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Biomedical subjects

William T Carpenter

Publications and source records attributed to William T Carpenter.

31 records · Page 2Linked to original sources
PubMed2004

Summer birth and deficit schizophrenia: a pooled analysis from 6 countries.

BACKGROUND: In some reports, summer birth has been associated with deficit schizophrenia. Deficit schizophrenia and nondeficit schizophrenia also differ in several other ways. OBJECTIVE: To conduct a combined analysis of the published and unpublished data sets from the northern hemisphere that relate deficit and nondeficit schizophrenia to month of birth. DATA SOURCES: Studies of season of birth in which it was possible to make a deficit/nondeficit categorization. STUDY SELECTION: Published studies with samples of convenience and all known population-based studies with the deficit/nondeficit categorization were included. The studies came from 6 countries. DATA EXTRACTION: Three published studies of samples of convenience, 2 population-based prevalence studies, and 5 population-based studies that approximated incident samples were included. Month of birth was compared for deficit and nondeficit schizophrenia, using meta-analytic fixed-effects models. DATA SYNTHESIS: A group x month goodness-of-fit chi2 showed a significant difference between deficit and nondeficit subjects in season of birth (P < .001) in the studies that approximated incidence. This difference was largely due to an increase in deficit schizophrenia births in June and July (odds ratio, 1.9; 95% confidence interval, 1.3-2.9). Similar results were found in the prevalence studies. A similar pattern was found in 2 of the 3 samples of convenience, but when combined, these 3 samples did not show a significant deficit/nondeficit difference. CONCLUSIONS: Deficit schizophrenia has a season of birth pattern that differs from that of nondeficit schizophrenia. This analysis supports the notion of a separate disease within schizophrenia.

Cohort Studies↗
PubMed2004

The deficit syndrome in schizophrenia: implications for the treatment of negative symptoms.

Schizophrenia psychopathology clusters around several symptom domains. One of these domains is negative symptomatology. We have defined the deficit syndrome as a disease entity characterized by the presence of primary enduring negative symptoms. A focus on primary negative symptoms demonstrates that deficit and nondeficit schizophrenia subgroups differ on clinical features, associated neuroimaging findings, neuropsychological and neurological measures, pattern of risk factors, and pharmacological response profiles. In the present article we focus on the importance of the distinction between primary and secondary negative symptoms for pathophysiology research. The development and mechanistic understanding of anti-negative symptom drugs may be informative regarding pathophysiology of primary negative symptoms. Although new antipsychotics are effective for secondary negative symptoms they have shown no efficacy for the deficit syndrome and new mechanisms of drug action appear to be required to address this aspect of the disease syndrome. The loss of precious human experiences and the association with poor long-term functional outcome justifies a focused and dedicated effort to discover the causes and treatments of this distinctive aspect of schizophrenia.

Affect↗
PubMed2004

At issue: A model for academic/industry collaboration.

Relationships between academia and industry are increasingly intimate and commercial. While opportunities are created for each partner, there are also important conflict of interest issues. Particularly challenging is ensuring that universities maintain their traditional role in public science while partnering with a commercial entity with a tradition of proprietary science. We describe a collaboration where the interests and values of each partner were articulated in advance and conflict of interest issues were resolved before legal and business arrangements were established in a contract. We discuss the principles involved and the resolutions achieved in the hope that it may provide a useful model for addressing academic/industry scientific collaborations.

Academic Medical Centers↗
PubMed2003

The Declaration of Helsinki and clinical trials: a focus on placebo-controlled trials in schizophrenia.

OBJECTIVE: The authors' goal was to consider ethical approaches to placebo-controlled clinical trials in the light of the evolving Declaration of Helsinki, with special attention to applications to research on schizophrenia. METHOD: They review the Helsinki position on placebos, including the 2002 Clarification, exploring the potential negative effects of banning placebos in studies involving conditions for which at least partially effective treatments exist. The Clarification is examined as an approach to this issue that, in contrast to earlier formulations, better acknowledges the complexity of clinical research and the need for protocol-specific determinations. Placebo controls in schizophrenia studies are used to illustrate issues relevant to all clinical research on therapeutic interventions. RESULTS: The Helsinki Clarification provides a basis for operationalizing criteria for review of placebo use in clinical trials. Six criteria are proposed for judging the ethical acceptability of placebo controls, including the likelihood that the intervention being tested will have clinically significant advantages over existing treatments, the presence of compelling reasons for placebo use, subject selection that minimizes the possibility of serious adverse consequences, and a risk-versus-benefit analysis that favors the advantages from placebo use over the risks to subjects. CONCLUSIONS: The Helsinki Clarification constitutes an important advance in international approaches to placebo use, requiring protocol-by-protocol judgments on complex issues of clinical research ethics. When operationalized, it provides review boards with a useful methodology for reaching determinations on the appropriateness of placebo controls in particular studies.

Controlled Clinical Trials as Topic↗
PubMed2003

The relationship of clozapine and haloperidol treatment response to prefrontal, hippocampal, and caudate brain volumes.

OBJECTIVE: The study was designed to assess the predictive relationship between brain structure volume and positive and negative symptom response to clozapine and haloperidol. METHOD: Partially responsive outpatients with schizophrenia who participated in a 10-week, parallel-group, double-blind comparison of clozapine and haloperidol and who had an available magnetic resonance imaging scan were included in the current study. Prefrontal gray and white matter, hippocampal, and caudate volumes were manually measured. The Scale for the Assessment of Negative Symptoms (SANS) and the Brief Psychiatric Rating Scale (BPRS) were used to assess symptom changes. The Simpson-Angus Rating Scale was used to assess extrapyramidal symptoms. RESULTS: Twenty-two patients randomly assigned to clozapine and 23 patients assigned to haloperidol met study entry criteria. There were significant interactions between treatment and right prefrontal gray matter volume for BPRS total score and SANS total score. There were no significant treatment-by-brain structure interactions for BPRS positive symptom items. Right prefrontal gray matter volume was also related to differential treatment effects for the BPRS subscales of anxiety/depression and hostility and the Simpson-Angus Rating Scale akathisia item. CONCLUSIONS: These results suggest that there is a differential interaction among clozapine and haloperidol, brain structure, and treatment response. Partially responsive patients with larger brain volumes may be more likely to experience the benefits of clozapine treatment, but they may be more vulnerable to side effects and experience a subsequent worsening of their symptoms when treated with haloperidol.

Adult↗
PubMed2002

From clinical trial to prescription.

There are many steps between drug discovery and prescribing for a patient. Each step has problems. In this issue of ARCHIVES, Klein and colleagues propose changes in clinical trials that would result in more meaningful information for the treating physician. Of particular importance is the gap between what a physician needs to know and what is produced in the clinical trials that leads to approval of a new drug by the US Food and Drug Administration (FDA). Their recommendations for improving clinical trials are cogent, but broad-based implementation depends on an organizational structure and political effectiveness not presently in place. Most important, as the authors note, is an effective work group representing industry, regulatory agencies, and academic and federal science, addressing clinical trials issues with public participation. While improved quality and relevance of data from clinical trials will strengthen the scientific foundation of pharmacotherapy, other problems impede the delivery of objective information to the treating physician. Most hotly debated is the role of money in the creation and dissemination of knowledge.

Clinical Trials as Topic↗
PubMedDate not supplied

Adverse effects and laboratory parameters of high-dose olanzapine vs. clozapine in treatment-resistant schizophrenia.

Patients with treatment-resistant schizophrenia pose a major challenge to caregivers since only clozapine is documented as having superior efficacy in this population. Although olanzapine is similar to clozapine in structure and receptor profile, it has not been proven to have superior efficacy for this patient group. Nonetheless, olanzapine is being increasingly used in higher doses as clinicians attempt to find a more effective and tolerable therapy for refractory patients. Furthermore, there are little data comparing olanzapine and clozapine in this population. Thirteen patients participated in a randomized double-blind 16-week crossover study of clozapine therapy (450 mg/day) compared to high doses of olanzapine (50 mg/day). No patients on olanzapine responded while 20% responded to clozapine treatment. Olanzapine patients tended to experience higher rates of anticholinergic effects such as dry mouth (80 vs. 20%) and blurry vision (40 vs. 0%). Clozapine-treated patients had higher rates of sialorrhea (80 vs. 10%), sweating (50 vs. 10%), dyspepsia (70 vs. 30%), and lethargy (90 vs. 60%). Neither treatment was associated with significant akathisia. Liver enzyme elevation and lipids were higher with clozapine treatment. Mean weight gain in the initial 8 weeks was 3.4 kg for olanzapine and 1.2 kg for clozapine. High doses of olanzapine during 8 weeks of treatment did not increase lipids and liver enzymes like clozapine did. Olanzapine at 50 mg/day may be associated with more anticholinergic effects and weight gain than clozapine.

Adult↗