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benefits and harms of NIs for influenza in all age groups by reviewing all clinical study reports of published and unpublished randomised, placebo-controlled trials and regulatory comments.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

Advanced Biopolymer-Based Nanocomposites and Hybrid Materials

The exploitation of naturally occurring polymers to engineer advanced nanocomposites and hybrid materials is the focus of increasing scientific activity, explained by growing environmental concerns and interest in the peculiar features and multiple functionalities of these macromolecules. Natural polymers, such as polysaccharides and proteins, present a remarkable potential for the design of all kinds of materials for application in a multitude of domains. This Special Issue collected the work of scientists on the current developments in the field of multifunctional biopolymer-based nanocomposites and hybrid materials with a particular emphasis on their production methodologies, properties, and prominent applications. Thus, materials related to bio-based nanocomposites and hybrid materials manufactured with different partners, namely natural polymers, bioactive compounds, and inorganic nanoparticles, are reported in the Special Issue Advanced Biopolymer-Based Nanocomposites and Hybrid Materials

Patient-reported outcomes after discontinuation of long-term topical corticosteroid treatment for atopic dermatitis: a targeted cross-sectional survey

Topical corticosteroid (TCS) treatment is widely prescribed for atopic dermatitis (AD). However, TCS treatment is associated with tachyphylaxis, and discontinuation after long-term use may cause exacerbation of symptoms. Some AD patients are reluctant to use TCS.To evaluate patient-reported short- and long-term outcomes after discontinuation of TCS treatment for AD.Questionnaires were distributed to adult AD patients (n=1,812) of doctors who did not recommend TCS as first-line therapy for patients who preferred to avoid TCS. Data collected included current TCS use, duration of TCS use, past discontinuation of TCS use, exacerbation of symptoms after discontinuation of TCS use, and limitations to daily activities because of AD.Of 918 respondents, 97.7% had used TCS, of whom 92.3% had experienced discontinuation of TCS use. After discontinuation, 63.9% experienced their most severe AD symptoms ever. The severity of exacerbation of symptoms was significantly correlated with the length of TCS use (

Oseltamivir and early deterioration leading to death: A proportional mortality study for 2009A/H1N1 influenza

Objective: To examine the epidemiological association between sudden deterioration leading to death and Tamiflu use. Design: Proportional mortality study. Setting: Japan. Participants: 162 deaths without deterioration before the first consultation among all 198 deaths of mostly confirmed 2009A/H1N1 influenza. Population at risk: Age-specific population of influenza patients prescribed Tamiflu and Relenza. Main outcome measure: Age-stratified pooled odds ratio (OR) for early (within 12 hours) deterioration and overall death of Tamiflu prescribed to Relenza prescribed patients. Results: Of 119 deaths after Tamiflu was prescribed, 38 deteriorated within 12 hours (28 within 6 hours), while of 15 deaths after Relenza, none deteriorated within 12 hours. Pooled OR for early deterioration and overall death were 5.88 (95% CI: 1.30 to 26.6, p = 0.014) and 1.91 (p = 0.031) respectively. Baseline characteristics including risk factors did not contribute to early deterioration after Tamiflu use. Conclusions: These data suggest Tamiflu use could induce sudden deterioration leading to death especially within 12 hours of prescription. These findings are consistent with sudden deaths observed in a series of animal toxicity studies, several reported case series and the results of prospective cohort studies. From "the precautionary principle" the potential harm of Tamiflu should be taken into account and further detailed studies should be conducted