Quality control of vital capacity as a primary outcome measure during phase III therapeutic clinical trial in amyotrophic lateral sclerosis.

Currently, ALS clinical trials require large sample size and the participation of many clinical evaluators to perform the outcome measure. High variability due to testers, instruments, or patients performance errors may result in systematic bias or random error leading to erroneous or uninterpretable results. Consequently, a quality control system that aims to produce high quality data in terms of reproducibility and accuracy to ensure reliability of the primary outcome measure is essential. In this paper we report our experience in preparing and executing a prospective quality control system that was implemented in conjunction with a large multicenter, multinational randomized placebo-controlled phase III clinical trial in ALS. We have shown that a prospective quality control system is highly effective to ensure inter- and intra-rater reliability of vital capacity as a primary outcome measure during the entire trial.

Sleep variables in anorexia nervosa: evolution with weight restoration.

OBJECTIVE: Studies on sleep patterns in anorexia nervosa (AN) have yielded inconsistent results. Therefore, we have studied the evolution of subjective and objective sleep characteristics in AN patients before and after weight restoration. METHOD: Thirty-four severely underweight AN inpatients of the restrictive subtype had a polysomnographic sleep registration at the time of admission and after weight restoration. Subjective sleep quality was also measured with self-report instruments. RESULTS: Objective sleep variables did not change with weight restoration, whereas subjective quality of sleep did improve. Percentage of underweight at admission and amount of slow wave sleep were predictors of the length of time required for weight restoration. DISCUSSION: The finding that weight restoration does not affect polysomnographic sleep variables in AN patients seems to contradict previous studies.

Cardiac involvement and CTG expansion in myotonic dystrophy.

Although cardiac complications are well known in myotonic dystrophy (DM), patients rarely manifest symptoms of cardiac disease, and if so they most often show conduction abnormalities or arrhythmia. In this study, specific cardiac findings were reviewed in 79 patients with DM. No correlation was found between the cardiac assessments and the CTG expansion. Thus, for a single patient the cardiac involvement in the disease can not be predicted from the findings of the genetic investigation. On the other hand, a clear positive relationship of the PR interval with the QRS duration was revealed, as well as a positive correlation between the age of the DM patient and the QRS duration, which increases with 0,54 ms/year. Systolic dysfunction, evaluated by transthoracic echocardiography, seems to be quite uncommon. In 32 % of the patients with a normal ECG, the 24 h Holter monitoring showed arrhythmias and conduction abnormalities. Based on these findings we recommend a follow up of DM patients not only based on the ECG, but also through 24 h Holter monitoring.

Daytime sleepiness and its evaluation.

Basic models of sleepiness, focusing on the homeostatic and circadian components of sleepiness, are able to predict important fluctuations of sleepiness. However, they fail in explaining certain sleepiness phenomena, as for instance in insomnia patients. To meet this shortcoming, modern models incorporate the arousal component of sleepiness, in addition to the sleep drive. While these models mainly concentrate on short-term changes in sleepiness, "state" sleepiness, there are indications that a stable characteristic level of sleepiness, "trait" sleepiness, is also an important determinant of a person's level of sleepiness. This leads to a conceptualization of sleepiness in which situational factors modify a basal level of sleep drive and arousal. It implies that sleepiness is not a unitary concept and can reflect essentially different states. Multiple sleepiness assessment tools have been proposed in the past. The majority of them offer valuable information, but they do not grasp all aspects of sleepiness. We should bear in mind that tools for assessing sleepiness are always operationalizations reflecting the theoretical framework the investigator has on sleepiness. Hence, rather than searching for a gold standard for the measurement of sleepiness, future research effort should be aimed at linking the various measurement techniques with the hypothesized underlying components of sleepiness on a sound empirical basis.