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Childhood epilepsy, attention problems, and ADHD: review and practical considerations.

Children with epilepsy have a significant risk for problems with attention and/or attention deficit hyperactivity disorder. Clinical studies suggest a prevalence of 30% to 40%. Inattention is more common than hyperactivity and impulsivity. Additional central nervous system dysfunction and intractable seizures are major risk factors. Treatment should include psychoeducational interventions and medication. Stimulant drugs are safe and effective in children with epilepsy and currently are first-line agents for treatment of attention problems in this population.

Attention↗

Hypnotic accumulation and hangover in elderly inpatients: a controlled double-blind study of temazepam and nitrazepam.

The hypnotic and residual sedative effects of the first and seventh of seven regular night-time doses of nitrazepam 5 mg, temazepam 20 mg, and placebo were studied in 58 elderly inpatients. Plasma temazepam and nitrazepam concentrations rose by about 50% and 113% respectively between the mornings of day 1 and day 7. Patients reported sleeping well more often after the first dose of either hypnotic (p less than 0.05), but there was no difference after the seventh dose. Reaction time was unchanged on the morning after the first dose but was significantly prolonged after the seventh dose of both hypnotics (p less than 0.01). The time taken to eliminate the letter E from a page of prose tended to be prolonged after the first dose of both drugs (temazepam v placebo, p less than 0.05; nitrazepam v placebo, not significant) and was further prolonged on the morning after the seventh dose of nitrazepam (nitrazepam v placebo, p less than 0.05). Thus plasma accumulation of the drug was associated with a deterioration in daytime performance. This change in performance did not correlate with age, cerebral blood flow, or plasma concentration, but patients of low intelligence tended to be more severely affected.

Aged↗

Critiquing anesthetic management: the "ATTENDING" computer system.

ATTENDING, a computer system under development using Artificial Intelligence techniques, is designed to critique an anesthetist's preoperative plan for anesthetic management. The system receives as input: 1) a list of a patient's medical problems; 2) a planned surgical procedure; and 3) an anesthetic plan outlining the agents and techniques to be used for premedication, induction, intubation, and maintenance of general or regional anesthesia. ATTENDING critiques this plan, discussing the risks and benefits of the proposed approach and of other reasonable approaches. To critique a physician's plan, the ATTENDING system must be able to 1) explore alternative approaches to a patient's management in a flexible fashion; 2) assess the relative risks and benefits of these alternatives; and 3) produce a readable, easily understood analysis written in English prose. This article describes how these design issues are addressed in ATTENDING's current implementation. The ATTENDING system is presently being used in a tutorial mode which allows self-evaluation by an anesthetist.

Anesthesia↗

Some important pitfalls in the diagnosis and treatment of bacterial meningitis in children.

Some of the common errors and problems of the physician who cares for the child with bacterial meningitis are: 1) misdiagnosis; 2) inappropriate handling of cerebrospinal fluid; 3) inadequate assessment of therapeutic responses; 4) inappropriate drug therapy; 5) improper treatment of seizures; 6) inadequate care of increased intracranial pressure; 7) inappropriate evaluation of persistent fever; 8) inappropriate fluid therapy; 9) inadequate investigation of persistent neurologic deficit; 10) overvigorous treatment of subdural effusion; 11) inadequate assessment of neurologic or psychologic impairment; and 12) inadequate consideration of possible underlying defects.

Anti-Bacterial Agents↗

Role of the endogenous gastrointestinal microflora in postoperative wound sepsis.

Most infections following gastrointestinal surgery are caused by the escape of endogenous microorganisms at the time of operation. A thorough understanding of the gastrointestinal microflora in health and disease is essential to the intelligent treatment of postoperative septic complications. The oral flora found under certain circumstances in the proximal gastrointestinal tract is usually penicillin sensitive. Both aerobic and anaerobic resident microflora of the distal ileum and colon are penicillin resistant; therefore, other antibiotic agents must be prescribed for successful treatment of sepsis following resection of these organs.

Animals↗

Risperidone reduces aggression in boys with a disruptive behaviour disorder and below average intelligence quotient: analysis of two placebo-controlled randomized trials.

The present study aimed to analyse the effect of risperidone on a priori defined core aggression items. Data were pooled from 163 boys (aged 5-12 years, with or without comorbid attention-deficit/hyperactivity disorder) with a DSM-IV diagnosis of either conduct disorder or oppositional defiant disorder who had participated in either of two identical, 6-week, randomized, double-blind, placebo-controlled trials. All received treatment with either placebo or oral risperidone solution (0.01-0.06 mg/kg/day). Subjects had below average intelligence [intelligence quotient (IQ) 36-84] and a score of > or =24 on the Conduct Problem subscale of the Nisonger Child Behaviour Rating Form (N-CBRF). An expert advisory panel selected six core aggression items from the N-CBRF, from which a total Aggression Score (AS, range 0-18) was constructed. Compared to those treated with placebo, risperidone-treated subjects experienced significantly greater mean decreases from baseline in the AS at each of weeks 1-6 (P<0.001). By study endpoint, aggression among risperidone-treated subjects had declined by 56.4% (mean baseline AS 10.1; mean endpoint AS 4.4), which was more than twice that of placebo-treated subjects (mean baseline AS 10.6; mean endpoint AS 8.3; 21.7% reduction). Risperidone was efficacious in reducing symptoms of aggression in boys of below average IQ with disruptive behaviour disorders.

Aggression↗

Drug interactions between prescribed and over-the-counter medication.

The use and availability of over-the-counter (OTC) medication is increasing. Although regulatory agencies take care to assure than nonprescription medications are safe and effective, these drugs still have the potential to have clinically significant interactions with prescription medicines. The major classes of OTC medication to be considered in this light include antacids, histamine H2 receptor antagonists, NSAIDs, cough and cold preparations and the antiasthma products. Healthcare providers and patients/consumers should be educated regarding possible drug interactions, patient drug regimens should be simplified where possible, and all therapeutic failures and adverse reactions should be investigated with regard to the potential contribution of OTC drug products. Regulatory agencies and pharmaceutical manufacturers should ensure that nonprescription drug labelling is complete and intelligible to meet these objectives. Consideration should be given to improving the postmarketing surveillance of OTC medications.

Antacids↗

Unusual toxicities with TNF inhibition: heart failure and drug-induced lupus.

Serious and unexpected adverse events, such as heart failure and drug-induced lupus, have been reported in patients receiving TNF inhibitor therapy. These events generally are easily recognizable, although they cannot be predicted nor avoided, other than by drug avoidance altogether Many patients have great benefit from anti-TNF therapies. Their intelligent use requires a firm understanding of these rare toxicities, so as to minimize the morbidity associated with their uncommon occurrence.

Antibodies, Monoclonal↗

Human pharmacokinetics, excretion, and metabolism of the anthracycline antibiotic menogaril (7-OMEN, NSC 269148) and their correlation with clinical toxicities.

In a Phase I study, menogaril (7-OMEN) was administered daily for 5 days/course, every 21-28 days. Dosages of 3.5, 7, 11.5, 17, and 31.5 mg/m2 were infused over 1 h, and dosages of 42, 50, and 56 mg/m2 were infused over 2 h. Pharmacokinetics was studied at all dosages. Plasma and urine samples were collected from 24 patients, and bile samples were also collected from 2 patients. 7-OMEN and metabolites were measured by high performance liquid chromatography. 7-OMEN was the major plasma fluorescent species at all times, with only trace amounts of N-demethyl menogaril observed. 7-OMEN disappeared from plasma biexponentially with t1/2 alpha 0.19 +/- 0.04 (mean +/- SE) h and t1/2 beta 13.22 +/- 1.54 h. Plasma pharmacokinetics of 7-OMEN was linear from 3.5-56 mg/m2; area under the curve increased proportionally with dosage. Total body clearance of 7-OMEN was 28.18 +/- 3.33 liter/m2/h, Vc was 224 +/- 30.8 liter/m2, and Vss was 370 +/- 25.7 liter/m2. Plasma pharmacokinetics of 7-OMEN studied on multiple days of a given course were similar. Urinary excretion of 7-OMEN and fluorescent metabolites accounted for 5.4 +/- 0.4% of the daily dose. Parent compound still represented greater than or equal to 80% of urinary drug fluorescence after 24 h. N-demethyl menogaril was the only other fluorescent drug species detected in urine. In two patients with biliary tract drains, biliary excretion of drug fluorescence accounted for 2.2-4.2% of the daily dose. Only 7-OMEN and N-demethyl menogaril were detected in bile by high performance liquid chromatography and thin layer chromatography. 7-OMEN was the major fluorescent biliary species, but, by 24 h, N-demethyl menogaril accounted for approximately 40% of biliary drug fluorescence. When considered in light of each patient's observed toxicities, excellent relationships were observed between the plasma area under the curve of 7-OMEN and the percentage of decreases in WBC and absolute neutrophil count. These latter findings should be useful in developing more precise and intelligent dosing schemes for 7-OMEN.

Antineoplastic Agents↗

Minimal hepatic encephalopathy: diagnosis by neuropsychological and neurophysiologic methods.

Minimal hepatic encephalopathy (mHE) consists of cognitive deficits found on neuropsychological and/or neurophysiologic methods in patients with liver disease, present most commonly in cirrhosis. Patients suffering from mHE may have psychomotor slowing and cognitive deficits affecting their ability to perform many activities of daily life, especially driving and other activities requiring subtle cognitive abilities. It has been now been shown that patients with mHE improve after treatment with agents like lactulose and other therapeutic interventions. Neuropsychological and neurophysiologic tests have been widely used and have shown the greatest promise for the detection of mHE. Commonly used psychometric tests include trailmaking tests (number and figure connection tests) and Wechsler Adult Intelligence Scale (WAIS) for verbal and performance skills. Among the various neuropsychological or psychometric tests, trailmaking tests and block design and digit symbol tests from WAIS-performance battery appear to be adequate for diagnosis of mHE. Standardized tests including NCT A and B, line tracing, serial dotting test and digits-symbol test (PSE syndrome test) validated in German patients need validation in other populations. Both exogenous evoked potentials and endogenous event-related potentials have been used extensively in diagnosing mHE. However, the event-related P300 wave is the most consistent wave and can be considered the electrophysiological counterpart of the psychometric tests as both involve active use of the cognitive faculties. Other new tests like the critical flicker frequency have shown some promise but further studies are required to substantiate initial results. In conclusion, a combination of at least two psychometric (trailmaking tests [NCT or FCT], block design and digit symbol test) and neurophysiological tests (P300 auditory evoked potential or electroencephalography with mean dominant frequency) appears to be optimal in detecting mHE.

Electroencephalography↗

Voice and swallowing in patients enrolled in a larynx preservation trial.

BACKGROUND: The main goals of larynx preservation protocols are preservation of a functional larynx with intact voice and maintenance of normal deglutition. However, few studies have addressed functional outcomes. OBJECTIVES: To evaluate voice and swallowing in patients enrolled in a larynx preservation protocol. DESIGN AND SETTING: Acoustic analysis of 15 patients and videofluoroscopic evaluation of 14 patients who underwent chemoradiotherapy in an attempt to preserve the larynx. PATIENTS: Forty-three patients with larynx or hypopharynx squamous cell carcinomas were treated with weekly paclitaxel (30 mg/m2) and cisplatin (20 mg/m2) concurrent to radiotherapy (180-rad/d fraction [1.8 Gy] to 7040 rad [70.4 Gy]). Voice was analyzed perceptually and acoustically in 15 patients. Videofluoroscopic evaluation of swallowing was performed in 14 patients, focusing on oropharyngeal motility disorders, stasis, laryngeal penetration, aspiration, and dysphagia severity. RESULTS: Vocal analysis produced normal results in 1 patient, mild dysphonia in 4, moderate dysphonia in 6, and severe dysphonia in 4. The mean fundamental frequency for acoustic analysis was 131.4 Hz for men and 109.8 Hz for women. Acoustic measures of perturbation and noise were above the reference limits, indicating changes in the voice signal. Swallowing analysis showed inefficient bolus preparation in 13 patients and changes in the bolus propulsion in 12. Stasis was observed in all areas of the oropharynx. Five patients had reduction in laryngeal elevation, and 12 had stasis in the hypopharynx. Five patients presented with silent aspiration. We detected functional swallowing in 3 patients, mild dysphagia in 7, mild or moderate dysphagia in 2, and severe dysphagia in 2. CONCLUSIONS: Laryngeal preservation resulted in voice and swallowing abnormalities, but they tend to be mild to moderate, allowing intelligible communication and efficient swallowing in most patients.

Adult↗

Menarche, menstruation, sexual relations and contraception of adolescent females with Down syndrome.

Fifteen female adolescents with Down syndrome (DS) and 33 female controls without this syndrome were surveyed on age of menarche, menstruation, sexual relations and contraception. All probands and controls were born between 1 January 1965 and 31 December 1970. The day of census was December 31, 1985. All probands and controls were living permanently in the Danish county of Aarhus on this day. Persons close to the DS patients (parents/foster-parents/permanent staff) were interviewed on the above-mentioned topics. All controls were interviewed themselves. The average age of menarche was 13.6 years for probands and 13.5 years for controls. The average duration of the bleeding was 5.5 days for probands and 5.4 days for controls. The average length of the cycle was 28.3 days for probands and 28.6 days for controls. Thirteen DS patients had not had sexual intercourse (no information was available for 2 probands). Twenty-four controls had and 9 had not had sexual intercourse. There is a significant difference between probands and controls concerning use of oral and other contraceptives.

Adolescent↗

Physiology, pharmacology and parasitology.

The developing resistance to current chemical classes of broad-spectrum anthelmintics and insecticides presents an undeniable threat to the long-term viability of the animal health industry. Alternative treatment strategies including vaccines, biological control and breeding of parasite-resistant animals are unlikely to be widely available in the near future and even then they will be integrated with chemotherapy. The significant cost of research and development of new therapeutics for food-producing animals, together with the small market share of animal health products, particularly in Australia and New Zealand, is a positive disincentive for drug development. The chemical actives that are currently available are all that we are likely to have for the foreseeable future and they must be used more efficiently. Understanding the pharmacokinetic behaviour of antiparasitics and recognising the potential for the animal's physiological characteristics to assist drug action is crucial. Careful administration, coupled with a reduction of feed intake before oral anthelmintic treatment, maximises drug availability and therefore increases efficacy of the benzimidazole and ivermectin compounds. This is a cost-effective option that can be employed immediately, which not only increases efficacy of "older" compounds but will be instrumental in prolonging the useful life of the newer drugs. Taking care to apply topical insecticide formulations directly along the backline immediately after shearing will maximise even diffusion of active around the sheep flanks to contact lice inhabiting sites remote from the point of drug application. The use of "intelligent" formulation and delivery of existing compounds, based on knowledge of host physiological and pharmacological responses, holds the key to effective antiparasitic treatment.

Animals↗

Continual planning and scheduling for managing patient tests in hospital laboratories.

Hospital laboratories perform examination tests upon patients, in order to assist medical diagnosis or therapy progress. Planning and scheduling patient requests for examination tests is a complicated problem because it concerns both minimization of patient stay in hospital and maximization of laboratory resources utilization. In the present paper, we propose an integrated patient-wise planning and scheduling system which supports the dynamic and continual nature of the problem. The proposed combination of multiagent and blackboard architecture allows the dynamic creation of agents that share a set of knowledge sources and a knowledge base to service patient test requests.

Artificial Intelligence↗

Child development following exposure to tricyclic antidepressants or fluoxetine throughout fetal life: a prospective, controlled study.

OBJECTIVE: Previous work suggested that first-trimester exposure to tricyclic antidepressants or fluoxetine does not affect adversely child IQ and language development. However, many women need antidepressants throughout pregnancy to avoid morbidity and suicide attempts. Little is known about the fetal safety of tricyclic antidepressants and fluoxetine when taken throughout pregnancy. The goal of this study was to assess the effects of tricyclic antidepressants and fluoxetine used throughout gestation on child IQ, language, and behavior. METHOD: In a prospective study, mother-child pairs exposed throughout gestation to tricyclic antidepressants (N=46) or fluoxetine (N=40) and an unexposed, not depressed comparison group (N=36) were blindly assessed. The three groups were compared in terms of the children's IQ, language, behavior, and temperament between ages 15 and 71 months. The authors adjusted for independent variables such as duration and severity of maternal depression, duration of pharmacological treatment, number of depression episodes after delivery, maternal IQ, socioeconomic status, cigarette smoking, and alcohol use. RESULTS: Neither tricyclic antidepressants nor fluoxetine adversely affected the child's global IQ, language development, or behavior. IQ was significantly and negatively associated with duration of depression, whereas language was negatively associated with number of depression episodes after delivery. CONCLUSIONS: Exposure to tricyclic antidepressants or fluoxetine throughout gestation does not appear to adversely affect cognition, language development, or the temperament of preschool and early-school children. In contrast, mothers' depression is associated with less cognitive and language achievement by their children. When needed, adequate antidepressant therapy should be instituted and maintained during pregnancy and postpartum.

Antidepressive Agents↗

Health, neurologic, and cognitive status of HIV-infected, long-surviving, and antiretroviral-naive Ugandan children.

OBJECTIVE: The purpose of this study was to assess the health status and school-age neurodevelopmental progress of antiretroviral treatment (ARVT)-naive, HIV-infected Ugandan children who had been followed as part of cohorts of children born to HIV-infected and -noninfected mothers between 1989 and 1993. METHODS: Twenty-eight children, aged 6 to 12 years, vertically infected with HIV-1 and never treated with ARVT were evaluated in terms of health status, neurologic, and psychometric testing. A randomly selected group of 42 seroreverters and 37 HIV-1 negative children who were age- and gender-matched and who had been followed in the same cohorts were evaluated also. The families studied were homogenous in their socioeconomic status. None of the mothers or children had received ARVT or been exposed to illicit drugs. RESULTS: The HIV-infected children showed significantly more evidence of acute malnutrition. They also had more illness, especially parotitis, otitis media, upper respiratory infections, and lymphadenopathy. However, they did not differ significantly in neurologic and cognitive assessments when compared with age- and gender-matched seroreverter and HIV-negative children. They were in the normal range with respect to neurologic and psychometric development measures. CONCLUSIONS: These children seem to represent a significant subgroup of HIV-infected child survivors for whom the progress of the disease is less aggressive throughout early life. Given the fact that many infants, especially in developing countries, continue to be born without the benefit of perinatal ARVT, there will likely continue to be many older HIV-infected children in the same situation as those described in this follow-up study. They will not have been recognized as being HIV-infected. It is important that such children be identified and offered access to ARVT and other appropriate support services.

Anti-Retroviral Agents↗