ABSTRACT
Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
ABSTRACT
Background@#and Purpose The rate of donepezil discontinuation and the underlying reasons for discontinuation in Asian patients with Alzheimer’s disease (AD) are currently unknown. We aimed to determine the treatment discontinuation rates in AD patients who had newly been prescribed donepezil in routine clinical practice in Asia. @*Methods@#This 1-year observational study involved 38 institutions in seven Asian countries, and it evaluated 398 participants aged 50–90 years with a diagnosis of probable AD and on newly prescribed donepezil monotherapy. The primary endpoint was the rate of donepezil discontinuation over 1 year. Secondary endpoints included the reason for discontinuation,treatment duration, changes in cognitive function over the 1-year study period, and compliance as assessed using a clinician rating scale (CRS) and visual analog scale (VAS). @*Results@#Donepezil was discontinued in 83 (20.9%) patients, most commonly due to an adverse event (43.4%). The mean treatment duration was 103.67 days in patients who discontinued. Among patients whose cognitive function was assessed at baseline and 1 year, there were no significant changes in scores on the Mini-Mental State Examination, Montreal Cognitive Assessment, and Trail-Making Test–Black and White scores, whereas the Clinical Dementia Rating score increased significantly (p<0.001). Treatment compliance at 1 year was 96.8% (306/316) on the CRS and 92.6±14.1% (mean±standard deviation) on the VAS. @*Conclusions@#In patients on newly prescribed donepezil, the primary reason for discontinuation was an adverse event. Cognitive assessments revealed no significant worsening at 1 year, indicating that continuous donepezil treatment contributes to the maintenance of cognitive function.
ABSTRACT
Objective:To survey the status of antihypertensive therapy knowledge and hypertension management among general practitioners in community health centers (CHCs) in China.Methods:Based on the eastern, western, southern and northern regions of the country, 350 CHCs were selected from 11 cities across the country with stratified sampling method for study sites, and one general practitioner was selected from each CHC. The questionnaire survey was conducted from March 12 to April 20, 2018 among 350 participants. The content of the questionnaire included the proportion of hypertensive patients in the consultation, treatment target rate, antihypertensive drugs and protocol, the medication compliance, follow-up, blood pressure self-measurement, and the impact of hierachical medical system on CHC.Results:Total 350 valid questionnaires were recovered. The survey showed that: (1) Among the patients treated by general practitioners, 46% (30%, 60%) were hypertensive patients including 41% (40%, 55%) with primary hypertension and 42% (40%, 50%) with secondary hypertension; 72% (60%, 80%) of the patients had comorbidities, including dyslipidemia, diabetes, and coronary heart disease. (2) Western medicine was the main antihypertensive treatment [90% (82%, 100%) ], calcium channel blockers were the most commonly used antihypertensive drug [46%(30%,60%)], the therapeutic protocol was mainly single agent [35% (25%, 50%) ]or free combination [50% (40%, 60%) ]; the stable(9.1±0.8), long-acting (9.0±0.9) and high standard reaching rate (8.1±1.1) antihypertensive drugs were first considered, and the standard reaching rate of hypertension treatment was 61% (50%, 75%) . (3) The regular follow-up rate, adherence to blood pressure self-test rate and long-term regular medication rate was 60%(50%,70%), 51%(40%,70%) and 65%(50%,70%), respectively. The factors affecting patients′ compliance were history of cardiovascular diseases (8.4±1.1)and patients′ cognition of disease(8.3±1.1). General practitioners believed that the positive effects of the hierarchical diagnosis and treatment system include helping to establish a closer relationship with patients [62.6% (219/350)] and improving patient compliance for community preferential reimbursement policies[58.6% (205/350) ]. The challenges faced by CHC included higher patient expectations [52.8% (185/350)] and increased outpatient visits [52.6% (184/350)]. Insufficient diagnostic equipment [68.3% (239/350)], inadequate dispensing [52.3% (183/350)] and other issues restricted the development of CHC, and the clinical competence of general practitioners [51.7% (181/350)] need to be improved.Conclusion:Patients with hypertension account for about half of the total number of visits in community health service centers, and most of them are comorbid with cardiovascular and cerebrovascular diseases or risk factors. The long-term treatment compliance and self-management of blood pressure need to be further improved.
ABSTRACT
Objective:To assess the concept and clinical practice of general practitioners in community health service centers (CHCs) on the use of antiplatelet drugs (APD) to prevent cardiovascular diseases(CVD).Methods:Based on the eastern, western, southern and northern regions of the country, 350 CHCs were selected from 11 cities across the country with stratified sampling method for study sites, and one general practitioner was selected from each CHC. The questionnaire survey was conducted from March 12 to April 20, 2018 among 350 participants. The content of the questionnaire included the situation of CVD patients, application of APD in primary/secondary prevention of CVD (schemes and regimes), the prescription concept of APD, and influencing factors.Results:Total 350 valid questionnaires were recovered. The survey showed that among all patients general practitioners routinely took care, 46% (30%, 60%) were hypertensive patients; 96.6% (338/350) of the general practitioners said that they had carried out primary prevention, mainly for patients with hypertension, diabetes, dyslipidemia or carotid artery plaque, and 34% (20%, 45%) of the patients had taken primary prevention drugs; the use of APD only accounted for 47% (35%, 60%) , among which 87% (80%, 95%) was aspirin. The main impediments were lack of awareness of disease from patients[ (8.0±1.4) points] and lack of awareness of primary prophylaxis from general practitioners[ (7.3±1.4) points]. The survey also showed that 28% (20%, 35%) and 17% (10%, 20%) patients were diagnosed as coronary heart disease and stroke, respectively; 83% (80%, 95%) of patients with coronary heart disease or stroke used APD for secondary prophylaxis; for coronary heart disease patients, 82% (70%, 95%) taking aspirin or clopidogrel, 18% (5%, 30%) taking aspirin and clopidogrel for 11 months; for stroke patients, 85% (80%, 95%) taking aspirin or clopidogrel, 15% (5%, 20%) taking aspirin and clopidogrel for 9 months. Compared with clopidogrel, aspirin had a relatively high score for clinical experience (8.3±1.1) and reasonable cost of treatment (8.3±1.3) .Most coronary heart disease patients (68%±15%) and stroke patients (70%±17%) took APD regularly. The lack of knowledge of disease [(8.4±1.1) points] and awareness of regular medication [(8.2±1.2) points] were the main factors affecting compliance of patients.Conclusion:The use of APD in primary prevention of CVD for general practitioners is insufficient, and there is still a big gap between the standardization and the practice in secondary prevention; in particular, the selection of APDs and treatment course should strictly follow the guidelines.
ABSTRACT
Objective@#To analyze the urination behavior in spring among college students in Hebei Province.@*Methods@#In March 2017, the subjects were recruited in a college in Baoding, Hebei Province. And 156 students completed the investigation. The urine samples of 24 hour was collected for 3 consecutive days by special device, and the volume, the voids and the time of urine were measured.@*Results@#The average volume of urine per day was 1 279 mL, the average void of urine per day was 6.2, and the average volume of urine per time was 209 mL. The volume of urine and void were mainly at the time of after lunch, the volume, the proportion of the volume and void of urine were 406 mL, 31.0% and 1.7 times respectively. The volumes and the voids of urine were different in different time periods(P<0.05). The volume of urine, the proportion of the volume and the voids of urine were mainly at the time of morning, followed by the afternoon. The average volume of urine per day was 535 mL, the proportion of the volume was 44.1% and the average void of urine was 2.3, in the morning. There were significant differences in the voids of urine, the volumes of urine and the voids of urine in different time periods between boys and girls(χ2=73.71, 47.48, 34.92; 35.17, 21.30, 20.69; 37.02, 25.30, 15.32, P<0.05). The void of urine was negatively correlated with the average volume of urine per time(r=-0.61, P<0.01); the volume of urine was positively correlated with the average volume of urine per time(r=0.79, P<0.01); the void was not correlated with the volume of urine(P<0.05).@*Conclusion@#The urination behaviour of college students in Hebei Province was mainly at the time of after lunch, in the morning and in the afternoon. The college students had unhealthy urination behavior, which was in need of related health education.
ABSTRACT
Objective To explore the clinical value of 18F-fluorodeoxyglucose (FDG) PET/CT in assessing antineutrophil cytoplasmic antibody-associated vasculitis (AAV).Methods Fifteen patients (7 males,8 females,age (66±11) years) with AAV between January 2015 and June 2017 were retrospectively analyzed.There were 6 patients diagnosed as granulomatosis with polyangiitis (GPA),7 diagnosed as microscopic polyangiitis (MPA) and 2 diagnosed as eosinophilic granulomatosis with polyangiitis (EGPA).All patients underwent 18 F-FDG PET/CT and the image features were observed and analyzed.The maximum standardized uptake value (SUVmax) of the positive lesion was measured.The relationship between the SUVmax and C reactive protein (CRP) was analyzed with Pearson correlation.The SUVmax and the number of lesion sites were compared by two-sample t test between the CRP-elevated and CRP-normal patients.Results A total of 56 lesions in the 14 of 15 AAV patients were detected by PET/CT.The positive findings distributed in 15 tissues and organs,including the nasopharynxes (n =9),lungs (n =9),kidneys (n =8),spleen (n =6),lymph nodes (n =6),bone marrow (n =4),skin (n =3),prostate (n =2),aortas (n =2),vertebral soft tissues (n =2),orbita (n =1),parotid gland (n =1),thyroid gland (n =1),liver (n =1) and pancreas (n=1).The 60.7％ (34/56) of lesions were clinically unsuspected occult lesions.GPA lesions mainly invaded the nasopharynxes,lungs and kidneys;MPA lesions mainly invaded the kidneys and spleen;EGPA lesions mainly invaded the nasopharynxes,lymph nodes and bone marrow.There was no significant correlation between the level of CRP and the SUVmax of AAV lesions (r=0.462,P＞0.05).No differences in the SUVmax were observed between patients with elevated CRP levels and those with normal CRP levels (t=1.451,P＞0.05).But more lesion sites were observed in patients with elevated CRP (t=3.456,P＜0.05).Conclusions 18F-FDG PET/CT shows positive findings in multiple sites in AAV patients,including clinically unsuspected sites.This imaging technique may be a useful tool for diagnosis and evaluation of AAV.
ABSTRACT
Objective To investigate the association of red cell distribution width (RDW) with all-cause and cardiovascular disease (CVD)-related mortality in patients undergoing continuous ambulatory peritoneal dialysis (CAPD).Methods A retrospective analysis was performed on 207 patients who initiated CAPD for more than 3 months between July 2005 and March 2016 in the First Hospital Affiliated to Zhengzhou University.Baseline data on demographic,clinical and biochemical variables as well as comorbidities were obtained;medications and clinic outcomes were recorded.According to receiver operator characteristic curve (ROC) analysis,patients were divided into high RDW (RDW ＞ 15.1％) and low RDW (RDW≤ 15.1％) groups.The data of two groups were compared and Spearman's correlation analysis was used to explore the association of RDW with clinical and biochemical parameters.Survival curves were calculated using Kaplan-Meier method.Cox regression model was employed to analyze risk factors of all-cause and CVD-related mortality.Results In this study,207 CAPD patients were enrolled.The overall median survival time was 80 months.And the median survival time of high RDW group (68 patients) and low RDW group (139 patients) were 59 months and 96 months,respectively.There were statistical differences in diastole pressure,hemoglobin,hematocrit,serum albumin,intact parathyroid hormone (iPTH),eGFR,cholesterol,lipoprotein a,4-hour dialysate-to-plasma ratio for creatinine (4hD/Pcr),total Ccr (P ＜ 0.05,respectively);the two groups also varied in the proportion of chronic obstructive pulmonary disease,cardiovascular disease and hyperlipidemia,as well as in the use of iron supplements,angiotensin-converting enzyme (ACE) inhibitors or angiotensin Ⅱ receptor blockers (ARB),and beta-receptor blockers (P＜0.05,respectively).Cardiovascular event was a leading cause of mortality.Kaplan-Meier survival curves showed that the high RDW group had higher all-cause and CVD-related mortality compared with the low RDW group (P ＜ 0.01).The 1-year,3-year,and 5-year patient survivals of the high RDW and low RDW group were 87.97％ vs 97.01％,58.02％ vs 81.53％,and 41.62％ vs 67.96％,respectively,demonstrating significant differences (P=0.001).Multivariate Cox regression analysis showed that high RDW was independent risk factor for all-cause mortality (HR=1.212,95％CI:1.007-1.458,P=0.042) and CVD-related mortality (HR=1.697,95％ CI:1.030-2.795,P=0.038).Conclusion RDW is associated with mortality risks in CAPD patients and can be stratified as a valuable indicator for the risk of death.
ABSTRACT
Objective To investigate whether the JAK2/STAT3 signaling pathway is involved in the epithelial-mesenchymal transition (EMT) of peritoneal mesothelial cells in uremic peritoneal dialysis (PD) rats.Methods A total of 48 male Sprague-Dawley (SD) rats were randomly separated into six groups:normal control group (NC group,n=8),sham group (n=8),uremic group (n=8),PD group (n=8),S3I-201 control group (n=8) and S3I-201 group (n=8).Uremic model generated by 5/6 nephrectomy surgery in rats was established.The rats of PD group,S3I-201 control group and S3I-201 group received daily infusion of 4.25％ glucose-based peritoneal dialysate fluid (3 ml/100 g) from PD catheters for 28 days.Rats of S3I-201 group were injected with STAT3 inhibitor S3I-201 (2.5 mg/kg) solution from the catheters every other day;the same dose of the solvent of S3I-201 was simultaneously given to S3I-201 control group rats.After PD for 28 days,peritoneal function,pathologic changes,and microvessel density (MVD) were evaluated.Creatinine,urea nitrogen and interleukin-6 (IL-6) concentration in blood and dialysate,and protein and mRNA levels of phospho-JAK2 (p-JAK2),phospho-STAT3 (p-STAT3),E-cadherin,alpha-smooth muscle actin (α-SMA) and vascular endothelial growth factor (VEGF) in peritoneum were determined.Results Uremia and peritoneal dialysate could aggravate the peritoneal function and elevate peritoneal thickness and MVD.They could also increased the concentration of IL-6 in blood and dialysate and the expression levels of α-SMA,VEGF,p-JAK2 and p-STAT3 in peritoneum,while lowering E-cadherin expression in peritoneum.These manifestations were even more remarkable in PD group compared to those in uremic group.There was no statistical difference between the S3I-201 control group and the PD group as regards all the index (all P ＞ 0.05).Compared with the S3I-201 control group,the rats treated with S3I-201 showed better peritoneal function.S3I-201 could reduce peritoneal thickness (P＜0.05),MVD (P＜0.05),the concentration of IL-6 in blood and dialysate,the mRNA and protein expression of α-SMA,VEGF,p-JAK2 and p-STAT3 (all P ＜ 0.05),while enhance the mRNA and protein expression of E-cadherin (all P ＜ 0.05).Conclusions After STAT3 is inhibited,the peritoneal thickness,MVD and IL-6 concentration in PD rats are decreased,and EMT is also inhibited,while peritoneal function is improved.The JAK2/STAT3 signaling pathway may thus be involved in the process of EMT of peritoneum in uremic peritoneal dialysis rats by regulating the expression of IL-6.
ABSTRACT
CAR-T cell therapy that targets surface antigens to kill tumor cells specifically has recently become another cornerstone in tumor immunotherapy. In this study, a lentiviral expression plasmid of CAR targeting human epidermal growth factor receptor 2 (HER2) was constructed by genetic engineering. The recombinant plasmid was co-transfected with other packaging plasmids into HEK293T cells by calcium phosphate precipitation to generate lenti-car, which are CAR lentiviral particles. HER2-specific CAR-T cells were obtained by transducing human peripheral blood mononuclear cells with lenti-car. Their specific inhibitory effects on HER2-positive and HER2-negative tumor cells were analyzed in vitro. The constructed CAR-T cells were specifically activated by HER2-expressing tumor cells as indicated by secretion of IFN-γ and IL-2. The inhibitory rate on HER2-positive SK-OV-3 cell line was (58.47±1.72)%, significantly higher than that on the mock-treated control group (P<0.05). The inhibitory rate on HER2-negative K562 cell lines was (11.74±2.37)%, which was not significantly different from that on the control group (P>0.05). Furthermore, when we transfected a HER2-expressing vector into K562, the inhibitory rate increased to (30.41±7.59)%, which was higher than that on HER2-negative K562 (P<0.05). Thus, the constructed second-generation HER2-specific CAR-T cells specifically suppressed growth of tumor cells overexpressing HER2 protein, suggesting that HER2-specific CAR-T cells might prove useful for immunotherapy of HER2-positive cancer.
ABSTRACT
Objective Retrospectively evaluate low dose computed tomography (CT) as part of a combined 18F-NaF positron emission tomography (18F-NaFPET/CT) examination in lung cancer patients suspected of bone metastases. Methods 118 of 122 lesions with increased uptake of 18F-NaF were assessed. Characteristics of bone metastases on CT images were reviewed by radiologists. Results 27 of 47 metastases presented as sites of increased uptake with corresponding lytic or sclerotic changes on low dose CT. Other 20 show normal or non-specific appearing bone on CT. Most benign lesions (67 of 71,94%)have a benign appearance on low-dose CT. Conclusions Low dose CT images were useful in precisely diagnosing bone metastasis. Negative low dose CT appearance to the abnormal foci on PET may be a reliable sign of metastases.