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Negative symptoms: a path analytic approach to a double-blind, placebo- and haloperidol-controlled clinical trial with olanzapine.

OBJECTIVE: The authors investigated whether primary negative symptoms of schizophrenia are enduring or treatment-responsive. METHODS: Previously, a double-blind, random-assignment trial of the novel antipsychotic olanzapine (in low, medium, and high dose ranges), placebo, or haloperidol (10-20 mg/day) for 335 schizophrenic inpatients was conducted for up to 52 weeks. Changes in the treatment groups from baseline to endpoint in summary scores on the Scale for the Assessment of Negative Symptoms (SANS) and several secondary measures were compared. This article describes a path analysis to determine to what extent the total treatment effect on negative symptoms was direct or indirect (i.e., mediated by differential effects on positive symptoms, extrapyramidal symptoms, or mood). RESULTS: Significantly greater improvement was achieved with high-dose olanzapine than with placebo or haloperidol. Olanzapine had a significantly greater direct effect than placebo on all SANS dimensions except anhedonia-asociality. Olanzapine also demonstrated a significantly greater direct effect than haloperidol on negative symptoms, especially on the dimensions of affective flattening and avolition-apathy. Olanzapine's superior effects were replicated in a subgroup with SANS-defined prominent negative symptoms (N = 116) and a subgroup with a BPRS-defined cross-sectional proxy for the deficit state (N = 117). CONCLUSIONS: These results suggest that the negative symptoms of schizophrenia are directly responsive to treatment. The significantly greater direct and indirect effects of olanzapine than of haloperidol on negative symptoms are likely related to olanzapine's pleotrophic pharmacology, which includes dopaminergic, serotonergic, muscarinic, and adrenergic activities. The results contribute to the hypothesis that negative symptoms may be under the influence of several neurotransmitters within one or more neuroanatomic circuits.

Adolescent↗

The contribution of somatic symptoms to the diagnosis of depressive disorder in Parkinson's disease: a discriminant analytic approach.

This study assessed the sensitivity of individual depressive symptoms and their relative contribution to the diagnosis of depressive disorder in patients with Parkinson's disease. The Structured Clinical Interview for DSM-IV Depression and the Hamilton and Montgomery-Asberg depression rating scales (Ham-D, MADRS) were administered to 149 consecutive nondemented patients. The contribution of the individual items of these scales to the diagnosis of "depressive disorder" was calculated by discriminant analysis. The discriminant models based on the Ham-D and MADRS scores were both highly significant. Nonsomatic core symptoms of depression had the highest correlation coefficient. Somatic items had mostly low correlation coefficients, with the exception of reduced appetite and early morning wakening (late insomnia). Nonsomatic symptoms of depression appear to be the most important for distinguishing between depressed and nondepressed patients with Parkinson's disease, along with reduced appetite and early morning awakening.

Aged↗

Independence of changes in behavior from cognition and function in community-dwelling persons with Alzheimer's disease: a factor analytic approach.

The authors' main objective was to investigate the relationship between changes in psychopathological, cognitive and activity of daily living (ADL) instrument scores over 12 months in community-dwelling persons with Alzheimer's disease (AD). A secondary objective was to evaluate the validity of dividing the Clinical Dementia Rating (CDR), a global dementia staging instrument into cognitive and functional subscores. Changes in measures of psychopathology, cognition and function between the baseline and 12-month visits were entered into these post hoc analyses of data from a one-year clinical trial to evaluate behavioral, cognitive and functional assessment instruments for use in clinical trials with AD patients. Exploratory factor analysis was used to determine whether there was independence between changes in any of these three domains of interest for this disease population; participants were a cohort of 187 well-characterized, community-dwelling persons with AD. One-year change in the behavioral symptoms of this cohort of persons with AD was statistically independent from changes in scores on cognitive and functional measures. Some evidence of independence of 12 month changes in cognitive and functional measures was found. Cognitive and functional subscores for the CDR were supported. These findings suggest that changes in behavior and cognition in dementia may have distinct pathophysiologies.

Activities of Daily Living↗

Sulcus vocalis: a rational analytical approach to diagnosis and management.

The term sulcus vocalis has been applied to a spectrum of disorders ranging from minor vocal fold indentations to destructive lesions causing severe dysphonia. To clarify the pathophysiology and to develop a more rational approach to treatment, we report a series of sulcus patients including 20 surgical cases. Clinical and histopathologic analysis produced a clinically useful classification: type 1 is a physiologic variant accentuated by atrophy but with intact lamina propria; types 2 (sulcus vergeture) and 3 (sulcus vocalis) are characterized by severe dysphonia, loss of vibratory activity, and destruction of the functional superficial lamina propria. These latter cases respond favorably to microsurgery designed to remove destroyed tissue, release scar contracture, and promote mucosal redraping by regional undermining. Further study of the extracellular matrix of the superficial lamina propria (Reinke's space) might indicate a common pathway in the pathogenesis of sulcus deformities and other related benign vocal fold lesions.

Adult↗

ADHD and reading disabilities: a cluster analytic approach for distinguishing subgroups.

Data suggest that children with reading disability (RD) and non-RD children with attention-deficit/hyperactivity disorder (ADHD) may comprise distinct subgroups. Research has been hampered by variance in definitional criteria, which results in the study of different subgroups of children. Using cluster analysis, this study empirically divided children with ADHD (N = 54), based on their Full Scale IQ (FSIQ) and reading ability. Four distinct subgroups emerged in which cognitive, behavioral, and neurochemical function was compared. Cluster 1 was of average FSIQ and reading scores; Cluster 2 was of average FSIQ but showed impairment in reading; Cluster 3 had high FSIQ and reading scores; and Cluster 4 had low scores in both domains. The groups had different patterns of cognitive, behavioral, and neurochemical function, as determined by discrepancies in Verbal-Performance IQ, academic achievement scores, parent aggression ratings, and a measure of noradrenergic function. These distinctions are discussed with regard to etiology, treatment, and long-term outcome.

Aggression↗

Treatment choice in gastric carcinoma. A decision-analytic approach.

Physicians frequently face decisions whether or not to undertake a treatment that carries an immediate risk but offers a potential cure. However, data directly comparing life expectancies of similar groups of patients with and without that treatment are rarely available and in fact could not ethically be obtained. We present an indirect mathematical technique for computing the two life expectancies and specifically apply this approach to evaluating surgery for patients with gastric carcinoma without known metastases. We demonstrate that surgery increases life expectancy for average men and women up to age 80 and does not alter life expectancy at age 90. Hence surgery is the appropriate treatment for patients who are either risk-neutral or risk-seeking in their attitudes comparing the short-term hazards with the long-term benefits of surgery.

Adult↗

Subtypes of schizophrenia: a cluster analytic approach.

OBJECTIVES: To identify empirical subtypes of schizophrenia, based upon the symptoms recorded over the duration of the illness, and to validate the resulting clusters against other systems that are used for subtyping schizophrenia. METHOD: Data for 55 symptoms of schizophrenia over the history of the illness from 107 chronic schizophrenia patients were analyzed using hierarchical cluster analysis with Euclidean distance and Ward's method. Except for 1 patient, all met DSM-III criteria. There were 40 men and 67 women, average (SD) age of 38.2 (9.91) years, with a mean (SD) hospitalization of 27.9 (27.35) months. RESULTS: No clear and unambiguous solution for the number of clusters was evident. Examination of the clusters led to further analysis of 2- and 6-cluster solutions. These were contrasted with DSM-III, DSM-III-R, and DSM-IV criteria and with the subtypes taken from the literature. There was limited support for any of these types, with none replicating, including the paranoid-nonparanoid distinction. CONCLUSIONS: Empirical clusters derived from lifetime symptom data failed to agree with either the established DSM or other empirically derived subtypes. Subtypes may have little utility when the variability of symptoms over the longitudinal course of the illness is considered.

Adult↗

Estimating the population impact of an intervention: a decision-analytic approach.

The aim of this paper is to highlight the role for decision analysis in assessing outcomes of medical interventions at a population level. The basic steps of decision analysis are introduced and an illustrative hypothetical preventive intervention is examined. Specific modelling challenges that arise when estimating the population impact of an intervention are described and each is accompanied by an example. Decision analysis can provide useful information for health policy decision makers by identifying the intervention(s) with the largest beneficial impact on health over a wide range of assumptions. In addition, by focusing attention on the parameters with the greatest influence on projected outcomes, decision analysis can aid in identifying critical areas for future research.

Cost-Benefit Analysis↗

Quantification of ADMA: analytical approaches.

Methylated L-arginine analogs are involved in nitric oxide synthase activity regulation. Methods based on high-performance liquid chromatography with fluorescence, capillary electrophoresis, or ion exchange chromatography with absorbance detection were first applied for the quantitative determination of N-monomethyl-L-arginine (NMMA), asymmetric dimethylarginine (ADMA) and symmetric dimethylarginine (SDMA) in human blood and urine. These assays revealed elevated circulating levels of ADMA in various diseases and gave accumulating evidence of the usefulness of ADMA as a cardiovascular risk factor. However, the methods used are hampered by the fact that NMMA, ADMA and SDMA can be distinguished from L-arginine only by means of chromatographic separation. This has promoted the development of alternatives that involve mass spectrometry (MS) technology. Today, various MS-based approaches such as liquid chromatography (LC)-MS, LC-MS/MS, gas chromatography (GC)-MS, and GC-MS/MS are available. L-arginine and its analogs have been subjected to LC-MS analysis with and without further derivatization to their o-phthaldialdehyde derivatives. For these methods, labelled L-arginine was used as the internal standard. The first MS-based method that distinguishes NMMA, ADMA, SDMA and L-arginine by mass-to-charge (m/z)-ratio has been reported by Tsikas et al. This GC-MS approach has been further improved by Albsmeier et al by introducing labelled ADMA as an internal standard. As an alternative to existing methods, a commercially available ELISA kit has recently been developed and validated.

Arginine↗

Conduct disorder and hyperactivity: II. A cluster analytic approach to the identification of a behavioural syndrome.

Sixty boys, aged from 6 to 10 years, were studied after their referral to psychiatric clinics for antisocial or disruptive behaviour. Their scores on reliable measures of hyperactivity, defiant behaviour, emotional disorder and attention deficit were taken for the home, school and clinic settings; and subjected to two techniques of cluster analysis. Both gave a similar set of clusters, one of which had high scores on all measures of hyperactivity and attention deficit. Membership of this cluster was associated with a lower IQ, a younger age of problem onset and referral, an abnormal neurological examination, a history of developmental delay, smaller family size, poor peer relationships and a high rate of accidental injuries; and it predicted a good response to stimulant medication in a controlled trial. Other research on the classification of hyperactivity is discussed, and proposals are made for the criteria of a rather narrow definition of 'hyperkinetic conduct disorder'.

Antisocial Personality Disorder↗

Subjective and objective dimensions of quality of life in psychiatric patients: a factor analytical approach: The South Verona Outcome Project 4.

BACKGROUND: Both subjective and objective information is necessary to assess quality of life (QOL). AIMS: To explore the role of subjective and objective QOL dimensions and their cross-sectional and longitudinal predictors. METHOD: The relationship between QOL, as measured by the Lancashire Quality of Life Profile (LQL), and demographic variables, diagnosis, psychopathology, disability, functioning, affect balance, self-esteem, service use and service satisfaction was investigated at two points in time, using factor analysis and multiple regression techniques. RESULTS: One subjective and two objective LQL factors with strong face validity were identified. Cross-sectional predictors of the subjective factor were primarily subjective measures; longitudinally, few predictors of this factor were identified. The cross-sectional and longitudinal predictors of the objective factors were primarily demographic and observer-rated measures. CONCLUSIONS: Subjective and objective data are distinct types of information. Objective measures may be more suitable in detecting treatment effects. Subjective information is necessary to complete the QOL picture and to enhance the interpretation of objective data.

Adolescent↗

Fear of success, fear of failure, and the imposter phenomenon: a factor analytic approach to convergent and discriminant validity.

A sample of 104 mid-level managers completed measures of fear of success, fear of failure, and the imposter phenomenon. First- and second-order factor analyses indicated that the instruments tapped two personality domains, lack of self-confidence and the competitive neurosis. Results are discussed in terms of the most appropriate use of the instruments employed in the analysis and the need to avoid redundancy in the development and popularization of new psychological constructs.

Journal Article↗

A factor analytic approach to distinguish pure and co-occurring dimensions of proactive and reactive aggression.

This study used a confirmatory factor model to distinguish pure and co-occurring dimensions of proactive and reactive aggression, and examined the relation between parenting variables and these dimensions of aggression in a sample of 100 children (9 to 12 years of age; 69 boys). Confirmatory factor analysis (CFA) supported 3 dimensions of proactive and reactive aggression: pure proactive, pure reactive, and their co-occurrence. Parenting variables differentially related to the pure and co-occurring dimensions of aggression. Findings indicate that CFA provides a promising approach for conceptualizing aggression on a continuum and allows researchers to distinguish pure and co-occurring dimensions of proactive and reactive aggression.

Aggression↗