Relative Efficacy of AS03-Adjuvanted Pandemic Influenza A(H1N1) Vaccine in Children: Results of a Controlled, Randomized Efficacy Trial

Background. the vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to <10 years of age in a multinational study conducted during 2010-2011.Methods. A total of 6145 children were randomly assigned at a ratio of 1: 1: 1 to receive 2 injections 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009 (H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed.Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. the VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). the benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group.Conclusion. the 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics.GlaxoSmithKline BiologicalsUniv Melbourne, Murdoch Childrens Res Inst, Carlton, Vic 3010, AustraliaUniv Melbourne, Melbourne Sch Populat & Global Hlth, Carlton, Vic 3010, AustraliaGlaxoSmithKline Vaccines, King of Prussia, PA USANovavax, Rockville, MD USAMary Chiles Gen Hosp, Dept Pediat, Manila, PhilippinesDe La Salle Hlth Sci Inst, Dept Pediat, Dasmarinas City, PhilippinesRes Inst Trop Med, Dept Hlth, Muntinlupa, PhilippinesUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilFac Ciencias Med Santa Casa São Paulo, Dept Pediat, São Paulo, BrazilAssoc Fundo Incent Pesquisa, São Paulo, BrazilInst Costarricense Invest Clin, San Jose, Costa RicaNatl Inst Publ Hlth Mexico, Cuernavaca, Morelos, MexicoUniv Autonoma Nuevo Leon, Serv Med, Monterrey, MexicoInst Nacl Pediat Mexico, Mexico City, DF, MexicoHosp Gen Durango, Durango, MexicoPhramongkutklao Hosp, Infect Dis Unit, Dept Pediat, Bangkok, ThailandKhon Kaen Univ, Dept Pediat, Fac Med, Khon Kaen, ThailandNatl Healthcare Grp Polyclin, Singapore, SingaporeCtr Estudios Infect Pediat, Cali, ColombiaGlaxoSmithKline Vaccines, Wavre, BelgiumGlaxoSmithKline Vaccines, Rixensart, BelgiumUniversidade Federal de São Paulo, Dept Pediat, São Paulo, BrazilWeb of Scienc

Oxygen vacancies activating surface reactivity to favor charge separation and transfer in nanoporous BiVO4 photoanodes

The sluggish catalytic reactivity on the surface of most semiconductors is a common obstacle in developing photo-electrochemical (PEC) electrodes. Loading cocatalysts becomes a plausible scenario but remains challenging in the integration with semiconductors due to the complicated interfacial issues. This work introduces an feasible strategy of activating surface reactivity, alternative to cocatalysis, in cooperating with semiconductor photoactivity to boost PEC performance. We apply an ionized argon plasma technology on three-dimensional (3D) nanoporous BiVO4 (BVO) to controllably generate surface oxygen vacancies, which enable surface activation favoring charge separation and transfer towards water oxidation reaction (WOR). A remarkable photocurrent density of 4.32 mA cm−2 is achieved at 1.23 V versus reversible hydrogen electrode (RHE) under AM 1.5 G illumination, which is a record among the reported single BVO photoanodes and even surpasses the performances of most cocatalyst-assisted ones. This study provides an alternative solution to sluggish catalytic kinetics on semiconductor photoelectrodes, thus paving a novel avenue to modulate cooperation with photoactivity in PEC technology.This work was supported by the National Natural Science Foundation of China (Nos. 11974303, 11674276 and 11774302), the ANU Futures Scheme (Q4601024), the Australian Research Council (DP190100295, LE190100014), and the Qing Lan Project of Jiangsu Province and the Talent Program of Yangzhou Universit

Relative efficacy of AS03-adjuvanted pandemic influenza A(H1N1) vaccine in children: Results of a controlled, randomized efficacy trial

Background. The vaccine efficacy (VE) of 1 or 2 doses of AS03-adjuvanted influenza A(H1N1) vaccine relative to that of 2 doses of nonadjuvanted influenza A(H1N1) vaccine in children 6 months to /California/7/2009(H1N1)-AS03 vaccine at dose 1 and saline placebo at dose 2, 2 doses 21 days apart of A/California/7/2009(H1N1)-AS03 vaccine (the Ad2 group), or 2 doses 21 days apart of nonadjuvanted A/California/7/2009(H1N1) vaccine (the NAd2 group). Active surveillance for influenza-like illnesses continued from days 14 to 385. Nose and throat samples obtained during influenza-like illnesses were tested for A/California/7/2009(H1N1), using reverse-transcriptase polymerase chain reaction. Immunogenicity, reactogenicity, and safety were assessed. Results. There were 23 cases of confirmed 2009 pandemic influenza A(H1N1) (A[H1N1]pdm09) infection for the primary relative VE analysis. The VE in the Ad2 group relative to that in the NAd2 group was 76.8% (95% confidence interval, 18.5%-93.4%). The benefit of the AS03 adjuvant was demonstrated in terms of the greater immunogenicity observed in the Ad2 group, compared with the NAd2 group. Conclusion. The 4-8-fold antigen-sparing adjuvanted pandemic influenza vaccine demonstrated superior and clinically important prevention of A(H1N1)pdm09 infection, compared with nonadjuvanted vaccine, with no observed increase in medically attended or serious adverse events. These data support the use of adjuvanted influenza vaccines during influenza pandemics. Clinical Trials Registration. NCT01051661. © 2014 The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America

A Bayesian reanalysis of the Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial

Background Timing of initiation of kidney-replacement therapy (KRT) in critically ill patients remains controversial. The Standard versus Accelerated Initiation of Renal-Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial compared two strategies of KRT initiation (accelerated versus standard) in critically ill patients with acute kidney injury and found neutral results for 90-day all-cause mortality. Probabilistic exploration of the trial endpoints may enable greater understanding of the trial findings. We aimed to perform a reanalysis using a Bayesian framework. Methods We performed a secondary analysis of all 2927 patients randomized in multi-national STARRT-AKI trial, performed at 168 centers in 15 countries. The primary endpoint, 90-day all-cause mortality, was evaluated using hierarchical Bayesian logistic regression. A spectrum of priors includes optimistic, neutral, and pessimistic priors, along with priors informed from earlier clinical trials. Secondary endpoints (KRT-free days and hospital-free days) were assessed using zero–one inflated beta regression. Results The posterior probability of benefit comparing an accelerated versus a standard KRT initiation strategy for the primary endpoint suggested no important difference, regardless of the prior used (absolute difference of 0.13% [95% credible interval [CrI] − 3.30%; 3.40%], − 0.39% [95% CrI − 3.46%; 3.00%], and 0.64% [95% CrI − 2.53%; 3.88%] for neutral, optimistic, and pessimistic priors, respectively). There was a very low probability that the effect size was equal or larger than a consensus-defined minimal clinically important difference. Patients allocated to the accelerated strategy had a lower number of KRT-free days (median absolute difference of − 3.55 days [95% CrI − 6.38; − 0.48]), with a probability that the accelerated strategy was associated with more KRT-free days of 0.008. Hospital-free days were similar between strategies, with the accelerated strategy having a median absolute difference of 0.48 more hospital-free days (95% CrI − 1.87; 2.72) compared with the standard strategy and the probability that the accelerated strategy had more hospital-free days was 0.66. Conclusions In a Bayesian reanalysis of the STARRT-AKI trial, we found very low probability that an accelerated strategy has clinically important benefits compared with the standard strategy. Patients receiving the accelerated strategy probably have fewer days alive and KRT-free. These findings do not support the adoption of an accelerated strategy of KRT initiation

Regional Practice Variation and Outcomes in the Standard Versus Accelerated Initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) Trial: A Post Hoc Secondary Analysis.

ObjectivesAmong patients with severe acute kidney injury (AKI) admitted to the ICU in high-income countries, regional practice variations for fluid balance (FB) management, timing, and choice of renal replacement therapy (RRT) modality may be significant.DesignSecondary post hoc analysis of the STandard vs. Accelerated initiation of Renal Replacement Therapy in Acute Kidney Injury (STARRT-AKI) trial (ClinicalTrials.gov number NCT02568722).SettingOne hundred-fifty-three ICUs in 13 countries.PatientsAltogether 2693 critically ill patients with AKI, of whom 994 were North American, 1143 European, and 556 from Australia and New Zealand (ANZ).InterventionsNone.Measurements and main resultsTotal mean FB to a maximum of 14 days was +7199 mL in North America, +5641 mL in Europe, and +2211 mL in ANZ (p p p p p p p p = 0.007).ConclusionsAmong STARRT-AKI trial centers, significant regional practice variation exists regarding FB, timing of initiation of RRT, and initial use of continuous RRT. After adjustment, such practice variation was associated with lower ICU and hospital stay and 90-day mortality among ANZ patients compared with other regions