The Molecular Epidemiology and Evolution of Murray Valley Encephalitis Virus: Recent Emergence of Distinct Sub-lineages of the Dominant Genotype 1

© 2015 Williams et al. Background: Recent increased activity of the mosquito-borne Murray Valley encephalitis virus (MVEV) in Australia has renewed concerns regarding its potential to spread and cause disease. Methodology/Principal Findings: To better understand the genetic relationships between earlier and more recent circulating strains, patterns of virus movement, as well as the molecular basis of MVEV evolution, complete pre-membrane (prM) and Envelope (Env) genes were sequenced from sixty-six MVEV strains from different regions of the Australasian region, isolated over a sixty year period (1951–2011). Phylogenetic analyses indicated that, of the four recognized genotypes, only G1 and G2 are contemporary. G1 viruses were dominant over the sampling period and found across the known geographic range of MVEV. Two distinct sub-lineages of G1 were observed (1A and 1B). Although G1B strains have been isolated from across mainland Australia, Australian G1A strains have not been detected outside northwest Australia. Similarly, G2 is comprised of only Western Australian isolates from mosquitoes, suggesting G1B and G2 viruses have geographic or ecological restrictions. No evidence of recombination was found and a single amino acid substitution in the Env protein (S332G) was found to be under positive selection, while several others were found to be under directional evolution. Evolutionary analyses indicated that extant genotypes of MVEV began to diverge from a common ancestor approximately 200 years ago. G2 was the first genotype to diverge, followed by G3 and G4, and finally G1, from which subtypes G1A and G1B diverged between 1964 and 1994. Conclusions/Significance: The results of this study provides new insights into the genetic diversity and evolution of MVEV. The demonstration of co-circulation of all contemporary genetic lineages of MVEV in northwestern Australia, supports the contention that this region is the enzootic focus for this virus

Effects of perceived cost, service quality, and customer satisfaction on health insurance service continuance

This paper aims to contribute to the universal discourse on financial services continuance behavior by examining the impact of service cost on customers\u27 service-quality perception and service continuance intention. It presents the results of an empirical study that has explored the impacts of service cost, service quality, and customer satisfaction on health insurance customers\u27 behavioral intention toward continuing or discontinuing with their service providers. Very few studies had examined the impact of service cost on service-quality perception. Our study attempts to fill that gap. A sample of 820 customers was surveyed, and 624 usable responses were analyzed with ANOVA, standard multiple regression, and logistic regression. Our findings indicate that, although highly satisfied health insurance customers will most likely retain their current service providers, customer dissatisfaction does not necessarily lead to discontinuance. Our results also provide some operational implications for health insurance managers, with strategies for reducing attrition and improving customer retention

Oral steroids for resolution of otitis media with effusion in children (OSTRICH): a double-blinded, placebo-controlled randomised trial

Background Children with persistent hearing loss due to otitis media with effusion are commonly managed by surgical intervention. A safe, cheap, and effective medical treatment would enhance treatment options. Underpowered, poor-quality trials have found short-term benefit from oral steroids. We aimed to investigate whether a short course of oral steroids would achieve acceptable hearing in children with persistent otitis media with effusion and hearing loss. Methods In this individually randomised, parallel, double-blinded, placebo-controlled trial we recruited children aged 2–8 years with symptoms attributable to otitis media with effusion for at least 3 months and with confirmed bilateral hearing loss. Participants were recruited from 20 ear, nose, and throat (ENT), paediatric audiology, and audiovestibular medicine outpatient departments in England and Wales. Participants were randomly allocated (1:1) to sequentially numbered identical prednisolone (oral steroid) or placebo packs by use of computer-generated random permuted block sizes stratified by site and child's age. The primary outcome was audiometry-confirmed acceptable hearing at 5 weeks. All analyses were by intention to treat. This trial is registered with the ISRCTN Registry, number ISRCTN49798431. Findings Between March 20, 2014, and April 5, 2016, 1018 children were screened, of whom 389 were randomised. 200 were assigned to receive oral steroids and 189 to receive placebo. Hearing at 5 weeks was assessed in 183 children in the oral steroid group and in 180 in the placebo group. Acceptable hearing was observed in 73 (40%) children in the oral steroid group and in 59 (33%) in the placebo group (absolute difference 7% [95% CI −3 to 17], number needed to treat 14; adjusted odds ratio 1·36 [95% CI 0·88–2·11]; p=0·16). There was no evidence of any significant differences in adverse events or quality-of-life measures between the groups. Interpretation Otitis media with effusion in children with documented hearing loss and attributable symptoms for at least 3 months has a high rate of spontaneous resolution. A short course of oral prednisolone is not an effective treatment for most children aged 2–8 years with persistent otitis media with effusion, but is well tolerated. One in 14 children might achieve improved hearing but not quality of life. Discussions about watchful waiting and other interventions will be supported by this evidence

C-reactive protein point-of-care testing for safely reducing antibiotics for acute exacerbations of chronic obstructive pulmonary disease: the PACE RCT

Background Most patients presenting with acute exacerbations of chronic obstructive pulmonary disease (AECOPD) in primary care are prescribed antibiotics, but these may not be beneficial, and they can cause side effects and increase the risk of subsequent resistant infections. Point-of-care tests (POCTs) could safely reduce inappropriate antibiotic prescribing and antimicrobial resistance. Objective To determine whether or not the use of a C-reactive protein (CRP) POCT to guide prescribing decisions for AECOPD reduces antibiotic consumption without having a negative impact on chronic obstructive pulmonary disease (COPD) health status and is cost-effective. Design A multicentre, parallel-arm, randomised controlled open trial with an embedded process, and a health economic evaluation. Setting General practices in Wales and England. A UK NHS perspective was used for the economic analysis. Participants Adults (aged ≥ 40 years) with a primary care diagnosis of COPD, presenting with an AECOPD (with at least one of increased dyspnoea, increased sputum volume and increased sputum purulence) of between 24 hours’ and 21 days’ duration. Intervention CRP POCTs to guide antibiotic prescribing decisions for AECOPD, compared with usual care (no CRP POCT), using remote online randomisation. Main outcome measures Patient-reported antibiotic consumption for AECOPD within 4 weeks post randomisation and COPD health status as measured with the Clinical COPD Questionnaire (CCQ) at 2 weeks. For the economic evaluation, patient-reported resource use and the EuroQol-5 Dimensions were included. Results In total, 653 participants were randomised from 86 general practices. Three withdrew consent and one was randomised in error, leaving 324 participants in the usual-care arm and 325 participants in the CRP POCT arm. Antibiotics were consumed for AECOPD by 212 out of 274 participants (77.4%) and 150 out of 263 participants (57.0%) in the usual-care and CRP POCT arm, respectively [adjusted odds ratio 0.31, 95% confidence interval (CI) 0.20 to 0.47]. The CCQ analysis comprised 282 and 281 participants in the usual-care and CRP POCT arms, respectively, and the adjusted mean CCQ score difference at 2 weeks was 0.19 points (two-sided 90% CI –0.33 to –0.05 points). The upper limit of the CI did not contain the prespecified non-inferiority margin of 0.3. The total cost from a NHS perspective at 4 weeks was £17.59 per patient higher in the CRP POCT arm (95% CI –£34.80 to £69.98; p = 0.408). The mean incremental cost-effectiveness ratios were £222 per 1% reduction in antibiotic consumption compared with usual care at 4 weeks and £15,251 per quality-adjusted life-year gained at 6 months with no significant changes in sensitivity analyses. Patients and clinicians were generally supportive of including CRP POCT in the assessment of AECOPD. Conclusions A CRP POCT diagnostic strategy achieved meaningful reductions in patient-reported antibiotic consumption without impairing COPD health status or increasing costs. There were no associated harms and both patients and clinicians valued the diagnostic strategy. Future work Implementation studies that also build on our qualitative findings could help determine the effect of this intervention over the longer term. Trial registration Current Controlled Trials ISRCTN24346473. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 15. See the NIHR Journals Library website for further project information