Time to study discontinuation, relapse, and compliance with atypical or conventional antipsychotics in schizophrenia and related disorders.

To more clearly clarify the efficacy of the atypical antipsychotics compared to conventional antipsychotics, we add data on the outcome of patients diagnosed with schizophrenia from two large, international clinical trials comparing olanzapine with haloperidol (n = 1996) and olanzapine with risperidone (n = 339). Both studies comprised double-blinded, placebo controlled, random assignment trials. Health outcomes reported include: (i) time to discontinuation in the trial; (ii) clinical relapse; and (iii) time to drug non-compliance. When outcome was measured as time to discontinuation due to adverse events or lack of efficacy, olanzapine showed superiority over haloperidol and no difference compared to risperidone. Of those patients who had an initial response, there was no significant difference between olanzapine and haloperidol when outcome was measured using either: (i) 52-week relapse rates or (ii) time to first non-compliance. Using the measures of study discontinuation, relapse and non-compliance, in one trial the atypical antipsychotic olanzapine was superior to haloperidol, while in a second trial there were no differences between olanzapine and risperidone.

Analysis of the QTc interval during olanzapine treatment of patients with schizophrenia and related psychosis.

BACKGROUND: There may be a temporal association between some antipsychotics and prolongation of the heart-rate-corrected QT interval (QTc) representing a delay in ventricular repolarization. QTc prolongation significantly exceeding normal intra-individual and interindividual variation may increase the risk of ventricular tachydysrhythmias, especially torsade de pointes, and therefore, sudden cardiac death. METHOD: Electrocardiogram recordings obtained as part of the safety assessment of olanzapine in 4 controlled, randomized clinical trials (N = 2,700) were analyzed. These analyses were conducted to characterize any change in QTc temporally associated with olanzapine, compared with placebo, haloperidol, and risperidone, in acutely psychotic patients (DSM-III-R and DSM-IV) and to characterize variability and temporal course of the QTc in this patient population. Changes from baseline to minimum and maximum QTc were tested for significance, and baseline to acute-phase endpoint change in mean QTc was tested for significance within treatments and for differences between olanzapine and comparators. The possibility of a linear relationship between dose of olanzapine and mean change in QTc, as well as incidence of treatment-emergent prolongation of QTc (change from < 430 msec at baseline to > or =430 msec at endpoint), was tested. RESULTS: The incidence of maximum QTc > or = 450 msec during treatment was approximately equal to the incidence of QTc > or =450 msec at baseline. CONCLUSION: Results of these analyses suggest that olanzapine, as therapeutically administered to patients with schizophrenia and related psychoses, does not contribute to QTc prolongation resulting in potentially fatal ventricular arrhythmias.

Urinary incontinence in United States Air Force female aircrew.

OBJECTIVE: To determine if flying high-performance military aircraft capable of sustaining up to 9g increases the incidence of incontinence in United States Air Force female aircrew. METHODS: An anonymous survey addressing urinary incontinence was conducted among Air Force active-duty women on flying status. Respondents were asked if they had ever leaked urine and, if so, how much and at what time: off-duty, on-duty (not flying), or while flying. The survey was approved by the Air Force Surgeon General's Office and the Air Force Survey Branch. RESULTS: Two hundred seventy-four of 426 surveys were completed and returned, for a response rate of 64.3%. The overall prevalence of incontinence was found to be 26.3% (72 of 274). Of the women complaining of incontinence, 88.9% (64 of 72) stated that it had occurred off-duty, 31.9% (23 of 72) stated that it had occurred on-duty (not flying), and 18.1% (13 of 72) stated that it had occurred while flying. Risk factors for incontinence included crew position, vaginal parity, and age. The type of aircraft flown did not affect the incidence of reported incontinence. CONCLUSION: The rate of urinary incontinence among female Air Force aircrew is similar to rates found in other surveys of the general population. Flying high-performance military aircraft did not affect the rate of incontinence.

The psychosis of schizophrenia: prevalence, response to atypical antipsychotics, and prediction of outcome.

BACKGROUND: Psychosis is a defining feature of schizophrenia consisting of formal thought disorder, delusions, and hallucinations. Although psychosis is present in the majority of patients with schizophrenia, the prevalence, responsiveness to atypical antipsychotic drug therapy, and prediction of outcome of individual psychotic symptoms in a population of well-diagnosed patients with schizophrenia have not been conclusively established. METHODS: This paper examined the prevalence, responsiveness to the atypical antipsychotic olanzapine, and relationship to outcome of individual psychotic symptoms using data from a previously reported large multicenter, double-blind clinical trial of olanzapine (mean daily dose at endpoint = 13.6 +/- 6.9 mg/day). RESULTS: The most frequently reported psychotic symptoms at baseline were delusions (65%), conceptual disorganization (50%), and hallucinations (52%), and the majority of patients (68%) experienced from one to three symptoms. Additionally, with olanzapine treatment there were significant improvements (p < .001) in baseline to endpoint Positive and Negative Symptom Scale (PANSS) psychotic item scores, with the largest effect sizes observed for hallucinatory behavior, unusual thought content, suspiciousness/persecution, and delusions. During the acute phase of the trial, quality of life was correlated significantly with baseline conceptual disorganization (p = .038) and unusual thought content (p = .023), and time spent in the hospital was correlated with unusual thought content (p = .005). CONCLUSIONS: The implications of these for the clinical management of schizophrenia are discussed.

Olanzapine versus haloperidol in the treatment of schizoaffective disorder. Acute and long-term therapy.

BACKGROUND: The effectiveness of antipsychotic monotherapy in schizoaffective disorder is limited, and further constrained by safety concerns. AIMS: We aimed to compare the efficacy, tolerability and safety profile of the new pharmaceutical, olanzapine, with haloperidol. METHOD: Data were assessed from 300 DSM-III-R schizoaffective subjects from a larger double-blind prospective international study. Subjects were randomly allocated to six weeks of olanzapine (5-20 mg) or haloperidol (5-20 mg) treatment; responders were followed for up to one year of double-blind, long-term maintenance therapy. RESULTS: Olanzapine-treated patients achieved a statistically significant greater improvement than haloperidol treated patients on overall measures of efficacy, including clinical response. Significantly fewer olanzapine patients left the study early, and fewer adverse events were observed among those receiving olanzapine. During maintenance, olanzapine-treated patients continued to experience additional improvement, with fewer EPS but more weight gain than those on haloperidol. CONCLUSIONS: Olanzapine demonstrated substantial advantages over the conventional antipsychotic haloperidol in the management of schizoaffective disorder.

A pharmacodynamic model for the action of the antibiotic imipenem on Pseudomonas aeruginosa populations in vitro.

The standard method for measuring in vitro antibiotic efficacy is based on a point observation of bacterial activity 18 hours after inoculation. The method, while simple, forgoes significant information by ignoring the dynamics of the interactions between antibiotic and bacteria. This paper proposes a simple dynamic model describing these interactions. The model consists of two non-linear differential equations of the S-system type. Its parameter values are estimated, through the minimization of residual errors, from data on the effect of the carbapenem antibiotic imipenem on Pseudomonas aeruginosa. The model adequately describes the dynamic behavior of the bacterial populations in the presence of the antibiotic: beginning with drug administration, then through the decline of the bacterial population and possibly ending with bacterial resurgence.

A meta-analytical approach examining the potential relationship between talc exposure and ovarian cancer.

The concern that use of talc or talc-containing substances in the perineal region of women may subject them to an increased risk for ovarian cancer has become an important issue in the study of ovarian cancer. The purpose of this paper is to examine whether this concern, heightened by several epidemiological studies purporting to show an increased risk, is valid. Epidemiological studies examining the possibility of this relationship are reviewed, and meta-analyses of their results are performed. The conclusion reached herein is that the evidence regarding the risk of ovarian cancer associated with talc exposure is equivocal, and further examination of the relationship is required before a sound conclusion can be made.