Assessment and treatment of low-rate high-intensity problem behavior.

Functional analysis of low-rate aggression was conducted during extended observation periods and showed behavior to be maintained by positive reinforcement. Treatment consisted of variable-momentary differential reinforcement of other behavior and was successful in reducing problem behavior throughout these extended observation periods.

Recognizing Ullrich-Turner syndrome by discriminant analysis of craniofacial structure.

In the present paper, we propose an efficient strategy for identification of craniofacial anomalies in the Ullrich-Turner syndrome (UTS). Standardized portrait- and profile-photographs were taken of 21 UTS patients with X-monosomy and 21 normal females. Twenty-seven craniofacial parameters were read from the photographs. The data were analyzed by discriminant analysis, a multivariate statistical method. The result was a function represented by a linear combination of all those craniofacial parameters which best separate the two groups. The discriminant function was applied to 15 additional patients with UTS of various cytogenetic types. All 15 patients were classified correctly. The technique facilitates syndrome-recognition and is a contribution toward the study of karyotype-phenotype relations.

Assessment of small health risks based on exact sample sizes.

Exact sample sizes and critical numbers of cases for the rejection of a known event probability (10(-2) to 10(-6)) in favour of an increased probability (1.5- to 50-fold) at levels -alpha;beta- = -0.05; 0.10- and -alpha;beta- = -0.10;0.05- are presented. The numbers are thoroughly validated using the characteristics of the confidence interval for the unknown true event probability. Equivalence is shown to be obtainable for the tolerated maximal value of the relative risk and the upper limit of the confidence interval for the true event probability. Also demonstrated is the use of the tables for planned actions to reduce given empirical risks. In addition, use of the tables is shown for judging results from given data sets.

Acetylsalicylic acid--reocclusion--prophylaxis after angioplasty (ARPA-study). A randomized double-blind trial of two different dosages of ASA in patients with peripheral occlusive arterial disease.

We report on a randomized controlled clinical trial in patients with peripheral occlusive arterial disease who have been successfully treated with angioplasty. The efficacy and the rate of side effects of two doses of ASA (300 mg vs. 1000 mg daily) have been compared during a treatment period of 6 months after angioplasty. It was planned to include a total of 600 patients in the trial. A predefined interim analysis of 200 patients which was performed after the actual inclusion of 218 patients showed identical reocclusions rates and a very similar frequency of side effects in both treatment groups. The study was then terminated since it was not expected that further continuation would lead to a relevant difference between the two treatment groups concerning efficacy or side effects. Patients already included in the trial at the interim evaluation were included in the final analysis, leading to a total number of 223 patients. Finally 112 patients had been randomized to receive a daily dose of 300 mg ASA and 111 patients to receive 1000 mg ASA. Reocclusions occurred in 18 patients (16%) on 300 mg of ASA/day and in 20 patients (18%) receiving 1000 mg ASA/day. The study was interrupted because of side effects in 27 patients (24%) in the 300 mg/day group and in 27 patients (24%) in the 1000 mg/day group. Mostly subjective gastric complaints were the cause of interruption in 17 patients (15%) in the 300 mg group and in 21 patients (19%) receiving the higher dose regimen. So the reocclusion rate was identical in both dosage-groups.(ABSTRACT TRUNCATED AT 250 WORDS)

HLA-associations in Leponex/Clozaril (clozapine)-induced granulocytopenia and agranulocytosis. Statistical viewpoints.

This paper describes a statistical analysis of the simultaneous occurrence of 48 human leucocyte antigens (HLAs) in an attempt to predict whether a patient treated with clozapine will develop granulocytopenia or agranulocytosis. Whereas the numerical results show that use of HLAs does not appear to satisfy the intended purpose, emphasis is placed on the statistical methodology recommended for a problem of this type. Other work in this area is critically discussed.

Planning controlled clinical trials on the basis of descriptive data analysis.

In controlled clinical trials the problem of multiplicity of desired inferential statements finds attention at an increasing rate. In this paper the previously proposed concept of Descriptive Data Analysis (DDA), situated between Confirmatory and Exploratory Data Analysis, is applied to the planning aspects of controlled trials for which the problem of multiplicity exists. The (non-Bayesian) DDA planning concept should provide the investigator with tools to draw final conclusions from data of several variables possibly observed at several time points in possibly several groups of subjects by combining his pre-trial medical experience with descriptive inferential statements (confidence intervals and test results) at nominal significance levels. DDA also provides for confirmatory statements concerning individual null hypotheses and partially global hypotheses.

Statistical aspects of neurophysiologic topography.

The multitude of electrodes and the large number of EEG variables used in neurophysiologic topography call for new inferential statistical concepts in the analysis of data from corresponding studies. These concepts must take into consideration that significance levels and confidence coefficients lose their numerical meaning in situations with many significance tests and/or interval estimates performed on the data from one sample of subjects or patients. The application of one of these concepts. Descriptive Data Analysis (DDA), is discussed, using the data from a real EEG mapping example. Also, the use of DDA is proposed for the judgement of normality of EEG maps.

Some correlations in geriatric patients between EEG parameters and clinical status as evaluated using the observer-rated SCAG rating scale. A retrospective study.

In a retrospective analysis, correlations were sought between pretreatment electroencephalographic and clinical data obtained in 18 therapeutic studies conducted in elderly patients according to almost identical protocols. Power spectrum analysis was applied to the EEG tracings, while clinical status was observer-rated using the Sandoz clinical assessment - geriatric (SCAG) scale. The study population comprised a total of 286 patients between the ages of 51 and 97 years (median age 70 years), 162 of whom were male (median age 68 years) and 124 female (median age 73 years). A 2-week washout period and several 'adaptation recordings' preceded the pretreatment EEGs used in this analysis. These tracings were recorded under resting conditions between 8 and 10 a.m. and were followed by an assessment of clinical status. Spearman rank correlations with 4 EEG parameters--total slow waves, alpha and beta waves, and dominant alpha frequency--were computed for all 18 SCAG items and for 'overall impression of patient' as well as for 5 SCAG factors. All 96 - (19 + 5) X 4 - correlation coefficients were formally tested for statistical significance at the nominal level of alpha = 0.05. In this analysis, 9 of the 18 items, 'overall impression' and two of the factors ('apathy' and 'somatic dysfunction') showed nominally significant correlations with at least 1 of the 4 EEG variables. As expected, a positive correlation was found between percentage slow-wave activity and degree of clinical impairment. In addition correlations were identified between clinical data and alpha and beta activity.(ABSTRACT TRUNCATED AT 250 WORDS)

Determination of the central effects of the asthma prophylactic ketotifen, the bronchodilator theophylline, and both in combination: an application of quantitative electroencephalography to the study of drug interactions.

Ketotifen (Zaditen) is a new, orally active benzocycloheptathiophene derivative for use in the prophylaxis of asthma. Besides possessing anti-allergic properties, it also has H1-receptor mediated antihistaminic activity. Drugs which block H1-receptors are known to have some sedative properties. On the other hand the bronchodilator theophylline is a CNS stimulant. We investigated whether these side-effects could be reduced by concomitant administration. In a balanced-sequence crossover study, 12 healthy males received placebo, 1 mg ketotifen + 300 mg theophylline, 1 mg ketotifen + 600 mg theophylline, and each drug separately at 1-week intervals. Quantified electroencephalograms, cardiovascular and behavioral measurements, symptom reports, and blood drug assays were used to assess the drug interaction. Results showed EEG and behavioral effects with both ketotifen and theophylline alone which were less evident with the drugs in combination. Blood drug levels were not altered by combined drug administration. These findings suggest a mutual attenuation of the CNS effects of ketotifen and theophylline at therapeutic doses and encourage their combined use in asthma therapy. The combined effect may be optimized by modifying formulations or timing. The applicability of quantitative EEG to such problems is well demonstrated.

Pharmaco-EEG and Psychometric study of the effect of single doses of temazepam and nitrazepam.

A double-blind, daytime, placebo-controlled study was carried out in 12 healthy volunteers to investigate the effects of single doses of 5, 15 and 30 mg temazepam and of 5 and 10 mg nitrazepam on the EEG, psychomotor performance, subjective mental and emotional status, blood pressure and heart rate. Each subject received all 6 treatments in a random sequence at intervals of 1 week. The EEG tracings were evaluated quantitatively by spectral analysis. Psychomotor performance was assessed by means of the tapping test. Subjective mental and emotional status were assessed using the Bond and Lader analogue self-rating scale. Procedures were carried out before and at 1/2, 1, 2, 4, 6, 7, 8 and 9 h after drug administration, with the exception of the tapping test, which was carried out before and, again, after 2 and 7 h. EEG estimates of equipotency, based on magnitude of peak effect, were as follows: 15 mg temazepam approximately 5 mg nitrazepam; and 30 mg temazepam greater than or equal to 10 mg nitrazepam. At these approximately equipotent doses, temazepam had a somewhat earlier onset of action on the EEG, a clearly shorter duration of EEG action, and lesser impairment of psychomotor performance than nitrazepam. Qualitatively, both drugs had similar effects on the subjective mental and emotional states of the subjects. There were no clinically relevant changes in mean or individual sitting and standing blood pressure values. After temazepam, but not after nitrazepam, heart rate increased (maximal mean change 10 bpm) as part of a normal startle response to arousal. The results suggest that temazepam has less hangover potential than nitrazepam.

[Representative studies of the vitamin D status of 2-year-old children in Frankfurt am Main]. / Repräsentative Untersuchungen zur Vitamin-D-Versorgung zweijähriger Kleinkinder in Frankfurt/M.

In a representative sample population of 421 two-year-old Frankfurt children studied for vitamin-D nutritional status, only one case of subclinical rickets was discovered. 93.3% of the children have been a regular vitamin-D supplements during the first 12 month of life, but only 32.7% of them continued to receive the supplement beyond the age of one year. Risk groups were not identified, neither with regard to ethnic groups, nor smaller vitamin-D doses, or any other aspect.

Significance testing of many variables. Problems and solutions.

More than one variable of interest in pharmaco-EEG studies is the rule rather than the exception. The many-variables situation may arise from several types of EEG variables and/or from repeated measurements of these variables through time. In many cases, multivariate analysis techniques are not suitable for application. As an alternative, the analyst usually applies individual (univariate) tests for all variables and/or time points. This significance testing of many variables causes problems because of the so-called 'alpha-inflation', i.e. the inflation of the probability for the 'error of the first kind' to reject a null hypothesis although it is valid. To counteract this effect (which invalidates the significance levels used for hypothesis testing), various procedures have been proposed some of which are discussed in the present paper. All procedures involve so-called 'alpha-adjustments', and two procedures are based upon the assumption that the investigator demands that at least a given percentage of all individual null hypotheses considered will be rejected or are not valid, respectively.