Objective:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objective To explore whether virtual reality(VR)combined with computerized cogni-tive training intervention can improve the cognitive function in elderly stroke patients.Methods A total of 202 stroke patients admitted to our department from January 2022 to January 2024 were recruited and randomly divided into control group(101 cases,traditional cognitive training intervention)and study group(101 cases,VR combined with computerized cognitive training in-tervention).Before and after 3 months of intervention,Montreal Cognitive Assessment Scale(MoCA),Mini-Mental State Examination(MMSE),National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FMA),Activities of Daily Living Scale(ADL)were applied,serum levels of dopamine,neuropeptide Y(NPY),5-hydroxytryptamine(5-HT)and norepineph-rine(NE)were detected,and P300 wave of event-related potential was measured.The results were compared before and after intervention,and between the two groups.Results After intervention,the scores of MoCA,MMSE and FMA,the levels of NPY,5-HT,NE,dopamine,and the ampli-tude of P300 wave were obviously higher in both groups when compared with those before inter-vention(P＜0.05).The study group obtained notably higher MoCA score(27.64±0.62 vs 26.83±0.65),MMSE score(27.67±0.61 vs 26.83±0.62),NPY,5-HT,NE,dopamine,FMA score and amplitude of P300 wave after intervention than the control group(P＜0.01).The NIHSS score,ADL score and latency in the two groups after intervention were significantly lower than those before intervention(P＜0.05),and the above indicators in the study group were significantly low-er than the control group(P＜0.01).Conclusion VR combined with computerized cognitive training intervention can effectively improve the cognitive function,neurological function,motor function and daily life function,and enhance the neurotransmitter levels in elderly stroke patients.

Objective:To investigate the influence of continuous infusion with long time on infusion precision of infusion pump,and establish a predictive model for flow velocity to predict the change of flow velocity of infusion pump after infusion with long time,so as to provide reference for the use of infusion pump in clinical treatment.Methods:Six infusion sets of different models,numbered A to F,were selected.A 24-hour continuous infusion experiment was conducted using an infusion pump with the above six infusion sets.The flow rate of the infusion pump was set to 100 mL/h,and real-time data of the infusion speed was recorded to evaluate the performance changes of the infusion pump under long-term continuous infusion.A flow rate prediction model for the infusion pump was established based on the research data,and the accuracy of the model was verified.Results:After 24 hours of continuous infusion,the infusion accuracy of infusion sets A to F showed varying degrees of decline over time.The final infusion accuracies were 96.47%,97.95%,92.56%,88.41%,89.26%,93.93%,respectively,with corresponding flow rate errors of 3.53%,2.05%,7.44%,11.59%,10.74%,6.07%.The prediction model established in this study was used to predict the flow rate of the infusion pump during 24-36 hours of continuous infusion.Compared with the actual flow rate under the same conditions,the difference was not statistically significant(P>0.05).Conclusion:Long-term continuous infusion affects the infusion accuracy of the infusion pump,resulting in a decrease in infusion speed.The established flow rate prediction model can accurately predict the flow rate of the infusion pump after long-term continuous infusion,providing a useful reference for the clinical application of infusion pumps.

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:The study investigated the full-time Clinical Research Coordinators (CRCs) working in hospitals on their current working situation and explored affecting factors to provide suggestions for a professional and systemic clinical research workforce establishment in municipal medical institutions.Methods:A questionnaire survey was designed for CRCs in municipal hospitals in Shanghai, descriptive and one-way cross-tabulation analysis were conducted, using t-test for continuous numerical variables, rank-sum test for count variables and chi-square test for categorical variables.Results:Totaling 177 CRCs in 9 municipal hospitals in Shanghai answered the questionnaire. The average age of the respondents was 28.56±7.299 years old. Their professional background was mainly nursing and pharmacy (139/177, 87.53%), and bachelor degree (114/177, 64.41%). Averagely worked 2.50±1.632 years, the average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. The CRCs employed by hospitals mainly undertook Investigator-Initiated clinical Trial/Research projects (IITs) (26/36, 72.22%), while the CRCs employed by SMO companies mainly undertook Industry-Sponsored Clinical Trial (IST) projects (96/141, 68.09%). 85.88% (152/117) of CRCs held GCP certificates valid within three years, and the proportion of CRCs employed by hospitals held GCP certificates was lower than that of SMO companies ( P<0.05). Among the CRCs employed by hospitals, 23 (63.89%) said they had no position or were not clear about their position; The CRCs in SMO companies were mainly primary and intermediate (χ 2=84.119, P<0.05). The average number of research projects undertaken by CRC was 3.45±2.179, and the average number of cumulative projects involved was 8.72±9.341. Conclusions:With the development of clinical research, the full-time specialized CRCs in medical institutions mainly have 2 sources: from SMO/CRO companies or self-employment by medical institutions. In general, there are still problems in the CRC talent team as unclear entry standards, insufficient, lack career positioning planning, large mobility, imperfect training system, and imperfect promotion mechanism. It is suggested to unify occupational access standards and set specialty in colleges or universities. Strengthen post-service education and training system, establish multi-party collaborative training mechanism, standardize the assessment and evaluation, improve the job title promotion system, to promote the rapid development of CRC team.

Objective To explore the clinical efficacy of low-frequency pulse therapy combined with ingestion-swallowing training in the treatment of patients with post-stroke dysphagia.Methods A retrospective study was conducted on 122 patients with post-stroke dysphagia admitted in our hospital from January 2022 to January 2024.According to different interventions,they were divid-ed into a control group(ingestion-swallowing training on the basis of conventional treatment,60 cases)and a combined treatment group(low-frequency pulse therapy and the treatments in the control group,62 cases).Before and after treatment,VFSS and standard swallowing assessment(SSA)were performed,hyoid bone movement displacement(hyoid bone forward and upward)and vertebrobasilar artery blood flow indicators[pulsatility index(PI),mean blood flow velocity(Vm),systolic blood flow velocity(Vs)]were observed,and serum levels of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected in all the patients.The chan-ges in quality of life(swallow quality of life questionnaire)and occurrence of complications during treatment were observed in the two groups.Results In both groups after treatment,the VFSS score,quality of life score and swallowing symptom score,hyoid bone forward and upward dis-tances,vertebrobasilar artery Vm and Vs,and serum NGF and BDNF levels were all risen signifi-cantly while the SSA score and vertebrobasilar artery PI were obviously declined when compared with the levels before treatment(P＜0.05).After treatment,the combined treatment group had more remarkably improved VFSS score,quality of life score,swallowing symptom score,hyoid bone forward and upward distances,vertebrobasilar Vm and Vs,and serum NGF and BDNF levels,and more notably declined SSA score and vertebrobasilar PI than the control group(P＜0.05,P＜0.01).No statistical difference was seen in the total incidence of complications between the combined treatment group and control group(4.8％vs 10.0％,P＞0.05).Conclusion Com-bined low-frequency pulse therapy and ingestion-swallowing training can effectively promote the recovery of swallowing function,increase the activity of hyoid bone,promote the vertebrobasilar artery blood flow and neurotrophic conditions,and thus improve the quality of life in patients with post-stroke dysphagia,with less complications.

Objective:To investigate the influence of continuous infusion with long time on infusion precision of infusion pump,and establish a predictive model for flow velocity to predict the change of flow velocity of infusion pump after infusion with long time,so as to provide reference for the use of infusion pump in clinical treatment.Methods:Six infusion sets of different models,numbered A to F,were selected.A 24-hour continuous infusion experiment was conducted using an infusion pump with the above six infusion sets.The flow rate of the infusion pump was set to 100 mL/h,and real-time data of the infusion speed was recorded to evaluate the performance changes of the infusion pump under long-term continuous infusion.A flow rate prediction model for the infusion pump was established based on the research data,and the accuracy of the model was verified.Results:After 24 hours of continuous infusion,the infusion accuracy of infusion sets A to F showed varying degrees of decline over time.The final infusion accuracies were 96.47%,97.95%,92.56%,88.41%,89.26%,93.93%,respectively,with corresponding flow rate errors of 3.53%,2.05%,7.44%,11.59%,10.74%,6.07%.The prediction model established in this study was used to predict the flow rate of the infusion pump during 24-36 hours of continuous infusion.Compared with the actual flow rate under the same conditions,the difference was not statistically significant(P>0.05).Conclusion:Long-term continuous infusion affects the infusion accuracy of the infusion pump,resulting in a decrease in infusion speed.The established flow rate prediction model can accurately predict the flow rate of the infusion pump after long-term continuous infusion,providing a useful reference for the clinical application of infusion pumps.

Objective:To investigate the efficacy and safety of intravesical injections of botulinum toxin A (BTX-A) for the treatment of pediatric refractory urinary frequency and incontinence (UFI), and to analyze the factors predicting the therapeutic effect of BTX-A injections.Methods:A retrospective case series study was made on 35 children with UFI [(12.3±4.2) years old], including 13 males (37.1%) and 22 females (62.9%), treated in the First Affiliated Hospital of Zhengzhou University from January 2021 to March 2024.Urotherapy and drug treatments were ineffective in all children, who then received intravesical injections of BTX-A.The urodynamic study (UDS) was performed 1 week before treatment and 3 months after treatment, and the Overactive Bladder Symptom Score (OABSS) and Incontinence Quality of Life (I-QOL) were collected.Perioperative and postoperative adverse events were also recorded.A global response assessment (GRA) score of ≥2 at 3 months postoperatively was defined as effective treatment.According to the postoperative GRA score, the patients were divided into effective and ineffective groups to explore the predictive factors affecting the outcome of BTX-A treatment, such as age, gender, preoperative urodynamic parameters, and the types of urinary incontinence. t-test was used to compare quantitative data such as age, UDS parameters, OABSS, and I-QOL scores.The comparison of count data such as gender and urinary incontinence types was conducted using Fisher′s exact test. Results:The bladder compliance, bladder capacity ratio, OABSS and I-QOL scores of patients significantly improved after BTX-A injection (all P<0.05).The 77.1% (27/35) of the patients were satisfied with BTX-A treatment effects.The main adverse event during the follow-up was a temporary increase in postvoid residual urine after injecting BTX-A (7 cases), which was alleviated by the Creade action or clean intermittent catheterization.There was significant difference in age [(13.00±4.32) years vs.(10.00±2.67) years] and preoperative bladder compliance [(11.21±5.74) mL/cmH 2O vs.(5.13±2.42) mL/cmH 2O] between effective (27 cases) and ineffective groups (8 cases) ( t=2.383, 2.899, all P<0.05).The differences in preoperative bladder capacity ratio, maximum filling detrusor pressure, postvoid residual urine, voiding efficiency, gender, and the types of urinary incontinence were not statistically significant between the two groups (all P>0.05). Conclusions:Intravesical injection of BTX-A is a safe and effective treatment for children with refractory UFI.A young age and poor bladder compliance at treatment are associated with poor prognosis of BTX-A treatment.

Objective To explore whether virtual reality(VR)combined with computerized cogni-tive training intervention can improve the cognitive function in elderly stroke patients.Methods A total of 202 stroke patients admitted to our department from January 2022 to January 2024 were recruited and randomly divided into control group(101 cases,traditional cognitive training intervention)and study group(101 cases,VR combined with computerized cognitive training in-tervention).Before and after 3 months of intervention,Montreal Cognitive Assessment Scale(MoCA),Mini-Mental State Examination(MMSE),National Institutes of Health Stroke Scale(NIHSS),Fugl-Meyer Assessment(FMA),Activities of Daily Living Scale(ADL)were applied,serum levels of dopamine,neuropeptide Y(NPY),5-hydroxytryptamine(5-HT)and norepineph-rine(NE)were detected,and P300 wave of event-related potential was measured.The results were compared before and after intervention,and between the two groups.Results After intervention,the scores of MoCA,MMSE and FMA,the levels of NPY,5-HT,NE,dopamine,and the ampli-tude of P300 wave were obviously higher in both groups when compared with those before inter-vention(P＜0.05).The study group obtained notably higher MoCA score(27.64±0.62 vs 26.83±0.65),MMSE score(27.67±0.61 vs 26.83±0.62),NPY,5-HT,NE,dopamine,FMA score and amplitude of P300 wave after intervention than the control group(P＜0.01).The NIHSS score,ADL score and latency in the two groups after intervention were significantly lower than those before intervention(P＜0.05),and the above indicators in the study group were significantly low-er than the control group(P＜0.01).Conclusion VR combined with computerized cognitive training intervention can effectively improve the cognitive function,neurological function,motor function and daily life function,and enhance the neurotransmitter levels in elderly stroke patients.

Objective To explore the clinical efficacy of low-frequency pulse therapy combined with ingestion-swallowing training in the treatment of patients with post-stroke dysphagia.Methods A retrospective study was conducted on 122 patients with post-stroke dysphagia admitted in our hospital from January 2022 to January 2024.According to different interventions,they were divid-ed into a control group(ingestion-swallowing training on the basis of conventional treatment,60 cases)and a combined treatment group(low-frequency pulse therapy and the treatments in the control group,62 cases).Before and after treatment,VFSS and standard swallowing assessment(SSA)were performed,hyoid bone movement displacement(hyoid bone forward and upward)and vertebrobasilar artery blood flow indicators[pulsatility index(PI),mean blood flow velocity(Vm),systolic blood flow velocity(Vs)]were observed,and serum levels of nerve growth factor(NGF)and brain-derived neurotrophic factor(BDNF)were detected in all the patients.The chan-ges in quality of life(swallow quality of life questionnaire)and occurrence of complications during treatment were observed in the two groups.Results In both groups after treatment,the VFSS score,quality of life score and swallowing symptom score,hyoid bone forward and upward dis-tances,vertebrobasilar artery Vm and Vs,and serum NGF and BDNF levels were all risen signifi-cantly while the SSA score and vertebrobasilar artery PI were obviously declined when compared with the levels before treatment(P＜0.05).After treatment,the combined treatment group had more remarkably improved VFSS score,quality of life score,swallowing symptom score,hyoid bone forward and upward distances,vertebrobasilar Vm and Vs,and serum NGF and BDNF levels,and more notably declined SSA score and vertebrobasilar PI than the control group(P＜0.05,P＜0.01).No statistical difference was seen in the total incidence of complications between the combined treatment group and control group(4.8％vs 10.0％,P＞0.05).Conclusion Com-bined low-frequency pulse therapy and ingestion-swallowing training can effectively promote the recovery of swallowing function,increase the activity of hyoid bone,promote the vertebrobasilar artery blood flow and neurotrophic conditions,and thus improve the quality of life in patients with post-stroke dysphagia,with less complications.