An exploratory haloperidol-controlled dose-finding study of ziprasidone in hospitalized patients with schizophrenia or schizoaffective disorder.

Ninety patients with schizophrenia or schizoaffective disorder according to DSM-III-R criteria participated in this double-blind, exploratory, dose-ranging trial. After a single-blind washout period of 4 to 7 days, patients were randomly assigned to receive one of four fixed doses of the new antipsychotic, ziprasidone 4 (N = 19), 10 (N = 17), 40 (N = 17), or 160 (N = 20) mg/day or haloperidol 15 mg/day (N = 17) for 4 weeks. A dose-response relationship among ziprasidone groups was established for improvements in Clinical Global Impression Severity (CGI-S) score (p = 0.002) but not in Brief Psychiatric Rating Scale (BPRS) total score (p = 0.08). The intent-to-treat analysis of mean changes from baseline in the BPRS total, BPRS Psychosis core, and CGI-S scores demonstrated that ziprasidone 160 mg/day was comparable with haloperidol in reducing overall psychopathology and positive symptoms and was superior to ziprasidone 4 mg/day. Despite the small sample size and short duration of the trial, the improvement in CGI-S with both ziprasidone 160 mg/day and haloperidol 15 mg/day was statistically significantly greater than with ziprasidone 4 mg/day (p = 0.001 andp = 0.005, respectively). The percentage of patients classified as responders on both the BPRS total (> or = 30% improvement) and CGI-Improvement (score of 1 or 2) scales in the ziprasidone 160 mg/day group was similar to that in the haloperidol group and nonsignificantly greater than that in the ziprasidone 4 mg/day group. On all assessments of clinical efficacy, the improvements associated with ziprasidone 4 mg/day, 10 mg/day, and 40 mg/day were similar. Concomitant benztropine use at any time during the study was less frequent with ziprasidone 160 mg/day (15%) than with haloperidol (53%). Haloperidol was associated with a sustained hyperprolactinemia, unlike ziprasidone, where only transient elevations in prolactin that returned to normal within the dosing interval were observed. Ziprasidone was well tolerated, and the incidence of adverse events was similar in all groups. The results of this study suggest that ziprasidone 160 mg/day is as effective as haloperidol 15 mg/day in reducing overall psychopathology and positive symptoms of an acute exacerbation of schizophrenia or schizoaffective disorder but has a lower potential to induce extrapyramidal symptoms.

Rheumatoid arthritis treated with tenidap and piroxicam. Clinical associations with cytokine modulation by tenidap.

OBJECTIVE: To compare the effects of tenidap and piroxicam on acute-phase protein and cytokine levels in the blood of rheumatoid arthritis (RA) patients and to explore their associations with clinical disease activity. METHODS: A double-blind, randomized, crossover trial in 49 patients with active RA compared 6 weeks of treatment with tenidap (120 mg/day) versus 6 weeks of treatment with piroxicam (20 mg/day). RESULTS: Median values for C-reactive protein (CRP), Westergren erythrocyte sedimentation rate (ESR), serum amyloid A (SAA) protein, and interleukin-6 (IL-6) were significantly lower after tenidap treatment compared with piroxicam treatment, even in the presence of stable background treatment with prednisone, methotrexate, or prednisone plus methotrexate. The median within-patient treatment differences (after tenidap minus after piroxicam) in the CRP, ESR, SAA, and IL-6 values were -1.7 mg/dl, -10.0 mm/hour, -22.0 micrograms/ml, and -3.7 pg/ml, respectively, and represent -60.4%, -17.7%, -35.5%, and -26.1% of the respective baseline levels. IL-6 levels were positively correlated with CRP and SAA. Plasma IL-1 beta was generally below the level of detection. Tumor necrosis factor alpha levels were similar after tenidap and after piroxicam. Treatment differences for 4 of 7 clinical parameters favored tenidap, but did not reach statistical significance. IL-6, CRP, and ESR were significantly correlated with clinical treatment differences. Tenidap and piroxicam toleration were similar, although tenidap-treated patients exhibited a reversible increase in urinary protein excretion. CONCLUSION: Tenidap was differentiated from piroxicam by lower levels of acute-phase proteins, ESR, and IL-6 after tenidap treatment. These treatment differences were significantly correlated with clinical parameters.

Effects of mid-point imputation on the analysis of doubly censored data.

Doubly censored data arise in some cohort studies of the AIDS incubation period because the time of infection may be known only up to an interval defined by two successive screening tests for HIV antibody. A simple analytic approach is to impute the infection time by the mid-point of the interval and then apply standard survival techniques for right censored data. The objective of this paper is to investigate the statistical properties of such a mid-point imputation approach. We investigated the asymptotic bias of the Kaplan-Meier estimate, coverage probabilities of associated confidence intervals, bias in hazard ratio, and the size of the logrank test. We show that the statistical properties of mid-point imputation depend strongly on the underlying distributions of infection times and the incubation periods, and the width of the interval between screening tests. In the absence of treatment, the median incubation period of HIV infection is approximately 10 years, and we conclude that, for this situation, mid-point imputation is a reasonable procedure for interval widths of 2 years or less.

Absence of significant differences in intestinal parasite prevalence estimates after examination of either one or two stool specimens.

The authors undertook a retrospective search of intestinal parasite laboratory records obtained from 200 consecutive-day pairs of stool specimens to compare prevalence estimates from the first and second stool examinations. The laboratory results had previously been recorded as part of a screening program offered to Southeast Asian refugees arriving in Montréal, Québec, Canada, between July 1982 and February 1983. No statistically significant differences in either overall prevalences or parasite-specific prevalences were observed. This suggests that, at least in some population-based situations, single stool examinations provide estimates of intestinal parasite prevalence which are as valid as those from the routine examination of two consecutive-day specimens. Blinded studies must be undertaken to accurately assess the true value of multiple specimen submission in epidemiologic studies.