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Classification of observational data with artificial neural networks versus discriminant analysis in pharmacoepidemiological studies--can outcome of fluoxetine treatment be predicted?

For several years, there has been an ongoing discussion about appropriate methodological tools to be applied to observational data in pharmacoepidemiological studies. It is now suggested by our research group that artificial neural networks (ANN) might be advantageous in some cases for classification purposes when compared with discriminant analysis. This is due to their inherent capability to detect complex linear and nonlinear functions in multivariate data sets, the possibility of including data on different scales in the same model, as well as their relative resistance to "noisy" input. In this paper, a short introduction is given to the basics of neural networks and possible applications. For demonstration, a comparison between artificial neural networks and discriminant analysis was performed on a multivariate data set, consisting of observational data of 19738 patients treated with fluoxetine. It was tested, which of the two statistical tools outperforms the two other in regard to the therapeutic response prediction from the clinical input data. Essentially, it was found that neither discriminant analysis nor ANN are able to predict the clinical outcome on the basis of the employed clinical variables. Applying ANN, we were able to rule out the possibility of undetected suppressor effects to a greater extent than would have been possible by the exclusive application of discriminant analysis.

Antidepressive Agents, Second-Generation↗

Quality of life and the patient's response to treatment.

Quality of life resides mainly in an individual's satisfaction with his role at work, at home, and in his community. Illness and treatment affect quality of life to the extent that they damage an individual's ability to perform these roles to his own satisfaction. Clinicians will increasingly have to take account of quality of life in assessing the effect of an illness and of their treatment for it. This is particularly so in chronic diseases for which there is no "cure" and in asymptomatic conditions, such as hypertension.

Antihypertensive Agents↗

Intermittent subcutaneous apomorphine injection treatment for parkinsonian motor oscillations.

Eight patients with severe Parkinsonian motor oscillations have been treated with the dopamine receptor agonist apomorphine by intermittent subcutaneous self-injection as an adjunct to oral anti-Parkinsonian medication. The dopamine receptor antagonist domperidone was also given by mouth to prevent nausea. Six patients remain on chronic treatment (mean period 6.5 months) with improved control of motor function in each case. Four have had major enhancement of their quality of life. Benefits of this treatment stem from the training of patients to use intelligent behaviour to administer a promptly acting and effective pharmacological agent, thereby exercising a degree of direct control over previously unpredictable variations in motor performance.

Administration, Oral↗

Memory function in schizophrenia.

Memory impairment in schizophrenia has been reported in several studies during the last decades. Issues related to the interpretation of such deficits are discussed. Research strongly suggests specific memory dysfunction in schizophrenia that may be neither drug induced nor secondary consequences of attentional disorders. Our own longitudinal data indicate that these deficits deviate from normal function in a relatively stable way. Although medial temporal lobe structures seems to be of special importance, memory function may be vulnerable to a variety of neurobiological abnormalities.

Adult↗

Population policy options.

In the review by Kristie Macrakis of Beyond the Wall: Memoirs of an East and West German Spy by Werner Stiller, with Jefferson Adams (editor and translator) [Brassey's (US), McLean, VA, 1992; Maxwell Macmillan, London, UK, 1992] (17 Dec., p. 1908), it is stated that physicist Rolf Dobbertin, who denies any spying, was "sent to Paris in 1956 to study at the expense of the Stasi," was "sentenced to 12 years in prison," and "sat in a French jail for five years before he was released in 1991." Legal documents show that Dobbertin, who was arrested in January 1979 for acts of "communication with agents of a foreign power, dealings that could be harmful [intelligence de nature à nuire] to the military or diplomatic situation of France or to its essential economic interest," was jailed until May 1983. He was subsequently tried in 1990 and sentenced to 12 years in prison, but was acquitted of the above charge by a special Assize Court in a second trial in November 1991. According to Dobbertin, he studied continuously at the University of Rostock from 1952 until 1958, and then taught at the University of Berlin for one year before beginning his work in 1959 at the Centre Nationale de la Recherche Scientifigue in France, where he continues to be employed.

Developing Countries↗

Neuropsychological performance in medicated and unmedicated patients with Tourette's disorder.

OBJECTIVE: To date, there have been no formal investigations of neuropsychological performance in patients with Tourette's disorder who are taking psychotropic medications. The authors conducted this study to provide such information. METHOD: They examined the neuropsychological performance of 96 patients 6-18 years old who met DSM-III-R criteria for Tourette's disorder; 51 of these patients were taking neuroleptic medications and 45 were not. The groups were well matched with regard to age, sex, education, and duration of symptoms. Each group was given a complete neuropsychological test battery as well as instruments rating symptoms of Tourette's disorder, obsessive-compulsive characteristics, and other behavioral disturbances. RESULTS: The patients taking medications did not differ from those not taking medications on any of the neuropsychological, intellectual, or educational measures. In addition, the groups did not differ with regard to level of Tourette's disorder symptoms. CONCLUSIONS: The results of this investigation suggest that patients with Tourette's disorder who do not experience intolerable side effects from neuroleptic medications are able to perform on educational, intellectual, and neuropsychological tests at a level comparable to that of unmedicated patients. These results have positive implications for patients with Tourette's disorder who respond to neuroleptic medications.

Adolescent↗

[Detecting psychopathological symptoms in psychopharmacological studies on the course of disease (author's transl)].

Rating scales and self-rating scales are still indispensable for the estimation of psychopathological symptoms and their variations in the course of treatment with psychopharmacologic agents. So significant progress can be recognized in measurment of intelligence, degree of severity of functional psychoses, states of cerebral defects and of endogenous depressions. The promising results of this experience encourage intensifying the development of such test instruments concerning non-psychotic psychic disturbances as well as schizophrenic psychoses.

Anxiety↗

Effects of neuroleptic medications on the cognition of patients with schizophrenia: a review of recent studies.

In this review, we have examined the effects of neuroleptic medications on neurocognitive functions in articles published since 1990. Based on recent work and reviews of older studies, neuroleptics do not appear to have marked positive or negative effects on working memory or secondary memory. In contrast, neuroleptic medications appear to have a salutary effect on sustained vigilance or response readiness. The relationship or lack thereof between changes in cognition and changes in clinical state (produced by neuroleptics) is also discussed.

Antipsychotic Agents↗

Clinical significance of diffuse delta EEG activity in chronic schizophrenia.

1) Forty-three chronic schizophrenics with diffuse delta activity (DDA) in their rest-awake EEGs were compared with 23 chronic schizophrenics with normal EEGs. 2) The DDA group was divided into three sub-groups according to the temporal persistence of DDA: brief, intermittent, and prolonged. The intermittent DDA is analogous to intermittent rhythmic delta activity (IRDA). 3) The disorganized type of schizophrenia was frequent in the DDA group and the residual type was frequent in the normal EEG group. 4) The doses of neuroleptics, as well as those of phenothiazines and butyrophenones, were higher in the DDA than in the normal group. 5) The frequency of co-administration of carbamazepine was higher in the DDA than in the normal group, and the rate increased with the degree of abnormality. 6) In a 1 year follow-up of the DDA group, reducing doses of neuroleptics resulted in a tendency for DDA to disappear, and reducing the doses of adjunctive carbamazepine caused DDA to disappear. 7) There was no correlation between DDA and the psychiatric symptoms, intelligence level, or CT findings.

Antipsychotic Agents↗

International Commission for Protection Against Environmental Mutagens and Carcinogens. Two million rodent carcinogens? The role of SAR and QSAR in their detection.

The accurate prediction of chemical carcinogenicity can only be achieved by a balanced consideration of the following factors: the chemistry and metabolism of the test agent, the interaction between toxicity and genetic toxicity, the possibility of non-genotoxic events that trigger subsequent non-targeted mutagenesis, the difference between activities observed in vitro and in vivo, and the possible inadequacy and/or partiality of all datasets and observations. Extrapolation of activities within a series of congeners is usually possible, but predictions across different chemical classes/mechanisms of carcinogenicity are difficult. Artificial intelligence systems can be used to predict one or more of the above parameters given adequate learning sets, but the hope for a single, coherent and self-contained method of predicting all instances of carcinogenicity is unreal. The future of carcinogen/mutagen prediction lies with data-rich artificial intelligence systems based on known mechanistic principles used selectively within the context of chemical and biological human insight. The major current obstacle to progress is the assumption that mutagenicity and carcinogenicity are unitary phenomena that can be learned and predicted by artificial intelligence systems operating in isolation.

Alkylating Agents↗

Polymers and gels as molecular recognition agents.

Synthetic polymers and gels capable of molecular recognition are very useful in designing novel intelligent biomaterials. In this article we review the recent progress in both theoretical and experimental studies toward making heteropolymers and gels with biomimetic properties, specifically in relation to protein recognition. Knowledge obtained from protein-folding studies sheds much light on our understanding of the heteropolymer behavior. Consequently, it is possible to design synthetic heteropolymers with specific structure that can fold into unique conformations, form receptor-like cavities and recognize specific target molecules. Recent studies towards simplifying the requirement for the heteropolymer structures and the polymerization procedures are reviewed. Intelligent polymer gels can be designed with new and interesting characteristics of molecular imprinting. The results are encouraging for further investigation and design of synthetic gels with programmable collapsed structure might be achieved.

Drug Design↗

Measured intelligence in offspring of oral and nonoral contraceptive users.

A study has been made of measures of intelligence of 210 children (5 to 8 years of age) born to mothers who used oral and nonoral contraceptives pregestationally. Ninety-six of these children were born to mothers who used oral contraceptives, and one hundred and fourteen were born to mothers who used vaginal contraceptive methods. The intelligence of the children was measured in the form of the full-scale I.Q. score by the Wechsler Intelligence Scale for Children (WISC) adapted and normalized for Puerto Rico by the Puerto Rico Department of Education. A three-factor analysis of variance was performed on the data collected for comparison of the two groups. It was observed that there was no significant difference between the average I.Q. scores of children born to mothers using oral contraceptives and those born to the mothers using nonoral contraceptives. The average I.Q. in children of the oral contraceptive group was 85.04 and that in children of the nonoral contraceptive group was 85.54. Distributions for both groups were also found to be similar. No significant differences between means were observed for sex, age, and interacitons with the exception of the age and sex interaction, where, again, no specific, meaningful trend could be established. The average I.Q. in the sample fell very close to the center of the "normal" range of the WISC, Puerto Rican adaptation. The results of the study do not offer any evidence as to the effect of the use of oral contraceptives on the intelligence measure (by the WISC) of the offspring born to mothers using them pregestationally. The children under study, on an average, are of "normal" intelligence as measured by the Puerto Rican intelligence standards.

Adult↗