BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed...BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy p lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozol omide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent o f patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the r adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P < 0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.展开更多
AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conduct...AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conducted on 70 patients who underwent elective laparoscopic cholecystectomy under general anesthesia at Siriraj Hospital, Bangkok, from January 2006 to December 2007. Patients were randomized to receive either 20 mg parecoxib infusion 30 min before induction of anesthesia and at 12 h after the first dose (treatment group), or normal saline infusion, in the same schedule, as a placebo (control group). The degree of the postoperative pain was assessed every 3 h in the first 24 h after surgery, and then every 12 h the following day, using a visual analog scale. The consumption of analgesics was also recorded.RESULTS:There were 40 patients in the treatment group, and 30 patients in the control group. The pain scores at each time point, and analgesic consumption did not differ between the two groups. However,there were fewer patients in the treatment group than placebo group who required opioid infusion within the first 24 h (60% vs 37%, P=0.053).CONCLUSION: Perioperative administration of parecoxib provided no significant effect on postoperative pain relief after laparoscopic cholecystectomy. However, preoperative infusion 20 mg parecoxib could significantly reduce the postoperative opioid consumption.展开更多
Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sust...Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. Methods 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 μg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 μg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 μg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. Findings 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). Interpretation Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.展开更多
Context Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation(AF). Pulmonary vein isolation(PVI) with radiofrequency ablation may cur...Context Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation(AF). Pulmonary vein isolation(PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation. Objective To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF. Design, Setting, and Participants A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs. Intervention Patients were randomized to receive either PVI using radiofrequency ablation(n=33) or antiarrhythmic drug treatment(n=37), with a 1-year follow-up. Main Outcome Measures Recurrence of AF, hospitalization, and quality of life assessment. Results Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22(63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4(13%) of 32 patients who received PVI(P< .001). Hospitalization during 1-year follow-up occurred in 19(54%) of 35 patients in the antiarrhythmic drug group compared with 3(9%) of 32 in the PVI group(P< .001). In the antiarrhythmic drug group, the mean(SD) number of AF episodes decreased from 12(7) to 6(4), after initiating therapy(P=.01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2(6%) of 32 patients in the PVI group. Conclusion Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. 展开更多
Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal ...Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. Methods: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 ±26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. Results: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81%and 62%; TIPS, 88%and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. Conclusions: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.展开更多
文摘BACKGROUND: Glioblastoma, the most common primary brain tumor in adults, is us ually rapidly fatal. The current standard of care for newly diagnosed glioblasto ma is surgical resection to the extent feasible, followed by adjuvant radiotherapy. In this trial we compared radiotherapy alone with radiotherapy p lus temozolomide, given concomitantly with and after radiotherapy, in terms of e fficacy and safety. METHODS: Patients with newly diagnosed, histologically confi rmed glioblastoma were randomly assigned to receive radiotherapy alone (fraction ated focal irradiation in daily fractions of 2 Gy given 5 days per week for 6 we eks, for a total of 60 Gy) or radiotherapy plus continuous daily temozolomide (7 5 mg per square meter of body-surface area per day, 7 days per week from the fi rst to the last day of radiotherapy), followed by six cycles of adjuvant temozol omide (150 to 200 mg per square meter for 5 days during each 28-day cycle). The primary end point was overall survival. RESULTS: A total of 573 patients from 8 5 centers underwent randomization. The median age was 56 years, and 84 percent o f patients had undergone debulking surgery. At a median follow-up of 28 months, the median survival was 14.6 months with radiotherapy plus temozolomide and 12. 1 months with radiotherapy alone. The unadjusted hazard ratio for death in the r adiotherapy-plus-temozolomide group was 0.63 (95 percent confidence interval, 0.52 to 0.75; P < 0.001 by the log-rank test). The two-year survival rate was 26.5 percent with radiotherapy plus temozolomide and 10.4 percent with radiother apy alone. Concomitant treatment with radiotherapy plus temozolomide resulted in grade 3 or 4 hematologie toxic effects in 7 percent of patients. CONCLUSIONS: T he addition of temozolomide to radiotherapy for newly diagnosed glioblastoma res ulted in a clinically meaningful and statistically significant survival benefit with minimal additional toxicity.
基金Supported by Faculty of Medicine Siriraj Hospital Research Project Grant
文摘AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conducted on 70 patients who underwent elective laparoscopic cholecystectomy under general anesthesia at Siriraj Hospital, Bangkok, from January 2006 to December 2007. Patients were randomized to receive either 20 mg parecoxib infusion 30 min before induction of anesthesia and at 12 h after the first dose (treatment group), or normal saline infusion, in the same schedule, as a placebo (control group). The degree of the postoperative pain was assessed every 3 h in the first 24 h after surgery, and then every 12 h the following day, using a visual analog scale. The consumption of analgesics was also recorded.RESULTS:There were 40 patients in the treatment group, and 30 patients in the control group. The pain scores at each time point, and analgesic consumption did not differ between the two groups. However,there were fewer patients in the treatment group than placebo group who required opioid infusion within the first 24 h (60% vs 37%, P=0.053).CONCLUSION: Perioperative administration of parecoxib provided no significant effect on postoperative pain relief after laparoscopic cholecystectomy. However, preoperative infusion 20 mg parecoxib could significantly reduce the postoperative opioid consumption.
文摘Background Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response. Methods 307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 μg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 μg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 μg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment. Findings 49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%). Interpretation Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
文摘Context Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation(AF). Pulmonary vein isolation(PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation. Objective To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF. Design, Setting, and Participants A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs. Intervention Patients were randomized to receive either PVI using radiofrequency ablation(n=33) or antiarrhythmic drug treatment(n=37), with a 1-year follow-up. Main Outcome Measures Recurrence of AF, hospitalization, and quality of life assessment. Results Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22(63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4(13%) of 32 patients who received PVI(P< .001). Hospitalization during 1-year follow-up occurred in 19(54%) of 35 patients in the antiarrhythmic drug group compared with 3(9%) of 32 in the PVI group(P< .001). In the antiarrhythmic drug group, the mean(SD) number of AF episodes decreased from 12(7) to 6(4), after initiating therapy(P=.01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2(6%) of 32 patients in the PVI group. Conclusion Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF.
文摘Background &Aims: Variceal bleeding refractory to medical treatment with β-blockers and endoscopic therapy can be managed by variceal decompression with either surgical shunts or transjugular intrahepatic portal systemic shunts (TIPS). This prospective randomized trial tested the hypothesis that patients receiving distal splenorenal shunts (DSRS) would have significantly lower rebleeding and encephalopathy rates than TIPS in management of refractory variceal bleeding. Methods: A prospective randomized controlled clinical trial at 5 centers was conducted. One hundred forty patients with Child-Pugh class A and B cirrhosis and refractory variceal bleeding were randomized to DSRS or TIPS. Protocol and event follow-up for 2-8 years (mean, 46 ±26 months) for primary end points of variceal bleeding and encephalopathy and secondary end points of death, ascites, thrombosis and stenosis, liver function, need for transplant, quality of life, and cost were evaluated. Results: There was no significant difference in rebleeding (DSRS, 5.5%; TIPS, 10.5%; P = .29) or first encephalopathy event (DSRS, 50%; TIPS, 50%). Survival at 2 and 5 years (DSRS, 81%and 62%; TIPS, 88%and 61%, respectively) were not significantly different (P = .87). Thrombosis, stenosis, and reintervention rates (DSRS, 11%; TIPS, 82%) were significantly (P < .001) higher in the TIPS group. Ascites, need for transplant, quality of life, and costs were not significantly different. Conclusions: DSRS and TIPS are similarly efficacious in the control of refractory variceal bleeding in Child-Pugh class A and B patients. Reintervention is significantly greater for TIPS compared with DSRS. Because both procedures have equivalent outcomes, the choice is dependent on available expertise and ability to monitor the shunt and reintervene when needed.
