Comparative Effectiveness of Baloxavir Marboxil and Oseltamivir Treatment in Reducing Household Transmission of Influenza: A Post Hoc Analysis of the BLOCKSTONE Trial.

BACKGROUND: The transmission of influenza virus in households, especially by children, is a major route of infection. Prior studies suggest that timely antiviral treatment of ill cases may reduce infection in household contacts. The aim of the study was to compare the effects of oseltamivir (OTV) and baloxavir marboxil (BXM) treatment of index cases on the secondary attack rate (SAR) of influenza within household. METHODS: A post hoc analysis was done in BLOCKSTONE trial-a placebo-controlled, double-blinded post-exposure prophylaxis of BXM. Data were derived from the laboratory-confirmed index cases' household contacts who received placebo in the trial and also from household members who did not participate in the trial but completed illness questionnaires. To assess the SAR of household members, multivariate analyses adjusted for factors including age, vaccination status, and household size were performed and compared between contacts of index cases treated with BXM or OTV. RESULTS: In total, 185 index cases (116 treated with BXM and 69 treated with OTV) and 410 household contacts (201 from trial, 209 by questionnaire) were included. The Poisson regression modeling showed that the SAR in household contacts of index cases treated with BXM and OTV was 10.8% and 18.5%, respectively; the adjusted relative reduction in SAR was 41.8% (95% confidence interval: 1.0%-65.7%, p = 0.0456) greater with BXM than OTV. Similar reductions were found in contacts from the trial and those included by questionnaire. CONCLUSION: BXM treatment of index cases appeared to result in a greater reduction in secondary household transmission than OTV treatment.

Virtual reality perceptual training can improve the temporal discrimination ability of swinging during softball batting.

Perception and action uncoupling in fastball sports anticipatory training is often criticized. Nevertheless, perception-only training offers distinct advantages, such as flexibility concerning time, place, and injury limitations. Therefore, the effectiveness of this training approach warrants evaluation. This study developed a virtual reality (VR) training system based on the idea that the two visual pathways in the brain are associated with visual information attributes, rather than perception or action. A key feature of this study's perception-only training was its presentation of not only the opponent's kinematics but also the ball's flight information (the attributes that guide hitting) to train the visual system necessary for real situations. Seventeen female softball batters were assigned to two groups: a training group (N = 9) and a control group (N = 8). Only the training group underwent the VR anticipatory skill training to discriminate the different ball speeds. Both groups completed a perception test and an action test on the VR during the pre- and post-training periods. The perception test assessed response accuracy (RA) in discriminating ball speed, and the action test assessed the temporal difference in swing onset (delta onset). Comparison of these two outcome variables between groups revealed that perception-only training improved both perceptual and action responses. This study demonstrated the effectiveness of perception-only training and emphasized the need for its thoughtful utilization and design.

Determination of optimal prevention strategy for COVID-19 based on multi-agent simulation.

This study proposes a direction for the utilization of multi-agent simulation (MAS) to consider an optimal prevention strategy for the spread of the coronavirus disease of 2019 (COVID-19) through a pandemic modeling example in Japan. MAS can flexibly express macroscopic phenomena formed through the interaction of micro-agents modeled to act autonomously. The use of MAS can provide a variety of recommendations for bringing a pandemic under control, even in the case of the COVID-19 pandemic, which has become more intense as of 2021. However, models that do not consider individual heterogeneity, such as analytical Susceptible-Exposed-Infectious-Recovered (SEIR) models, are often used as predictive models for infectious diseases and the main reference for decision-making. In this study, we show that by constructing a MAS that simulates a metropolitan city in Japan in a simple manner while considering the heterogeneity of age and other background information, we can capture the effects of various measures such as vaccinations on the spread of infections in a more realistic setting. Moreover, it is possible to offer various recommendations for optimal strategies to suppress a pandemic by combining reinforcement learning with MAS. This study explicates the potential of MAS in the development of strategies to prevent the spread of infection.

Simplified Virtual Reality System Can Be Used to Evaluate the Temporal Discrimination Ability in Softball Batting as in the Real Environment.

Recently, virtual reality (VR) technology has developed rapidly and has increasingly come to be used in the sports field. VR technology ranges from large, highly immersive devices to simple devices such as smartphones, and the respective usefulness and shortcomings of different device types have been debated. Simple devices have advantages such as portability, but also provide only a weak sense of realism. It is important to understand the purpose and extent to which VR technologies can be used. Our purpose in this study was to briefly measure one of the cognitive-motor abilities used in softball batting: temporal discrimination ability in swing onset when a batter faces two types of balls thrown at different speeds. We investigated whether a simplified head-mounted display (HMD) system can evaluate such cognitive-motor ability to the same extent as in a real environment. Ten elite female softball batters swung at fastballs and slowballs randomly thrown by the same pitcher in both real and 3D VR environments, with the same range of trajectories. We then compared the temporal discrimination ability of swing onset analyzed by video analysis between environments. We found that the discrimination ability in VR is almost the same as in reality. In addition, questionnaire items on the VR system related to user experience and cybersickness showed overall promising responses. However, we also found that the system had some issues that need to be considered, such as leading to early swing onset and large variability in it. We discussed the usefulness and limitations of the VR system by combining the results for swing onset with the questionnaire responses. By understanding the characteristics of VR technology and using it as an efficient evaluation and training of players, the sports field can make significant progress.

Effects of Lusutrombopag on Post-invasive Procedural Bleeding in Thrombocytopenic Patients with Chronic Liver Disease.

INTRODUCTION: Thrombocytopenia can increase the bleeding risk in patients with chronic liver disease (CLD) undergoing invasive procedures. Prophylactic platelet transfusion (PT) is often performed to increase platelet counts in patients with CLD undergoing invasive procedures to prevent bleeding. Lusutrombopag, a small-molecule thrombopoietin receptor agonist, is expected to be an alternative therapy to prophylactic PT. This study aimed to compare the effects between lusutrombopag and PT. METHODS: Data were obtained from a Japanese administrative database (April 2008-May 2019). Patients aged ≥ 18 years who underwent planned invasive procedures after the first CLD diagnosis and were observed for ≥ 30 days prior to invasive procedures were considered eligible. Patients who underwent planned invasive procedures with lusutrombopag prescription at 5-30 days before the procedure were categorized as the lusutrombopag group, whereas those who received PT at 1 day before and/or on the same day as the procedure, without lusutrombopag prescription, were classified as the PT group. Outcomes, including bleeding frequency during hospitalization and average medical costs (costs for prophylactic treatment and total costs between the day of the invasive procedure and 30 days after the invasive procedure), were compared between the groups after matching. RESULTS: Among 738,878 patients with CLD, 379 cases for each group were identified after matching. The incidence of bleeding events was lower in the lusutrombopag group than in the PT group (3.7% vs. 8.2%, p < 0.001). Average medical costs were lower in the lusutrombopag group than in the PT group ($6667 as of August 2021 vs. $7170, p = 0.011). CONCLUSION: Lusutrombopag is suggested to be effective as a prophylactic treatment for bleeding prevention in patients with CLD undergoing planned invasive procedures.

Changes in Platelet Counts and Thrombocytopenia Risk in Patients with Chronic Liver Disease with Different Etiologies Using Real-World Japanese Data.

INTRODUCTION: Thrombocytopenia, a common complication of chronic liver disease (CLD), adversely affects the treatment in patients requiring invasive procedures. Multiple pathophysiological mechanisms contribute to the development of thrombocytopenia; thus, its incidence could differ among CLD etiologies. We investigated the risk of decline in platelet counts and developing thrombocytopenia across different CLDs in a real-world Japanese setting. METHODS: A Japanese claims database including 25 million patients (April 2008-August 2018) was used. Patients with at least one CLD diagnosis were classified into nine mutually exclusive categories: hepatitis B, hepatitis C, hepatitis B and C, unspecified viral hepatitis, autoimmune hepatitis, toxin/drug-induced hepatitis, alcoholic hepatitis, nonalcoholic steatohepatitis, and others. A random effects model was used to estimate the changes in platelet counts; proportional hazard analyses were used to examine factors associated with the incidence of thrombocytopenia based on the diagnosis. Patients with laboratory test data as variables were included in each analysis. RESULTS: The simulation included 68,536 patients. The mean values representing changes in the platelet count were significantly negative in the hepatitis C patients and negative, though non-significant, in the hepatitis B, toxin/drug-induced hepatitis, alcoholic hepatitis, and nonalcoholic steatohepatitis patients. In the proportional hazard analysis, 708 of 22,728 patients had thrombocytopenia. The hazard ratio (HR) was significantly high for patients with hepatitis B (HR, 2.879; p < 0.001), hepatitis C (HR, 1.876; p < 0.001), and hepatitis B and C (HR, 2.992; p < 0.001). CONCLUSION: A decreasing tendency in platelet counts was observed in most CLD etiologies, with hepatitis C showing a significant decrease. The incidence of thrombocytopenia was mostly associated with hepatitis B and/or C. Further research is warranted to elucidate the discrepancy between the decline in platelet counts and thrombocytopenia diagnosis, considering the factors relevant to the diagnosis, such as the frequency of outpatient visits and CLD treatment.

Reconstructing the household transmission of influenza in the suburbs of Tokyo based on clinical cases.

BACKGROUND: Influenza is a public health issue that needs to be addressed strategically. The assessment of detailed infectious profiles is an important part of this effort. Household transmission data play a key role in estimating such profiles. We used diagnostic and questionnaire-based data on influenza patients at a Japanese clinic to estimate the detailed infectious period (as well as incubation period, symptomatic and infectious periods, and extended infectious period after recovery) and the secondary attack ratio (SAR) of influenza for households of various sizes based on a modified Cauchemez-type model. RESULTS: The data were from enrolled patients with confirmed influenza who were treated at the Hirotsu Clinic (Kawasaki, Japan) with a neuraminidase inhibitor (NAI) during six northern hemisphere influenza seasons between 2010 and 2016. A total of 2342 outpatients, representing 1807 households, were included. For influenza type A, the average incubation period was 1.43 days (95% probability interval, 0.03-5.32 days). The estimated average symptomatic and infective period was 1.76 days (0.33-4.62 days); the extended infective period after recovery was 0.25 days. The estimated SAR rose from 20 to 32% as household size increased from 3 to 5. For influenza type B, the average incubation period, average symptomatic and infective period, and extended infective period were estimated as 1.66 days (0.21-4.61), 2.62 days (0.54-5.75) and 1.00 days, respectively. The SAR increased from 12 to 21% as household size increased from 3 to 5. CONCLUSION: All estimated periods of influenza type B were longer than the corresponding periods for type A. However, the SAR for type B was less than that for type A. These results may reflect Japanese demographics and treatment policy. Understanding the infectious profiles of influenza is necessary for assessing public health measures.

Patient journey through cases of depression from claims database using machine learning algorithms.

Health insurance and acute hospital-based claims have recently become available as real-world data after marketing in Japan and, thus, classification and prediction using the machine learning approach can be applied to them. However, the methodology used for the analysis of real-world data has been hitherto under debate and research on visualizing the patient journey is still inconclusive. So far, to classify diseases based on medical histories and patient demographic background and to predict the patient prognosis for each disease, the correlation structure of real-world data has been estimated by machine learning. Therefore, we applied association analysis to real-world data to consider a combination of disease events as the patient journey for depression diagnoses. However, association analysis makes it difficult to interpret multiple outcome measures simultaneously and comprehensively. To address this issue, we applied the Topological Data Analysis (TDA) Mapper to sequentially interpret multiple indices, thus obtaining a visual classification of the diseases commonly associated with depression. Under this approach, the visual and continuous classification of related diseases may contribute to precision medicine research and can help pharmaceutical companies provide appropriate personalized medical care.

Comparison of Household Transmission of Influenza Virus From Index Patients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study.

BACKGROUND: Baloxavir marboxil (baloxavir) is expected to reduce influenza transmission by rapid reduction of viral load. The incidence of household transmission was compared between index patients (IPs) treated with baloxavir and those treated with neuraminidase inhibitors. METHODS: Using a Japanese claims database, the first family members with influenza diagnosis during the 2018-2019 influenza season were identified as IPs, and the diagnosis date was designated day 1. According to the anti-influenza drug dispensed to the IP, their families were classified into the oral baloxavir group and 3 controls: oral oseltamivir group (a primary control), inhaled zanamivir group, and inhaled laninamivir group. A household transmission was defined as influenza diagnosed for any non-IP family members during days 3-8. The incidence of household transmission was compared between groups using a logistic regression model adjusting backgrounds of IPs. RESULTS: The proportion of families with household transmission was 17.98% (15 226 of 84 672) in the baloxavir group and 24.16% (14 983 of 62 004) in the oseltamivir group. The covariate-adjusted odds ratio (oseltamivir/baloxavir) was 1.09 (95% confidence interval [95% CI], 1.05-1.12), which indicated significantly lower incidence in the baloxavir group. The adjusted odds ratios (controls/baloxavir) against zanamivir and laninamivir were 0.93 (95% CI, .89-.97) and 0.99 (95% CI, .96-1.02), respectively. CONCLUSIONS: Baloxavir may contribute to reduction in household transmission compared with oseltamivir. In comparison between baloxavir and inhalants, a similar reduction was not shown and it might be due to unmeasured confounding by administration route differences.

Comparison of Hospitalization Incidence in Influenza Outpatients Treated With Baloxavir Marboxil or Neuraminidase Inhibitors: A Health Insurance Claims Database Study.

BACKGROUND: Baloxavir marboxil (baloxavir) is a single-dose, oral antiinfluenza drug with a novel mechanism of action. We compared the incidence of hospitalization in patients treated with baloxavir vs neuraminidase inhibitors. METHODS: In this retrospective, observational, cohort study, we used real-world patient data extracted from a Japanese health insurance claims database. The enrollment period was 1 October 2018 to 17 April 2019. On day 1, eligible patients (N = 339 007) received baloxavir, oseltamivir, zanamivir, or laninamivir. Baseline characteristics were standardized using the inverse probability of treatment weighting method. The primary end point was the incidence of hospitalization (days 2-14). Secondary end points included antibacterial use, secondary pneumonia, and additional antiinfluenza drug use. RESULTS: Compared with the baloxavir group, the incidence of hospitalization was greater in the oseltamivir group (risk ratio [RR] and 95% confidence interval [CI], 1.41 [1.00-2.00]; risk difference [RD] and 95% CI, 0.06 [.01-.12]) and zanamivir group (RR, 1.85 [1.23-2.78]; RD, 0.11 [.02-.20]). Oseltamivir-treated patients were less likely to require antibacterials than baloxavir-treated patients (RR, 0.87 [.82-.91]). However, oseltamivir-treated patients were more likely to be hospitalized with antibacterials (RR, 1.70 [1.21-2.38]) or antibacterial injection (RR, 1.67 [1.17-2.38]) than baloxavir-treated patients (post hoc analysis). Compared with baloxavir-treated patients, additional antiinfluenza drug use was greater in oseltamivir-, zanamivir-, and laninamivir-treated patients (RR, 1.51 [1.05-2.18], 2.84 [2.04-3.96], and 1.68 [1.35-2.10], respectively). CONCLUSIONS: Baloxavir is an efficacious antiinfluenza treatment that may reduce hospitalization compared with oseltamivir and zanamivir. CLINICAL TRIALS REGISTRATION: University hospital Medical Information Network Clinical Trials Registry (UMIN000038159).