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Biomedical subjects

M Borenstein

Publications and source records attributed to M Borenstein.

At least 37 records · Page 2Linked to original sources
PubMed1994

The case for confidence intervals in controlled clinical trials.

A statistical wit once remarked that researchers often pose the wrong question and then proceed to answer that question incorrectly. The question that researchers intend to ask is whether or not a treatment effect is clinically significant. The question that is typically asked, however, is whether or not the treatment effect is statistically significant--a question that may be only marginally related to the issue of clinical impact. Similarly, the response, in the form of a p value, is typically assumed to reflect clinical significance but in fact reflects statistical significance. In an attempt to address this problem the medical literature over the past decade has been moving away from tests of significance and toward the use of confidence intervals. Concretely, study reports are moving away from "the difference was significant with a p value under 0.01" and toward "the one-year survival rate was increased by 20 percentage points with a 95% confidence interval of 15 to 24 percentage points." By focusing on what the effect is rather than on what the effect is not confidence intervals offer an appropriate framework for reporting the results of clinical trials. This paper offers a non-technical introduction to confidence intervals, shows how the confidence intervals framework offers advantages over hypothesis testing, and highlights some of the controversy that has developed around the application of this method. Additionally, we make the argument that studies which will be reported in terms of confidence intervals should similarly be planned with reference to confidence intervals. The sample size should be set to ensure that the estimates of effect size will be reported not only with adequate power but also with appropriate precision.

Confidence Intervals↗
PubMed1994

Planning for precision in survival studies.

If the purpose of a clinical study is not only to test the null hypothesis but also to estimate the magnitude of the treatment effect, the study design should ensure not only that the study will have adequate power but also that it will enable the researcher to report the relevant parameters with an appropriate level of precision. This paper discusses the factors that control precision in survival studies and shows how a computer program may be used to address these issues. The program allows the user to systematically modify assumptions about the population (e.g. the magnitude of the hazard ratio or the attrition rate) and elements of the study design (e.g. sample size and trial duration), quickly identify the impact of these factors on the study's precision, and modify the study design accordingly. The program may also be used to compute power for a planned study, and confidence intervals for a completed study.

Computer Simulation↗
PubMed1994

The deficit state in first-episode schizophrenia.

OBJECTIVE: The prevalence, clinical correlates, and outcome of the deficit syndrome were determined for 70 patients ascertained in their first episode of schizophrenia and then followed through their recovery. METHODS: Patients were treated in a standardized manner and underwent baseline assessments of symptoms and adverse effects that were repeated at intervals throughout their inpatient and subsequent outpatient course. Forty-seven patients were followed for a minimum of 6 months after remission of their positive symptoms, allowing for an assessment of their deficit syndrome status. RESULTS: Using modified criteria of Carpenter et al. for the deficit syndrome, the authors found that two patients (4%) met all criteria for the deficit syndrome, nine (19%) had deficit symptoms (questionable deficit state), and 36 (77%) had no deficit symptoms. When patients who had not fully remitted or had remitted for less than 6 months were included, seven (10%) met deficit syndrome criteria, 11 (16%) had deficit symptoms, and 52 (74%) had no deficit symptoms. CONCLUSIONS: The prevalence of the deficit syndrome in first-episode schizophrenia varies depending on the criteria used and is lower than that previously described in more chronic patient samples. Patients without deficit symptoms had better premorbid functioning and a better global outcome than patients with deficit symptoms.

Adult↗
PubMed1994

Increase in caudate nuclei volumes of first-episode schizophrenic patients taking antipsychotic drugs.

OBJECTIVE: This study examined the pathomorphology of the caudate nuclei in first-episode schizophrenic patients with minimal previous neuroleptic exposure. METHOD: Magnetic resonance imaging (MRI) of the brain was used to examine longitudinally the caudate pathomorphology in 29 first-episode schizophrenic patients and 10 healthy comparison subjects. MRI scans were obtained after the subjects entered the study and at 18-month follow-up. The patients were treated with standardized neuroleptic regimens during the 18-month period. Volumetric assessments of the cerebral cortex, lateral ventricles, and caudate nuclei were performed on T1-weighted coronal brain sections. In addition, the patients were systematically evaluated for psychopathology at baseline and during treatment. RESULTS: Caudate volumes increased 5.7% in the patients during the 18-month treatment interval, whereas they decreased 1.6% in the comparison subjects over the same time period. Greater amounts of antipsychotic medication received by patients before the first scan and younger age at the time of the first scan were associated with larger increases in caudate volume. CONCLUSIONS: Caudate enlargement occurs early in the course of treatment in young first-episode schizophrenic patients. This may be a result of an interaction between neuroleptic treatment and the plasticity of dopaminergic neuronal systems in young patients.

Adult↗
PubMed1994

Dosage of haloperidol for mania.

BACKGROUND: We compared three doses of a neuroleptic as a treatment for mania. METHOD: Forty-seven newly admitted in-patients with mania were randomised to receive 10, 30, or 80 mg a day of oral haloperidol, under double-blind conditions for up to six weeks. All subjects received prophylactic benztropine. RESULTS: Repeated-measures analysis of variance and survival analysis showed no difference in outcome by the different doses. Excluding drop-outs (38%), most of whom left the study during the first two weeks, 72% of the subjects responded. Side-effects were minimal; there were no differences among the three doses. Non-responders received more adjunctive lorazepam than responders. CONCLUSIONS: The limited data suggest that more than 10 mg a day of haloperidol offers no advantage in mania.

Adult↗
PubMed1994

The resampling method of statistical analysis.

Some non-statisticians occasionally use improper statistical methodology due to a lack of appreciation for the model assumptions that underlie a particular technique. The resampling method is a recent attempt to solve statistical problems with a minimum of assumptions. In essence, resampling involves an intuitive approach to inferential statistics that obviates the need for the mathematically derived sampling distribution. The resampling approach takes advantage of readily accessible high-speed computers to do a computationally intensive Monte Carlo experiment on the available data. The resampling approach liberates the user from imposing assumptions that are sometimes dubious. It also directs one away from a black-box attitude toward statistical analysis and instead forces the user to consider the purpose of the inferential process. A particularly user-friendly implementation of resampling methods that addresses some of the problems faced by non-statisticians is found in a simple, yet powerful, computer program called "Resampling Stats," version 3.13.

Adult↗
PubMed1994

A note on the use of confidence intervals in psychiatric research.

The emphasis on hypothesis testing, which characterizes the majority of medical research, is often inappropriate because it focuses on statistical significance (the viability of the nil hypothesis) rather than substantive significance (the magnitude of the treatment effect). An alternative approach, the reporting of a treatment effect with the corresponding confidence interval, may better reflect the researcher's intent since these are the issues that are relevant to an informed clinical decision. Additionally, results reported in this format are less likely to be misinterpreted than results presented as p values since the precision with which the effect size is estimated would be reported separately from the effect size itself.

Psychiatry↗
PubMed1994

Blood levels of haloperidol and clinical outcome in schizophrenia.

Haloperidol levels in blood were measured in 55 acutely psychotic inpatients with schizophrenia, who were randomly assigned to three fixed doses of oral haloperidol. Nineteen of these subjects received 10 mg/day, 18 received 30 mg/day, and 18 of them received 80 mg/day. All of the subjects were treated under double-blind conditions for 6 weeks or until remission. Haloperidol and reduced haloperidol levels were measured in plasma and red blood cells at the end of 2, 4, and 6 weeks of treatment. There were statistically significant linear correlations between the dose of haloperidol and levels in blood. An examination of data for linear and curvilinear relationships between levels in blood and clinical response did not yield any statistically significant relations. The data did not support the concept of a "therapeutic window." The ratio of reduced haloperidol to haloperidol levels in plasma or red blood cells did not yield any statistically significant correlations to clinical outcome.

Adolescent↗
PubMed1993

Time course and biologic correlates of treatment response in first-episode schizophrenia.

OBJECTIVE: To examine the course and potential predictors of treatment response in the early phase of schizophrenia. DESIGN: Prospective study of an inception cohort. SETTING: Psychiatric division of an academic medical center with a suburban metropolitan catchment area. PATIENTS AND INTERVENTION: Seventy first-episode patients who had undergone four biologic assessment procedures (brain magnetic resonance imaging, behavioral response to methylphenidate hydrochloride, growth hormone levels, eye tracking) were treated with a standardized antipsychotic drug protocol until recovery. Response was measured in terms of psychopathology and degree of remission. RESULTS: Using survival analysis, the proportion of patients remitting by 1 year was estimated at 83%. Mean and median times to remission were 35.7 weeks and 11 weeks, respectively. No baseline demographic or psychopathologic measure significantly predicted time to or level of remission. However, males tended to be nonresponders to treatment and have diagnoses of schizophrenia rather than schizoaffective disorder. Brain pathomorphology and abnormal basal growth hormone significantly predicted time to remission. CONCLUSIONS: These results indicate that the antipsychotic treatment response of first-episode schizophrenics is better than chronic multiepisode patients and suggest that specific pathobiologic markers reflect pathophysiologic processes that mediate antipsychotic treatment response.

Adult↗
PubMed1993

Is the use of boxed gloves in an intensive care unit safe?

PURPOSE: To identify the type, rate, burden, and pattern of contamination of boxed, clean but nonsterile gloves in our intensive care unit (ICU). MATERIALS AND METHODS: The fingertips of the first, middle, and last two pairs of gloves in 29 boxes in routine service in our ICU were cultured. The first of each of these three sets were removed aseptically, the second in a routine fashion. RESULTS: We found 16 of 29 (55%) first pairs removed aseptically to be contaminated with a mean bioburden of 1.8 colony-forming units (CFU). The percentage contamination and bioburden did not change significantly with position in the box. Use of routine compared with strict aseptic technique increased the rate of contamination by only 11% (95% confidence interval [CI] -0.05 to +0.27 percentage points) and bioburden by only a mean of 3.4 colonies per pair (CI -0.51 to +4.90 CFU). The length of the time the boxes were open and in use was unrelated to whether the final aseptically removed pair was sterile or contaminated. The predominant organisms were coagulase-negative staphylococci. CONCLUSIONS: One half the pairs of latex examination gloves in our ICU were sterile despite repeated barehanded access to the boxes. Those contaminated exhibited a small bioburden of low pathogenic potential. No pattern of contamination or unsafe duration of box use were observed. The use of boxed, clean, nonsterile gloves appears safe for routine use in an ICU.

Bacterial Infections↗
PubMed1993

High plasma clozapine levels in tardive dyskinesia.

Studies in the literature that attempt to relate neuroleptic plasma levels to the development of tardive dyskinesia (TD) report inconsistent findings. As part of an open, long-term study, 60 schizophrenic and schizoaffective patients were started gradually on a b.i.d. schedule of the atypical antipsychotic drug clozapine. Blood samples were drawn weekly for 6 weeks and analyzed for a variety of constituents including clozapine plasma levels. Patients with higher levels of TD were found to have significantly higher levels of plasma clozapine and a higher ratio of plasma/dose than those with lower levels of TD. Our data suggests that schizophrenics with TD may have different pharmacokinetics, drug metabolism, and elimination processes than those without TD. Higher typical plasma neuroleptic levels may increase susceptibility to TD development. A second hypothesis implies that it is not the higher mean plasma level of a neuroleptic that is associated with TD but the greater fluctuations of plasma levels over time (i.e., a higher variance). This hypothesis is discussed in the context of our data.

Adult↗
PubMed1992

Associations between sexual experiences and fantasies in a nonpatient population: a preliminary study.

We have been interested in devising some methodology short of psychoanalytic therapy to study the relationship of conscious fantasy to personality trends and behavior. Presented here is a pilot study, utilizing the questionnaire technique, the sample consisting of 193 students enrolled at one prestigious urban university, that reports on the prevalence and content of conscious sexual fantasies in a normal (nonpatient) population and their relationship to sexual behaviors. Factor analysis suggested four experience and four fantasy clusters. Those individuals who score high on one experience factor are apt to score high on all other experience factors as well. The same is true of the fantasy factors. Our findings indicate that low sexual activity and low levels of sexual fantasy go together, whereas more sexual experience is connected to a greater range of sexual fantasy. Consequently, erotic fantasies cannot be viewed as compensation for lack of sexual outlet. Instead, there is a positive correlation between the two domains of sexual fantasies and sexual behaviors. Our overall results lead us to conclude that by and large, people are sexual generalists not specialists.

Adult↗
PubMed1991

Dosage of haloperidol for schizophrenia.

Eighty-seven newly admitted inpatients with schizophrenia were randomized to receive 10, 30, or 80 mg/d of oral haloperidol. They were treated under double-blind conditions for 6 weeks, less if their acute symptoms remitted sooner. Survival analysis showed no differences among the three treatments. Side effects were minimal in all three treatment groups, and there were no differences in side effects among the groups. These results suggest that dosages higher than 10 mg/d of haloperidol for most patients have no additional beneficial effect in the treatment of acute or exacerbated schizophrenia.

Acute Disease↗
PubMed1991

Effects of intravitreal dexamethasone on concentration of intravitreal vancomycin in experimental methicillin-resistant Staphylococcus epidermidis endophthalmitis.

Intravitreal corticosteroids in the treatment of bacterial endophthalmitis remain controversial. We utilized an experimental rabbit model of methicillin-resistant Staphylococcus epidermidis endophthalmitis (i) to calculate the intravitreal vancomycin concentration in rabbit eyes receiving intravitreal vancomycin alone or in combination with intravitreal dexamethasone and (ii) to determine whether an intravitreal steroid has any effect on intravitreal vancomycin levels. All right eyes were infected and all left eyes were uninfected. The rabbits were divided into two treatment groups: (i) 32 eyes (group I) were injected with intravitreal vancomycin, 1.0 mg (0.1 ml); (ii) 32 additional eyes (group II) were injected with intravitreal dexamethasone, 400 micrograms (0.1 ml), in addition to vancomycin. Measurement of intravitreal vancomycin concentration was performed following sacrifice, utilizing a microbiologic agar diffusion assay. Analyses of intravitreal vancomycin concentrations were performed by using model-independent parameters, with area under the concentration-time curves derived by trapezoidal approximation. The intravitreal vancomycin concentration was significantly lower in both uninfected and infected group II eyes (P less than 0.002). Analysis of intravitreal vancomycin concentration-time relationships was performed by using a nonlinear least-squares regression program; data best fit a one-compartment model. In addition, no vancomycin-dexamethasone interaction could be demonstrated. The reduced level of intravitreal vancomycin in the presence of intravitreal dexamethasone may have important clinical implications.

Animals↗
PubMed1991

The effects of clozapine on tardive dyskinesia.

This article reviews eight published studies that describe clozapine's effects on TD and examines the outcome of 30 patients with TD treated with clozapine for up to 36 months. These data indicate that TD response to clozapine is variable but that approximately 43% of cases, particularly those with dystonic features, improved after clozapine treatment. Methodological limitations of the studies described, however, preclude definitive conclusions, which must await appropriately controlled trials.

Adult↗
PubMed1991

The prevalence of tardive dyskinesia.

A total of 2250 subjects from psychiatric and geriatric settings was examined for abnormal involuntary movements by the same team of trained raters employing a standard examination technique and rating scale. "Spontaneous" dyskinesia rates were 1.3% among 400 healthy elderly people surveyed at senior citizens centers, 4.8% among medical geriatric inpatients and ranged from 0 to 2% among psychiatric patients never exposed to neuroleptics. For samples of neuroleptic-treated patients, prevalence rates ranged from 13.3% among patients at a voluntary psychiatric hospital to 36.1% among state hospital patients. Logistic regression analyses revealed a large effect of age on tardive dyskinesia prevalence and an interaction of age with sex. Among younger subjects, men had higher rates; among subjects over age 40, rates were higher for women. Edentulousness and presence of other neurological disorders were possible contributors to high rates for the elderly. Even with control for age, sex and duration of neuroleptic exposure, prevalence differed markedly across study site.

Adult↗