Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains ...resistant to current antiviral agents.
We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population.
In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval CI, 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively.
Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).
Baloxavir marboxil (baloxavir) is a polymerase acidic protein (PA) endonuclease inhibitor with clinical efficacy in the treatment of uncomplicated influenza, including in outpatients at increased ...risk for complications. The postexposure prophylactic efficacy of baloxavir in the household setting is unclear.
We conducted a multicenter, double-blind, randomized, placebo-controlled trial to evaluate the postexposure prophylactic efficacy of baloxavir in household contacts of index patients with confirmed influenza during the 2018-2019 season in Japan. The participants were assigned in a 1:1 ratio to receive either a single dose of baloxavir or placebo. The primary end point was clinical influenza, as confirmed by reverse-transcriptase-polymerase-chain-reaction testing, over a period of 10 days. The occurrence of baloxavir-selected PA substitutions associated with reduced susceptibility was assessed.
A total of 752 household contacts of 545 index patients were randomly assigned to receive baloxavir or placebo. Among the index patients, 95.6% had influenza A virus infection, 73.6% were younger than 12 years of age, and 52.7% received baloxavir. Among the participants who could be evaluated (374 in the baloxavir group and 375 in the placebo group), the percentage in whom clinical influenza developed was significantly lower in the baloxavir group than in the placebo group (1.9% vs. 13.6%) (adjusted risk ratio, 0.14; 95% confidence interval CI, 0.06 to 0.30; P<0.001). Baloxavir was effective in high-risk, pediatric, and unvaccinated subgroups of participants. The risk of influenza infection, regardless of symptoms, was lower with baloxavir than with placebo (adjusted risk ratio, 0.43; 95% CI, 0.32 to 0.58). The incidence of adverse events was similar in the two groups (22.2% in the baloxavir group and 20.5% in the placebo group). In the baloxavir group, the viral PA substitutions I38T/M or E23K were detected in 10 (2.7%) and 5 (1.3%) participants, respectively. No transmission of these variants from baloxavir-treated index patients to participants in the placebo group was detected; however, several instances of transmission to participants in the baloxavir group could not be ruled out.
Single-dose baloxavir showed significant postexposure prophylactic efficacy in preventing influenza in household contacts of patients with influenza. (Funded by Shionogi; Japan Primary Registries Network number, JapicCTI-184180.).
•This paper presents a systematic literature review discussing the privacy paradox.•Users are concerned about their privacy but undertake little to protect their data.•Risk-benefit evaluation or ...little risk assessment drives information disclosure.•Design solutions of mobile apps should be adapted to different cognitive styles.•Support users through automated user-centered systems and user-friendly interface.
Also known as the privacy paradox, recent research on online behavior has revealed discrepancies between user attitude and their actual behavior. More specifically: While users claim to be very concerned about their privacy, they nevertheless undertake very little to protect their personal data. This systematic literature review explores the different theories on the phenomenon known as the privacy paradox.
Drawing on a sample of 32 full papers that explore 35 theories in total, we determined that a user’s decision-making process as it pertains to the willingness to divulge privacy information is generally driven by two considerations: (1) risk-benefit evaluation and (2) risk assessment deemed be none or negligible. By classifying in accordance with these two considerations, we have compiled a comprehensive model using all the variables mentioned in the discussed papers. The overall findings of the systematic literature review will investigate the nature of decision-making (rational vs. irrational) and the context in which the privacy paradox takes place, with a special focus on mobile computing. Furthermore, possible solutions and research limitation issues will be discussed.
Several studies have focused on the effects of corporate social responsibility (CSR) fit on external stakeholders' evaluations of CSR activities, attitudes towards companies or brands, and behaviors. ...The results so far have been contradictory. A possible reason may be that the concept of CSR fit is more complicated than previously assumed. Researchers suggest that there may be different types of CSR fit, but so far no empirical research has focused on a typology of CSR fit. This study fills this gap, describing a qualitative content analysis of the congruence between six organizations and their various CSR activities. Ten annual reports and CSR reports were analyzed, and 102 specific CSR activities were identified. The results show that two levels of fit must be distinguished: based on the means for and the intended ends of the CSR activity. Furthermore, six different types of fit were found, focusing on (1) products and services, (2) production processes, (3) environmental impact, (4) employees, (5) suppliers, and (6) geographical location. Considering the above variety of fit possibilities, the findings emphasize the role of CSR communication as a means of creating fit perceptions.
Summary Background International travel contributes to the dissemination of antimicrobial resistance. We investigated the acquisition of extended-spectrum β-lactamase-producing Enterobacteriaceae ...(ESBL-E) during international travel, with a focus on predictive factors for acquisition, duration of colonisation, and probability of onward transmission. Methods Within the prospective, multicentre COMBAT study, 2001 Dutch travellers and 215 non-travelling household members were enrolled. Faecal samples and questionnaires on demographics, illnesses, and behaviour were collected before travel and immediately and 1, 3, 6, and 12 months after return. Samples were screened for the presence of ESBL-E. In post-travel samples, ESBL genes were sequenced and PCR with specific primers for plasmid-encoded β-lactamase enzymes TEM, SHV, and CTX-M group 1, 2, 8, 9, and 25 was used to confirm the presence of ESBL genes in follow-up samples. Multivariable regression analyses and mathematical modelling were used to identify predictors for acquisition and sustained carriage, and to determine household transmission rates. This study is registered with ClinicalTrials.gov , number NCT01676974. Findings 633 (34·3%) of 1847 travellers who were ESBL negative before travel and had available samples after return had acquired ESBL-E during international travel (95% CI 32·1–36·5), with the highest number of acquisitions being among those who travelled to southern Asia in 136 of 181 (75·1%, 95% CI 68·4–80·9). Important predictors for acquisition of ESBL-E were antibiotic use during travel (adjusted odds ratio 2·69, 95% CI 1·79–4·05), traveller's diarrhoea that persisted after return (2·31, 1·42–3·76), and pre-existing chronic bowel disease (2·10, 1·13–3·90). The median duration of colonisation after travel was 30 days (95% CI 29–33). 65 (11·3%) of 577 remained colonised at 12 months. CTX-M enzyme group 9 ESBLs were associated with a significantly increased risk of sustained carriage (median duration 75 days, 95% CI 48–102, p=0·0001). Onward transmission was found in 13 (7·7%) of 168 household members. The probability of transmitting ESBL-E to another household member was 12% (95% CI 5–18). Interpretation Acquisition and spread of ESBL-E during and after international travel was substantial and worrisome. Travellers to areas with a high risk of ESBL-E acquisition should be viewed as potential carriers of ESBL-E for up to 12 months after return. Funding Netherlands Organisation for Health Research and Development (ZonMw).
Although corporate greenwashing is a widespread phenomenon, few studies have investigated its effects on consumers. In these studies, consumers were exposed to organizations that boldly lied about ...their green behaviors. Most greenwashing practices in real life, however, do not involve complete lies. This article describes a randomized 3 × 2 experimental study in the cruise industry investigating the effects of various degrees of greenwashing. Six experimental conditions were created based on behavioral-claim greenwashing (an organization telling the truth vs. its telling lies or half-lies) and motive greenwashing (an organization acting on its own initiative vs. its taking credit for following legal obligations). Dependent variables were three corporate reputation constructs: environmental performance, product and service quality, and financial performance. Compared to true green behavior, lies and half-lies had similar negative effects on reputation. Taking credit for following legal obligations had no main effect. Only in the case of true green behavior did undeservedly taking credit affect reputation negatively. Overall, the findings suggest that only true green behavior will have the desired positive effects on reputation.
We investigated the consequences of colistin use in backyard chicken farms in Vietnam by examining the prevalence of mcr-1 in fecal samples from chickens and humans. Detection of mcr-1-carrying ...bacteria in chicken samples was associated with colistin use and detection in human samples with exposure to mcr-1-positive chickens.
From a cohort of 8534 individuals aged 18 years and older (6636 78% aged 18–55 years, 5065 59% female, 7863 92% White), they analysed the viral sequences from 311 participants who tested positive for ...SARS-CoV-2 more than 14 days after receiving two doses of the ChAdOx1 nCoV-19 vaccine or a meningococcal conjugate control vaccine. Infection and virus replication in the presence of partial immunity might result in evolution towards escape from vaccine-induced immunity. Reductions in vaccine efficacy rendered by circulating variants of concern might thus facilitate the emergence and spread of progressively resistant variants, especially when delaying or waiving second vaccine doses, with potential consequences for pandemic control.12–14 In summary, the early findings reported by Emary and colleagues suggest a meaningful degree of efficacy against the B.1.1.7 variant, which is encouraging.
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