Validity, reliability, and psychometric properties of a computerized, cognitive assessment test (Cognivue®).

BACKGROUND: Cognitive issues such as Alzheimer's disease and other dementias confer a substantial negative impact. Problems relating to sensitivity, subjectivity, and inherent bias can limit the usefulness of many traditional methods of assessing cognitive impairment. AIM: To determine cut-off scores for classification of cognitive impairment, and assess Cognivue® safety and efficacy in a large validation study. METHODS: Adults (age 55-95 years) at risk for age-related cognitive decline or dementia were invited via posters and email to participate in two cohort studies conducted at various outpatient clinics and assisted- and independent-living facilities. In the cut-off score determination study (n = 92), optimization analyses by positive percent agreement (PPA) and negative percent agreement (NPA), and by accuracy and error bias were conducted. In the clinical validation study (n = 401), regression, rank linear regression, and factor analyses were conducted. Participants in the clinical validation study also completed other neuropsychological tests. RESULTS: For the cut-off score determination study, 92 participants completed St. Louis University Mental Status (SLUMS, reference standard) and Cognivue® tests. Analyses showed that SLUMS cut-off scores of < 21 (impairment) and > 26 (no impairment) corresponded to Cognivue® scores of 54.5 (NPA = 0.92; PPA = 0.64) and 78.5 (NPA = 0.5; PPA = 0.79), respectively. Therefore, conservatively, Cognivue® scores of 55-64 corresponded to impairment, and 74-79 to no impairment. For the clinical validation study, 401 participants completed ≥ 1 testing session, and 358 completed 2 sessions 1-2 wk apart. Cognivue® classification scores were validated, demonstrating good agreement with SLUMS scores (weighted κ 0.57; 95%CI: 0.50-0.63). Reliability analyses showed similar scores across repeated testing for Cognivue® (R 2 = 0.81; r = 0.90) and SLUMS (R 2 = 0.67; r = 0.82). Psychometric validity of Cognivue® was demonstrated vs. traditional neuropsychological tests. Scores were most closely correlated with measures of verbal processing, manual dexterity/speed, visual contrast sensitivity, visuospatial/executive function, and speed/sequencing. CONCLUSION: Cognivue® scores ≤ 50 avoid misclassification of impairment, and scores ≥ 75 avoid misclassification of unimpairment. The validation study demonstrates good agreement between Cognivue® and SLUMS; superior reliability; and good psychometric validity.

Long-term add-on pregabalin treatment in patients with partial-onset epilepsy: pooled analysis of open-label clinical trials.

PURPOSE: To evaluate the safety, tolerability, and efficacy of long-term pregabalin as add-on therapy for patients with poorly controlled partial seizures. METHODS: Analysis of data from six long-term clinical trials involving 2,061 patients receiving open-label pregabalin 75-600 mg/day adjunctive therapy for partial onset epilepsy refractory to multiple antiepileptic drugs. RESULTS: Total pregabalin exposure was 3,877 person-years. The mean duration of pregabalin treatment was 534 days (range 0.3-8 years) and 59% completed 1 year. One-third of patients discontinued for lack of efficacy. The most common dose was >or=300 mg/day; over half took >or=450 mg/day. There was a mean reduction in the 28-day seizure rate of 25-40%, and more than 40% of all patients had a >or=50% reduction in seizures from baseline during the last 3 months of treatment. Twelve percent of all patients had a 6-month period continuously free of seizures. In the last year, 6% were seizure-free for the entire year. Pregabalin was generally well-tolerated and the safety profile favorable in patients treated for up to several years, with an adverse event (AE) profile similar to short-term placebo-controlled trials. Common AEs included CNS symptoms (dizziness, somnolence, headache, and asthenia), accidental injury, and weight gain. CNS AEs tended to be mild and transient. Rates of sudden unexpected death in epilepsy (SUDEP), mortality, cancer, and status epilepticus were within the expected range for this population. CONCLUSIONS: Adjunctive pregabalin was effective, generally well tolerated, and safe in the long-term treatment of partial seizures, and provided clinically meaningful seizure reduction and freedom without evidence of tolerance over 2 years of follow-up.

Hepatotoxic profile of catechol-O-methyltransferase inhibitors in Parkinson's disease.

Entacapone and tolcapone are selective catechol-O-methyltransferase (COMT) inhibitors developed recently as adjuncts to levodopa for the treatment of Parkinson's disease (PD). They extend the duration of action of levodopa. As a result, they increase 'on' time, decrease 'off' time and improve motor scores in patients with motor fluctuations. Both benefits and main side effects are related to increased dopaminergic activity. This paper reviews the use of those COMT inhibitors in PD with particular focus on the issue of hepatotoxicity. Neither tolcapone nor entacapone caused hepatotoxicity in preclinical studies. However, in 1998, four patients who were using tolcapone presented with serious liver dysfunction; three of them died due to acute liver failure. Tolcapone is now known to have the potential to cause hepatotoxicity in clinical use and experimental studies. It is now recommended that tolcapone be administered only in patients with motor fluctuations who are no longer satisfactorily treated with other medications for PD. Routine liver monitoring is now mandatory with this agent. Entacapone has been described as a well-tolerated and safe drug in recent experimental studies, human clinical trials and postmarketing surveillance. It can be offered to any patient with motor fluctuations and routine liver monitoring is not required.