leading causes of death from infectious diseases to degenerative diseases and a concomitant shift from a direct relationship to an inverse relationship between urban environment and mortality—produced the current mortality regime of the United States.


Placental Pathology in COVID-19


title: Further Evidence for Bias in Observational Studies of Influenza Vaccine Effectiveness: The 2009 Influenza A(H1N1) Pandemic

text: Preinfluenza periods have been used to test for uncontrolled confounding in studies of influenza vaccine effectiveness, but some authors have claimed that confounding differs in preinfluenza and influenza periods. We tested this claim by comparing estimates of the vaccine-mortality association during the 2009/2010 influenza year, when there was essentially no circulation of seasonal influenza in the United States, and 2007/2008, a typical influenza year. We pooled data on seniors (adults aged ≥65 years) from 7 US managed care organizations that participated in the Vaccine Safety Datalink Project. We defined influenza vaccination, all-cause mortality, and potential confounders from administrative databases. We quantified the vaccine-mortality association using Cox regression. During 2007/2008, the adjusted hazard ratio was 0.44 prior to influenza season, 0.62 during influenza season, and 0.71 after influenza season. A similar pattern was observed during 2009/2010, when any effect of seasonal influenza vaccine observed during all time periods must have resulted from confounding: 0.65 during the autumn, 0.80 during the winter, and 0.84 during the summer. In a year with minimal seasonal influenza, we found no evidence that confounding in autumn preinfluenza periods is qualitatively different from confounding in winter. This supports the use of preinfluenza periods as control time periods in studies of influenza vaccine effectiveness.


title: The 1918–1919 Influenza Pandemic in Portugal: A Regional Analysis of Death Impact

text: Although the impact of deaths occurring during the 1918–1919 influenza pandemic has been assessed in many archeo-epidemiologic studies, detailed estimates are not available for Portugal. We applied negative binomial models to monthly data on respiratory-related and all-cause deaths at the national and district levels from Portugal for 1916–1922. Influenza-related excess mortality was computed as the difference between observed and expected deaths. Poisson regression was used to estimate the association of geographic and sociodemographic factors with excess mortality. Two waves of pandemic influenza—July 1918 to January 1919 and April to May 1919—were identified, for which the excess all-cause death rate was 195.7 per 10,000 persons. All districts of Portugal were affected. The pandemic hit earlier in southeastern districts and the main cities, but excess mortality was highest in the northeast, in line with the high death burden experienced by northern Spanish provinces. During the period of intense excess mortality (fall/winter 1918–1919), population density was negatively associated with pandemic impact. This pattern changed during the March 1919 to June 1920 wave, when excess mortality increased with population density and in northern and western directions. Portuguese islands were less and later affected. Given the geographic heterogeneity evidenced in our study, subnational sociodemographic characteristics and connectivity should be integrated in pandemic preparedness plans.


title: Social Class and Excess Mortality in Sweden During the 1918 Influenza Pandemic

text: Consensus is lacking in the literature about the role of socioeconomic factors on influenza-associated deaths during the 1918 pandemic. Although some scholars have found that social factors were important, others have not. In this study, we analyzed differences in excess mortality by social class in Sweden during the 1918 pandemic. We analyzed individual-level mortality of the entire population aged 30–59 years by combining information from death records with census data on occupation. Social class was measured by an occupation-based class scheme. Excess mortality during the pandemic was measured as the number of deaths relative to the number occurring in the same month the year before. Social class differences in numbers of deaths were modeled using a complementary log-log model that was adjusted for potential confounding at the family, the residential (urban/rural), and the county levels. We found notable class differences in excess mortality but no perfect class gradient. Class differences were somewhat larger for men than for women.


title: Loose Ends in the Epidemiology of the 1918 Pandemic: Explaining the Extreme Mortality Risk in Young Adults

text: In the century since the 1918 influenza pandemic, insights have been sought to explain the pandemic’s signature pattern of high death rates in young adults and low death rates in the elderly and infants. Our understanding of the origin and evolution of the pandemic has shifted considerably. We review evidence of the characteristic age-related pattern of death during the 1918 pandemic relative to the “original antigenic sin” hypothesis. We analyze age-stratified mortality data from Copenhagen around 1918 to identify break points associated with unusual death risk. Whereas infants had no meaningful risk elevation, death risk gradually increased, peaking for young adults 20–34 years of age before dropping sharply for adults ages 35–44 years, suggesting break points for birth cohorts around 1908 and 1878. Taken together with data from previous studies, there is strong evidence that those born before 1878 or after 1908 were not at increased risk of dying of 1918 pandemic influenza. Although the peak death risk coincided with the 1889–1892 pandemic, the 1908 and 1878 break points do not correspond with known pandemics. An increasing number of interdisciplinary studies covering fields such as virology, phylogenetics, death, and serology offer exciting insights into patterns and reasons for the unusual extreme 1918 pandemic mortality risk in young adults.


Simulation: Keeping Pace With Pandemics


title: Practical Comparison of the BioFire FilmArray Pneumonia Panel to Routine Diagnostic Methods and Potential Impact on Antimicrobial Stewardship in Adult Hospitalized Patients with Lower Respiratory Tract Infections

text: Lower respiratory tract infections, including hospital-acquired and ventilator-associated pneumonia, are common in hospitalized patient populations. Standard methods frequently fail to identify the infectious etiology due to the polymicrobial nature of respiratory specimens and the necessity of ordering specific tests to identify viral agents. The potential severity of these infections combined with a failure to clearly identify the causative pathogen results in administration of empirical antibiotic agents based on clinical presentation and other risk factors. We examined the impact of the multiplexed, semiquantitative BioFire FilmArray Pneumonia panel (PN panel) test on laboratory reporting for 259 adult inpatients submitting bronchoalveolar lavage (BAL) specimens for laboratory analysis. The PN panel demonstrated a combined 96.2% positive percent agreement (PPA) and 98.1% negative percent agreement (NPA) for the qualitative identification of 15 bacterial targets compared to routine bacterial culture. Semiquantitative values reported by the PN panel were frequently higher than values reported by culture, resulting in semiquantitative agreement (within the same log(10) value) of 43.6% between the PN panel and culture; however, all bacterial targets reported as >10(5) CFU/ml in culture were reported as ≥10(5) genomic copies/ml by the PN panel. Viral targets were identified by the PN panel in 17.7% of specimens tested, of which 39.1% were detected in conjunction with a bacterial target. A review of patient medical records, including clinically prescribed antibiotics, revealed the potential for antibiotic adjustment in 70.7% of patients based on the PN panel result, including discontinuation or de-escalation in 48.2% of patients, resulting in an average savings of 6.2 antibiotic days/patient.


docid: khylexid

title: Authors’ correction for Euro Surveill. 2020;25(23)


title: COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database

text: In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.


title: COVID-19 and neurointerventional service worldwide: a survey of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana de Neuroradiologia Diagnostica y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN)

text: BACKGROUND: This survey was focused on the provision of neurointerventional services, the current practices of managing patients under COVID-19 conditions, and the expectations for the future. METHODS: Invitations for this survey were sent out as a collaborative effort of the European Society of Minimally Invasive Neurological Therapy (ESMINT), the Society of NeuroInterventional Surgery (SNIS), the Sociedad Iberolatinoamericana de Neuroradiologia Diagnostica y Terapeutica (SILAN), the Society of Vascular and Interventional Neurology (SVIN), and the World Federation of Interventional and Therapeutic Neuroradiology (WFITN). RESULTS: Overall, 475 participants from 61 countries responded (six from Africa (1%), 81 from Asia (17%), 156 from Europe (33%), 53 from Latin America (11%), and 172 from North America (11%)). The majority of participants (96%) reported being able to provide emergency services, though 26% of these reported limited resources. A decrease in emergency procedures was reported by 69% of participants (52% in ischemic and hemorrhagic stroke, 11% ischemic, and 6% hemorrhagic stroke alone). Only 4% reported an increase in emergency cases. The emerging need for social distancing and the rapid adoption of remote communication was reflected in the interest in establishing case discussion forums (43%), general online forums (37%), and access to angio video streaming for live mentoring and support (33%). CONCLUSION: Neurointerventional emergency services are available in almost all centers, while the number of emergency patients is markedly decreased. Half of the participants have abandoned neurointerventions in non-emergent situations. There are considerable variations in the management of neurointerventions and in the expectations for the future.