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benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.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

By design : negotiating flexible learning in the built environment discipline

The term ‘flexible education’ is now firmly entrenched within Australian higher education discourse, yet the term is a contested one imbued with a multiplicity of meanings. This paper describes a process designed to elucidate how the idea of flexible education can be translated into teaching models that are informed by the specific demands of disciplinary contexts. The process uses a flexible learning ‘matching’ tool to articulate the understandings and preferences of students and academics of the Built Environment to bridge the gap between student expectations of flexibility and their teacher’s willingness and ability to provide that flexibility within the limits of the pedagogical context and teaching resources. The findings suggest an informed starting point for educators in the Built Environment and other creative disciplines from which to traverse the complexities inherent in negotiating flexibility in an increasingly digital world

Postexposure Treatment and Animal Rabies, Ontario, 1958-2000

This paper investigates the relationship between animal rabies and postexposure treatment (PET) in Ontario by examining the introduction of human diploid cell vaccine (HDCV) in 1980 and the initiation of an oral rabies vaccination program for wildlife in 1989. Introducing HDCV led to an immediate doubling of treatments. Both animal rabies and human treatments declined rapidly after the vaccination program was introduced, but human treatments have leveled off at approximately 1,000 per year

Eliciting human intelligence: police source handlers' perceptions and experiences of rapport during covert human intelligence sources (CHIS) interactions

Rapport is an integral part of interviewing, viewed as fundamental to the success of intelligence elicitation. One collection capability is human intelligence (HUMINT), the discipline charged with eliciting intelligence through interactions with human sources, such as covert human intelligence sources (CHIS). To date, research has yet to explore the perceptions and experiences of intelligence operatives responsible for gathering HUMINT within England and Wales. The present study consisted of structured interviews with police source handlers (N = 24). Rapport was perceived as essential, especially for maximising the opportunity for intelligence elicitation. Participants provided a range of rapport strategies while highlighting the importance of establishing, and maintaining, rapport. The majority of participants believed rapport could be trained to some degree. Thus, rapport was not viewed exclusively as a natural skill. However, participants commonly perceived some natural attributes are required to build rapport that can be refined and developed through training and experience

The impact of rapport on intelligence yield: police source handler telephone interactions with covert human intelligence sources

Covert Human Intelligence Sources (CHIS) provide unique access to criminals and organised crime groups, and their collection of intelligence is vital to understanding England and Wales’ threat picture. Rapport is essential to the establishment and maintenance of effective professional relationships between source handlers and their CHIS. Thus, rapport-based interviewing is a fundamental factor to maximising intelligence yield. The present research gained unprecedented access to 105 real-life audio recorded telephone interactions between England and Wales police source handlers and CHIS. This research quantified both the rapport component behaviours (e.g., attention, positivity, and coordination) displayed by the source handler and the intelligence yielded from the CHIS, in order to investigate the frequencies of these rapport components and their relationship to intelligence yield. Overall rapport, attention and coordination significantly correlated with intelligence yield, while positivity did not. Attention was the most frequently used component of rapport, followed by positivity, and then coordination

Radium contamination in the area around Dalgety Bay

In this report, the Committee on Medical Aspects of Radiation in the Environment (COMARE) presents a comprehensive review of the radium contamination in the area around Dalgety Bay. This report covers the history of the site, the type and extent of the contamination, the recent investigations and the cancer epidemiology for the area. The report also considers the implications for other similarly contaminated sites

Infographic. How does exercise treatment compare with antihypertensive medications?

High systolic blood pressure (SBP) remains the major cause of premature death globally despite advances in pharmacological treatment.1 2 The global direct medical costs associated with hypertension treatment are estimated at $370 billion/year worldwide, with the healthcare savings from effective management of this condition projected at about$100 billion/year.3 Unfortunately, relatively little attention is given to non-pharmacological strategies, including structured exercise interventions. A recent network meta-analysis of randomised controlled trials (RCTs) published in the BJSM4 aimed to compare the effects of exercise interventions and medications on SBP. We highlight the key findings of this network meta-analysis that are particularly relevant for clinical practice and health policy.Sin financiación12.022 JCR (2019) Q1, 1/85 Sport Sciences3.712 SJR (2019) Q1, 48/2754 Medicine (miscellaneous), 1/284 Orthopedics and Sports Medicine, 1/207 Physical Therapy, Sports Therapy and Rehabilitation, 2/125 Sports ScienceNo data IDR 2019UE

Elimination of Arctic Variant Rabies in Red Foxes, Metropolitan Toronto

To control the arctic variant of rabies virus in red foxes, 332,257 bait doses containing live, attenuated Evelyn-Rokitnicki-Abelseth rabies vaccine were distributed in greater metropolitan Toronto during 1989–1999. Human and pet contact with bait was minimal, and no adverse reactions to the vaccine were noted. Significantly fewer rabid foxes were found during the 17 years after fox baiting (5 cases during 1990–2006) than in the 17 years before (96 cases during 1973–1989). The last report of a rabid fox in metropolitan Toronto was in 1996 (reporting period through September 2006), which confirms that distributing oral rabies vaccine bait is a feasible tactic for the control of rabies in foxes in urban environments