Retrospective evaluation of the effect of valproate therapy on transaminase elevations in patients with hepatitis C.

STUDY OBJECTIVE: To evaluate whether a relationship exists between valproate treatment and transaminase elevations in patients who are positive for hepatitis C virus (HCV). DESIGN: Retrospective medical record review. SETTING: Veterans affairs medical center. PATIENTS: A total of 214 HCV-positive patients; 28 were treated with valproate (study group), 186 were not (control group). INTERVENTION: Demographic characteristics; valproate treatment histories; plasma concentrations of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), albumin, and bilirubin; and exposure to other potentially hepatotoxic drugs, including probable alcohol abuse, were evaluated. MEASUREMENTS AND MAIN RESULTS: Hepatotoxicity was staged by comparing maximum ALT and AST values against upper limits of normal or patients' mean elevated baseline ALT and AST values. Data were analyzed using a logistic regression model. Control patients and those with longer durations of HCV were more likely (p<0.0171 and p<0.0142, respectively) to exhibit higher stages of hepatotoxicity. More valproate-treated patients were exposed to other potential hepatotoxins at the time of peak transaminase elevations (50% vs 39%, p<0.005), whereas more control patients received two or more potential hepatotoxins (13% vs 4%, p<0.00005). CONCLUSION: Valproate treatment, either alone or in the presence of other potential hepatotoxins, does not appear to be related to increased transaminase elevations in patients with HCV

Risperidone for aggression and self-injurious behavior in adults with mental retardation.

Risperidone has proven efficacy with reduced likelihood of causing extrapyramidal symptoms in the treatment of schizophrenia. Initial work suggests its utility in the management of aggression and self injury in patients with mental retardation. The use of risperidone in eight adult patients with moderate to profound mental retardation is described. Risperidone in these individuals was associated with significant reduction in aggression and self injurious behavior. Side effects were primarily those of sedation and restlessness. These cases illustrate the possible utility of risperidone in the treatment of aggression and self injury in adult patients with moderate to profound mental retardation.

Efficacy of lamotrigine in institutionalized, developmentally disabled patients with epilepsy: a retrospective evaluation.

The paper evaluates the efficacy of the newer anticonvulsant lamotrigine in a developmentally disabled patient population. A retrospective evaluation was done at two institutional centres to assess adjunctive lamotrigine (Lamictal) efficacy in a developmentally disabled population. Mean seizure frequency was compared between a 2-month pre-lamotrigine baseline period and a 2-month treatment period. A 3-month lamotrigine titration phase occurred between baseline and treatment periods. Seizure frequency data was obtained from standardized, daily seizure records. Adverse effect data was obtained from medical and nursing notes. An intent to treat analysis was performed. Data were analysed using Student's t-test for paired data. We evaluated 44 centre residents (25 male, 19 female, average age 33 +/- 11 years). Mean lamotrigine dose was 272 +/- 133 mg per day. A significant reduction in seizure frequency was noted. Seizure frequency (all seizures) was 10.1 +/- 11.2 during the baseline period vs. 5.8 +/- 7.9 seizures per month during the treatment period (P = 0.002). Thirty-two percent of patients (n = 14) had greater than a 75% reduction in seizure frequency. Twenty-three percent of patients (n = 10) had a 50-74% seizure reduction. Twenty-five percent of patients (n = 11) had less than a 50% reduction in seizures, while 20% (n = 9) had an increase in seizures. A significant reduction of 48% in generalized seizures (9.5 +/- 11.6 vs. 4.9 +/- 6.5 seizures per month, P = 0.013) was noted. Reductions in partial seizure frequency of 48% (7.9 +/- 10 vs. 4 +/- 6.6 seizures per month, P = 0.16) as well as in mixed-type seizures (19.9 +/- 9.3 was vs. 15 +/- 12.1 seizures per month, P = 0.11) were also seen; however, these changes did not reach significance. Overall, lamotrigine was well tolerated by the subject population. Adjunctive treatment with lamotrigine appears to be an efficacious and well-tolerated treatment for seizures in a significant percentage of developmentally disabled patients with epilepsy.

Clinical and economic aspects of risperidone treatment in adults with mental retardation and behavioral disturbance.

Risperidone, in conjunction with behavioral interventions, was used to reduce aggression and assault, self-injury, and property destruction in 33 institutionalized adults with mental retardation. Target behavior frequencies, global assessments by staff, wages earned by patients, and the institution's costs for assault-related injury to staff and lost work time were evaluated before and after initiation of risperidone treatment. Risperidone (1-8 mg/day) was associated with a 50 percent or greater reduction in at least one target behavior frequency in 61 percent of patients. After 6 months of treatment, 85 percent of patients were rated "improved" and 15 percent were rated "unchanged." Treated patients' wage earnings increased by 37 percent. The number of staff work days lost because of assault by treated patients decreased from 444 during the 6 months before initiation of risperidone to 29 during the 6 months after initiation. Sedation, pseudoparkinsonism, possible akathisia, and weight gain were noted in 9-12 percent of patients. No patients were withdrawn from risperidone because of intolerable side effects or lack of efficacy. The results of this evaluation suggest that risperidone is effective and well tolerated in this population.

Correlation of predicted versus measured creatinine clearance values in burn patients.

Four methods for predicting creatinine clearance (Ccr) from serum creatinine concentration (Scr) were evaluated in 19 male burn patients with burn wound sepsis. Measured Ccr values were calculated from 24-hour urinary catheter collections. Steady state Scr values were obtained during the same collection interval. Predicted Ccr values were derived from Scr using the methods of Cockcroft and Gault (Method II), Siersbaek-Nielsen, Kampmann and others (Method III) and Jeliffe (Methods I and IV). Wide differences between measured and predicted values were observed but were statistically significant (p less than 0.05) for Method I only. The smallest mean difference (+/-0.02 ml/min/1.73 m2) occurred with Method II measured-predicted data pairs. Method III predicted Ccr values which correlated best with measured values (r=0.770) and showed the least variability (+/-7.6 ml/min/1.73 m2). All methods appeared to overestimate when measured Ccr was less than 60 ml/min/1.73 m2. Use of estimated lean body weights did not improve correlations between predicted and measured Ccr values. While Methods II and III may provide useful initial approximations of Ccr in burn patients, reliance upon predicted Ccr values for dosage modification in burn patients may result in an insufficient reduction in dosage. Whenever possible, dosage regimens for drugs with narrow therapeutic margins should be developed or adjusted using pharmacokinetic values determined in the individual patient.