A randomized controlled trial of the effect of sublingual orally disintegrating olanzapine versus oral olanzapine on body mass index: the PLATYPUS Study.

BACKGROUND: Patients with schizophrenia and bipolar disorder have frequently reported weight gain during olanzapine treatment. Previous studies have observed a decrease in weight gain, or weight loss, in patients switching from standard olanzapine tablets (SOT) to orally disintegrating olanzapine (ODO) tablets. The primary objective of this study was to investigate the change in body mass index (BMI) in patients who had previously gained weight with SOT and continued with this therapy during the study period, compared with those patients who switched to ODO during the study period. METHODS: This was a 16-week, multicentre, randomized, double-blind, double-dummy, study of outpatients diagnosed with schizophrenia, schizoaffective disorder, related psychotic disorder or bipolar disorder, who were taking 5-20 mg SOT daily. Patients continued treatment with 5-20 mg olanzapine in a flexible single daily dose, and were randomized to either receive sublingual ODO plus an oral placebo, or sublingual placebo plus SOT. RESULTS: No statistically significant between group differences in mean change from baseline in BMI, weight or waist circumference were observed. Analysis of change in body weight from baseline, by pre-specified category (no change, loss of >or=1.5 kg, gain of >or=1.5 kg), revealed a significant difference between groups, favoring ODO patients, who also experienced a significant reduction in subjective appetite and better treatment compliance, compared to patients in the SOT group. CONCLUSIONS: In this study, patients treated with ODO experienced a similar mean change in BMI and weight from baseline, to those patients treated with SOT.

Olanzapine vs haloperidol in geriatric schizophrenia: analysis of data from a double-blind controlled trial.

OBJECTIVES: To compare the six-week clinical response and safety profile of schizophrenia patients, age > or =60 years, receiving olanzapine (OLZ) vs haloperidol (HAL) in a double blind, randomized trial. METHODS: Double-blind data on patients age > or =60 randomized to 5 mg/d OLZ (n=83) or 5 mg/d HAL (n=34) (Week 1) then flexibly dosed to 5-20 mg/d over six weeks, with a 48-week extension for responders, were analyzed post-hoc. Efficacy indices included the PANSS Total and PANSS Psychosis Core Total (PPCT). Safety measures included the Simpson-Angus Scale (SAS), Barnes Akathisia Scale (BAS), Abnormal Involuntary Movement Scale (AIMS), treatment-emergent adverse events, and laboratory values. Mixed model, repeated measures (MMRM) analyses were applied to all continuous data measured at each visit. Continuous data recorded only at phase completion or termination were analyzed with a fixed effect last observation carried forward (LOCF) model. Frequencies of categorical response data were analyzed using Fisher's exact methods. Differences were tested for significance at Week 6 using a two-sided alpha value of 0.05. RESULTS: HAL group (n=34; age range 60-80) received a mean modal dose 9.4 mg/d while OLZ group (n=83; age range 60-86) received a mean modal dose 11.9 mg/d. At Week 6, OLZ was superior to HAL on both the PANSS Total (p=0.015) and PPCT (p=0.043). Considering safety, OLZ was superior to HAL for the SAS and BAS (p<0.001; p<0.001). No spontaneous adverse event occurred more frequently with OLZ than with HAL. In patients never receiving adjunct anticholinergic therapy, no significant differences were present for anticholinergic-like side effects including blurred vision, dry mouth, constipation, or urinary difficulties. CONCLUSIONS: In elderly schizophrenia patients, olanzapine was more efficacious and better tolerated for extrapyramidal signs than was haloperidol. Olanzapine was equivalent to haloperidol for anticholinergic-like side effects when corrected for anticholingergic agents.

Are there any clinical indications for measuring IgG subclasses?

It is questionable as to whether a low serum concentration of one of the IgG subclasses identifies a disease state. A low IgG(1) concentration is found in primary or secondary immunodeficiency states but does not occur in isolation. Low IgG(2) concentration is associated with an increased risk of bacterial infections but only in some individuals and not in others. Isolated IgG(3) and IgG(4) deficiency have not been convincingly demonstrated. Therefore, the isolated finding of low concentrations of one or more IgG subclass does not identify individuals at risk. In contrast, the finding of low serum concentrations of antibodies to specific bacterial antigens (Haemophilus influenzae type B, pneumococcus, tetanus and diphtheria) does identify individuals at risk and these measurements should be used in preference to IgG subclass measurement.

Computerized measurement of cognitive impairment and associated neuropsychiatric dimensions.

This study aimed to cross-validate the capacity of a computer software program to detect and measure, using a measurement method applied to the content and form analysis of 5-minute speech samples, cognitive impairment and associated comorbid neuropsychiatric psychobiological dimensions in drug-abusing patients. At the University of California-Irvine (UCI) Neuropsychiatric Center, 28 drug-abusing inpatients using illegal drugs were clinically evaluated. Their scores for cognitive impairment derived by the computerized content analysis method were compared with scores derived from selected tests from the Halstead-Reitan Neuropsychological Test Battery, the computerized Automated Neuropsychological Assessment Metric Battery (ANAM), the Alzheimer's Disease Assessment Scale-Cognitive Portion, the Stroop Color and Word Test, the Symbol Digit Modalities Test, and the Controlled Oral Word Association Test. The statistical significance (P value) of the correlations of scores from these different measures with scores obtained from the computerized content analysis measures was less than .05 to .001. The comparative "hit rate," detecting cognitive impairment above the norms for each measure administered to these drug-abusing patients, for the computerized content analysis measures and some of the ANAM neuropsychological measures was 75% to 89%, and for the other neuropsychological measures, 25% to 64%. In conclusion, the computerized content analysis methodology applied to 5-minute verbal samples is a valid, rapid, easily administered measurement instrument for assessing the magnitude of cognitive impairment and comorbid neuropsychiatric dimensions.

Risperidone for the treatment of stuttering.

A randomized, double-blind, placebo-controlled study was conducted to assess the efficacy of risperidone in the treatment of developmental stuttering in 16 adults. Eight subjects received placebo and eight received risperidone at 0.5 mg once daily at night, increased to a maximum of 2 mg/day. After 6 weeks of treatment, decreases in all measures of stuttering severity were greater in the risperidone group than in the placebo group; the between-treatment difference was significant (p < 0.05) on the most important measure, the percentage of syllables stuttered. In the risperidone group, reductions from baseline in scores for the percentage of syllables stuttered, time stuttering as a percentage of total time speaking, and overall stuttering severity were significant (p < 0.01); changes in scores on the fourth measure of stuttering, duration, were not significant. No significant decreases occurred in the placebo group. Among the eight patients in the risperidone group, five responded best to 0.5 mg/day, with stuttering recurring at higher doses. The remaining three patients responded better with increasing doses of risperidone. Risperidone was generally well tolerated. The results of this small study indicate that risperidone may be effective in the treatment of developmental stuttering. This finding needs to be confirmed in a larger trial.

Management of child and adolescent stuttering with olanzapine: three case reports.

Vast arrays of medications have been used, with limited success, to manage stuttering. Haloperidol and risperidone are the only two medications that have shown efficacy via double-blind studies in controlling stuttering symptoms. We present the first case reports of olanzapine in the management of stuttering. Three case histories are presented: a 10-year-old boy, a 16-year-old male adolescent with developmental stuttering, and a 9-year-old boy with medication-induced stuttering whose symptoms are successfully controlled with olanzapine. These case studies suggest that olanzapine may be a pharmacologic option in the management of stuttering.

Stuttering: neuropsychiatric features measured by content analysis of speech and the effect of risperidone on stuttering severity.

Positron-emission tomographic (PET) studies and genetic research of stuttering have recently revealed underlying cerebral neurobiologic contributing factors in this disorder. We aimed to assess whether cognitive impairment and other neuropsychiatric dimensions could be detected through computerized content analysis of short samples of speech from stutterers, and whether administration of risperidone in a double-blind placebo-controlled study could decrease the severity of stuttering, as well as any of the neuropsychiatric features of these stutterers. A group of 21 stutterers with the developmental form of stuttering, an onset before age of 6 years, aged 20 to 74 years, and who were otherwise free of major medical or psychiatric problems, initially gave a 5-minute tape-recorded speech sample in response to purposely ambiguous instructions to talk about any interesting or dramatic life experiences. Then, half of these subjects (n = 10) were randomly selected to receive 6 weeks of risperidone treatment up to 2.0 mg/d and the other half (n = 11) were administered a placebo. Both groups of subjects gave a second verbal sample after 6 weeks of treatment. Significantly elevated cognitive impairment and social alienation-personal disorganization scores, derived from the computerized content of the initial 5-minute speech samples, were found. After 6 weeks, the risperidone group improved significantly on a measure of severity of stuttering but did not improve on the percentage of time spent stuttering. The placebo group did not improve on either measure of stuttering. The psychopathological processes of subjects who received risperidone treatment, including those with elevated cognitive impairment and social alienation-personal disorganization, did not change significantly. However, stutterers who had lower scores on verbal content analysis-derived shame anxiety, guilt anxiety, or hostility inward measures improved significantly more with risperidone than stutterers with higher scores on these measures. The findings of elevated cognitive impairment and social alienation-personal disorganization scores of adult stutterers with the early developmental form of stuttering are consistent with the neurobiologic abnormalities found in PET-scan and genetic research involving stutterers. Risperidone (< or =2.0 mg/d) can reduce the severity of stuttering while not significantly affecting the magnitude of neuropsychiatric dimensions such as cognitive impairment or social alienation-personal disorganization. The less the inward shame, guilt, or hostility of the stutterers, the better the beneficial effect of risperidone on the severity of stuttering.

Which patients with prostatic carcinoma require a staging bone scan?

OBJECTIVE: To determine whether the level of prostate-specific antigen (PSA) can be used to decide which patients with newly diagnosed prostatic carcinoma require a staging bone scan. PATIENTS AND METHODS: Of patients referred during an 18-month period for a staging bone scan, 98 (median age 72 years, range 52-89) had had their serum PSA level determined within 4 weeks of the bone scan and were assessed retrospectively for the presence of bony metastases. RESULTS: Of the 98 patients, 26 who had bone scans showing bony metastases had a PSA level > 40 ng/mL. Reviewing the other published studies showed that in those newly diagnosed patients with a PSA level of < 20 ng/mL, the probability of having bony metastases detected on a bone scan was < 1%. CONCLUSIONS: A staging bone scan can be omitted in the vast majority of patients with newly diagnosed prostatic carcinoma and a PSA level < 20 ng/mL.

Glycosyl phosphatidyl inositol phospholipase D activity in human serum.

We measured serum glycosyl phosphatidyl inositol phospholipase D (GPI-PLD) by its alkaline phosphatase releasing activity in healthy and diseased individuals. Linearity with respect to serum concentration was obtained only with very low serum volumes (below about 0.2 microL) necessitating a large predilution of serum to avoid potential artefacts. The assay was sufficiently precise for routine use. Patients with liver disease had lower activities and those with renal disease had higher activities than healthy controls. Following liver transplantation there was no correlation between GPI-PLD and conventional markers of liver function but there was a marked correlation with cholesterol concentration. These observations suggest that liver is a major source of GPI-PLD in serum. Its function remains unknown.

A novel capillary collection method for obtaining current glycosylated haemoglobin levels in diabetic children.

A simple method for collecting capillary blood for measurement of glycosylated haemoglobin (HbA1c) was developed that allows samples to be obtained at home and then mailed to the laboratory 2 weeks before a hospital visit. A single drop of blood is collected into a 2 ml plastic tube and sent for HbA1c assay on the Diamat HPLC system which has inter- and intra-assay coefficients of variation < 2.6 and < 1.2%, respectively. Results of simultaneously obtained venous and capillary samples in 32 diabetic children agreed well with each other. A separate study of 25 patients was performed to determine whether transport conditions affected the samples. Posted samples were compared with venous samples; again the values were in good agreement. This method is now used routinely in the diabetic clinic. Its value was determined by questionnaire in 40 children with age range 4-17 years. No family experienced difficulty collecting samples and all samples received were suitable for analysis. Children preferred this method to blood collection in the clinic as they felt it was less traumatic and more convenient. Seventy-nine percent of them understood its value in the long-term control of diabetes. In 40.5% of visits changes to management were made at the clinic due to the availability of the results.

Investigation of the use of impermeable fluid barriers between pelleted and supernatant enzyme activity in a pseudohomogeneous enzyme immunoassay.

We have investigated the feasibility of performing an automated pseudohomogeneous enzyme immunoassay in which a separation step is not apparent to the user. This was achieved using a layer of silicone fluid, which is immiscible with aqueous solutions, as a physical barrier between the pelleted and supernatant enzyme. Initially we produced a manual assay based on the Serozyme T4 assay to demonstrate the feasibility of the approach. This assay showed good precision, parallelism and correlated with 'in house' results on patients' samples. Production of a fully automated assay was made difficult by the design of available equipment but none the less we demonstrated the feasibility of the automated approach by producing a standard curve for T4.

A kinetic assay for urea in undiluted urine specimens.

We describe a kinetic assay for quantifying urea in undiluted urine samples. The assay linearity extends to urea concentrations of 400 mmol/L, is free from interference from blood (10 mL/L) or bilirubin (1 mmol/L), is sufficiently precise for routine use, and correlates well with an established method for assay of diluted urine samples.