Carrie Irvine

Placebo-Controlled Study of Divalproex Sodium for Agitation in Dementia

The authors assessed the efficacy, tolerability, and safety of divalproex sodium for the treatment of agitation associated with dementia in a 6-week, randomized study of 56 nursing home patients with agitation and dementia treated with either placebo or individualized doses of divalproex sodium. Participants were blinded to treatment except for a physician-monitor and a pharmacist. When several covariates were taken into account, the drug/placebo difference in Brief Psychiatric Rating Scale Agitation scores became statistically significant (P=0.05). Sixty-eight percent of patients on divalproex were rated as showing reduced agitation on the Clinical Global Impression scale, vs. 52% on placebo (P=0.06 in the adjusted analysis). Side effects occurred in 68% of the divalproex group vs. 33% of the placebo group (P=0.03) and were generally rated as mild. This placebo-controlled study, despite some limitations, suggests possible short-term efficacy, tolerability, and safety of divalproex for agitation in dementia and supports further placebo-controlled studies.

Acute Respiratory Tract Infection in Daycare Centers for Older Persons

OBJECTIVE: To evaluate the rate of specific pathogens and clinical syndromes associated with acute respiratory tract infections (ARTI) in frail older persons attending daycare.

An expanded version of the Hammersmith Functional Motor Scale for SMA II and III patients.

PURPOSE To develop and evaluate an expanded version of the Hammersmith Functional Motor Scale allowing for evaluation of ambulatory SMA patients. PROCEDURES Thirty-eight patients with SMA type II or III were evaluated using the Gross Motor Function Measure and the Hammersmith Functional Motor Scale. Based on statistical and clinical criteria, we selected 13 Gross Motor Function Measure items to develop an expanded HFMS. The expanded Hammersmith Functional Motor Scale was validated by comparison with the Gross Motor Function Measure minus the 13 items (GMFM-75) and an assessment of clinical function. The reliability of the expanded Hammersmith Functional Motor Scale in 36 patients was established. FINDINGS The expanded Hammersmith Functional Motor Scale was highly correlated with the GMFM-75 and the clinical function assessment (p=0.97, and p=0.90). The expanded Hammersmith Functional Motor Scale showed excellent test-retest reliability (International Coordinating Committee = 0.99). CONCLUSIONS The expanded Hammersmith Functional Motor Scale allows assessment of high functioning SMA type II and III patients. Ease of administration and correlation with established motor function measures justify use in future SMA clinical trials.

Carbamazepine treatment of agitation in nursing home patients with dementia: a preliminary study.

OBJECTIVE: To determine the effects of carbamazepine versus placebo on ratings of behavior in agitated nursing home patients with dementia.

Tourette's syndrome in a special education population A pilot study involving a single school district

To determine whether children requiring special education represent a high-risk group for identifying Tourettes syndrome (TS), we performed direct examinations for the presence of tics in 35 special education and 35 regular classroom students from a single school district. Of the special education students, nine (26%) had definite or probable tics as compared with only two (6%) of the regular classroom students. About one-third of the students with tics currently meet diagnostic criteria for TS and probably more will do so in the future. About one-half of the subjects with tics have evidence of obsessive-compulsive behavior (OCB) or an attention-deficit hyperactivity disorder (ADHD). For three randomly selected students with definite tics, direct examinations of first-degree relatives revealed the presence of tics in all families. Subject to the limitations of this pilot study, we conclude that TS and related tic disorders are commonly associated with the need for special education in this single school district. TS might also be an important contributor to school problems in the childhood population at large and may be a highly prevalent condition. In addition, we conclude that childhood tics are associated with OCB and ADHD, are genetically determined, and are part of the TS clinical spectrum.

Observational Study of Spinal Muscular Atrophy Type 2 and 3: Functional Outcomes Over 1 Year

OBJECTIVE To characterize the short-term course of spinal muscular atrophy (SMA) in a genetically and clinically well-defined cohort of patients with SMA. DESIGN A comprehensive multicenter, longitudinal, observational study. SETTING The Pediatric Neuromuscular Clinical Research Network for SMA, a consortium of clinical investigators at 3 clinical sites. PARTICIPANTS Sixty-five participants with SMA types 2 and 3, aged 20 months to 45 years, were prospectively evaluated. INTERVENTION We collected demographic and medical history information and determined the SMN 2 copy number. MAIN OUTCOME MEASURES Clinical outcomes included measures of motor function (Gross Motor Function Measure and expanded Hammersmith Functional Motor Scale), pulmonary function (forced vital capacity), and muscle strength (myometry). Participants were evaluated every 2 months for the initial 6 months and every 3 months for the subsequent 6 months. We evaluated change over 12 months for all clinical outcomes and examined potential correlates of change over time including age, sex, SMA type, ambulatory status, SMN2 copy number, medication use, and baseline function. RESULTS There were no significant changes over 12 months in motor function, pulmonary function, and muscle strength measures. There was evidence of motor function gain in ambulatory patients, especially in those children younger than 5 years. Scoliosis surgery during the observation period led to a subsequent decline in motor function. CONCLUSIONS Our results confirm previous clinical reports suggesting that SMA types 2 and 3 represent chronic phenotypes that have relatively stable clinical courses. We did not detect any measurable clinical disease progression in SMA types 2 and 3 over 12 months, suggesting that clinical trials will have to be designed to measure improvement rather than stabilization of disease progression.

A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster.

ABSTRACT Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health‐related quality of life, there have been no randomized clinical trials of oral medications specifically for its ongoing treatment. A randomized clinical trial was conducted in which 87 subjects ⩾50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24 h ⩾ 3 on a 0–10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled‐release (CR) oxycodone, gabapentin, or placebo. Subjects were evaluated for adverse effects of treatment, acute pain, and health‐related quality of life. The results showed that CR‐oxycodone and gabapentin were generally safe and were associated with adverse events that reflect well‐known effects of these medications. Discontinuing participation in the trial, primarily associated with constipation, occurred more frequently in subjects randomized to CR‐oxycodone (27.6%) compared with placebo (6.9%). Treatment with CR‐oxycodone reduced the mean worst pain over days 1–8 (p = 0.01) and days 1–14 (p = 0.02) relative to placebo but not throughout the entire 28‐day treatment period as pain resolved in most subjects. Gabapentin did not provide significantly greater pain relief than placebo, although the data for the first week were consistent with a modest benefit. By demonstrating that CR‐oxycodone is safe, generally adequately tolerated, and appears to have efficacy for relieving acute pain, the results of this clinical trial provide a foundation for evidence‐based treatment for acute pain in herpes zoster.

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.