BACKGROUND: Disease-modifying therapies have been approved for the treatment of relapsing multiple sclerosis (RMS). The present study aims to examine the safety of teriflunomide in Chinese patients with RMS. METHODS: This non-randomized, multi-center, 24-week, prospective study enrolled RMS patients with variant (c.421C>A) or wild type ABCG2 who received once-daily oral teriflunomide 14 mg. The primary endpoint was the relationship between ABCG2 polymorphisms and teriflunomide exposure over 24 weeks. Safety was assessed over the 24-week treatment with teriflunomide. RESULTS: Eighty-two patients were assigned to variant ( n  = 42) and wild type groups ( n  = 40), respectively. Geometric mean and geometric standard deviation (SD) of pre-dose concentration (variant, 54.9 [38.0] μg/mL; wild type, 49.1 [32.0] μg/mL) and area under plasma concentration-time curve over a dosing interval (AUC tau ) (variant, 1731.3 [769.0] μg∙h/mL; wild type, 1564.5 [1053.0] μg∙h/mL) values at steady state were approximately similar between the two groups. Safety profile was similar and well tolerated across variant and wild type groups in terms of rates of treatment emergent adverse events (TEAE), treatment-related TEAE, grade ≥3 TEAE, and serious adverse events (AEs). No new specific safety concerns or deaths were reported in the study. CONCLUSION: ABCG2 polymorphisms did not affect the steady-state exposure of teriflunomide, suggesting a similar efficacy and safety profile between variant and wild type RMS patients. REGISTRATION NCT04410965, https://clinicaltrials.gov .
Humans ; Crotonates/adverse effects* ; Toluidines/adverse effects* ; Nitriles ; Hydroxybutyrates ; Female ; Male ; Adult ; ATP Binding Cassette Transporter, Subfamily G, Member 2/genetics* ; Middle Aged ; Multiple Sclerosis, Relapsing-Remitting/genetics* ; Prospective Studies ; Young Adult ; Neoplasm Proteins/genetics* ; East Asian People

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Objective It conducted a grounded theory on the factors influencing the sense of job significance of hospital administrators to provide suggestions and references for the promotion of high-quality development of hospital management work.Methods From April to September 2023,it interviewed 23 administrators from various departments across Provinces/Cities,including Zhejiang,Heilongjiang,Guangdong,Shanghai,Henan,Jilin,Sichuan and others,using a theoretical sampling method.Employing Grounded Theory,it encoded over transcriptional information at three levels.Results Three-level coding process yielded 66 free nodes,19 initial concepts,7 main categories,and 3 dimensions,leading to the development of a theoretical model encompassing existence,relatedness,and growth.Conclusion The job meaning for hospital administrators is shaped by existence,relatedness,and growth.It recommend revising performance assessments,fostering an empowering culture,enhancing informal communication,providing professional growth pathways,and offering diverse career development options to deepen administrators'job meaning.

Background The substantial health damage attributed to heat waves, along with their increasing intensity and frequency in the context of global warming, highlights the importance of exploring the health effects of heat waves. Objective To calculate the excess heat stroke cases during heat waves in the summer of 2013—2023 in Shanghai, analyze the association between heat waves and heat stroke, and to further explore the modifying effects of heat wave characteristics on heat stroke. Methods Using a retrospective ecological study design, data on heat stroke cases were collected from the heat stroke case reporting system of the Chinese Center for Disease Control and Prevention, and concurrent meteorological data from Xujiahui Meteorological Station. A heat wave was defined as at least 3 consecutive days with daily maximum temperature meeting or exceeding 35 ℃ in this study, excess heat stroke cases related to heat waves were assessed as the difference between the numbers of heat stroke cases observed on a given day and the corresponding 31 d (15 d before and after that day) moving average, and statistical analyses using generalized linear model based on time series study were performed to assess the impact of heat waves on heat stroke. Results Overall 25 heat waves during the study period were observed, leading to a total of estimated 792.6 extra heat stroke cases. The risk of heat stroke significantly increased during heat waves (RR=2.60, 95%CI: 2.08, 3.26), but no statistically significant differences in heat wave effects were observed among different genders, ages, or regions. In terms of the timing of heat waves, the risk of heat stroke was highest during the first heat wave (RR=3.58, 95%CI: 2.82, 4.55), which was significantly higher than that during the second heat wave (RR=2.19, 95%CI: 1.66, 2.90), and no significant effect was observed during the third or subsequent heat waves. The impact of heat waves on heat stroke persisted for more than 4 d, with the risk higher on the fourth day and beyond (RR=2.95, 95%CI: 2.28, 3.83), significantly higher than on the first day of heat wave (RR=1.74, 95%CI: 1.18, 2.56). Conclusion Heat waves had a substantial effect on heat stroke in Shanghai from 2013 to 2023, and special attention need to be paid to heat waves with early onset and long duration.