Objective: To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis. Design: Multicenter, ...Objective: To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis. Design: Multicenter, randomized, double-blind, placebo-control, prospective trial. Setting: A total of 43 outpatient clinics in 10 European countries. Patients: Of 348 patients screened, 319 with moderate or severe refractory chronichanddermatitiswererandomized, in the ratioof1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events. Interventions: Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months. Main Outcome Measure: Physician’s global assessment of overall chronic hand dermatitis severity. Results: Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53%of patients, and up to a 70%mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose. Conclusion: Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.展开更多
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
In the recent two decades, there have been major advances in the development of theories and techniques in the practice of psychotherapy. The latest trends are characterized by shortening of treatment duration especia...In the recent two decades, there have been major advances in the development of theories and techniques in the practice of psychotherapy. The latest trends are characterized by shortening of treatment duration especially in the field of dynamic psychotherapy, growing popularity with the use of treatment manuals, integration of specific theories and techniques from different orientations, and objective evaluation of treatment outcomes. The reasons and impacts for these significant advances are discussed with respect to clinical practice.展开更多
BACKGROUND: Medical therapy with methotrexate is a standard practice for the commonly encountered problem of ectopic pregnancy. Methotrexate is excreted predominantly by the kidney and should be used with extreme caut...BACKGROUND: Medical therapy with methotrexate is a standard practice for the commonly encountered problem of ectopic pregnancy. Methotrexate is excreted predominantly by the kidney and should be used with extreme caution in renal insufficiency. All physicians who administer methotrexate must understand its mechanism of action, distribution, and elimination to minimize potential risks to the patient. CASE: A young, dialysis-dependent woman received a standard dose of methotrexate for an ectopic pregnancy. Prolonged methotrexate exposure resulted. The consequences-pancytopenia, desquamation, acute respiratory distress syndrome, and profound bowel ischemia-ultimately led to her death. CONCLUSION: Methotrexate, even at extremely low doses, can be fatal in patients with renal insufficiency. Alternative means of therapy should be sought for women with ectopic pregnancy and renal failure.展开更多
文摘Objective: To assess the efficacy and safety of oral alitretinoin (9-cis-retinoic acid), 10 mg/d, 20 mg/d, and 40 mg/d, compared with placebo control, in the treatment of chronic hand dermatitis. Design: Multicenter, randomized, double-blind, placebo-control, prospective trial. Setting: A total of 43 outpatient clinics in 10 European countries. Patients: Of 348 patients screened, 319 with moderate or severe refractory chronichanddermatitiswererandomized, in the ratioof1:1:1:1, to 4 treatment groups and received allocated intervention. Of 75 patients who withdrew, 24 withdrew owing to adverse events. Interventions: Placebo or 10 mg, 20 mg, or 40 mg of oral alitretinoin (9-cis-retinoic acid) taken once daily for 12 weeks. Safety was assessed for all patients during a follow-up period of 4 weeks, and responders were observed for a follow-up period of 3 months. Main Outcome Measure: Physician’s global assessment of overall chronic hand dermatitis severity. Results: Alitretinoin led to a significant and dose-dependent improvement in disease status, with responses in up to 53%of patients, and up to a 70%mean reduction in disease signs and symptoms. Treatment was generally well tolerated, with dose-dependent effects comprising headache, flushing, mucocutaneous events, hyperlipidemia, and decreased hemoglobin and decreased free thyroxin levels. Three months after discontinuation of treatment, the rate of relapse was 26%, independent of dose. Conclusion: Alitretinoin given at well-tolerated doses induced substantial clearing of chronic hand dermatitis in patients refractory to conventional therapy.
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.
文摘In the recent two decades, there have been major advances in the development of theories and techniques in the practice of psychotherapy. The latest trends are characterized by shortening of treatment duration especially in the field of dynamic psychotherapy, growing popularity with the use of treatment manuals, integration of specific theories and techniques from different orientations, and objective evaluation of treatment outcomes. The reasons and impacts for these significant advances are discussed with respect to clinical practice.
文摘BACKGROUND: Medical therapy with methotrexate is a standard practice for the commonly encountered problem of ectopic pregnancy. Methotrexate is excreted predominantly by the kidney and should be used with extreme caution in renal insufficiency. All physicians who administer methotrexate must understand its mechanism of action, distribution, and elimination to minimize potential risks to the patient. CASE: A young, dialysis-dependent woman received a standard dose of methotrexate for an ectopic pregnancy. Prolonged methotrexate exposure resulted. The consequences-pancytopenia, desquamation, acute respiratory distress syndrome, and profound bowel ischemia-ultimately led to her death. CONCLUSION: Methotrexate, even at extremely low doses, can be fatal in patients with renal insufficiency. Alternative means of therapy should be sought for women with ectopic pregnancy and renal failure.
