Sandra Plumb

Treatment of ADHD in children with tics: A randomized controlled trial

BACKGROUND The treatment of children with attention deficit hyperactivity disorder (ADHD) and Tourette syndrome (TS) has been problematic because methylphenidate (MPH)--the most commonly used drug to treat ADHD--has been reported to worsen tics and because clonidine (CLON)--the most commonly prescribed alternative--has unproven efficacy. METHODS The authors conducted a multicenter, randomized, double-blind clinical trial in which 136 children with ADHD and a chronic tic disorder were randomly administered CLON alone, MPH alone, combined CLON + MPH, or placebo (2 x 2 factorial design). Each subject participated for 16 weeks (weeks 1-4 CLON/placebo dose titration, weeks 5-8 added MPH/placebo dose titration, weeks 9-16 maintenance therapy). RESULTS Thirty-seven children were administered MPH alone, 34 were administered CLON alone, 33 were administered CLON + MPH, and 32 were administered placebo. For our primary outcome measure of ADHD (Conners Abbreviated Symptom Questionnaire--Teacher), significant improvement occurred for subjects assigned to CLON (p < 0.002) and those assigned to MPH (p < 0.003). Compared with placebo, the greatest benefit occurred with combined CLON + MPH (p < 0.0001). CLON appeared to be most helpful for impulsivity and hyperactivity; MPH appeared to be most helpful for inattention. The proportion of individual subjects reporting a worsening of tics as an adverse effect was no higher in those treated with MPH (20%) than those being administered CLON alone (26%) or placebo (22%). Compared with placebo, measured tic severity lessened in all active treatment groups in the following order: CLON + MPH, CLON alone, MPH alone. Sedation was common with CLON treatment (28% reported moderate or severe sedation), but otherwise the drugs were tolerated well, including absence of any evident cardiac toxicity. CONCLUSIONS Methylphenidate and clonidine (particularly in combination) are effective for ADHD in children with comorbid tics. Prior recommendations to avoid methylphenidate in these children because of concerns of worsening tics are unsupported by this trial.

Test–Retest reliability of the Unified Parkinson's Disease Rating Scale in patients with early Parkinson's disease: Results from a multicenter clinical trial

Our objective was to assess the test–retest reliability of the Unified Parkinsons Disease Rating Scale (UPDRS). The UPDRS is the most widely used instrument for measuring severity of parkinsonian symptoms in clinical research and in practice. The validity and inter‐rater reliability of this scale have been previously studied. We examined the test–retest (intrarater) reliability of the UPDRS and derived subscales. Four hundred patients with early‐stage Parkinsons disease (PD) who were participating in a multicenter clinical trial were evaluated using the UPDRS on two separate occasions (screening and baseline visits) prior to receiving treatment. The same neurologist at each center rated the subjects at both examinations that were, on average, 14.6 ± 7.6 days apart (range 3–36 days). Test–retest reliability was estimated using the intraclass correlation coefficient (ICC) for the total UPDRS score, the mental, ADL, and motor subscale scores, and other derived subscale scores. Weighted kappa statistics were calculated for individual UPDRS items. The ICCs for the UPDRS scores were as follows: total score, 0.92; mental, 0.74; ADL, 0.85; motor, 0.90. ICCs for derived symptom‐based scales ranged from 0.69–0.88. Reliability of specific items was generally lower than for summary scales. Reliability was slightly better in patients for whom the testing interval was within 14 days. Based on conventional standards, the UPDRS scores were found to have excellent test–retest reliability in this sample of patients with early PD rated by academic movement disorder specialists. The findings are in agreement with previous reports on interrater reliability.

Rasagiline improves quality of life in patients with early Parkinson's disease

The objective of this study was to determine the effects of rasagiline as monotherapy on quality of life (QOL) in patients with early Parkinsons disease (PD). Rasagiline, a potent, second‐generation, irreversible, selective monoamine oxidase B inhibitor improves PD symptoms in patients with early PD. Patients with early untreated PD were randomly assigned to once‐daily rasagiline 1 mg/day, rasagiline 2 mg/day, or placebo in a 6‐month, double‐blind trial (n = 404). At the end of 6 months, patients entered the preplanned, active‐treatment phase in which those receiving 1 mg/day and 2 mg/day of rasagiline continued on their previously assigned dosages and those receiving placebo switched to rasagiline 2 mg/day, while maintaining blinding to treatment assignments. QOL was measured with the Parkinsons Disease Quality of Life questionnaire (PDQUALIF) at 0, 14, 26, and 52 weeks after randomization. Analysis of the change in PDQUALIF scores from baseline to 6 months showed adjusted treatment effects (with 95% confidence interval) favoring rasagiline over placebo of −2.91 units (−5.19, −0.64, P = 0.01) for the 1 mg/day group and −2.74 units (−5.02, −0.45, P = 0.02) for the 2 mg/day. Subscore analysis attributed most of this benefit to the self‐image/sexuality domain. At 12 months (n = 266), with all groups receiving rasagiline for at least 6 months, no significant differences in PDQUALIF scores were seen between groups. Rasagiline improved QOL compared with placebo. This QOL improvement appears to be accounted for primarily by the symptomatic benefit of rasagiline.

A Study of Chorea After Tetrabenazine Withdrawal in Patients With Huntington Disease

Objective: To assess tetrabenazine (TBZ) efficacy by evaluating the change in Huntington disease-associated chorea resulting from TBZ treatment withdrawal. Methods: Thirty patients treated in the long term were randomized to 1 of 3 groups assigned to withdraw from TBZ in a double-blind, staggered fashion during a 5-day period. Results: The chorea scores of subjects withdrawn from TBZ treatment increased by 5.3 units from days 1 to 3, whereas the scores of the group with partial or no withdrawal of TBZ treatment increased by 3.0 units (P = 0.0773). A post hoc analysis of the linear trend was positive for reemergent chorea (P = 0.0486). No serious adverse events were reported after abrupt withdrawal of TBZ treatment. Conclusions: The trend for reemergence of chorea in patients with Huntington disease who were withdrawn from TBZ treatment is consistent with the findings from previous studies, thus showing the effectiveness of TBZ in reducing chorea.

BGRAPH: A Program for Biplot Multivariate Graphics

BGRAPH (Tsianco, 1980) is an inter-active conversational program to perform biplot multivariate graphics. The program generates two-and three-dimensional biplot displays based on the singular value decomposition (SVD) of a matrix and the resulting rank 2 or 3 approximations. Three dimensional displays may be either orthogonal projections, perspective projections, stereograms or analyglyphs. Other capabilities of the program include subset selection, selective labeling of points, rotation of axes, construction of ellipsoids of concentration, MANOVA biplots and plot storage.