Updated efficacy and safety of taletrectinib in patients (pts) with ROS1+ non-small cell lung cancer (NSCLC)

Background Taletrectinib is a potent, next-generation, CNS-active, ROS1 tyrosine kinase inhibitor (TKI) with selectivity over TRKB. In previous reports from TRUST-I, taletrectinib showed meaningful clinical efficacy and was well tolerated in pts with ROS1+ NSCLC (n = 109) regardless of crizotinib (CRZ) pretreatment status. We report updated efficacy and safety data with ~1.5 yr follow-up. Methods TRUST-I is a multicenter, open-label, single-arm study with two cohorts: ROS1 TKI-naive and CRZ-pretreated. Pts in both cohorts received taletrectinib 600 mg QD. Key study endpoints included IRC-confirmed ORR (cORR), DoR, disease control rate (DCR), PFS, and safety. A pooled analysis of ORR, PFS, and safety including pts from additional clinical trials was also conducted. Results In the 109 pts from TRUST-I (enrolled prior to Feb 2022) the median follow-up was 18.0 mo in TKI-naive (n = 67) and 16.9 mo in CRZ-pretreated pts (n = 42). cORR was 92.5% in TKI-naive and 52.6% in CRZ-pretreated pts (table). Median DoR (mDoR) and mPFS were not reached. Intracranial-ORR was 91.6%;ORR in pts with G2032R was 80.0%. In a pooled analysis with phase I studies, ORR was 89.5% and 50.0% for TKI-naive and CRZ-pretreated pts, respectively;mPFS was 33.2 mo and 9.8 mo. In 178 pts treated at 600 mg QD, treatment-emergent adverse events (TEAEs) were 92.7%;most (64.0%) were grade 1-2. The most common TEAEs were increased AST (60.7%), increased ALT (55.6%), and diarrhea (55.6%). Neurological TEAEs (dizziness, 18.5%;dysgeusia, 12.4%) and discontinuations due to TEAEs (3.4%) were low. Further updated results will be presented. [Formula presented] Conclusions With additional follow-up, taletrectinib continued to demonstrate meaningful efficacy outcomes including high response rates, prolonged PFS, robust intracranial activity, activity against G2032R, and tolerable safety with low incidence of neurological AEs. Clinical trial identification NCT04395677. Editorial acknowledgement Medical writing and editorial assistance were provided by Arpita Kulshrestha of Peloton Advantage, LLC, an OPEN Health company, and funded by AnHeart Therapeutics, Inc Legal entity responsible for the study AnHeart Therapeutics, Inc. Funding AnHeart Therapeutics, Inc. Disclosure S. He: Financial Interests, Personal, Other, Employment: AnHeart Therapeutics. T. Seto: Financial Interests, Institutional, Research Grant: AbbVie, Chugai Pharmaceutical, Daiichi Sankyo, Eli Lilly Japan, Kissei Pharmaceutical, MSD, Novartis Pharma, Pfizer Japan, Takeda Pharmaceutical;Financial Interests, Personal, Other, Employment: Precision Medicine Asia;Financial Interests, Personal, Speaker's Bureau, Honoraria for lectures: AstraZeneca, Bristol-Myers Squibb, Chugai Pharmaceutical, Covidien Japan, Daiichi Sankyo, Eli Lilly Japan, Kyowa Hakko Kirin, MSD, Mochida Pharmaceutical, Nippon Boehringer Ingelheim, Novartis Pharma, Ono Pharmaceutical, Pfizer Japan, Taiho Pharmaceutical, Takeda Pharmaceutical, Towa Pharmaceutical. C. Zhou: Financial Interests, Personal, Other, Consulting fees: Innovent Biologics Qilu, Hengrui, TopAlliance Biosciences Inc;Financial Interests, Personal, Speaker's Bureau, Payment or honoraria: Eli Lilly China, Sanofi, BI, Roche, MSD, Qilu, Hengrui, Innovent Biologics, C-Stone LUYE Pharma, TopAlliance Biosciences Inc, Amoy Diagnositics, AnHeart. All other authors have declared no conflicts of interest.Copyright © 2023 International Association for the Study of Lung Cancer. Published by Elsevier Inc.

Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: Experts' consensus statement (Fourth Edition). TT -.

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS - CoV - 2) infections have raged globally for more than 2 years. China has always adopted scientific and effective prevention and control measures to achieved some success. However, with the continuous variation of SARS - CoV -2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex. With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS - CoV - 2 infection in children in China. Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis,and according to the clinical characteristics and experience of children's cases,and puts forward recommendaions on the diagnostic criteria,laboratory examination,treatment,prevention and control of children's cases for providing reference for further guidance of effective prevention and treatment of SARS - CoV - 2 infection in children in China.Copyright © 2022 Chinese Journal of Applied Clinical Pediatrics. All rights reserved.

Implications of Design Assumptions for Pressure Sewer Network Performance: A New Zealand Study

Pressure sewer networks offer a flexible alternative to more traditional gravity-based systems for the conveyance of wastewater. Some of the issues associated with pressure sewer networks (e.g., odor, septicity) arise from inappropriate design assumptions. Daily inflow volumes are a crucial part of the design of pressure sewer systems;gravity design parameters are presently used to design pressure sewer networks in New Zealand. This study analyzed flow data from six representative pressure sewer networks (approximately 24% of operating pump units in New Zealand) to identify the daily inflow volumes per connected pump unit. The results indicated that the median inflow volume was approximately 410 L/pump unit/day. This inflow is much lower than current council design standard assumptions, which range from 650 to 1,000 L/pump unit/day. Pressure sewer network designs using higher daily loading rates may result in oversized networks that are detrimental to the network's operation and performance, especially for meeting minimum self-cleansing velocities and wastewater retention times. The data collection period included the first COVID-19 lockdown in New Zealand. Four lockdown levels were introduced, with Level 4 and Level 3 being the most restrictive and requiring all but essential workers to stay and work from home. Levels 1 and 2 allowed people to return to their place of work. The data indicated that the Level 4 lockdown period caused a 25% increase in daily inflow volumes. In comparison, the Level 3 and 2 lockdown periods increased the daily inflow volumes by 20% and 15%, respectively. The analysis also included the networks' wet-weather responses. Minor rain events did not significantly affect the daily inflow volumes. However, gravity networks that have been retrofitted with pressure sewer networks may be more subject to aging or damaged laterals and illegal stormwater connections, both of which are likely to result in a more significant wet-weather response. The paper also discusses the issues associated with an overreliance on standardized design methods without understanding their proper application and the pitfalls of adopting gravity sewer design assumptions for pressure sewer network designs. The findings of this paper will further allow determination of the sensitivity of network design outcomes, performance, and maintenance requirements to the design methods and assumptions for pressure sewer networks, not only in New Zealand but in any country that uses the technology. © 2022 American Society of Civil Engineers.

Diagnosis, treatment and prevention of severe acute respiratory syndrome coronavirus 2 infection in children: Experts' consensus statement (Fourth Edition)

Since December 2019, severe acute respiratory syndrome coronavirus 2(SARS - CoV - 2) infections have raged globally for more than 2 years. China has always adopted scientific and effective prevention and control measures to achieved some success. However, with the continuous variation of SARS - CoV -2 cases and imported cases from abroad, the prevention and control work has become more difficult and complex. With the variation of the mutant strain, the number of cases in children changed, and some new special symptoms and complications were found, which proposed a new topic for the prevention and treatment of SARS - CoV - 2 infection in children in China. Based on the third edition, the present consensus according to the characteristics of the new strain, expounded the etiology, pathology, pathogenesis,and according to the clinical characteristics and experience of children's cases,and puts forward recommendaions on the diagnostic criteria,laboratory examination,treatment,prevention and control of children's cases for providing reference for further guidance of effective prevention and treatment of SARS - CoV - 2 infection in children in China. © 2022 Chinese Journal of Applied Clinical Pediatrics. All rights reserved.

Adaptive scheme for crowd counting using off-the-shelf wireless routers

Since the outbreak of the world-wide novel coronavirus pandemic, crowd counting in public areas, such as in shopping centers and in commercial streets, has gained popularity among public health administrations for preventing the crowds from gathering. In this paper, we propose a novel adaptive method for crowd counting based on Wi-Fi channel state information (CSI) by using common commercial wireless routers. Compared with previous researches on device-free crowd counting, our proposed method is more adaptive to the change of environment and can achieve high accuracy of crowd count estimation. Because the distance between access point (AP) and monitor point (MP) is typically non-fixed in real-world applications, the strength of received signals varies and makes the traditional amplitude-related models to perform poorly in different environments. In order to achieve adaptivity of the crowd count estimation model, we used convolutional neural network (ConvNet) to extract features from correlation coefficient matrix of subcarriers which are insensitive to the change of received signal strength. We conducted experiments in university classroom settings and our model achieved an overall accuracy of 97.79% in estimating a variable number of participants. © 2022 CRL Publishing. All rights reserved.

Anxiety status and influencing factors of active psychological counselors in Shanghai under COVID-19 epidemic

Objective: To evaluate the impact of COVID-19 epidemic on anxiety status of active psychological counselors in Shanghai, China. Methods: We collected the demographic information of participants, cognition and attention to COVID-19, attitude towards the disappearance of COVID-19 and answers to the State-Trait Anxiety Inventory (STAI) on the Shanghai online psychological counseling platform from Feb 4th, 2020 to Mar 11st, 2020.Multiple Logistic regression was used to analyze the associations between COVID-19 epidemic and State-anxiety and Trait-anxiety. Results: Of 704 participants with an average age of 33.24 years (ranging from 18 to 73 years), the mean State-scores and Trait-scores were 44.49±6.31 and 46.19±5.22, respectively.In multivariate Logistic regression analysis, after gender stratification and adjustment of related variables, we found that for males, engaging in relevant prevention and control work was associated with a lower risk for medium or high State-anxiety (OR=0.28, 95%CI:0.09-0.89), and holding a intensively positive attitude was associated with a lower risk for medium or high Trait-anxiety (OR=0.25, 95%CI:0.07-0.87);while for females, those with medical background had a lower risk for State-anxiety (OR=0.17, 95%CI:0.03-0.92), and those paying moderate attention to epidemic had a lower risk for Trait-anxiety (OR=0.22, 95%CI:0.07-0.69). Conclusion: COVID-19 epidemic had different effects on the anxiety status of psychological counselors with different characteristics.Psychological counselors who have poor cognition of the epidemic, excessive attention to the epidemic, low hope for the disappearance of the epidemic, and non-disease prevention and control profession are more susceptible to greater anxiety, which are the key objects of protection in the event of public health emergencies. © 2021, Editorial Department of Fudan University Journal of Medical Sciences. All right reserved.