Efficacy and Safety of Ensitrelvir in Patients With Mild-to-Moderate Coronavirus Disease 2019: The Phase 2b Part of a Randomized, Placebo-Controlled, Phase 2/3 Study.

BACKGROUND: This phase 2b part of a randomized phase 2/3 study assessed the efficacy and safety of ensitrelvir for mild-to-moderate coronavirus disease 2019 (COVID-19) during the Omicron epidemic. METHODS: Patients were randomized (1:1:1) to orally receive ensitrelvir fumaric acid 125 mg (375 mg on day 1) or 250 mg (750 mg on day 1) or placebo once daily for 5 days. The co-primary endpoints were the change from baseline in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) titer on day 4 and time-weighted average change from baseline up to 120 hours in the total score of predefined 12 COVID-19 symptoms. Safety was assessed through adverse events. RESULTS: A total of 341 patients (ensitrelvir 125-mg group: 114; ensitrelvir 250-mg group: 116; and placebo group: 111; male: 53.5-64.9%; mean age: 35.3-37.3 years) were included in the efficacy analyses. The change from baseline in SARS-CoV-2 titer on day 4 was significantly greater with both ensitrelvir doses than with placebo (differences from placebo: -0.41 log10 50% tissue-culture infectious dose/mL; P < .0001 for both). The total score of the 12 COVID-19 symptoms did not show a significant difference between the ensitrelvir groups and placebo group. The time-weighted average change from baseline up to 120 hours was significantly greater with ensitrelvir versus placebo in several subtotal scores, including acute symptoms and respiratory symptoms. Most adverse events were mild in severity. CONCLUSIONS: Ensitrelvir treatment demonstrated a favorable antiviral efficacy and potential clinical benefit with an acceptable safety profile. CLINICAL TRIALS REGISTRATION: Japan Registry of Clinical Trials: jRCT2031210350 (https://jrct.niph.go.jp/en-latest-detail/jRCT2031210350).

Baloxavir safety and clinical and virologic outcomes in influenza virus-infected pediatric patients by age group: age-based pooled analysis of two pediatric studies conducted in Japan.

BACKGROUND: Anti-influenza treatment is important for children and is recommended in many countries. This study assessed safety, clinical, and virologic outcomes of baloxavir marboxil (baloxavir) treatment in children based on age and influenza virus type/subtype. METHODS: This was a post hoc pooled analysis of two open-label non-controlled studies of a single weight-based oral dose of baloxavir (day 1) in influenza virus-infected Japanese patients aged < 6 years (n = 56) and ≥ 6 to < 12 years (n = 81). Safety, time to illness alleviation (TTIA), time to resolution of fever (TTRF), recurrence of influenza illness symptoms and fever (after day 4), virus titer, and outcomes by polymerase acidic protein variants at position I38 (PA/I38X) were evaluated. RESULTS: Adverse events were reported in 39.0 and 39.5% of patients < 6 years and ≥ 6 to < 12 years, respectively. Median (95% confidence interval) TTIA was 43.2 (36.3-68.4) and 45.4 (38.9-61.0) hours, and TTRF was 32.2 (26.8-37.8) and 20.7 (19.2-23.8) hours, for patients < 6 years and ≥ 6 to < 12 years, respectively. Symptom and fever recurrence was more common in patients < 6 years with influenza B (54.5 and 50.0%, respectively) compared with older patients (0 and 25.0%, respectively). Virus titers declined (day 2) for both age groups. Transient virus titer increase and PA/I38X-variants were more common for patients < 6 years. CONCLUSIONS: The safety and effectiveness of single-dose baloxavir were observed in children across all age groups and influenza virus types. Higher rates of fever recurrence and transient virus titer increase were observed in children < 6 years. TRIAL REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information JapicCTI-163,417 (registered 02 November 2016) and JapicCTI-173,811 (registered 15 December 2017).

Open-label study of the safety, pharmacokinetics, and effectiveness of a 2 mg/kg dose of baloxavir marboxil 2% granules in children <20 kg with influenza.

INTRODUCTION: Baloxavir marboxil is an oral anti-influenza drug with demonstrated safety and efficacy in pediatric patients when a 2% granules formulation is administered at 1 mg/kg. This study assessed safety, effectiveness, and pharmacokinetics of a higher dose (2 mg/kg) of baloxavir marboxil 2% granules in pediatric patients weighing <20 kg. METHODS: This multicenter, open-label, noncontrolled study was conducted at 15 sites in Japan (January 2019-March 2020; JapicCTI-194577). Patients aged <12 years with confirmed influenza received a single oral dose of baloxavir marboxil at 2 mg/kg if body weight was <10 kg or 20 mg if ≥ 10 to <20 kg. Safety, pharmacokinetics, effectiveness (time to illness alleviation [TTIA] of influenza; time to resolution of fever; virus titer), and polymerase acidic protein (PA) substituted viruses were assessed over 22 days. RESULTS: 45 patients, all aged ≤6 years, were enrolled. Adverse events were reported in 24 (53.3%) patients, most commonly nasopharyngitis, diarrhea, and upper respiratory tract infection. Median (95% confidence interval [CI]) TTIA was 37.8 (27.5-46.7) hours; median (95% CI) time to resolution of fever was 22.0 (20.2-28.6) hours. A >4 log decrease in mean viral titer occurred at day 2 and a subsequent temporary 1-2 log increase in patients with influenza A(H3N2) and B. Treatment-emergent PA/I38X-substituted virus was detected in 16/39 (41.0%) patients, but no prolonged TTIA or time to resolution of fever was associated with its presence. CONCLUSIONS: Baloxavir granules administered at 2 mg/kg in children <20 kg were well tolerated, with symptom alleviation similar to 1 mg/kg.

Baloxavir Marboxil in Japanese Pediatric Patients With Influenza: Safety and Clinical and Virologic Outcomes.

BACKGROUND: We assessed the safety and effectiveness of baloxavir marboxil administration in Japanese children with influenza. METHODS: This open-label study administered 1 weight-adjusted dose of baloxavir to 107 children aged 1-11 years with laboratory-confirmed, febrile influenza virus infection of ≤48 hours duration. RESULTS: Adverse events (AEs) were reported in 34.6% of patients, most commonly vomiting (7.5%); no serious AEs or AEs causing discontinuation occurred. The median time to alleviation of influenza illness was 44.6 hours (95% confidence interval, 38.9-62.5 hours), to resolution of fever was 21.4 hours, and to sustained cessation of infectious viral shedding was 24.0 hours. However, viruses with amino acid substitutions in the viral polymerase acidic protein at position I38 (PA/I38T/M) emerged in 18 of 77 (23.4%) patients. Emergence was associated with longer infectious virus detectability (median time, 180.0 hours) and time to illness alleviation (median, 79.6 vs 42.8 hours in patients without PA/I38T/M-substituted viruses). Among patients with PA/I38T/M-substituted virus emergence, those with baseline hemagglutinin inhibition (HAI) antibody titer <40 experienced delay in time to illness alleviation (median, 85.4 vs 56.0 hours in patients with higher baseline HAI antibody titer). CONCLUSIONS: A single, oral dose of baloxavir marboxil was well tolerated and rapidly reduced viral titers, but the common emergence of PA/I38T/M-substituted viruses warrants consideration of alternative dosing regimens in young children. CLINICAL TRIALS REGISTRATION: Japan Pharmaceutical Information Center Clinical Trials Information (Japic CTI-163417).

Serum surfactant protein D as a predictive biomarker for the efficacy of pirfenidone in patients with idiopathic pulmonary fibrosis: a post-hoc analysis of the phase 3 trial in Japan.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disorder with a variable disease course. The recent advancement of antifibrotic therapy has increased the need for reliable and specific biomarkers. This study aimed to assess alveolar epithelial biomarkers as predictors for the efficacy of the antifibrotic drug pirfenidone. METHODS: We conducted a post-hoc analysis of the prospective, multicenter, randomized, placebo-controlled, phase 3 trial of pirfenidone in Japan (total, n = 267; pirfenidone, n = 163; placebo, n = 104). Logistic regression analysis was performed to extract parameters that predicted disease progression, defined by a ≥ 10% relative decline in vital capacity (VC) from baseline and/or death, at week 52. For assessment of serum surfactant protein (SP)-D, SP-A and Krebs von den Lungen (KL)-6, all patients were dichotomized by the median concentration of each biomarker at baseline to the high and low biomarker subgroups. Associations of these concentrations were examined with changes in VC at each time point from baseline up to week 52, along with progression-free survival (PFS). Additionally, the effect of pirfenidone treatment on serial longitudinal concentrations of these biomarkers were evaluated. RESULTS: In the multivariate logistic regression analysis, body mass index (BMI), %VC and SP-D in the pirfenidone group, and BMI and %VC in the placebo group were indicated as predictors of disease progression. Pirfenidone treatment reduced the decline in VC with statistical significance in the low SP-D and low SP-A subgroups over most of the treatment period, and also prolonged PFS in the low SP-D and low KL-6 subgroups. Furthermore, SP-D levels over time course were reduced in the pirfenidone group from as early as week 8 until the 52-week treatment period compared with the placebo group. CONCLUSIONS: Serum SP-D was the most consistent biomarker for the efficacy of pirfenidone in the cohort trial of IPF. Serial measurements of SP-D might have a potential for application as a pharmacodynamic biomarker. Trial registration The clinical trial was registered with the Japan Pharmaceutical Information Center (JAPIC) on September 13, 2005 (registration No. JapicCTI-050121; http://Clinicaltrials.jp ).

Functional ionic liquids for enhancement of Li-ion transfer: the effect of cation structure on the charge-discharge performance of the Li4Ti5O12 electrode.

As the development of high energy-density Li-ion batteries moves ahead, ensuring safety of the batteries has become increasingly important. Among the unique physicochemical properties of ionic liquids, thermal stability can be one of the answers to the challenge. The use of ionic liquids, however, causes critical issues concerning the kinetics of Li-ion transfer at the electrode-electrolyte interface. In the present study, ionic liquids consisting of 1-((2-methoxyethoxy)methyl)-1-methylpiperidinium (PP1MEM) or 1-hexyl-1-methylpiperidinium (PP16) and bis(trifluoromethanesulfonyl)amide (TFSA) were applied to an electrolyte for Li-ion batteries, and we investigated the effect of cation structure on interfacial Li-ion transfer using Li4Ti5O12 as a model electrode by means of Raman spectroscopy and electrochemical impedance spectroscopy. It was found that the ether functional group in the PP1MEM cation has the meaningful function; the cation structure reduces the electrostatic interaction between the Li ion and TFSA anions in an ionic liquid electrolyte. The solvation number of the TFSA anion per Li ion consequently became smaller than that in PP16-TFSA, and the lower solvation number in PP1MEM-TFSA allowed the facile Li-ion diffusion in the electrolyte bulk rather than the interfacial Li-ion transfer and significantly improved the rate performance. The results offer the prospect of utilization of PP1MEM-TFSA as an electrolyte solvent. The knowledge obtained from this study contributes to the development of next-generation Li-ion batteries having both high energy density and high safety.

Effects on anemia of drug adjustment in patients with chronic hepatitis C during telaprevir-combined therapy.

AIM: Anemia is the most common adverse event in patients with chronic hepatitis C virus (HCV) treated with telaprevir (TVR) combined triple therapy. We examined the effects of drug dose adjustment on anemia and a sustained viral response (SVR) during combination therapy. MATERIAL AND METHODS: This study enrolled 62 patients treated with TVR (2,250 mg) for 12 weeks plus pegylated interferon-alpha-2b and ribavirin for 24 weeks. The patients were assigned randomly to the TVR-standard or -reduced groups before treatment. At the occurrence of anemia (hemoglobin < 12 g/dL), the TVR-reduced group received 1500 mg TVR plus the standard dose of ribavirin, whereas the TVR-standard group received the standard TVR dose (2,250 mg) and a reduced dose of ribavirin (200 mg lower than prescribed originally). The safety and SVR at 24 weeks were compared between the TVR-standard (n = 28) and TVR-reduced (n = 25) groups. RESULTS: No differences in the proportion of patients who became HCV RNA-negative were detected between the TVR-standard and -reduced groups (72 and 72% at week 4, 79 and 84% at the end of treatment, and 76 and 80% at SVR24, respectively). Two groups had comparable numbers of adverse events, which led to the discontinuation of TVR in 14 patients of TVR-standard group and in 14 of TVR-reduced group. A lower incidence of renal impairment was observed in the TVR-reduced group (6%) than the TVR-standard group (11%, not statistically significant). CONCLUSIONS: TVR dose adjustment could prevent anemia progression without weakening the anti-viral effect during triple therapy in HCV-patients.

Coating of Chlorophylls a and b Enhanced Photoelectrochemical Capacitor Reaction of TiO2/MnO2 Composite Electrode.

We prepared composite electrodes using TiO2 coated with chlorophylls a and b as photoelectric conversion material and MnO2 as energy storage material and investigated their photoelectrochemical capacitor properties. The coating with the combination of chlorophylls a and b improved the photoelectric conversion function of TiO2, compared with the coating with each alone. Na+ adsorption on MnO2 was enhanced with increasing the chlorophyll coating amount. The reason is that more chlorophylls a and b absorb visible light in different wavelengths to promote an easier photoexcited electron transfer to MnO2, just as they improve the efficiency of photosynthesis reactions in nature.

Efficacy and Safety of Ensitrelvir for Asymptomatic or Mild COVID-19: An Exploratory Analysis of a Multicenter, Randomized, Phase 2b/3 Clinical Trial.

BACKGROUND: This phase 2b/3, randomized, placebo-controlled trial explored the efficacy and evaluated the safety of ensitrelvir. This trial involved individuals with asymptomatic infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and patients with mild symptoms of coronavirus disease 2019 (COVID-19). METHODS: The trial was conducted at 57 medical institutions in Japan, South Korea, and Vietnam (study period: January 6-August 14, 2022). Eligible participants were randomized (1:1:1) to the ensitrelvir 125-mg, ensitrelvir 250-mg, or placebo group, received the allocated intervention orally, and were followed up until Day 28. Participants self-rated the severity of 14 typical COVID-19 symptoms and recorded the data in an electronic diary. RESULTS: In total, 572 participants (194, 189, and 189 in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively) were included in the intention-to-treat population. Ensitrelvir 125-mg group observed a 77% reduction in the risk of developing any of the 14 COVID-19 symptoms or fever and a 29% reduction in the risk of worsening of such symptoms or fever versus placebo (statistically nonsignificant). The viral RNA, viral titer, and time to infectious viral clearance observed a statistically significant decrease versus placebo. Most treatment-related adverse events (TEAEs) were mild to moderate in severity, and the most common TEAE observed across groups was a decrease in high-density lipoprotein. CONCLUSIONS: Our exploratory results suggest a potential reduction in the risk of development or worsening of COVID-19 symptoms with ensitrelvir. Ensitrelvir showed antiviral efficacy and was well tolerated. TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT2031210350.

Prevention of Post COVID-19 Condition by Early Treatment with Ensitrelvir in the Phase 3 SCORPIO-SR Trial.

This exploratory analysis of the double-blind, phase 3, SCORPIO-SR trial assessed the effect of ensitrelvir in preventing post coronavirus disease 2019 (COVID-19) condition (PCC). Patients with mild-to-moderate COVID-19 were randomized (1:1:1) within 120 hours of symptom onset; received 5-day oral ensitrelvir 125 mg (375 mg on day 1), 250 mg (750 mg on day 1), or a matching placebo once daily; and were assessed for the severity of typical PCC symptoms using a self-administered questionnaire. In total, 341, 317, and 333 patients were assessed in the ensitrelvir 125-mg, ensitrelvir 250-mg, and placebo groups, respectively (mean age, 35.6-36.5 years; men, 53.3%-58.3%). On days 85, 169, and 337, ensitrelvir 125-mg treatment showed 32.7% (95% confidence interval [CI]: -30.6, 66.1), 21.5% (95% CI: -37.3, 55.6), and 24.6% (95% CI: -43.7, 60.9) reductions versus placebo, respectively, in the risk of any of the 14 acute-phase COVID-19 symptoms (at least one mild, moderate, or severe symptom with general health not returning to the usual level). Ensitrelvir 250-mg treatment showed 10.9% (95% CI: -67.0, 52.8), 9.5% (95% CI: -56.6, 48.0), and 30.6% (95% CI: -36.2, 65.5) risk reductions versus placebo on days 85, 169, and 337, respectively. Risk reductions were observed in any of the 4 neurological symptoms and were more pronounced among patients with high acute-phase symptom scores at baseline and among those with a baseline body mass index ≥25 kg/m2. Ensitrelvir treatment in the acute phase of COVID-19 may reduce the risk of various symptoms associated with PCC. TRIAL REGISTRATION NUMBER: jRCT2031210350.

Real-time PCR assays for hepatitis C virus RNA (genotype 1) is useful for evaluating virological response to the treatment with peginterferon-alpha2b and ribavirin.

BACKGROUND: The real-time PCR, such as Abbott RealTime assay, have replaced end-point PCR, such as Amplicor assays, for the measurement of HCV RNA. However, 'response-guided therapy' to use on-treatment response for tailoring the duration of treatment with peginterferon-alpha and ribavirin has not been fully evaluated for real-time PCR. METHODS: 43 patients with HCV genotype 1 (24 who had complete early virological responses (cEVR) on Amplicor assay and received 48-week therapy, and 19 who had late virological responses (LVR) and received 72-week therapy) were recruited. Using a RealTime assay, we retrospectively measured HCV RNA in stored sera. RESULTS: In 10 samples obtained during therapy, HCV RNA was undetectable on the Amplicor assay, but detectable on the RealTime assay. Among patients with cEVR on the Amplicor assay, those with detectable HCV RNA on the RealTime assay at week 12 were less likely to have a sustained virological response (SVR) than those without (2/4 vs 17/20, p = 0.116). Among patients with LVR on the Amplicor assay, those with HCV RNA detectable on the RealTime assay at week 24 were significantly less likely to have SVR than those without (1/4 vs 12/15, p = 0.041). CONCLUSIONS: The RealTime assay may be useful for tailoring duration of treatment for the patient with HCV genotype 1.

Benefits of artificially induced pleural effusion and/or ascites for percutaneous radiofrequency ablation of hepatocellular carcinoma located on the liver surface and in the hepatic dome.

BACKGROUND/AIMS: Radiofrequency ablation (RFA) with artificial pleural effusion and/or artificial ascites has recently been recognized as a useful device for the treatment of hepatocellular carcinoma (HCC). However, the indication of this technique is unclear and its therapeutic efficacy is undetermined. METHODOLOGY: We decided the precise indication for the use of artificial infusion. Artificial pleural effusion was indicated for tumors located on the dorsal side of the liver surface in the right lobe. Artificial ascites were indicated for (i) tumors located on the ventral side of the liver surface in the right lobe; (ii) tumors that could not be completely visualized but located near the liver surface in the right lobe; and (iii) tumors on the liver surface and adjacent to organs. RESULTS: The total local recurrence rates at 1 and 2 years were 4% and 22%, respectively. The estimated survival rates of 32 naïve patients at 1 and 3 years were 90% and 78%, respectively. The local recurrence rates of a tumor size of <3 cm and >3 cm at 2 years were 22% and 17%, respectively. CONCLUSIONS: RFA with artificial pleural effusion and/or ascites is effective for tumors located on the liver surface and in the hepatic dome.

Impact of Low Temperatures on the Lithiation and Delithiation Properties of Si-Based Electrodes in Ionic Liquid Electrolytes.

Lithium-ion batteries are used in various extreme environments, such as cold regions and outer space; thus, improvements in energy density, safety, and cycle life in these environments are urgently required. We investigated changes in the charge and discharge properties of Si-based electrodes in ionic liquid electrolytes with decreasing temperature and the cycle life at low temperature. The reversible capacity at low temperature was determined by the properties of the surface film on the electrodes and/or the ionic conductivity of the electrolytes. The electrode coated with a surface film formed at a low temperature exhibited insufficient capacity. In contrast, a Si-only electrode precoated with the surface film at room temperature exhibited a cycle life at low temperatures in ionic liquid electrolytes longer than that in conventional organic liquid electrolytes. Doping phosphorus into Si led to improved cycling performance, and its impact was more noticeable at lower temperatures.

Improvement of the Anode Properties of Lithium-Ion Batteries for SiO x with a Third Element.

Silicon oxide (SiO x ) has been placed into practical use as an anode active material for next-generation Li-ion batteries because it has a higher theoretical capacity than graphite anodes. However, the synthesis method is typically vapor deposition, which is expensive, and the poor electron conductivity of SiO x restricts high performance. In this study, we prepared M/SiO x active materials consisting of SiO x and a third element (M = Al, B, Sn) using a low-cost mechanical milling (MM) method and investigated their electrode properties as Li-ion battery anodes. Also, the authors added a third element to improve the conductivity of the SiO2 matrix. Al, B, and Sn were selected as elements that do not form a compound with Si, exist as a simple substance, and can be dispersed in SiO2. As a result, we confirmed that SiO x has a nanostructure of nanocrystalline Si dispersed in an amorphous-like SiO2 matrix and that the third element M exists not in the nanocrystalline Si but in the SiO2 matrix. The electron conductivity of SiO x was improved by the addition of B and Sn. However, it was not improved by the addition of Al. This is because Al2O3 was formed in the insulator due to the oxidization of Al. The charge-discharge cycle tests revealed that the cycle life was improved from 170 cycles to 330 or 360 cycles with the addition of B or Sn, respectively. The improvement in electron conductivity is assumed to make it possible for SiO2 to react with Li ions more uniformly and form a structure that can avoid the concentration of stress due to the volume changes of Si, thereby suppressing the electrode disintegration.

Anode Properties of Cr x V1-x Si2/Si Composite Electrodes for Lithium-Ion Batteries.

We have reported the effects of substituting a transition metal in silicide on the electrochemical performance of the silicide/Si composite anode for lithium-ion batteries (LIBs); the Cr0.5V0.5Si2/Si electrode exhibited much better cyclability compared with CrSi2/Si and VSi2/Si electrodes. Herein, we investigated the electrochemical performance of a Cr x V1-x Si2/Si slurry electrode for its application in LIBs, and the results obtained were compared to those of a gas deposition (GD) electrode, which was comprised of only active materials. The slurry electrode exhibited a superior cycling life as with the GD electrode. After charge-discharge cycles, the expansion of the electrode thickness of CrSi2/Si and Cr0.5V0.5Si2/Si was smaller than that of VSi2/Si, and VSi2 was significantly pulverized compared with the other silicides. It is considered that VSi2 deformed easily by the stress from Si expansion and pulverized because the hardness of VSi2 was the smallest among the silicides used in this study. These results reveal that Cr0.5V0.5Si2/Si has great potential as an anode material for next-generation LIBs and hardness is an important property for compositing silicide with Si.

Regeneration of Nicotinamide Adenine Dinucleotide Phosphate by a Chlorophyll a-Coated TiO2 Film Electrode.

A TiO2 electrode was coated with chlorophyll a to regenerate nicotinamide adenine dinucleotide phosphate (NADPH), which can enhance the photovoltages of the electrodes for photoelectrochemical capacitors. The photovoltage of an uncoated TiO2 electrode was high during the first cycle but then steadily reduced owing to the oxidization of NADPH in the electrolyte during the photo-charge-discharge cycling. By contrast, a chlorophyll a-coated TiO2 electrode maintained high photovoltages for 100 cycles. Residual NADPH concentrations after 100 cycles increased from 73% to 90% because of the coating, demonstrating that NADPH was regenerated by photoexcited chlorophyll a similar to a photosynthetic reaction in nature.

Lithiation/Delithiation Properties of Lithium Silicide Electrodes in Ionic-Liquid Electrolytes.

We investigated the impact of electrolyte difference on lithiation and delithiation properties of a Li1.00Si electrode to improve the Coulombic efficiency (CE) of Si-based electrodes. The results of X-ray diffraction, Raman spectroscopy, and soft X-ray emission spectroscopy demonstrated that a portion of the Li in Li1.00Si desorbed by simply immersing the electrode in an ionic-liquid electrolyte, that is, the phase transition of Li1.00Si to Si occurred. In contrast, this phenomenon was not confirmed in an organic-liquid electrolyte. Instead, the desorbed Li was consumed for the formation of a surface film; thus, the Li in Li1.00Si did not elute into the electrolyte. The addition of vinylene carbonate (VC) to the ionic-liquid electrolyte suppressed the phase transition of Li1.00Si to Si. Although the Li1.00Si electrode showed a low initial CE and poor cycling performance in a VC-free electrolyte, the electrode exhibited a high CE and a remarkable cycle life in the VC-added electrolyte. It was considered that no desorption of the mechanically added Li in Li1.00Si contributed to the superior cycle life; thus, the characteristic ductility, malleability, and high electrical conductivity of lithium silicide should improve the electrochemical performance.

Reaction Behavior of a Silicide Electrode with Lithium in an Ionic-Liquid Electrolyte.

Silicides are attractive novel active materials for use in the negative-electrodes of next-generation lithium-ion batteries that use certain ionic-liquid electrolytes; however, the reaction mechanism of the above combination is yet to be clarified. Possible reactions at the silicide electrode are as follows: deposition and dissolution of Li metal on the electrode, lithiation and delithiation of Si, which would result from the phase separation of the silicide, and alloying and dealloying of the silicide with Li. Herein, we examined these possibilities using various analysis methods. The results revealed that the lithiation and delithiation of silicide occurred.

Indium-Doped Rutile Titanium Oxide with Reduced Particle Length and Its Sodium Storage Properties.

We hydrothermally synthesized In-doped rutile TiO2 particles in an anionic surfactant solution and investigated the influences of In doping and the particle morphology on the Na+ storage properties. The solid solubility limit was found to be 0.8 atom % in In-doped TiO2. In the case where no surfactant was used, the best anode performance was obtained for 0.8 atom % In-doped TiO2 electrode by the benefits of three doping effects: (i) expanded diffusion-path size, (ii) improved electronic conductivity, and (iii) reduced electron charge density in the path. Further enhancement in the performance was achieved for the In-doped TiO2 with a reduced particle length by the synthesis in the surfactant solution. This electrode exhibited a better cycle stability and maintained a high discharge capacity of 240 mA h g-1 for 200 cycles. The reason is probably that Na+ can be inserted in the inner part of TiO2 particles because of its reduced particle length.

Baloxavir Marboxil 2% Granules in Japanese Children With Influenza: An Open-label Phase 3 Study.

BACKGROUND: A granule formulation of baloxavir marboxil, a selective inhibitor of influenza cap-dependent endonuclease, was newly developed for children with difficulty swallowing tablets. METHODS: A multicenter open-label study was conducted during the 2017-2018 influenza season to assess the safety, pharmacokinetics and clinical/virologic outcomes of single, oral, weight-based doses of baloxavir granules in Japanese children infected with influenza virus. The primary clinical endpoint was the time to illness alleviation of influenza. RESULTS: All 33 enrolled children completed the study and received baloxavir (1 mg/kg for 12 children weighing <10 kg, 10 mg for 21 children weighing 10 to <20 kg). Detected viruses were influenza B (36.4%), A(H1N1)pdm09 (33.3%) and A(H3N2) (27.3%). Adverse events (AEs) were reported in 54.5% of children. No deaths, serious AEs or AEs leading to discontinuation were reported. The mean (SD) plasma concentrations of baloxavir acid at 24 hours post-dose were 72.8 (24.0) and 51.3 (19.3) ng/mL in the 1-mg/kg and 10-mg dose groups, respectively. The median time to illness alleviation (95% confidence interval) was 45.3 (28.5-64.1) hours. A >4-log decrease in infectious viral titer occurred on day 2 and a temporary 2-log increase on day 4. Polymerase acidic protein/I38T/M-substituted viruses were detected in 5 children infected with influenza A, but none with influenza B. CONCLUSIONS: Baloxavir granules and the weight-based dose regimen were considered to be well tolerated in children, with rapid influenza virus reduction and associated symptom alleviation. Evidence of baloxavir activity against influenza B was observed, but further data are required for confirmation.