Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. For...Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.展开更多
Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-E...Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.展开更多
Phase Ⅰ of clinical trials is the first stage of clinical pharmacology and body safety evaluation,including body tolerance test and pharmacokinetics test.The aim is providing evidence for dosage regimen and be the co...Phase Ⅰ of clinical trials is the first stage of clinical pharmacology and body safety evaluation,including body tolerance test and pharmacokinetics test.The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase Ⅱ of clinical trials.This text discussed the technique and requirement of phase Ⅰ of new drugs' clinical tolerance trials.展开更多
BACKGROUND Obesity is a global health problem that is continuing to increase in the young population.In Brazil,the frequency of obesity in 2018 was 19.8%.Several comorbidities are directly associated with obesity,such...BACKGROUND Obesity is a global health problem that is continuing to increase in the young population.In Brazil,the frequency of obesity in 2018 was 19.8%.Several comorbidities are directly associated with obesity,such as non-alcoholic fatty liver disease(NAFLD),which is considered the most common liver disorder in Western countries and affects up to 46%of adults.Bariatric surgery is effective in treating obesity and can improve NAFLD;however,the effect of bariatric surgery on body composition,phase angle(PA),and improving NAFLD needs to be further studied.AIM To analyze the PA in the postoperative period of bariatric surgery and to correlate it with changes in body composition and liver disease.METHODS This study is a retrospective cohort study of the analysis of the medical records of patients undergoing bariatric surgery in a reference center of a teaching hospital in Porto Alegre over a 2-year period.Patients older than 18 years whose record contained all information relevant to the study were included.The data analyzed were body composition and PA through electrical bioimpedance and NAFLD through liver biopsy in the pre-and postoperative period.The level of significance adopted for the statistical analyses was 5%.RESULTS We evaluated 379 patients with preoperative data.Regarding PA,169 patients were analyzed,and 33 patients had liver biopsy pre-and postoperatively with NAFLD information.In total,79.4%were female,with a mean age of 39.1±10.6 years.The average body mass index(BMI)was 45.9±7.5 kg/m².The PA showed a mean of 5.8±0.62°in the preoperative period and a significant reduction in the postoperative period.A postoperative reduction in body composition data(skeletal muscle mass,fat percentage,fat mass,body cell mass,BMI and visceral fat area)was shown as well.Regarding liver disease,all patients presented a reduction in the degrees and stages of liver disease in the postoperative period,and some had no degree of liver disease at all.CONCLUSION PA decreased after bariatric surgery,with a direct correlation with weight loss and changes in body composition.The decrease in PA was not correlated with the improvement in NAFLD.展开更多
Aim: Comparing the results of acute phase infectious endocarditis surgery between two periods. Methods and Results: The study is about 2 series, series A between 1993 and 1997, and series B between 1998 and 2012, resp...Aim: Comparing the results of acute phase infectious endocarditis surgery between two periods. Methods and Results: The study is about 2 series, series A between 1993 and 1997, and series B between 1998 and 2012, respectively 13 and 51 patients. The two periods were similar concerning the number of patients per year, which was 3.12 cases/year for series A and 3.64 cases/year for series B. The authors noted a change in epidemiological profile, with an increase of median age (31 y.o for series A and 37 y.o for series B), and the emergency of endocarditis on prosthetic valve (none on series A and 8 cases for series B). Surgical indications and results didn’t change too much, hospital mortality rate was 15.3% for series A and 17.6% for series B. Conclusion: Infectious endocarditis is still a major public healthcare problem in developing countries, despite the development of diagnostic tools and patient care. Prevention is still the major asset in the treatment of this disease.展开更多
文摘Aim To assess the safety and tolerance of adefovir dipivoxil （ADV） in Chinese healthy volunteers. Methods A total of 52 healthy volunteers, 26 males and 26 females, aged from 19 to 26 were enrolled in the study. Forty-two subjects were randomized into 5, 10, 20, 40, and 60 mg dose groups （6 - 10 subjects in each） matched by sex and weight for single-dose trial. Ten subjects were orally given 10 mg of ADV tablets once daily for 7 d for multiple-dose trial. Physical examination, vital signs examination, electrocardiography, type-B ultrasonography, chest fluoroscopy, routine blood test, routine urine test, coagulation tests, and blood biochemical test were conducted on schedule and statistically evaluated. Results Asthenia frequently occurred in multiple-dose trial, nausea, abdominal pain, and diarrhea occurred in both single- and multiple-dose trials. ALT, bilirubin, CK, and LDH were slightly elevated. All adverse reactions and laboratory abnormalities were mild, and the frequency and severity were not related to doses. Conclusion ADV is safe and well tolerated in Chinese healthy volunteers at dose of 5 - 60 mg oncedaily or 10 nag once daily for 7 d. The recommended oral dosage regimen is 10 mg once daily. Attention should be paid to renal and liver functions, CK, AMY and LDH, if we take ADV for a long period of time.
文摘Objective:Fluzoparib(SHR3162)is a novel,potent poly(ADP-ribose)polymerases(PARP)1,2 inhibitor that showed anti-tumor activity in xenograft models.We conducted a phaseⅠ,first-in-human,dose-escalation and expansion(D-Esc and D-Ex)trial in patients with advanced solid cancer.Methods:This was a 3+3 phaseⅠD-Esc trial with a 3-level D-Ex at 5 hospitals in China.Eligible patients for DEsc had advanced solid tumors refractory to standard therapies,and D-Ex enrolled patients with ovarian cancer(OC).Fluzoparib was administered orally once or twice daily(bid)at 11 dose levels from 10 to 400 mg/d.Endpoints included dose-finding,safety,pharmacokinetics,and antitumor activity.Results:Seventy-nine patients were enrolled from March,2015 to January,2018[OC(47,59.5%);breast cancer(BC)(16,20.3%);colorectal cancer(8,10.1%),other tumors(8,10.1%)];48 patients were treated in the D-Esc arm and 31 in the D-Ex arm.The maximum tolerated dose(MTD)was 150 mg bid,with a half-life of 9.14 h.Grade 3/4 adverse events included anemia(7.6%)and neutropenia(5.1%).The objective response rate(ORR)was 30%(3/10)in patients with platinum-sensitive OC and 7.7%(1/13)in patients with BC.Among patients treated with fluzoparib≥120 mg/d,median progression-free survival(m PFS)was 7.2[95%confidence interval(95%CI),1.8-9.3]months in OC,9.3(95%CI,7.2-9.3)months in platinum-sensitive OC,and 3.5(range,2.0-28.0)months in BC.In patients with germline BC susceptibility gene mutation(g BRCAMut)(11/43 OC;2/16 BC),m PFS was 8.9 months for OC(range,1.0-23.2;95%CI,1.0-16.8)and 14 and 28 months for BC(those two patients both also had somatic BRCAMut).Conclusions:The MTD of fluzoparib was 150 mg bid in advanced solid malignancies.Fluzoparib demonstrated single-agent antitumor activity in BC and OC,particularly in BRCAMut and platinum-sensitive OC.
文摘Phase Ⅰ of clinical trials is the first stage of clinical pharmacology and body safety evaluation,including body tolerance test and pharmacokinetics test.The aim is providing evidence for dosage regimen and be the cornerstone of the preliminary assessment of efficacy and safety of phase Ⅱ of clinical trials.This text discussed the technique and requirement of phase Ⅰ of new drugs' clinical tolerance trials.
文摘BACKGROUND Obesity is a global health problem that is continuing to increase in the young population.In Brazil,the frequency of obesity in 2018 was 19.8%.Several comorbidities are directly associated with obesity,such as non-alcoholic fatty liver disease(NAFLD),which is considered the most common liver disorder in Western countries and affects up to 46%of adults.Bariatric surgery is effective in treating obesity and can improve NAFLD;however,the effect of bariatric surgery on body composition,phase angle(PA),and improving NAFLD needs to be further studied.AIM To analyze the PA in the postoperative period of bariatric surgery and to correlate it with changes in body composition and liver disease.METHODS This study is a retrospective cohort study of the analysis of the medical records of patients undergoing bariatric surgery in a reference center of a teaching hospital in Porto Alegre over a 2-year period.Patients older than 18 years whose record contained all information relevant to the study were included.The data analyzed were body composition and PA through electrical bioimpedance and NAFLD through liver biopsy in the pre-and postoperative period.The level of significance adopted for the statistical analyses was 5%.RESULTS We evaluated 379 patients with preoperative data.Regarding PA,169 patients were analyzed,and 33 patients had liver biopsy pre-and postoperatively with NAFLD information.In total,79.4%were female,with a mean age of 39.1±10.6 years.The average body mass index(BMI)was 45.9±7.5 kg/m².The PA showed a mean of 5.8±0.62°in the preoperative period and a significant reduction in the postoperative period.A postoperative reduction in body composition data(skeletal muscle mass,fat percentage,fat mass,body cell mass,BMI and visceral fat area)was shown as well.Regarding liver disease,all patients presented a reduction in the degrees and stages of liver disease in the postoperative period,and some had no degree of liver disease at all.CONCLUSION PA decreased after bariatric surgery,with a direct correlation with weight loss and changes in body composition.The decrease in PA was not correlated with the improvement in NAFLD.
文摘Aim: Comparing the results of acute phase infectious endocarditis surgery between two periods. Methods and Results: The study is about 2 series, series A between 1993 and 1997, and series B between 1998 and 2012, respectively 13 and 51 patients. The two periods were similar concerning the number of patients per year, which was 3.12 cases/year for series A and 3.64 cases/year for series B. The authors noted a change in epidemiological profile, with an increase of median age (31 y.o for series A and 37 y.o for series B), and the emergency of endocarditis on prosthetic valve (none on series A and 8 cases for series B). Surgical indications and results didn’t change too much, hospital mortality rate was 15.3% for series A and 17.6% for series B. Conclusion: Infectious endocarditis is still a major public healthcare problem in developing countries, despite the development of diagnostic tools and patient care. Prevention is still the major asset in the treatment of this disease.
