Psychotic-like experiences in a community sample of 8000 children aged 9 to 11 years: an item response theory analysis.

BACKGROUND: Psychotic-like experiences (PLEs) in the general population are common, particularly in childhood, and may constitute part of a spectrum of normative development. Nevertheless, these experiences confer increased risk for later psychotic disorder, and are associated with poorer health and quality of life. METHOD: This study used factor analytic methods to determine the latent structure underlying PLEs, problem behaviours and personal competencies in the general child population, and used item response theory (IRT) to assess the psychometric properties of nine PLE items to determine which items best represented a latent psychotic-like construct (PSY). A total of 7966 children aged 9-11 years, constituting 95% of eligible children, completed self-report questionnaires. RESULTS: Almost two-thirds of the children endorsed at least one PLE item. Structural analyses identified a unidimensional construct representing psychotic-like severity in the population, the full range of which was well sampled by the nine items. This construct was discriminable from (though correlated with) latent dimensions representing internalizing and externalizing problems. Items assessing visual and auditory hallucination-like experiences provided the most information about PSY; delusion-like experiences identified children at more severe levels of the construct. CONCLUSIONS: Assessing PLEs during middle childhood is feasible and supplements information concerning internalizing and externalizing problems presented by children. The hallucination-like experiences constitute appropriate items to screen the population to identify children who may require further clinical assessment or monitoring. Longitudinal follow-up of the children is required to determine sensitivity and specificity of the PLE items for later psychotic illness.

Concurrent weekly cisplatin chemotherapy and radiotherapy in a haemodialysis patient with locally advanced cervix cancer.

AIMS: Concurrent cisplatin chemo-radiotherapy improves outcome in cervical carcinoma. In haemodialysis patients, cisplatin is potentially hazardous. We report the treatment of a haemodialysis patient with cervix cancer using cisplatin-based chemo-radiation. Mathematical modelling using toxicity data from a range of cisplatin dosages and schedules reported in published studies was undertaken. MATERIALS AND METHODS: The patient was treated using weekly cisplatin chemotherapy 25mg/m(2). The serum platinum levels were measured. Correlations between reported toxicity and platinum levels for a variety of cisplatin schedules in published studies were evaluated. RESULTS: Treatment was completed with no interruptions and minimum acute toxicity. The platinum levels rose progressively. The elimination half-life was prolonged at 6.6-7.5 days. The percentage extraction varied between 7.7 and 41.0%. The cumulative cisplatin dose correlated with neurotoxicity (P=0.002). Myelotoxicity correlated with the peak cisplatin level in the first 15 days of treatment (P=0.01). With an elimination half-life of 7.5 days, 35 mg/m(2) weekly is predicted to have the same risk of myelotoxicity and neurotoxicity as 40 mg/m(2) weekly in a patient with normal renal function. CONCLUSIONS: Weekly cisplatin chemotherapy 25mg/m(2) can be delivered safely in a haemodialysis patient. Dialysis is effective in eliminating platinum even if carried out more than 3h after infusion, but it should commence as soon as possible after cisplatin infusion, as the incidence of myelotoxicity is related to the peak platinum level.

Factors affecting antipyrine metabolism in West African villagers.

Saliva half-life of antipyrine was studied in 49 healthy Gambians between 20 and 60 yr of age of whom 27 were male (mean age, 44.5) and 22 female (mean age, 39.1). Body wieght, height, ponderal index, albumin, and hemoglobin were moderately reduced compared to accepted normal values. Antipyrine half-life was 13.6 +/- 0.58 (SEM) hr. Multiple regression analysis showed that sex, cola nut consumption, hemoglobin in women, and height in men were statiscally significant independent predictors of antipyrine half-life. Half-life was shorter in women, decreased with an increase in height in men, and was prolonged by cola nut consumption. Half-life in women increased with hemoglobin. These factors explained 36% of the variation and suggest that geographic differences in the environment could be important in drug metabolism in man.

Destruction of chlorpromazine during absorption in the rat in vivo and in vitro.

1. Concentrations of total radioactivity in plasma of rats given intravenous and oral (35)S-chlorpromazine, were similar. Concentrations of unchanged drug, however, were lower after oral doses.2. Chlorpromazine circulated in solution through isolated loops of rat intestine was rapidly absorbed by the tissue. Measurements of glucose transport and histological examination indicated that the tissue was intact. In these in vitro experiments some of the chlorpromazine was converted to products, which together with unchanged drug, were partly retained in the intestinal wall and partly transferred to the serosal side of the tissue. Observations at three concentrations supported the hypothesis that transfer of unchanged drug occurred by passive diffusion.3. Conversion of chlorpromazine to metabolites in the intestine in vivo, would account for the differences in concentrations of chlorpromazine and total radio-activity in plasma after oral doses.

Comparative central nervous system effects and pharmacokinetics of neu-metoclopramide and metoclopramide in healthy volunteers.

Metoclopramide, a drug used for the relief of nausea and emesis, is currently under development as a radio- and chemosensitizing agent. Its usefulness in high doses, however, is limited by its central nervous system side effects. Neu-metoclopramide (Neu-Sensamide), a novel, concentrated, phosphate-buffered, pH-adjusted (pH = 6.5-7.0) formulation of metoclopramide, has been shown to have an improved side-effect profile in animal studies. The present double-blind, four-way crossover study compared the central nervous system effects and pharmacokinetics of neu-metoclopramide (intravenously and intramuscularly at 1.8 mg/kg) with intravenous metoclopramide and intramuscular placebo in 19 healthy male volunteers. Eight participants withdrew from the study, one because of noncompliance and seven because of adverse events. A total of 28 central nervous system events were observed with intravenous metoclopramide administration, whereas 16, 15, and 6 such events were attributed to intravenous neu-metoclopramide, intramuscular neu-metoclopramide, and placebo, respectively. Extra-pyramidal effects occurred on 10 occasions: 7 after intravenous metoclopramide, 2 after intravenous neu-metoclopramide, and 1 after intramuscular neu-metoclopramide. No significant differences were observed in the pharmacokinetic profiles of the three formulations of metoclopramide. It may be speculated, therefore, that the molecular conformational changes inherent to neu-metoclopramide result in a reduced side-effect profile compared with conventional metoclopramide formulations.

Radioimmunoassay of amitriptyline and nortriptyline in body fluids.

A radioimmunoassay for the measurement of amitriptyline and nortriptyline in serum, saliva, and urine is described. The sensitivity of the assay is such that 0.5 ng/ml of drug can be measured, although the assay does not distinguish between amitriptyline and nortriptyline. Other tricyclic compounds cross-react with the antiserum to varying degrees, but the metabolites of amitriptyline did not significantly cross-react. Total tricyclic compounds were detected in serum and saliva after single oral doses of amitriptyline, although the absorption was slow.

A bioavailability study of two preparations of tamoxifen after single doses.

The bioavailability of two different tablet formulations of tamoxifen was studied in twelve healthy male volunteers. Two tablets, each of 10 mg, of both preparations were administered orally at intervals of two weeks in a randomized cross-over design. Samples of blood for tamoxifen measurement were taken for up to 48 h following administration. Tamoxifen was measured by an HPLC method sensitive to 2.0 ng ml(-1). The area under the concentration-time curve was similar for both preparations. The study, therefore, did not demonstrate any differences between the bioavailability of the two preparations of tamoxifen.

The evolution of the pathway and its role in improving patient care.

OBJECTIVES: Redesign in healthcare has increased the focus on the needs of the patient. The redesign process typically involves a review of current practice using the patient pathway before considering possible improvements. The patient pathway can serve various roles, and it may be mapped in different ways using a variety of media. This paper reviews the evolution of the patient pathway comparing the merits of different media. METHODS: Simple approaches to mapping pathways can be most useful. However, experience in the redesign of Unscheduled Care in NHS Fife suggests that computer-based, hierarchical pathway models using stylised icons offer many advantages. RESULTS AND CONCLUSIONS: Such approaches can increase the effectiveness of pathways in the redesign process, providing both the detail and the system view in an accessible graphical form. This enhanced capability helps staff analyse current practice and visualise and assess redesign options. In addition, the pathway can fulfil new roles as a training tool and an effective basis for organising knowledge about patient care.