B1tta/Drug-ACE huggingface dataset:
[Title]: Olanzapine for self-injurious, aggressive, and disruptive behaviors in intellectually disabled adults: a retrospective, open-label, naturalistic trial.
[Abstract]: BACKGROUND: The effectiveness of olanzapine in treating challenging behaviors in the intellectually disabled and its ability to substitute for conventional antipsychotic drugs were evaluated. METHOD: A total of 20 institutionalized adults with a mean age of 42.7 years (range, 18-55 years) with intellectual disability and aggression, self-injurious behavior, destructive/disruptive behavior, or combinations of these behaviors were studied. These individuals were receiving multiple psychotropic medications at baseline and were given additional treatment with the atypical antipsychotic agent olanzapine. The mean dose of olanzapine was 9.1 mg/day (range, 2.5-22.5 mg/day). Effectiveness was determined by retrospective review of the summaries of quarterly neuropsychiatric behavioral reviews and retrospective review of longitudinal behavioral graphs of target symptoms. Data were collected from 1995 to 2000. RESULTS: A significant decrease in global challenging behaviors and specific target behaviors (i.e., aggression, self-injurious behaviors, destructive/disruptive behaviors) occurred (p <.05). A numerical decrease in the dosage of concurrent conventional antipsychotic medications occurred over the course of the first 6 months of olanzapine therapy, and a statistically significant (p <.005) decrease from the start of olanzapine therapy occurred in those subjects who received olanzapine for longer than 6 months (mean = 20.3 months). A significant increase in weight occurred in the subject group during the first 6 months of olanzapine treatment (p <.006), and sedation and constipation were the other common side effects noted. CONCLUSIONS: Olanzapine was found to be effective in the treatment of challenging behaviors in the intellectually disabled and in part could be substituted for administration of conventional antipsychotic drugs.
[Drug-Disease]: Olanzapine - aggression
[Title]: Pharmacokinetic-pharmacodynamic modeling of morphine-6-glucuronide-induced analgesia in healthy volunteers: absence of sex differences.
[Abstract]: BACKGROUND: Morphine-6-glucuronide (M6G) is a metabolite of morphine and a micro-opioid agonist. To quantify the potency and speed of onset-offset of M6G and explore putative sex dependency, the authors studied the pharmacokinetics and pharmacodynamics of M6G in volunteers using a placebo-controlled, randomized, double-blind study design. METHODS: Ten men and 10 women received 0.3 mg/kg intravenous M6G and placebo (two thirds of the dose as bolus, one third as a continuous infusion over 1 h) on separate occasions. For 7 h, pain tolerance was measured using gradually increasing transcutaneous electrical stimulation, and blood samples were obtained. A population pharmacokinetic (inhibitory sigmoid Emax)-pharmacodynamic analysis was used to analyze M6G-induced changes in tolerated stimulus intensity. The improvement in model fits by inclusion of covariate sex was tested for significance. P values less than 0.01 were considered significant. Taking into account previous morphine data, a predictive pharmacokinetic-pharmacodynamic model was constructed to determine the contribution of M6G to morphine analgesia. RESULTS: M6G concentrations did not differ between men and women. M6G caused analgesia significantly greater than that observed with placebo (P &lt; 0.01). The M6G analgesia data were well described by the pharmacokinetic-pharmacodynamic model. The M6G effect site concentration causing a 25% increase in current (C25) was 275 +/- 135 nm (population estimate +/- SE), the blood effect site equilibration half-life was 6.2 +/- 3.3 h, and the steepness parameter was 0.71 +/- 0.18. Intersubject variability was 167% for C25 and 218% for the effect half-life. None of the model parameters showed sex dependency. CONCLUSIONS: A cumulative dose of 0.3 mg/kg M6G, given over 1 h, produces long-term analgesia greater than that observed with placebo, with equal dynamics (potency and speed of onset-offset) in men and women. Possible causes for the great intersubject response variability, such as genetic polymorphism of the micro-opioid receptor and placebo-related phenomena, are discussed. The predictive pharmacokinetic-pharmacodynamic model was applied successfully and was used to estimate M6G analgesia after morphine in patients with normal and impaired renal function.
[Drug-Disease]: M6G - pain
[Title]: An open-label trial of sildenafil addition in risperidone-treated male schizophrenia patients with erectile dysfunction.
[Abstract]: BACKGROUND: Sexual dysfunction frequently occurs in treated and untreated patients with schizophrenia. Sildenafil is used for treatment of erectile dysfunction caused by diverse factors. The aim of our study was to evaluate its potential value, safety, and effect on compliance with anti-psychotic medications in risperidone-treated male schizophrenia patients suffering from erectile dysfunction. METHOD: In a 6-week open-label trial, sildenafil was administered to 12 male schizophrenia (DSM-IV) patients, treated with risperidone and reporting erectile dysfunction. The starting dose was 25 mg with the possibility to increase the dose to 75 mg. Three patients who did not respond stopped sildenafil treatment after 3 weeks. The effect on sexual function was assessed by the International Index of Erectile Function and the Valevski-Weizman Male Sexual Function scale. RESULTS: Nine (75%) of the 12 patients completed the 6-week trial, and 3 patients (25%) stopped taking sildenafil after 3 weeks due to lack of response. We observed statistically significant improvements in all sexual function domains (desire, erectile function, orgasmic function, intercourse satisfaction, and overall satisfaction) in the 9 patients who completed the trial and in most of the domains for all 12 study participants. More than half (8/12; 67%) of the patients exhibited partial or much improvement. CONCLUSION: Sildenafil is a useful agent for the treatment of erectile dysfunction in risperidone-treated male schizophrenia patients.
[Drug-Disease]: Sildenafil - erectile dysfunction
[Title]: Low dose daily iron supplementation improves iron status and appetite but not anemia, whereas quarterly anthelminthic treatment improves growth, appetite and anemia in Zanzibari preschool children.
[Abstract]: Iron deficiency and helminth infections are two common conditions of children in developing countries. The consequences of helminth infection in young children are not well described, and the efficacy of low dose iron supplementation is not well documented in malaria-endemic settings. A 12-mo randomized, placebo controlled, double-blind trial of 10 mg daily iron and/or mebendazole (500 mg) every 3 mo was conducted in a community-based sample of 459 Zanzibari children age 6-71 mo with hemoglobin > 70 g/L at baseline. The trial was designed to examine treatment effects on growth, anemia and appetite in two age subgroups. Iron did not affect growth retardation, hemoglobin concentration or mild or moderate anemia (hemoglobin < 110 g/L or < 90 g/L, respectively), but iron significantly improved serum ferritin and erythrocyte protoporphyrin. Mebendazole significantly reduced wasting malnutrition. but only in children <30 mo old. The adjusted odds ratios (AORs) for mebendazole in this age group were 0.38 (95% CI: 0.16, 0.90) for weight-for-height less than -1 Z-score and 0.29 (0.09, 0.91) for small arm circumference. In children <24 mo old, mebendazole also reduced moderate anemia (AOR: 0.41, 0.18, 0.94). Both iron and mebendazole improved children's appetite, according to mothers' report. In this study, iron's effect on anemia was limited, likely constrained by infection, inflammation and perhaps other nutrient deficiencies. Mebendazole treatment caused unexpected and significant reductions in wasting malnutrition and anemia in very young children with light infections. We hypothesize that incident helminth infections may stimulate inflammatory immune responses in young children, with deleterious effects on protein metabolism and erythropoiesis.
[Drug-Disease]: Mebendazole - anemia
[Title]: Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.
[Abstract]: BACKGROUND: Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS: Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P &lt; 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS: Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.
[Drug-Disease]: omapatrilat - hypertension
[Title]: Omapatrilat and enalapril in patients with hypertension: the Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial.
[Abstract]: BACKGROUND: Recent reports suggest that existing antihypertensive agents may not have sufficient efficacy to control blood pressure (BP) in many patients. Omapatrilat, an agent under development, has been shown to have significantly greater antihypertensive efficacy than existing agents, but may also carry increased risk of angioedema. We compared the efficacy and safety of omapatrilat to a representative angiotensin-converting enzyme (ACE) inhibitor, enalapril. METHODS: The Omapatrilat Cardiovascular Treatment vs. Enalapril (OCTAVE) trial is a multicenter, randomized, double-blind, active-controlled, 24-week trial in 25,302 patients with untreated or uncontrolled hypertension conducted in 3298 office-based sites in 12 countries. Subjects were randomized to omapatrilat 10 mg or enalapril 5 mg as initial therapy for hypertension (group 1, n = 9292), replacement for existing antihypertensive therapy (group 2, n =11,224), or in addition to existing antihypertensive therapy (group 3, n = 4751). Study drug was force-titrated at week 2 and electively titrated at weeks 4 and 6 to a maximum of omapatrilat 80 mg or enalapril 40 mg once daily. At weeks 8 and 16, adjunctive antihypertensive medications were added electively to achieve target BP. RESULTS: Omapatrilat reduced systolic BP 3.6 mm Hg more than enalapril at week 8, and was associated with less use of adjunctive antihypertensive therapy by week 24 (19% v 27%; P &lt; 0.001 for both comparisons). Subjects randomized to omapatrilat were more likely to reach BP target, regardless of demographics or comorbid conditions and whether omapatrilat was used as initial therapy, replacement for existing therapy, or in addition to existing therapy. Angioedema was more frequent with omapatrilat than enalapril (2.17% v 0.68%). Two omapatrilat-treated subjects experienced angioedema with airway compromise, which was successfully treated. CONCLUSIONS: Omapatrilat provided broadly superior antihypertensive efficacy when used in a setting resembling clinical practice. Angioedema was more common than with enalapril but life-threatening angioedema was rare. The risk-benefit profile for omapatrilat in clinical use therefore appears likely to be favorable in appropriate patients.
[Drug-Disease]: enalapril - hypertension
[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.
[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P&lt;0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.
[Drug-Disease]: cis-platinum - osteosarcoma
[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.
[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P&lt;0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.
[Drug-Disease]: doxorubicin - osteosarcoma
[Title]: Prediction of response to neoadjuvant chemotherapy for osteosarcoma by gene-expression profiles.
[Abstract]: To establish a method for predicting the response to chemotherapy for osteosarcoma (OS), we performed expression profile analysis using cDNA microarray consisting of 23,040 genes. Hierarchical clustering based on the expression profiles of 19 biopsy samples of OS demonstrated two major clusters, one of which consisted exclusively of typical OS, i.e. conventional central OS in long bone of patients in the second decade. A set of genes was identified to characterize this subgroup, some of which have previously indicated some relation to carcinogenesis. Thirteen of the 19 patients were treated with an identical protocol of chemotherapy containing doxorubicin, cis-platinum and ifosfamide, and histological examination of resected specimens after operation classified 6 cases as responder and 7 as non-responder. A comparison of expression profiles of these two groups identified 60 genes whose expression levels were likely to be correlated with the response to chemotherapy (P&lt;0.008). A drug response scoring (DRS) system was developed based on the expression levels of these genes, which proved to be applicable to predict the response to chemotherapy irrespective for the subclassification of OS. The reliability of the DRS system was further confirmed by testing additional 5 OS cases. These results indicated that scoring system based on gene-expression profiles might be useful to predict the response to chemotherapy for OS.
[Drug-Disease]: ifosfamide - osteosarcoma
[Title]: Clonidine treatment of hyperactive and impulsive children with autistic disorder.
[Abstract]: Many autistic children have associated problems of inattention, impulsivity, and hyperactivity that limit the effectiveness of educational and behavioral interventions. Few controlled psychopharmacologic trials have been conducted in autistic children to determine which agents may be effective for these associated features. Eight male children (8.1 +/- 2.8 years) with autistic disorder, diagnosed by DSM-III-R criteria, completed a placebo-controlled, double-blind crossover trial of clonidine. Subjects were included in the study if they had inattention, impulsivity, and hyperactivity that was excessive for their developmental level. Subjects had not tolerated or responded to other psychopharmacologic treatments (neuroleptics, methylphenidate, or desipramine). Teacher ratings on the Aberrant Behavior Checklist irritability, stereotypy, hyperactivity, and inappropriate speech factors were lower during treatment with clonidine than during treatment with placebo. Attention deficit disorder with hyperactivity: Comprehensive Teacher's Rating Scale ratings were not significantly improved during the study, except for oppositional behavior. Parent Conners Abbreviated Parent-Teacher Questionnaire ratings significantly improved during clonidine treatment. Clonidine led to increased ratings of the side effects of drowsiness and decreased activity. Clinician ratings (Children's Psychiatric Rating Scale Autism, Hyperactivity, Anger and Speech Deviance factors; Children's Global Assessment Scale; Clinical Global Impressions efficacy) of videotaped sessions were not significantly different between clonidine and placebo. Clonidine was modestly effective in the short-term treatment of irritability and hyperactivity in some children with autistic disorder.
[Drug-Disease]: Clonidine - Attention deficit disorder
[Title]: Clonidine treatment of hyperactive and impulsive children with autistic disorder.
[Abstract]: Many autistic children have associated problems of inattention, impulsivity, and hyperactivity that limit the effectiveness of educational and behavioral interventions. Few controlled psychopharmacologic trials have been conducted in autistic children to determine which agents may be effective for these associated features. Eight male children (8.1 +/- 2.8 years) with autistic disorder, diagnosed by DSM-III-R criteria, completed a placebo-controlled, double-blind crossover trial of clonidine. Subjects were included in the study if they had inattention, impulsivity, and hyperactivity that was excessive for their developmental level. Subjects had not tolerated or responded to other psychopharmacologic treatments (neuroleptics, methylphenidate, or desipramine). Teacher ratings on the Aberrant Behavior Checklist irritability, stereotypy, hyperactivity, and inappropriate speech factors were lower during treatment with clonidine than during treatment with placebo. Attention deficit disorder with hyperactivity: Comprehensive Teacher's Rating Scale ratings were not significantly improved during the study, except for oppositional behavior. Parent Conners Abbreviated Parent-Teacher Questionnaire ratings significantly improved during clonidine treatment. Clonidine led to increased ratings of the side effects of drowsiness and decreased activity. Clinician ratings (Children's Psychiatric Rating Scale Autism, Hyperactivity, Anger and Speech Deviance factors; Children's Global Assessment Scale; Clinical Global Impressions efficacy) of videotaped sessions were not significantly different between clonidine and placebo. Clonidine was modestly effective in the short-term treatment of irritability and hyperactivity in some children with autistic disorder.
[Drug-Disease]: Clonidine - autistic disorder
[Title]: [The influence of lamivudine therapy on the course of chronic hepatitis B in renal allograft recipients].
[Abstract]: The aim of this study was to evaluate efficacy and safety of lamivudine therapy in renal allograft recipients with chronic hepatitis B infection. Twenty-four patients with chronic hepatitis B after renal transplantation were observed. We obtained HBV replication blockage in 95% of patients, in half of them also ALT normalisation was observed. Delayed HBV replication blockage was observed in patients with prolonged duration of haemodialysotherapy or HBV infection and HCV coinfection, although listed parameters did not influence overall treatment efficacy. After lamivudine discontinuation HBV replication relapsed, in part of patients with ALT activity elevation. We did not observed any serious adverse reactions under lamivudine therapy.
[Drug-Disease]: lamivudine - chronic hepatitis B