[Psychological assessment of children with lymphoblastic leukemia after intensive polychemotherapy combined with irradiation of the brain].
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Adolescent↗
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Results for “Intelligent agents”
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A Bayesian framework for intent-to-treat analysis with missing data.
In longitudinal clinical trials, one analysis of interest is an intention-to-treat analysis, which groups subjects according to the randomized treatment regardless of whether they stayed on that treatment or not. When in addition to going off the randomized treatment subjects may also drop out of the study and be lost to follow-up, it is unclear what an intention-to-treat analysis should be. If measurements are made after treatment drop-out on a random sample of subjects who drop the treatment, then Hogan and Laird (1996, Biometrics 52, 1002-1017) present a random effects model, well suited to this type of analysis, which fits a two-piece linear spline to the data with the knot at the time the assigned treatment is dropped. This article presents a Bayesian approach to fitting a similar two-piece linear spline model and shows how the model can be applied to data that have no off-treatment observations.
Acquired Immunodeficiency Syndrome↗
Are cognitive and educational development affected by age at which prophylactic therapy is given in acute lymphoblastic leukaemia?
Altogether 129 children with acute lymphoblastic leukaemia in remission, all of whom had completed treatment, were assessed using standardised intelligence and attainment tests. A control group of 67 healthy siblings was also assessed. Results showed that the patients were functioning within the average range of intelligence several years after completing treatment but that they had significantly lower intelligence quotients (IQs) than their siblings. Only patients who received cranial irradiation when aged 7 years or more were no different in intelligence from their siblings. Patients who were treated under the age of 3 years were found to have significantly lower IQs than patients who received the same treatment at an older age and a group of healthy children matched for age, sex, and parental occupation. This finding has practical implications for the management and education of younger patients with acute lymphoblastic leukaemia.
Adolescent↗
Effect of selection of molecular descriptors on the prediction of blood-brain barrier penetrating and nonpenetrating agents by statistical learning methods.
The ability or inability of a drug to penetrate into the brain is a key consideration in drug design. Drugs for treating central nervous system (CNS) disorders need to be able to penetrate the blood-brain barrier (BBB). BBB nonpenetration is desirable for non-CNS-targeting drugs to minimize potential CNS-related side effects. Computational methods have been employed for the prediction of BBB-penetrating (BBB+) and -nonpenetrating (BBB-) agents at impressive accuracies of 75-92% and 60-80%, respectively. However, the majority of these studies give a substantially lower BBB- accuracy, and thus overall accuracy, than the BBB+ accuracy. This work examined whether proper selection of molecular descriptors can improve both the BBB- and the overall accuracies of statistical learning methods. The methods tested include logistic regression, linear discriminate analysis, k nearest neighbor, C4.5 decision tree, probabilistic neural network, and support vector machine. Molecular descriptors were selected by using a feature selection method, recursive feature elimination (RFE). Results by using 415 BBB+ and BBB- agents show that RFE substantially improves both the BBB- and the overall accuracy for all of the methods studied. This suggests that statistical learning methods combined with proper feature selection is potentially useful for facilitating a more balanced and improved prediction of BBB+ and BBB- agents.
Artificial Intelligence↗
VSV-tumor selective replication and protein translation.
The emergence of vesicular stomatatis virus (VSV) as a potent antitumor agent has made a dissection of the molecular determinants of host-cell permissiveness to this virus an important objective. Such insight would not only enable the intelligent design of future generations of recombinant VSV vectors to combat disease, but may also resolve general features of cellular transformation that may be exploited by this virus, and perhaps other oncolytic viruses. The defective pathways underlining the oncolytic activity of VSV remain to be fully determined but recent data indicates that flaws in innate immune responses, involving the interferon (IFN) system, may commonly occur in tumor cells and thus play a large role in facilitating oncolysis. Aside from the IFN system, however, it is almost certain that other key cellular pathways may be similarly defective and therefore cooperatively contribute towards mediating rapid oncolytic virus activity. Recent data have indicated that defects in cancer cell translational regulation could be one area that may be exploited by VSV. Certainly, all viruses require cellular protein synthesis pathways to facilitate their replication and many have devised numerous mechanisms to ensure that viral mRNAs become translated at the expense of the host. Using VSV as a model, this review will discuss some of the recent developments in the fields of innate immunity and translational regulation that may help explain mechanisms of viral oncolysis.
Immunity, Innate↗
Long-term use of risperidone in children with disruptive behavior disorders and subaverage intelligence: efficacy, safety, and tolerability.
OBJECTIVE: The aim of this study was to assess the long-term efficacy and tolerability of risperidone in the treatment of children and adolescents with disruptive behavior disorder (DBD) and below-average intelligence (IQ < 84) over a cumulative period of 2 years. METHODS: We followed 48 patients (6-15 years of age), who had previously completed a 1- year open-label study of risperidone, for an additional year of treatment. Efficacy was assessed using the conduct problem subscale of the Nisonger Child Behavior Rating Form (N-CBRF) as a primary outcome measure; other N-CBRF subscales, the Aberrant Behavior Checklist (ABC), and the Clinical Global Impression (CGI) of severity were secondary efficacy measures. Safety and tolerability were also assessed. RESULTS: Of the 48 patients enrolled in this extension study, 33 (69%) completed the trial. The efficacy benefits from the original study were maintained over the course of the extension study. Safety and tolerability were good overall, with the number of adverse events (AEs) decreasing in the extension trial, compared to the original trial. Six patients (13%) discontinued owing to AEs. Weight gain observed in the original trial stabilized during this extension trial. Cognitive testing demonstrated small, but significant, improvements in cognitive ability. CONCLUSIONS: Risperidone is safe and effective in treating DBDs in children over a cumulative period of 2 years.
Adolescent↗
[Psychological analysis of the causes of attempted suicide using toxic agents].
The purpose of the study was to analyse the biological, environmental and personality causes leading to suicide attempts. The study included 168 patients after suicidal intoxication basing on anamnesis from subjects studied and members of their families. The intelligence quotient and electroencephalographical examination has also been performed in subjects studied. The main causes of suicidal attempts were the unproper familial and educational environment, the lack of close relations with members of family, the lack of adequate reference patterns of social roles, the lowered resistance against difficult situations and the tendency to impulsive actions in a part of subjects studied conditioned biologically. The frequent cause of suicidal attempt was in demonstration focusing the attentions of relatives on difficult problems arising from life situation.
Adolescent↗
Intelligence and adaptive function in children diagnosed with brain tumour during infancy.
BACKGROUND: Late effects of treatment in children diagnosed and treated for brain tumours in infancy is a major concern. Assessment of infants presenting with brain tumours is difficult and there is little information available regarding the development of infants prior to treatment and hence the impact of the tumour itself on developmental outcomes. AIM: To describe the development of children diagnosed with brain tumours in infancy and to document their cognitive and adaptive function at school entry. METHOD: Infants were psychologically evaluated at the time of diagnosis of a brain tumour and during their fifth or sixth year in preparation for school entry. RESULTS: Children diagnosed with brain tumours in infancy display developmental delays in a number of areas of adaptive function. By the time these children are school age they display further compromise in cognitive and academic skills and adaptive behaviour. Higher levels of deficit at follow-up were associated with tumour location in the supratentorium, younger age at diagnosis and longer time since diagnosis. The effect of radiotherapy could not be determined because of differing degrees of developmental compromise in the treatment groups at baseline. CONCLUSION: Brain tumours in infancy confer a risk of poor developmental progress at the time of diagnosis. These children display additional compromise of development by the time they reach school age. Research protocols evaluating the impact of treatment in infants diagnosed with brain tumours need to take account of the developmental status of the child at diagnosis.
Adaptation, Psychological↗
Bacterial resistance to antibiotics in acute respiratory infections (ARIs).
In this review article, we make suggestions on how to approach the increasing problem worldwide of bacterial acute respiratory infections resistant to antibiotics. After a brief description of the main mechanisms of bacterial resistance, i.e., enzymatic inactivation by beta-lactamases, reduction in the permeability of the outer membrane and the development of PBPs that have decreased affinity for the antibiotic, we analyze documented experiences on the response to different groups of antibiotics (beta- lactam antibiotics, cephalosporins, carbapenems and quinolones), of the most commonly isolated bacteria from invasive respiratory infections (Haemophilus influenzae, Streptococcus pneumoniae and Moraxela (Branhamella) catarrhalis. Antimicrobial agent susceptibility in vivo and in vitro testing and the correlation of their results provide the basic information for the adoption of adequate policies and strategies for better use of antibiotics in bacterial respiratory infections; proper surveillance would allow to make intelligent changes in such a policy. Standardized recommendations for clinical practice on the use of antibiotics could be misleading, iatrogenic, and could complicate the resistance problem. To prevent and control the rise and spread of bacterial resistance, an interdisciplinary approach is needed.
Acute Disease↗
Drug therapy in attention-deficit hyperactivity disorder.
Of 292 patients (210 males and 82 females) receiving medication for attention-deficit hyperactivity disorder (ADHD), 272 (93%) responded well to sustained-release dextroamphetamine (D-Amp) and 21 patients (7%) to sustained-release methylphenidate (MPD). The dose of D-Amp ranged from 0.2 to 3.6 mg/kg/day and the dose of MPD from 1.4 to 7.7 mg/kg/day, without side effects requiring cessation of therapy. This suggests that the clinical improvement rate can be increased to nearly 100% in appropriate situations.
Adolescent↗
Pharmaco-EEG profiles of antidepressants. Pharmacodynamic studies with fluvoxamine.
1 Antidepressant drugs produce significant changes in human brain function as reflected in the quantitatively analysed EEG. Two main types of pharmaco-EEG profiles may be differentiated: a thymeretic (desipramine-like) profile characterised mainly by an alpha increase suggesting activating properties and a thymoleptic (imipramine- or amitriptyline-like) profile showing a concomitant increase of slow and fast activities and a decrease in alpha activity indicating also sedative qualities. A small number of compounds exhibit still different profiles. 2 Aside from determining the type of EEG changes, the pharmaco-EEG method seems to be of value in determining time and dose efficacy relations at the target organ, the human brain. Moreover, the relationships between pharmacodynamics and pharmacokinetics may be determined. 3 Fluvoxamine, a selective 5-hydroxytryptamine (5-HT) re-uptake inhibitor from the new class of 2-aminoethyloximethers of aralkylketones, produced a typical thymoleptic pharmaco-EEG profile after oral doses of 75 mg in a double-blind placebo-controlled study involving 10 healthy volunteers. Fluvoxamine (75 mg) induced less augmentation of slow activity than 75 mg imipramine, indicating less sedative properties of fluvoxamine than imipramine. 4 After 75 mg fluvoxamine psychometric tests demonstrated a tendency towards an improvement in attention, concentration, psychomotor activity, after-effect and mood and a significant increase in critical flicker fusion frequency as compared with placebo. Comparison with the reference drug, 75 mg imipramine, revealed a significant superiority of fluvoxamine regarding concentration, psychomotor activity, tapping, reaction time, mood and affectivity. 5 Side-effects (mostly tiredness) were seen in five out of 10 subjects after 75 mg fluvoxamine and in eight out of 10 subjects after 75 mg imipramine. There were no clinically relevant changes in pulse, systolic and diastolic blood pressure.
Adult↗
The impact of intellectual functioning on symptoms and service use in schizophrenia.
BACKGROUND: This study aims to evaluate differences in the clinical profiles and use of psychiatric services by people with schizophrenia with and without borderline intellectual functioning. Both groups in this study were receiving standard community psychiatric care. METHODS: A naturalistic sample of 372 people with schizophrenia completed the National Adult Reading Test. Data were collected prospectively over 18 months on psychiatric symptoms and service use. Three hundred and thirteen had normal intellectual functioning (mean age 43, range 20-76 years) and 59 had borderline or lower intellectual functioning (mean age 45, range 21-81 years). This was defined by a National Adult Reading Test error score of more than 40. RESULTS: People with borderline or lower intellectual functioning had a lower quality of life, more severe psychotic symptoms, reduced functioning and fewer antidepressant prescriptions. There were no significant differences in service use including hospital admission. CONCLUSIONS: People with schizophrenia and borderline or lower intellectual functioning are a more disabled group within general adult psychiatric services who should be the focus of initiatives for improved service delivery.
Activities of Daily Living↗
Febrile seizures: current concepts.
Approximately 2 to 5 per cent of all children experience seizures in association with their febrile illness. In a vast majority of instances, these seizures are of benign nature without any long-term adverse implications. A small percentage of these children develop recurrent febrile seizures and a still smaller percentage develop epilepsy. Several studies have attempted to identify those children who are at risk to develop either recurrences or subsequent epilepsy, while others have examined different modalities of management of children with febrile seizures. This review presents an overview of the problem based on the findings of these studies.
Age Factors↗
Flurazepam hydrochloride, a benzodiazepine hypnotic.
Flurazepam hydrochloride is a benzodiazepine derivative marketed for use as a hypnotic agent. Flurazepam is more effective than placebo and is as effective as other hypnotic drugs in most short-term controlled studies. In long-term dosage studies, flurazepam's efficacy persists while other hypnotics become ineffective. Flurazepam has relatively minor effects upon rapid eye movement (REM) sleep and does not lead to REM rebound; this may reduce the likelihood of drug dependence. Flurazepam does not cause enzyme induction and probably presents little hazard of abuse or overdosage. The rational use of hypnotic agents depends as much upon the underlying cause of the sleep disorder as upon the choice of a particular drug. When hypnotic therapy is indicated, flurazepam appears to have advantages over other drugs currently available in the United States.
Animals↗
Computer support for collaboration in medical education.
This paper introduces I-Help, an intelligent learning environment to facilitate peer help exchanges and collaborative learning in university education. I-Help's private and public discussion areas are presented, and the agent-based pairing of suitable partners, based on student models, is illustrated.
Canada↗
[The sense of using psychotropic drugs in infantile psychoses].
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Autistic Disorder↗
Neurobehavioral effects of prenatal origin: sex hormones.
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Adolescent↗
Comparison of psychomotor functions and sedation following premedication with oral diazepam and clonidine in children.
In a prospective, double-blind, controlled, randomized study, the psychomotor functions and sedation were assessed after premedication with diazepam and clonidine in children. Forty children in the age-group of 5-8 years, undergoing elective surgery under general anesthesia were studied. Twenty children (group 1) received oral clonidine 4 microg/kg, and 20 children (group 2) received oral diazepam 0.2 mg/kg, 120 minutes before induction of anesthesia. Sedation and psychomotor functions were assessed in both groups, before and after 60-90 minutes of administration of premedication. The results of the study showed that mean sedation score in group 1 was 8 +/- 1.07, and 9 +/- 0.64 in group 2. On intergroup comparison the sedation was found to be comparatively better in group 2 than group 1 (p < 0.05). The performance of psychomotor functions decreased after premedication in both the groups as compared to that before premedication (p < 0.05). The psychomotor functions were depressed more in diazepam group than in the clonidine group (p < 0.05). Thus, it is concluded that clonidine produces good sedation and causes less effect on psychomotor functions and therefore can be used for premedication in children.
Administration, Oral↗