Feasibility study for the manufacture of zero gravity pharmaceuticals, immunological, and viral agents, appendices

For abstract, see N74-32929

The Burden of Avian Influenza Viruses in Community Ponds in California

Emerging influenza viruses continue to challenge public health. The problem is public health science professionals have been battling emerging human influenza diseases with tactile and reactionary methods because there is a lack of knowledge and data at the human-animal interface. This research was a baseline study of the proportion of influenza A virus (IAV) in urban and rural communities in California. The population was artificial recirculating water ponds in the geographic locations of rural and urban Californian communities. Surface water samples [N = 182] were collected from artificial recirculating ponds in California. Positivity for IAV was verified by real time RT-PCR, MDCK cells for virus infectivity, nucleotide sequencing of the RNA genome, and phylogenic analysis of IAV H5N1 strains. The proportion of IAV in rural and urban ponds favored the greater burden of IAV in urban ponds over rural ponds. The presence of waterfowl and IAV M gene sequence positivity were found not to be significantly related. The geochemical properties--pH, salinity, and water temperature at time of collection--were not predictors of IAV infectivity. This baseline research study validated these water ponds as resource sites for IAV surveillance and monitoring. The social change implications of this study can be recognized at the national and international levels, to the population level, and to the individual level by providing geospatial analysis and spatial-temporal data for IAV surveillance, initiating biosecurity measures to protect poultry industries in the United States and Brazil, and contributing to the current IAV strain library. Contributions to the IAV strain library may be used to develop vaccines against human pandemics

Pandemics and United States Pharmaceutical Stocks’ Rates of Return

Understanding the stock market in the 21st century is very important to investors as well as company executives. All publicly traded companies get most of their financing by issuing stock on the various stock markets of the world. These stocks are then brought and sold to investors. The research in this dissertation used the event study methodology to evaluate the United States stock market rate of return for pharmaceutical stocks impacted by pandemics in 2009 and 2020. Using the stocks\u27 historical data before and after the announcement of a pandemic by the World Health Organization, this event study will see if the pandemic affects the stocks\u27 rate of return

Clinical studies of epidemic influenza and pandemic COVID-19 to improve the chain of patient care: from bedside diagnostics to long-term complications :

Tidlig diagnostikk og rask og målrettet behandling kan forbedre utfallet av influensa og Covid-19 sykdom. Gjennom prospektive, kontrollerte observasjonsstudier har vi vist betydningen av rask diagnostikk for å redusere liggetid og starte tidlig antiviral behandling mot influensa, samt definert langtidsplager etter mild Covid-19 infeksjon. Under influensasesongen i 2018/2019 undersøkte vi effekten av å bruke en pasientnær nukleinsyrebasert influensa hurtigtest i akuttmottaket på Haukeland Sykehus sammenlignet med rask, standard laboratoriediagnostikk på Haraldsplass Diakonale Sykehus. Vi fant at den pasientnære hurtigtesten var raskere, og reduserte tidsbruk fra triage til influensatesting. Bruk av hurtigtest var forbundet med mer målrettet isolasjonsbruk og kortere sykehusopphold. Begge sykehus initierte antiviral behandling i >80% av bekreftede influensatilfeller. Pasientnær hurtigtest var ikke forbundet med lavere forbruk av antibiotika (gitt til >70%) eller kortere antibiotikakurer, som antyder at anibiotikastyrings-verktøy i forløpet etter akuttmottak kan være vel så viktig for å forbedre forskrivningspraksis. Bekymring om overforbruk av antibiotika økte under Covid-19 pandemien. Derfor undersøkte vi antibiotikabruk blant innlagte koronapasienter i Bergen under den første bølgen av pandemien. Vi sammenlignet med 2018/2019 influensapasienter fra samme sykehus, samt nasjonale tall over alle Covid-19 relaterte sykehus-innleggelser i Norge i 2020. Vi så at Covid-19 pasienter fikk færrest antibiotikakurer, men det var et høyere forbruk av resistensdrivende antibiotika. Videre så vi en positiv utvikling med redusert antibiotikabruk hos Covid-19 pasienter som ble innlagt i andre bølge av pandemien, sammenlignet med den første. Til slutt undersøkte vi forekomst av restplager, også kalt «long Covid» blant hjemmeisolerte Covid-19 pasienter opp til 18 måneder etter akutt Covid-19 sykdom. Nesten halvparten av pasientene hadde restplager. Vanligst var utmattelse, hukommelse- og konsentrasjonsvansker og tungpust, og ved 12 måneder var forekomsten av disse plagene mye høyere enn blant en aldersjustert seronegativ kontrollgruppe. SARS-CoV-2 spesifikke immunsvar korrelerte også med restplager. Totalt sett så vi at Covid-19 pasienter hadde økt risiko for en rekke symptomer, og at for de fleste tar det lang tid å bli kvitt plagene.Current knowledge indicates that early diagnosis along with timely and targeted management have the potential to improve the outcomes after Influenza and SARS-CoV-2. During the influenza season 2018/2019, we investigated the effect of implementing an ultra-rapid molecular influenza point-of-care test (POCT) in the emergency department (ED) (intervention hospital), compared to the use of rapid laboratory-based diagnostics (control hospital). We showed that influenza POCT was more rapid, reducing the time from triage to testing, allowing correct isolation of patients, and reduced the length of stay. Both hospitals similarly prescribed antivirals to >80% of influenza patients. The influenza POCT was not associated with reduced rate (>70% overall) or duration of antibiotic treatment, suggesting that antibiotic stewardship measures beyond the ED are important to improve targeted antibiotic use. The concern of overuse of antibiotics in respiratory viral infections increased in the SARS-CoV-2 pandemic. Hence, we investigated antibiotic treatment in patients hospitalized during the first COVID-19-wave in Bergen, and compared to antibiotic treatment of our influenza patients and all nationally registered COVID-19 hospitalised patients. COVID-19 patients were prescribed fewer antibiotics than influenza patients, although more resistance-driving antibiotics were used. There was a positive development from the first to second COVID-19 pandemic wave, with reduced antibiotic use. We then investigated the long-term complications of non-severe COVID-19 in home isolated patients up to 18 months after acute infection, named long COVID. We found that up to 18 months, almost half of the patients had one or more residual symptoms, with fatigue, memory problems, concentration problems and dyspnea being most common. The symptom burden at 12 months was significantly higher after infection compared to age- and time-period matched seronegative controls, and we found humoral and cellular SARS-CoV-2 specific immune correlates of symptom sequelae. Overall, our studies demonstrated an excess risk of multiple symptoms, associated with COVID-19, and that recovery from symptoms is slow in most individuals. In conclusion, this work has shown the importance of timely diagnostics for reducing patient length of stay and timely antiviral treatment and defined the long-term complications after mild COVID-19.Doktorgradsavhandlin

An epidemiological study of swine influenza in south China

Swine influenza (SI) can result in a significant economic loss for the pig industry and potentially lead to pandemic influenza in humans. Although SI is prevalent in south China, the epidemiological characteristics of its occurrence in this area were not known prior to the study described in this thesis. This study was mainly conducted in Guangdong Province to: estimate the prevalence of SI; identify risk factors for SI infection in pig farms; assess the knowledge, beliefs and practices (KBP) of pig industry workers towards SI; describe the movement network of live pigs via the wholesale live pig markets; identify anthropogenic, meteorological and geographical factors associated with swine, human and avian influenza viral infection in pigs in south China; and provide evidence of the benefit of risk-based surveillance to address the pandemic influenza threat in south China. A cross-sectional survey was conducted in 153 commercial pig farms in Guangdong Province. The farm-level prevalence of farmer-perceived SI during a six-month period was estimated to be 58% (95% CI: 48 - 68%). Statistically significant risk factors for SI were the presence of poultry on the farm (OR=3.24, 95% CI: 1.52-6.94), the ability of wild birds to enter the piggery (OR=2.50, 95% CI: 1.01-6.16) and failure to implement effective disinfection measures before workers entered the piggery (OR=2.65, 95% CI: 1.04-6.78). A KBP study on local pig industry workers comprising 153 pig farmers, 21 pig traders and 16 pig trade workers revealed that only 33.7% of those surveyed believed that SI could infect humans, and many undertook practices that were unsafe for SI. The lack of awareness about the zoonotic risk of SI (OR = 3.19, 95%CI: 1.67 - 6.21) was associated with not using personal protective equipment when having contact with pigs. Social network analysis on the movement of live pigs through four local wholesale live pig markets indicated that the source counties with the highest risk of having SI via the market trading system were in the central, northern and western regions of Guangdong Province. Risk-based control strategies were shown to result in a greater reduction of the magnitude of a potential epidemic of SI compared to a non-targeted control strategy. Analysis of three year’s sero-surveillance data on SI highlighted that pig farms from south China had exposure to multiple strains of influenza A, including human and avian strains. Spatial modelling identified determinants, such as elevation above sea level, chicken density and the human population density, as important predictors for avian and human influenza infection in pigs within counties. The counties in the delta area of the Pearl River in Guangdong Province and those surrounding Poyang Lake in Jiangxi province had a higher risk of infection with avian or human influenza strains in pigs than other counties in Guangdong, Guangxi, Jiangxi and Fujian provinces. It is concluded that SI is endemic in south China and, although there is the potential for the emergence of pandemic strains of porcine origin, improved on-farm biosecurity and changes to husbandry and trade practices could minimise the likelihood of a pandemic occurring

Tail biting in pigs: is it possible to rear the heavy pig avoiding tail docking?

Tail biting in pigs has been identified as a behavioural problem for decades. It has serious consequences for animal welfare and for the income of the farmers The inability to prevent occurrence of this adverse behavior under commercial farm conditions has resulted in the majority of pig producers considering necessary to dock the tails of all piglets as a preventative measure. This management choice, represents both an animal welfare and an ethical issue, as highlighted in the EU Directive 2008/120 on pig welfare which constrains routine tail docking and emphasizes the need to find alternative preventative strategies. Tail biting prevalence studies have been conducted in most of the UE Countries, but cross-study comparisons appear difficult for the different populations considered. Moreover, most of the data did not concern heavy pig production, with a lack of a complete description of the problem in a prolonged rearing context. The first step of this thesis was to identify the real prevalence of tail biting in Italy, completing an European picture. Moreover, an epidemiological approach was adopted in order to identify the management and housing factors influencing tail biting in the specific heavy pig rearing context. The study highlighted a low incidence of lesions in Italy (0.15% of affected animals on a sample of 79,780 animals). This could be related to the great percentage, (close to 100%), of docked pigs, but at the same time suggested that rearing heavy pigs in a prolonged fattening cycle does not seems to worsen the risk of tail biting. Furthermore, were identified several risk factors for tail biting on heavy pig commercial farms. Results could be relevant to the pig industry in order to reduce the economical losses due to tail biting, giving emphasis to the respect of animal welfare legislation regarding space allowance, the availability of adequate environmental enrichment and environmental parameters such as ammonia concentration and temperature. Once a causal risk factor has been demonstrated on farm, measures should be taken to minimize the incidence of tail biting, thereby enhancing animal welfare. A second step was to evaluate the welfare of undocked pigs in the specific heavy pig rearing context, investigating the feasibility to avoid tail docking in a prolonged fattening phase. Gender and the presence of straw were also considered in their effect on tail biting by evaluating welfare indicators such as blood parameters, culling rate, behavior, and lesions at ears and tail. Further investigations were conducted on mortality rate, causes of death, and the presence of lung lesions and oesophago -gastric ulcer (OGU) at slaughter. The outcome of the study suggests that the combined use of solid floors, compliance with the parameters established by EU legislation on the protections of pigs in terms of space allowance, environment parameters, and presence of chains and sawdust as enrichments seems to allow the fattening of heavy pigs without performing tail docking with no outbreak of injurious tail biting. Straw therefore seems to be an important tool in both increasing explorative behavior and preventing biting and lesions, particularly in the early stage of fattening. Furthermore, results at slaughter reveal the beneficial effects of straw on the susceptibility to gastric ulcer in the heavy pigs production system, for which very few data are available on this topic. The straw was beneficial, despite the fact that only a relatively small quantity was provided to pigs, allowing management problems due to slurry outflow obstruction or excessive farmer workload to be avoided. In a further field study, tail biting was evaluated throughout a entire producing cycle of heavy pigs, starting from weaning to slaughter. The aim was to investigate welfare and tail biting outbreaks also in the weaning phase, having available data of individually marked animals during their whole growth. Slatted floor was chosen as the most common floor type used in the heavy pig production, but even recognized as one of the mayor risk factors for tail biting. The outcome of the weaning phase was that undocked tails could represent an alternative recipient for exploration behavior in weaning pigs, with the consequence of greater incidence of tail lesions. However, seems that the higher level of lesions was related especially to the age. Probably, the social stress related to the progressive reduction of the space allowance due to the increasing size of the growing animals could be a relevant factor in display of tail biting. During the fattening phase, to avoid tail docking in pigs with a prolonged rearing cycle as for the heavy pig production, seems to provoke the rise of tail lesions. However, this finding, with the combined use of slatted floors, compliance with the parameters established by EU legislation in terms of space allowance and environmental parameters, and presence of chains and straw in a rack as enrichments, seems not associated to the variation of blood parameters and behavior, suggesting an insufficient intensity to cause severe welfare problems. Nevertheless, potential economical losses due to the injured tails should be considered even if not accompanied by evident poor welfare

Neuraminidase inhibitors for preventing and treating influenza in healthy adults and children

BACKGROUND: Neuraminidase inhibitors (NIs) are stockpiled and recommended by public health agencies for treating and preventing seasonal and pandemic influenza. They are used clinically worldwide. OBJECTIVES: To describe the potential benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments. SEARCH METHODS: We searched trial registries, electronic databases (to 22 July 2013) and regulatory archives, and corresponded with manufacturers to identify all trials. We also requested clinical study reports. We focused on the primary data sources of manufacturers but we checked that there were no published randomised controlled trials (RCTs) from non-manufacturer sources by running electronic searches in the following databases: the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, MEDLINE (Ovid), EMBASE, Embase.com, PubMed (not MEDLINE), the Database of Reviews of Effects, the NHS Economic Evaluation Database and the Health Economic Evaluations Database. SELECTION CRITERIA: Randomised, placebo-controlled trials on adults and children with confirmed or suspected exposure to naturally occurring influenza. DATA COLLECTION AND ANALYSIS: We extracted clinical study reports and assessed risk of bias using purpose-built instruments. We analysed the effects of zanamivir and oseltamivir on time to first alleviation of symptoms, influenza outcomes, complications, hospitalisations and adverse events in the intention-to-treat (ITT) population. All trials were sponsored by the manufacturers. MAIN RESULTS: We obtained 107 clinical study reports from the European Medicines Agency (EMA), GlaxoSmithKline and Roche. We accessed comments by the US Food and Drug Administration (FDA), EMA and Japanese regulator. We included 53 trials in Stage 1 (a judgement of appropriate study design) and 46 in Stage 2 (formal analysis), including 20 oseltamivir (9623 participants) and 26 zanamivir trials (14,628 participants). Inadequate reporting put most of the zanamivir studies and half of the oseltamivir studies at a high risk of selection bias. There were inadequate measures in place to protect 11 studies of oseltamivir from performance bias due to non-identical presentation of placebo. Attrition bias was high across the oseltamivir studies and there was also evidence of selective reporting for both the zanamivir and oseltamivir studies. The placebo interventions in both sets of trials may have contained active substances. Time to first symptom alleviation. For the treatment of adults, oseltamivir reduced the time to first alleviation of symptoms by 16.8 hours (95% confidence interval (CI) 8.4 to 25.1 hours, P 1000) and nausea whilst on treatment (RD 4.15%, 95% CI 0.86 to 9.51); NNTH = 25 (95% CI 11 to 116). AUTHORS' CONCLUSIONS: Oseltamivir and zanamivir have small, non-specific effects on reducing the time to alleviation of influenza symptoms in adults, but not in asthmatic children. Using either drug as prophylaxis reduces the risk of developing symptomatic influenza. Treatment trials with oseltamivir or zanamivir do not settle the question of whether the complications of influenza (such as pneumonia) are reduced, because of a lack of diagnostic definitions. The use of oseltamivir increases the risk of adverse effects, such as nausea, vomiting, psychiatric effects and renal events in adults and vomiting in children. The lower bioavailability may explain the lower toxicity of zanamivir compared to oseltamivir. The balance between benefits and harms should be considered when making decisions about use of both NIs for either the prophylaxis or treatment of influenza. The influenza virus-specific mechanism of action proposed by the producers does not fit the clinical evidence

Recent Developments in Smart Healthcare

Medicine is undergoing a sector-wide transformation thanks to the advances in computing and networking technologies. Healthcare is changing from reactive and hospital-centered to preventive and personalized, from disease focused to well-being centered. In essence, the healthcare systems, as well as fundamental medicine research, are becoming smarter. We anticipate significant improvements in areas ranging from molecular genomics and proteomics to decision support for healthcare professionals through big data analytics, to support behavior changes through technology-enabled self-management, and social and motivational support. Furthermore, with smart technologies, healthcare delivery could also be made more efficient, higher quality, and lower cost. In this special issue, we received a total 45 submissions and accepted 19 outstanding papers that roughly span across several interesting topics on smart healthcare, including public health, health information technology (Health IT), and smart medicine

Abstract book: poster week 4/15

Poster Week 4/15. ESTeSC – Coimbra Health School. November 30th – December 4th, 2015.info:eu-repo/semantics/draf