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C Beasley

Publications and source records attributed to C Beasley.

At least 19 recordsLinked to original sources
PubMed2001

Glycogen synthase kinase-3beta immunoreactivity is reduced in the prefrontal cortex in schizophrenia.

Cytoarchitectural abnormalities have been reported in the cortex in schizophrenia. These suggest a developmental origin for this disorder. The Wnt signalling pathway is involved in the regulation of brain development; disruption of this pathway may lead to abnormal cortical development. In this study levels of three components of the Wnt signalling pathway; glycogen synthase kinase-3beta(GSK-3beta), beta-catenin and dishevelled-2 (Dvl-2) were determined in the prefrontal cortex of ten schizophrenic and ten control individuals using immunoblotting. GSK-3beta levels were significantly reduced in the schizophrenic group, while levels of beta-catenin and Dvl-2 did not differ between groups. This provides further evidence for an abnormality of the Wnt signalling pathway in schizophrenia.

Adaptor Proteins, Signal Transducing↗
PubMed2001

Olanzapine plasma concentrations and clinical response: acute phase results of the North American Olanzapine Trial.

Olanzapine is an atypical antipsychotic that is effective in the treatment of schizophrenia. Olanzapine plasma concentrations > or = 9.3 ng/mL (24 hours postdose) have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanzapine concentrations and treatment response from the North American Double-Blind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meeting DSM-III-R criteria for schizophrenia were randomly assigned to receive olanzapine, haloperidol, or placebo. Patients who were randomly assigned to receive olanzapine were given daily doses ranging from 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma concentrations were obtained between 10 and 16 hours (11.7 +/- 1.7 hours) after the last dose was administered. Therapeutic response data and olanzapine concentrations used for analysis were obtained from the endpoint visit for each patient if the patient had been receiving a fixed olanzapine dose for at least the last 2 weeks of the study. Plasma concentrations from previous visits were used if endpoint concentrations were invalid. Response was defined as a > or = 20% reduction in Brief Psychiatric Rating Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity scale score of < or = 3 or a final BPRS score of < or = 35. The final ROC analysis included data from 84 patients and suggested an olanzapine concentration > or = 23.2 ng/mL to be a predictor of therapeutic response. Fifty-two percent of patients with 12-hour olanzapine concentrations > or = 23.2 ng/mL responded, whereas only 25% of patients with concentrations < 23.2 ng/mL responded. Furthermore, an olanzapine concentration > or = 23.2 ng/mL was a predictor of response in the Scale for the Assessment of Negative Symptoms (> or = 20% decrease and endpoint CGI < or = 3). Olanzapine concentrations were found to be a function of olanzapine dose (in milligrams per day) and gender such that prospective olanzapine dosing is feasible. A 12-hour olanzapine plasma concentration of > 23.2 ng/mL was a predictor of therapeutic response in acutely ill patients with schizophrenia. Males required a higher olanzapine dose to reach this threshold concentration than their female counterparts.

Acute-Phase Reaction↗
PubMed2000

Hematologic reference ranges in a population of patients with schizophrenia.

The potential hematotoxic effects of antipsychotic drugs are well known and may limit the use of some effective therapies. Although some previous studies have suggested that patients with schizophrenia may have altered "normal" values, only limited data were available. It is now believed that biological values do not usually follow a normal distribution; therefore, reference ranges are frequently used when interpreting laboratory tests in clinical practice and in research. However, it may be important to use disease-specific hematologic reference ranges when evaluating laboratory test results for patients with schizophrenia. In this study, data taken from patients with schizophrenia prior to treatment in previous phase II and phase III pharmaceutical studies were analyzed to produce reference ranges for a variety of hematologic parameters. An increased variability was shown in the reference ranges for all white blood cell indices between patients with schizophrenia and the population without schizophrenia. Certain reference values also showed heterogeneity for gender, age, and racial descent. This study suggests that abnormal hematologic findings in patients with schizophrenia should be assessed in the context of a valid reference range. This information will be of value to psychiatrists, laboratory scientists, and other physicians who encounter hematologic problems in patients with schizophrenia, as well as in the assessment of the adverse effects of new therapeutic agents.

Adolescent↗
PubMed1999

Fluoxetine efficacy in menopausal women with and without estrogen replacement.

UNLABELLED: A gradual decline in estrogen levels after the age of 40 may contribute to a higher rate of depression in women over 45 years of age. Estrogen replacement therapy (ERT) has been shown to produce cognitive and mood-enhancing effects in women and may facilitate antidepressant activity. METHODS: We examined the efficacy rates in women on ERT > or = 45 years (n = 40) compared to women > or = 45 years not on ERT (n = 132) and to women < 45 years (n = 396) and to men (n = 262) with major depression during fluoxetine 20 mg daily up to 8 weeks. Remitters with a HAM-D17 score < or = 7 from week 9 to 12 were then treated up to 1-year in a placebo-controlled, relapse-prevention trial. RESULTS: Efficacy rates were similar in women > or = 45 years on ERT when compared to women > or = 45 years taking fluoxetine alone, and when compared to women < 45 years and men taking fluoxetine. A Kaplan-Meier survival analysis in fluoxetine responders treated up to 26 weeks showed a somewhat greater relapse rate in women > or = 45 years taking ERT compared to other treatment groups (P < 0.06). LIMITATIONS: This study was retrospective nature and ERT was given in an uncontrolled fashion: 63% of women received estrogen alone while 37% also took intermittent progesterone. Other variables include the absence of hormonal documentation of menopausal status, no direct assessment of ERT compliance and the use of fixed-dose fluoxetine 20 mg daily. CONCLUSION: In contrast to prior reports suggesting that ERT may facilitate antidepressant activity, we observed similar efficacy in depressed women > or = 45 years taking fluoxetine plus ERT compared to those taking fluoxetine alone.

Antidepressive Agents, Second-Generation↗
PubMed1999

The public's willingness to discuss their preference for organ donation with family members.

We sought to assess the public's willingness to discuss their preference for organ donation with family members and to identify factors associated with willingness to discuss donation. We categorized individuals (N = 4365) with a preference for donation according to their willingness to discuss donation and used ordinal logistic regression analysis to identify factors related to their level of willingness. About half of those who want to donate have discussed this with a family member. Others were at various stages with respect to their commitment to discuss donation. Those in the more committed stages were more likely than others to have signed an organ donor card, to have seen information about organ donation, to be male, to be white or Hispanic, to know about donation issues, and to be comfortable with the idea of their own death. The decision to donate is ultimately made by family members of a suitable candidate for donation, yet nearly half of those who wish to donate have not made their wishes known. Interventions targeted to individuals at different stages of commitment are needed so that more family members can respond in accordance with their loved one's wishes.

Adolescent↗
PubMed1999

Correlates of support for organ donation among three ethnic groups.

Telephone interviews about organ donation were conducted with 4880 white respondents, 634 African-American respondents and 566 Hispanic respondents. Forty-three percent (42.9%) of whites, 31.2% of Hispanics and 22.6% of African-Americans reported that they were willing to donate their organs after their death (p < 0.001). Logistic regression analysis revealed three significant correlates of willingness to donate across all ethnic groups: having had a family discussion about end-of-life issues; the belief that a doctor does all he or she can to save a life before pursuing donation; and concerns about surgical 'disfigurement' of a relative's body after donation. Concerns in relation to body disfigurement were more prevalent among African-American and Hispanic respondents (p < 0.001) than among white respondents. Public education should: a) stress the need for family communication about end-of-life issues including organ donation; b) underline the fact that donation is considered only after all efforts to save the life of the patient are exhausted; and c) reassure minorities that the body of the donor is treated respectfully and not disfigured.

Adult↗
PubMed1999

Blood pressure changes during short-term fluoxetine treatment.

Recent reports of sustained hypertension in some patients receiving venlafaxine have rekindled concerns about antidepressant-induced hypertension. This study examined sitting and standing systolic and diastolic blood pressure, pulse rate, and rate of sustained hypertension in 796 depressed patients (mean +/- SD age, 40 +/- 11 years) taking fluoxetine 20 mg daily for up to 12 weeks. A modest reduction in sitting and standing systolic (p < 0.001) and diastolic (p < 0.001) blood pressure measures were observed in the entire patient sample. Patients with pretreatment diastolic blood pressure < 60 mmHg (N = 32) showed a modest increase in mean diastolic blood pressure (p < 0.001), whereas patients with pretreatment diastolic blood pressure > or = 90 mmHg and < or = 95 mmHg (N = 57) had a modest reduction in mean diastolic blood pressure (p < 0.001). Patients with preexisting, stable cardiovascular disease (including hypertension) (N = 35) showed no significant blood pressure change (p = not significant). Of the patients receiving fluoxetine, 1.7% had sustained hypertension for > or = 3 consecutive clinic visits-a rate significantly lower than that previously reported with venlafaxine (4.8%) (chi2 = 13.3, p < 0.001) and similar to that previously seen with placebo (2.1%). In conclusion, these data demonstrate a low rate of sustained hypertension (1.7%) during short-term fluoxetine treatment.

Adolescent↗
PubMed1999

Olanzapine versus haloperidol treatment in first-episode psychosis.

OBJECTIVE: It has been hypothesized that the morbidity and mortality associated with schizophrenia can be prevented by providing effective treatment during the first episode of psychosis. Hence, the authors examined patients with first-episode psychosis to determine the efficacy and safety of olanzapine and haloperidol treatment. METHOD: A subpopulation of first-episode patients (N=83) from a large prospective, multicenter, international, double-blind, 6-week acute treatment study was evaluated. These patients were selected from a pool of 1,996 patients who had a DSM-III-R diagnosis of schizophrenia, schizoaffective disorder, or schizophreniform disorder and who also met the following criteria: 1) the length of their current psychotic episode had to be 5 or fewer years, and 2) patients had to be 45 years of age or younger at onset of first psychotic symptoms. RESULTS: Compared to haloperidol, olanzapine showed a statistically significantly greater reduction in the Brief Psychiatric Rating Scale (BPRS) total and negative scores and in the Positive and Negative Syndrome Scale total and positive scores. Clinical response (defined as 40% or greater improvement in BPRS total score from baseline) was also statistically significantly higher in olanzapine-treated patients (67.2%) than in haloperidol-treated patients (29.2%). Olanzapine-treated patients further showed statistically significant improvements in the Simpson-Angus scale and Barnes Akathisia Scale scores, while haloperidol-treated patients showed a worsening on both measures. Compared to olanzapine-treated multiple-episode patients in the parent study, olanzapine-treated first-episode patients achieved an even statistically significantly higher response. Haloperidol-treated first-episode patients experienced statistically significantly more extrapyramidal symptoms than haloperidol-treated multiple-episode patients. CONCLUSIONS: In patients experiencing first-episode psychosis, olanzapine had a risk-benefit profile significantly superior to that of haloperidol. The study results suggest that novel antipsychotic agents such as olanzapine should be considered as a preferred option in first-episode psychosis, on the basis of both safety and efficacy advantages.

Age of Onset↗
PubMed1999

The influence of race on approaching families for organ donation and their decision to donate.

OBJECTIVES: This study examined whether patients' race was associated with their families' being approached for organ donation and agreeing to donation. METHODS: Logistic regression models were applied to data collected from records at 112 hospitals. RESULTS: The odds that a family of a White patient was approached for donation were nearly twice those for a family of an African American. The odds of donation also differed by race, but the magnitude varied by patient and hospital characteristics. CONCLUSIONS: Much attention directed toward racial disparity in donation has focused on attitudes of the public. The behavior of hospital staff also may be related to differences in rates.

Adolescent↗
PubMed1998

Use of pattern analysis to predict differential relapse of remitted patients with major depression during 1 year of treatment with fluoxetine or placebo.

BACKGROUND: Delayed and persistent ("true drug") improvement characterizes the response to antidepressant medication. Early or nonpersistent ("placebo") benefit is typical of a placebo response. The prediction was that patients with a true drug response would sustain their benefit best if they continued to receive the drug and that patients with a placebo response would have an equivalent prognosis whether they continued to receive the drug or were switched to placebo. METHODS: Patients with major depression who met the study's response criteria (a modified Hamilton Depression Rating Scale score < or =7 and failure to meet major depression criteria after each of the last 3 weeks following 12 to 14 weeks of treatment with fluoxetine hydrochloride, 20 mg/d) were enrolled in a 50-week randomized placebo substitution trial during which the return of depressive symptoms defined relapse. The timing and persistency of response during initial treatment defined true drug or placebo response patterns. RESULTS: Patients with a true drug response pattern relapsed significantly more frequently if they were switched to placebo than if they continued to receive fluoxetine (P<.001 for weeks 12-26, P<.005 for weeks 26-50, and P<.41 for weeks 50-62). Patients with a placebo response pattern had an equivalent outcome whether maintained on fluoxetine therapy or placebo (P< .20 for weeks 12-26, test invalid for weeks 26-50, and P<.67 for weeks 50-62). Patients with a placebo response pattern relapsed more often when they continued to receive fluoxetine than patients with a true drug response pattern (P<.01 for weeks 12-26, P<.10 for weeks 26-50, and P<.36 for weeks 50-62). CONCLUSIONS: These findings confirm that pattern analysis validly differentiates true drug from nonspecific initial responses and extend its use to the continuation and maintenance phases of treatment for depression. Investigations into the mechanisms of antidepressant activity might best be limited to those that can account for delayed efficacy. Fluoxetine's efficacy during the continuation and maintenance phases of treatment may be limited to patients with a true drug pattern of initial response.

Adolescent↗
PubMed1998

Hospital attitudes: preliminary findings from donor action pilot projects.

PURPOSE: As part of the Donor Action collaboration (Eurotransplant Foundation, The Netherlands; Organización National de Transplantes, Spain; and The Partnership for Organ Donation, USA), a hospital survey was administered to gather baseline data on staff attitudes about organ donation and level of self-reported skills/confidence in performing a range of organ donation roles. METHODS: A standard survey instrument was administered in two hospitals in Spain, two in The Netherlands and one in the UK. In four hospitals the survey was administered to all ICU staff; in one hospital it was administered to a random sample of hospital staff. The instrument was created in English, and translated into Spanish and Dutch for the hospitals in each country. RESULTS: Data were analysed by country and showed consistently strong perceptions that organ donation saves lives (97%). Support for donation (95%) and willingness to donate one's own organs (82%) were high in all three country samples. Significant differences in belief were observed when respondents were asked whether they agreed that organ donation helps families with their grief. The UK respondents were more likely to agree (57%), with lower levels of agreement in Spain (47%) and The Netherlands (14%) (P < 0.0001). Average ratings of skills/confidence were highest for notifying the transplant coordinator (49%) and comforting the family (48%) with lower confidence reported regarding explaining brain death (34%), introducing organ donation (32%), and requesting organ donation (26%). Ratings varied widely across countries with UK respondents expressing the highest level of self-reported confidence, and Spanish respondents the lowest level. For example, 77% of UK respondents reported themselves skilled/confident explaining brain death, versus 47% of Dutch respondents and 11% of Spanish respondents (P < 0.0001). Similar results were seen regarding requesting organ donation: UK 53%; The Netherlands 30%; Spain 13% (P < 0.0001). CONCLUSIONS: There has been a lack of data about hospital staff attitudes and skills to allow for comparison across national systems, and to support the targeting of specific strategies to the needs within different countries. These results show the feasibility of collecting and comparing data across national systems. These pilot findings also suggest that there may be important differences in attitudes and self-perceived skills/confidence across countries. Work remains to correlate attitudes and self-perceived skills to actual performance. It is noteworthy that the sense of staff preparedness was lowest in Spain which has the highest donation rates. This may reflect the degree to which role specialization in donation has been successfully integrated into hospital practice. Expansion of the survey to additional hospitals will help to answer such questions.

Attitude↗
PubMed1998

Safety of abrupt discontinuation of fluoxetine: a randomized, placebo-controlled study.

Selective serotonin reuptake inhibitors may be associated with new adverse events after abrupt discontinuation. Hypothesizing that the long half-life of fluoxetine would be protective, this study analyzed the effects of abrupt fluoxetine discontinuation during a randomized, double-blind, placebo-controlled study of depression maintenance treatment. After 12 weeks of fluoxetine treatment (20 mg/day), 395 responders were abruptly randomized to placebo (N = 96) or to continued fluoxetine (N = 299). Patients were seen at weeks 1, 2, 4, and 6 after randomization. Reports of new or worsened adverse events were similar for both groups at each visit after randomization. Patient discontinuations related to adverse events were also similar in both groups. Mild, self-limited lightheadedness or dizziness occurred in a small percentage of patients who discontinued fluoxetine treatment but was of little clinical significance. No cluster of symptoms suggestive of a discontinuation syndrome was observed. Abrupt discontinuation of fluoxetine treatment was well tolerated and did not seem to be associated with significant clinical risk. Fluoxetine may offer a potential safety advantage over shorter-acting agents with respect to treatment interruption and/or discontinuation and may be a better choice for those patients who are likely to miss doses because of travel or forgetfulness.

Adult↗
PubMed1998

Efficacy and safety of fluoxetine in treating bipolar II major depressive episode.

As many as 45% of patients with major depressive episode also meet DSM-IV criteria for bipolar II (BP II) disorder. Although some clinicians advocate using a mood stabilizer in treating BP II depression, antidepressant monotherapy has been less well studied in this disorder. As part of a prospective, placebo-controlled, relapse-prevention study in 839 patients, the efficacy and safety of short- and long-term fluoxetine treatment in patients with BP II major depression compared with patients with unipolar (UP) major depression was retrospectively examined. Eighty-nine BP II patients (mean age, 41+/-11 years) were compared with 89 age- and gender-matched UP patients and with 661 unmatched UP patients (mean age, 39+/-11 years). All received short-term fluoxetine therapy at 20 mg daily for up to 12 weeks. Complete remission was defined as a final Hamilton Rating Scale for Depression score < or = 7 by week 9 that was then maintained for 3 additional weeks. Remitted patients were then randomly assigned to receive double-blind treatment with one of the following: (1) fluoxetine 20 mg daily for 52 weeks; (2) fluoxetine for 38 weeks, then placebo for 14 weeks; (3) fluoxetine for 14 weeks, then placebo for 38 weeks; or (4) placebo for 52 weeks. Antidepressant efficacy was similar in BP and UP patients during short-term therapy. Discontinuation for lack of efficacy was lower in BP II (5%) than in UP (12%) patients (p = not significant [NS]), whereas dropouts for adverse events were similar in BP II (11%) and UP (9%) patients. During long-term relapse-prevention therapy, relapse rates were similar in BP II and UP patients (p = NS). During short-term fluoxetine therapy, three BP II (3.8%) versus no matched UP (p = NS) and 0.3% unmatched UP (p = 0.01) patients had a "manic switch." During long-term fluoxetine therapy, one (2%) BP II and three (1%) unmatched UP patients (one taking placebo) had a manic switch (p = NS). In conclusion, fluoxetine may be a safe and effective antidepressant monotherapy for the short-term treatment of BP II depression with a relatively low manic switch rate. Fluoxetine may also be effective in relapse-prevention therapy in patients with BP II disorder.

Adolescent↗
PubMed1998

Requesting organ donation: an interview study of donor and nondonor families.

BACKGROUND: Approximately half of the families asked to consider donation of a relative's organs decline to give consent. Understanding the difference between stated public support of organ donation and actual behavior is key to decreasing the shortage of donor organs. OBJECTIVES: To gain insight into the experiences of potential donor families and to define features of the donation-request process and other factors that are associated with consent for organ donation. METHODS: A structured telephone interview was conducted with the immediate next of kin of 164 medically suitable potential organ donors. Interviews 30 to 60 minutes long were held with members of both donor and nondonor families 4 to 6 months after the death of the study participant's relative. RESULTS: Several factors were associated with consent for organ donation: characteristics of the patient and the patient's family, beliefs and attitudes about organ donation and transplantation, whether the family knew the deceased's wishes about donation, the family's satisfaction with the hospital care that their relative received, specific aspects of the donation-request process, and the family's understanding of brain death. CONCLUSIONS: Organ donation rates could be increased by enhancing the quality of hospital care and ensuring that the request for donation is handled in a way that meets the families' informational and emotional needs.

Adolescent↗
PubMed1997

Double-blind comparison of olanzapine versus risperidone in the treatment of schizophrenia and other psychotic disorders.

Olanzapine and risperidone, both second-generation antipsychotic agents, represent two different pharmacologic strategies. Although they share some in vitro properties, they differ by virtue of their chemical structure, spectrum of receptor binding affinities, animal neuropharmacology, pharmacokinetics, and in vivo neuroimaging profile. Based on such differences, it was hypothesized that the two compounds would show distinct safety and/or efficacy characteristics. To test this hypothesis, an international, multicenter, double-blind, parallel-group, 28-week prospective study was conducted with 339 patients who met DSM-IV criteria for schizophrenia, schizophreniform disorder, or schizoaffective disorder. Results of the study indicated that both olanzapine and risperidone were safe and effective in the management of psychotic symptoms. However, olanzapine demonstrated significantly greater efficacy in negative symptoms (Scale for Assessment of Negative Symptoms summary score), as well as overall response rate (> or = 40% decrease in the Positive and Negative Syndrome Scale total score). Furthermore, a statistically significantly greater proportion of the olanzapine-treated than risperidone-treated patients maintained their response at 28 weeks based on Kaplan-Meier survival curves. The incidence of extrapyramidal side effects, hyperprolactinemia, and sexual dysfunction was statistically significantly lower in olanzapine-treated than risperidone-treated patients. In addition, statistically significantly fewer adverse events were reported by olanzapine-treated patients than by their risperidone-treated counterparts. Thus, the differential preclinical profiles of these two drugs were also evident in a controlled, clinical investigation. Olanzapine seemed to have a risk-versus-benefit advantage.

Adult↗