Can Antiviral Drugs Contain Pandemic Influenza Transmission?

Antiviral drugs dispensed during the 2009 influenza pandemic generally failed to contain transmission. This poses the question of whether preparedness for a future pandemic should include plans to use antiviral drugs to mitigate transmission

Impacts of organic and conventional crop management on diversity and activity of free-living nitrogen fixing bacteria and total bacteria are subsidiary to temporal effects

A three year field study (2007-2009) of the diversity and numbers of the total and metabolically active free-living diazotophic bacteria and total bacterial communities in organic and conventionally managed agricultural soil was conducted at the Nafferton Factorial Systems Comparison (NFSC) study, in northeast England. The result demonstrated that there was no consistent effect of either organic or conventional soil management across the three years on the diversity or quantity of either diazotrophic or total bacterial communities. However, ordination analyses carried out on data from each individual year showed that factors associated with the different fertility management measures including availability of nitrogen species, organic carbon and pH, did exert significant effects on the structure of both diazotrophic and total bacterial communities. It appeared that the dominant drivers of qualitative and quantitative changes in both communities were annual and seasonal effects. Moreover, regression analyses showed activity of both communities was significantly affected by soil temperature and climatic conditions. The diazotrophic community showed no significant change in diversity across the three years, however, the total bacterial community significantly increased in diversity year on year. Diversity was always greatest during March for both diazotrophic and total bacterial communities. Quantitative analyses using qPCR of each community indicated that metabolically active diazotrophs were highest in year 1 but the population significantly declined in year 2 before recovering somewhat in the final year. The total bacterial population in contrast increased significantly each year. Seasonal effects were less consistent in this quantitative study

Sigma-2 receptor ligand as a novel method for delivering a SMAC mimetic drug for treating ovarian cancer

BACKGROUND: The sigma-2 receptor has been validated as a biomarker for proliferating tumours. Second mitochondria-derived activator of caspase (Smac) is a protein released from mitochondria into the cytosol, leading to apoptosis. In this study, we investigated a sigma-2 ligand as a tumour-targeting drug delivery agent for treating ovarian cancer. METHODS: A sigma-2 ligand, SW 43, was conjugated with a Smac mimetic compound (SMC), SW IV-52s, to form SW III-123. The delivery function of the sigma-2 moiety and cell killing mechanisms of SW III-123 were examined in human ovarian cancer cell lines. RESULTS: SW III-123 internalisation into ovarian cancer cells was mediated by sigma-2 receptors. SW III-123, but not SW IV-52s or SW 43, exhibited potent cytotoxicity in human ovarian cancer cell lines SKOV-3, CaOV-3 and BG-1 after 24-h treatment, suggesting that the sigma-2 ligand successfully delivered SMC into ovarian cancer cells. SW III-123 induced rapid degradation of inhibitor of apoptosis proteins (cIAP1 and cIAP2), accumulation of NF-κB-inducing kinase (NIK) and phosphorylation of NF-κB p65, suggesting that SW III-123 activated both canonical and noncanonical NF-κB pathways in SKOV-3 cells. SW III-123 cleaved caspase-8, -9 and -3. Tumour necrosis factor alpha (TNFα) antibody markedly blocked SW III-123-induced cell death and caspase-3 activity in SKOV-3 cells, indicating that SW III-123 activated both intrinsic and extrinsic apoptotic pathways and induced TNFα-dependent cell death in SKOV-3 cells. CONCLUSION: Sigma-2 ligands are a promising tumour-targeting drug delivery agent. Sigma-2-conjugated SMC exemplifies a novel class of therapeutic drugs for treating ovarian cancer

Overview of data-synthesis in systematic reviews of studies on outcome prediction models

Background: Many prognostic models have been developed. Different types of models, i.e. prognostic factor and outcome prediction studies, serve different purposes, which should be reflected in how the results are summarized in reviews. Therefore we set out to investigate how authors of reviews synthesize and report the results of primary outcome prediction studies. Methods: Outcome prediction reviews published in MEDLINE between October 2005 and March 2011 were eligible and 127 Systematic reviews with the aim to summarize outcome prediction studies written in English were identified for inclusion. Characteristics of the reviews and the primary studies that were included were independently assessed by 2 review authors, using standardized forms. Results: After consensus meetings a total of 50 systematic reviews that met the inclusion criteria were included. The type of primary studies included (prognostic factor or outcome prediction) was unclear in two-thirds of the reviews. A minority of the reviews reported univariable or multivariable point estimates and measures of dispersion from the primary studies. Moreover, the variables considered for outcome prediction model development were often not reported, or were unclear. In most reviews there was no information about model performance. Quantitative analysis was performed in 10 reviews, and 49 reviews assessed the primary studies qualitatively. In both analyses types a range of different methods was used to present the results of the outcome prediction studies. Conclusions: Different methods are applied to synthesize primary study results but quantitative analysis is rarely performed. The description of its objectives and of the primary studies is suboptimal and performance parameters of the outcome prediction models are rarely mentioned. The poor reporting and the wide variety of data synthesis strategies are prone to influence the conclusions of outcome prediction reviews. Therefore, there is much room for improvement in reviews of outcome prediction studies. (aut.ref.

Optimal Design of Intervention Studies to Prevent Influenza in Healthy Cohorts

Background: Influenza cohort studies, in which participants are monitored for infection over an epidemic period, are invaluable in assessing the effectiveness of control measures such as vaccination, antiviral prophylaxis and nonpharmaceutical interventions (NPIs). Influenza infections and illnesses can be identified through a number of approaches with different costs and logistical requirements. Methodology and Principal Findings: In the context of a randomized controlled trial of an NPI with a constrained budget, we used a simulation approach to examine which approaches to measuring outcomes could provide greater statistical power to identify an effective intervention against confirmed influenza. We found that for a short epidemic season, the optimal design was to collect respiratory specimens at biweekly intervals, as well as following report of acute respiratory illness (ARI), for virologic testing by reverse transcription polymerase chain reaction (RT-PCR). Collection of respiratory specimens only from individuals reporting ARI was also an efficient design particularly for studies in settings with longer periods of influenza activity. Collection of specimens only from individuals reporting a febrile ARI was less efficient. Collection and testing of sera before and after influenza activity appeared to be inferior to collection of respiratory specimens for RT-PCR confirmation of acute infections. The performance of RT-PCR was robust to uncertainty in the costs and diagnostic performance of RT-PCR and serological tests

The relationship between childhood body weight and dental caries experience:an umbrella systematic review protocol

Abstract Background Obesity and dental caries are global public health problems which can impact in childhood and throughout the life course. In simple terms, childhood dental caries and body weight are linked via the common risk factor of diet. An association between dental caries and obesity has been described in a number of studies and reviews. However, similarly, a relationship has also been noted between low body weight and caries experience in children. This protocol will provide the framework for an umbrella review to address the following question: Does the available evidence support a relationship between dental caries experience and body weight in the child population? Methods This review protocol outlines the process to carry out an umbrella systematic review which will synthesise previous reviews of childhood dental caries experience and body weight. An umbrella review methodology will be used to examine the methodological and reporting quality of existing reviews. Discussion The final umbrella review aims to aggregate the available evidence in order to provide a summary for policymakers and to inform healthcare interventions. Systematic review registration PROSPERO CRD4201604730

Evaluating the Combined Effectiveness of Influenza Control Strategies and Human Preventive Behavior

Control strategies enforced by health agencies are a major type of practice to contain influenza outbreaks. Another type of practice is the voluntary preventive behavior of individuals, such as receiving vaccination, taking antiviral drugs, and wearing face masks. These two types of practices take effects concurrently in influenza containment, but little attention has been paid to their combined effectiveness. This article estimates this combined effectiveness using established simulation models in the urbanized area of Buffalo, NY, USA. Three control strategies are investigated, including: Targeted Antiviral Prophylaxis (TAP), workplace/school closure, community travel restriction, as well as the combination of the three. All control strategies are simulated with and without regard to individual preventive behavior, and the resulting effectiveness are compared. The simulation outcomes suggest that weaker control strategies could suffice to contain influenza epidemics, because individuals voluntarily adopt preventive behavior, rendering these weaker strategies more effective than would otherwise have been expected. The preventive behavior of individuals could save medical resources for control strategies and avoid unnecessary socio-economic interruptions. This research adds a human behavioral dimension into the simulation of control strategies and offers new insights into disease containment. Health policy makers are recommended to review current control strategies and comprehend preventive behavior patterns of local populations before making decisions on influenza containment

Incidence of Influenza in Healthy Adults and Healthcare Workers: A Systematic Review and Meta-Analysis

BACKGROUND: Working in healthcare is often considered a risk factor for influenza; however, this risk has not been quantified. We aimed to systematically review evidence describing the annual incidence of influenza among healthy adults and healthcare workers (HCWs). METHODS AND FINDINGS: We searched OVID MEDLINE (1950 to 2010), EMBASE (1947 to 2010) and reference lists of identified articles. Observational studies or randomized trials reporting full season or annual influenza infection rates for healthy, working age adult subjects and HCWs were included. Influenza infection was defined as a four-fold rise in antibody titer, or positive viral culture or polymerase chain reaction. From 24,707 citations, 29 studies covering 97 influenza seasons with 58,245 study participants were included. Pooled influenza incidence rates (IR) (95% confidence intervals (CI)) per 100 HCWs per season and corresponding incidence rate ratios (IRR) (95% CI) as compared to healthy adults were as follows. All infections: IR 18.7 (95% CI, 15.8 to 22.1), IRR 3.4 (95% CI, 1.2 to 5.7) in unvaccinated HCWs; IR 6.5 (95% CI, 4.6 to 9.1), IRR 5.4 (95% CI, 2.8 to 8.0) in vaccinated HCWs. Symptomatic infections: IR 7.5 (95% CI, 4.9 to 11.7), IRR 1.5 (95% CI, 0.4 to 2.5) in unvaccinated HCWs, IR 4.8 (95% CI, 3.2 to 7.2), IRR 1.6 (95% CI, 0.5 to 2.7) in vaccinated HCWs. CONCLUSIONS: Compared to adults working in non-healthcare settings, HCWs are at significantly higher risk of influenza