B1tta/Drug-ACE huggingface dataset:
[Title]: Equivalence of indapamide SR and enalapril on microalbuminuria reduction in hypertensive patients with type 2 diabetes: the NESTOR Study.
[Abstract]: OBJECTIVES: To test whether microalbuminuria in patients with type 2 diabetes and hypertension is primarily dependent on the severity of hypertension, and to compare the effectiveness of two antihypertensive drugs with opposite effects on the renin-angiotensin system [the diuretic, indapamide sustained release (SR), and an angiotensin-converting enzyme inhibitor, enalapril] in reducing microalbuminuria. DESIGN: A multinational, multicentre, controlled, double-blind, double-dummy, randomized, two-parallel-groups study over 1 year. METHODS: After a 4-week placebo run-in period, 570 patients (ages 60.0 +/- 9.9 years, 64% men) with type 2 diabetes, essential hypertension [systolic blood pressure (SBP) 140-180 mmHg, and diastolic blood pressure (DBP) &lt; 110 mmHg], and persistent microalbuminuria (20-200 microg/min) were allocated randomly to groups to receive indapamide SR 1.5 mg (n = 284) or enalapril 10 mg (n = 286) once a day. Amlodipine, atenolol, or both were added, if necessary, to achieve the target blood pressure of 140/85 mmHg. RESULTS: There was a significant reduction in the urinary albumin : creatinine ratio. Mean reductions were 35% [95% confidence interval (CI) 24 to 43] and 39% (95% CI 30 to 47%) in the indapamide SR and enalapril groups, respectively. Equivalence was demonstrated between the two groups [1.08 (95% CI 0.89 to 1.31%); P = 0.01]. The reductions in mean arterial pressure (MAP) were 16.6 +/- 9.0 mmHg for the indapamide SR group and 15.0 +/- 9.1 mmHg for the enalapril group (NS); the reduction in SBP was significantly greater (P = 0.0245 ) with indapamide SR. More than 50% of patients in each group required additional antihypertensive therapy, with no differences between groups. Both treatments were well tolerated. CONCLUSIONS: Indapamide-SR-based therapy is equivalent to enalapril-based therapy in reducing microalbuminuria with effective blood pressure reduction in patients with hypertension and type 2 diabetes.
[Drug-Disease]: Indapamide - hypertension
[Title]: Genetic dissection of drug effects in clinical practice: CLOCK gene and clozapine-induced diurnal sleepiness.
[Abstract]: Psychotic patients treated with clozapine often experience persistent daytime sleepiness. This is a frequent side effect of clozapine that may reduce patient compliance. We hypothesized that clozapine might interfere with the circadian rhythms regulated by the biological clock. In 171 patients with major psychosis, we investigated the association between hypersomnolence during clozapine therapy and a CLOCK gene polymorphism (3111 T/C substitution). Forty-six patients showed persistent daytime sleepiness and were classified as "sleepy". "Sleepy" patients were significantly more likely to have a mutated allele compared to both "non sleepy" patients and healthy subjects (chi2 = 20.36, d.f. = 1, P = 0.000007, and chi2 = 13.91, d.f. = 1, P = 0.0002, respectively). We conclude that an interaction between clozapine and the CLOCK gene polymorphism 3111 T/C substitution could explain persistent daytime sleepiness in a significant proportion of patients treated with clozapine.
[Drug-Disease]: clozapine - Psychotic
[Title]: A comparison of extrapyramidal symptoms in older outpatients treated with quetiapine or risperidone.
[Abstract]: OBJECTIVE: To compare the tolerability of quetiapine with risperidone in older outpatients. RESEARCH DESIGN AND METHODS: Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn). MAIN OUTCOME MEASURES: The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy. RESULTS: Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P &lt; 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores. CONCLUSIONS: Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.
[Drug-Disease]: quetiapine - psychotic disorders
[Title]: A comparison of extrapyramidal symptoms in older outpatients treated with quetiapine or risperidone.
[Abstract]: OBJECTIVE: To compare the tolerability of quetiapine with risperidone in older outpatients. RESEARCH DESIGN AND METHODS: Post hoc analysis of a subset of older patients (aged 60-80; n = 92) from a randomized, 4-month, multicenter, open-label trial comparing quetiapine and risperidone in an outpatient setting. Participants had various neuropsychiatric disorders associated with psychosis as defined by criteria from the Diagnostic and Statistical Manual of Mental Disorders (4th edn). MAIN OUTCOME MEASURES: The main outcome measure was an extrapyramidal symptoms (EPS) checklist, used to assess motor symptoms, including parkinsonism, at baseline and after treatment. The Positive and Negative Syndrome Scale (PANSS) and the Clinical Global Impression scale were used to assess therapeutic efficacy. RESULTS: Substantial EPS (defined as EPS requiring a dosage adjustment or use of medication to reduce EPS) occurred less often with quetiapine (median dosage, 200 mg/day) than with risperidone (median dosage, 3 mg/day); odds ratio, 0.31 (P &lt; 0.03). Quetiapine was also less likely than risperidone to cause akathisia or hypertonia. Both compounds produced comparable reductions in PANSS scores. CONCLUSIONS: Interpretation of findings in this report is limited by the open-label design of the study and the post hoc nature of this analysis. However, the results suggest that quetiapine, when given within the recommended dosage range, has a benign EPS profile, with potentially greater tolerability and comparable efficacy to risperidone in older outpatients with psychotic disorders.
[Drug-Disease]: risperidone - psychotic disorders
[Title]: Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine.
[Abstract]: Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.
[Drug-Disease]: lidocaine - pain
[Title]: Propofol-induced injection pain: comparison of a modified propofol emulsion to standard propofol with premixed lidocaine.
[Abstract]: Propofol is well known for its association with pain on injection. The most frequently used method to reduce this pain is premixture with lidocaine. Recently, a modified lipid emulsion of propofol containing medium-chain triglycerides (MCT) with long-chain triglycerides (LCT), in contrast to the usual LCT formulation, has been advocated to alleviate pain. In a randomized, prospective, controlled, double-blind study on 222 surgical patients, we compared the effect of the two solutions on the incidence and intensity of injection pain. Patients were randomly allocated to receive either propofol MCT/LCT (group M; n = 109) or standard propofol LCT with the addition of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of propofol (group L; n = 113). Pain scores were assessed using a verbal analog scale (VAS) ranging from 0-10. Group L was found to have significantly less pain on the injection of propofol (mean VAS, 2.5 +/- 2.9) (mean +/- sd) than group M (mean VAS, 3.8 +/- 3.2; P = 0.002). Regarding postoperative recall of pain on injection, patients in group L indicated significantly less pain (mean VAS, 2.2 +/- 2.4) than patients in group M (mean VAS, 3.0 +/- 2.7; P = 0.02). Premixing of 20 mg of lidocaine (2 mL of lidocaine 1%) to 200 mg of standard propofol LCT causes less pain on injection than propofol MCT/LCT and thus increases patient comfort.
[Drug-Disease]: triglycerides - pain
[Title]: Safety and efficacy of alamifovir in patients with chronic hepatitis B virus infection.
[Abstract]: BACKGROUND/AIMS: Alamifovir is a purine nucleotide analogue prodrug that shows potent activity against wild type and lamivudine resistant hepatitis B virus in preclinical studies. The aim of this study was to assess the safety and potential antiviral effects of alamifovir in humans. METHODS: A randomised, placebo controlled, dose escalation study of oral alamifovir was conducted in 66 chronic hepatitis B infected patients who were selected based on stable HBV DNA (&gt;10(5)copies/ml), with no significant liver pathology. They received either placebo or alamifovir at a total daily dose ranging from 2.5 to 20mg in single or divided doses for 28 days and were followed up for approximately 12 weeks after cessation of treatment. RESULTS: All doses showed significant antiviral activity, with mean plasma viral load reductions ranging from 1.5 to 2.6 log(10) after 28 days of dosing. Once and twice daily regimen for the same daily dose (5mg BID vs 10mg QD, 10mg BID vs 20mg QD) showed no apparent difference in the rate and extent of viral decline, or viral reduction at day 28. Post-treatment viral suppression was dose dependent. There were no serious adverse events attributable to study drug, nor were significant dose related events identified. CONCLUSIONS: Alamifovir has shown potent in vivo anti-HBV activity, with a favourable safety profile.
[Drug-Disease]: Alamifovir - chronic hepatitis B virus infection
[Title]: Comparison of adefovir and tenofovir in the treatment of lamivudine-resistant hepatitis B virus infection.
[Abstract]: Adefovir dipivoxil was recently approved for the treatment of wild-type and lamivudine-resistant hepatitis B virus (HBV) infection. Tenofovir disoproxil fumarate, a congender of adefovir that is used in the treatment of HIV infected patients, has recently been shown to also be effective in patients with lamivudine-resistant HBV infection. We therefore compared the two substances in a study of 53 patients defined by high HBV DNA (&gt;6 log10 copies/mL) levels and genotypic evidence of lamivudine resistance. Thirty-five patients received tenofovir for 72 to 130 weeks, and 18 received adefovir for 60 to 80 weeks. Changes in HBV DNA levels were followed for the complete period of 48 weeks. Early viral kinetics were compared on matched subgroups of 5 patients each. Individually, all tenofovir-treated patients showed a strong and early suppression of HBV DNA within a few weeks whether they were coinfected with HIV or were without comorbidity. In contrast, considerable individual variations in HBV DNA decline were observed in the adefovir group. Thus at week 48, only 44% of these patients had HBV DNA levels below 10(5) copies/mL in contrast to 100% of the tenofovir-treated patients (P = .001). No severe side effects were noticed in either group. No evidence of phenotypic viral resistance could be demonstrated in the tenofovir-treated patients in the long term (up to 130 weeks). In conclusion, tenofovir may become an effective alternative for the treatment of patients with lamivudine-resistant HBV infection.
[Drug-Disease]: tenofovir - HBV infection
[Title]: HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.
[Abstract]: PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.
[Drug-Disease]: docetaxel - breast cancer
[Title]: HER-2/neu as a predictive marker in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin or single-agent docetaxel.
[Abstract]: PURPOSE: To evaluate the predictive value of HER-2 in a population of advanced breast cancer patients randomly treated either with single-agent doxorubicin (A) or with single-agent docetaxel (T). EXPERIMENTAL DESIGN: Patients from this study participated in a phase III clinical trial in which doxorubicin or docetaxel was administered for advanced disease. HER-2 was evaluated by IHC. In all positive cases, FISH was used to confirm the HER-2 positive status. The different cohorts of patients identified by HER-2 were examined to assess a possible relationship between HER-2 status and treatment effect. RESULTS: Tumor samples were available for 176 of the 326 patients entered in the clinical trial (54%). HER-2 positivity was observed in 20% of the study population. A statistically significant interaction was found between response rates to the study drugs and HER-2 status, with HER-2 positive patients deriving the highest benefit from the use of T (odds ratio for HER-2 positive patients treated with T = 3.12 (95% CI 1.11-8.80), p = 0.03). The interaction between HER-2 and response rates to A and T was also confirmed by a multivariate analysis. No statistically significant interaction was found between HER-2 and drugs efficacy evaluated in terms of time to progression and overall survival, although in the HER-2 negative cohort A was at least as effective as T in term of overall survival. CONCLUSIONS: These results suggest that in HER-2 positive breast cancer patients docetaxel might be more active than doxorubicin, while in HER-2 negative patients doxorubicin might be at least as effective as docetaxel. Although the present results cannot have an impact on current practice, they allow us to formulate the hypothesis that HER-2 positive breast cancer is a heterogeneous disease with regard to sensitivity to anthracyclines and taxanes, and that this might be dependent upon other molecular markers including the p-53 and topoisomerase II alpha genes. This hypothesis is currently being tested prospectively in two different 'bench to bed-side' clinical trials.
[Drug-Disease]: doxorubicin - breast cancer
[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.
[Drug-Disease]: etoposide - nephroblastoma
[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.
[Drug-Disease]: melphalan - nephroblastoma
[Title]: Effective use of high-dose chemotherapy and autologous stem cell rescue for relapsed adult Wilms' tumor and a novel alteration in intron 1 of the WT1 gene.
[Abstract]: Adult Wilms' tumor (AWT) is a very rare and aggressive malignancy, and little information is available on effective therapy in adults. Although mutations in WT1 have been found in 10% to 15% of childhood Wilms' tumor patients, to date WT1 mutations in AWT patients have not been described. The authors describe a 47-year-old man with relapsed AWT and a novel germline alteration in intron 1 of WT1: IVS1-6 C-->A. This alteration may reduce the splicing efficiency for exon 2 and possibly results in exon skipping. The effective salvage chemotherapy contained ifosfamide, carboplatin, and etoposide and was followed by a high-dose chemotherapy that contained melphalan, carboplatin, and etoposide. Both chemotherapy regimens showed moderate treatment-related toxicity. This report is the first that indicates that adult nephroblastoma patients also may carry WT1 germline mutations.
[Drug-Disease]: carboplatin - nephroblastoma
[Title]: Common polymorphisms of the PPAR-gamma2 (Pro12Ala) and PGC-1alpha (Gly482Ser) genes are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.
[Abstract]: AIM/HYPOTHESIS: We investigated the effects of the common polymorphisms in the peroxisome proliferator-activated receptor gamma2 (PPAR-gamma2; Pro12Ala) and in PPAR-gamma coactivator 1alpha (PGC-1alpha; Gly482Ser) genes on the conversion from impaired glucose tolerance to type 2 diabetes in participants in the STOP-NIDDM trial. This trial aimed to study the effect of acarbose in the prevention of type 2 diabetes. METHODS: Genotyping was performed in 770 study subjects whose DNA was available. The Gly482Ser variant in the PGC-1alpha gene was determined with the polymerase chain reaction amplification, Hpa II enzyme digestion, and gel electrophoresis. The Pro12Ala polymorphism of the PPAR-gamma2 gene was determined by the polymerase chain reaction-single-strand conformation polymorphism analysis. RESULTS: The Pro12Pro genotype of the PPAR-gamma2 gene predicted the conversion to diabetes in women in the acarbose group (odds ratio 2.89, 95% CI 1.20 to 6.96; p=0.018). The 482Ser allele of the PGC-1alpha gene had a significant interaction with the mode of treatment (p=0.012), and in the placebo group the 482Ser allele was associated with a 1.6-fold higher risk for type 2 diabetes compared to the Gly482Gly genotype (95% CI 1.06 to 2.33; p=0.023). Acarbose prevented the development of diabetes independently of the genotype of the PPAR-gamma2 gene, but only the carriers of the 482Ser allele of the PGC-1alpha gene were responsive to acarbose treatment. CONCLUSION/INTERPRETATION: We conclude that the Pro12Pro genotype of the PPAR-gamma2 gene and the 482Ser allele of the PGC-1alpha gene are associated with the conversion from impaired glucose tolerance to type 2 diabetes in the STOP-NIDDM trial.
[Drug-Disease]: acarbose - type 2 diabetes