Heroes in community psychiatry: George Saslow MD, PhD.
Explore the source record for details and available documents.
Community Psychiatry↗
Biomedical subjects
David L Cutler
Publications and source records attributed to David L Cutler.
Introduction to the special issue on culture and community mental health.
Explore the source record for details and available documents.
Cultural Characteristics↗
A resident's experience in cross cultural/community psychiatry.
This report examines a psychiatric resident's consultation experience in a community psychiatry rotation serving South Asian women victims of intimate partner violence. It explores experiences related to negotiating and developing a partnership between culturally specific domestic violence services and community mental health services. It also discusses the resident's progression from consultant to administrator and ultimately to the rotation's termination.
Adult↗
The Professor of Public Psychiatry Model in Ohio: the impact on training, program innovation, and the quality of mental health care.
The Ohio Department of Mental Health and five of Ohio's University-based Departments of Psychiatry have developed strong working partnerships that have improved the quality of psychiatric residency education and Ohio's mental health services. Strategies integral to Ohio's Public Psychiatry Model include identifying a strong champion, integrating expert consultation, and developing consensus expectations using a small amount of catalytic funding. Successful outcomes include the establishment of public psychiatry leadership roles in Ohio's community and academic settings; positive community-focused residency training experiences; revised curricula; and spin-off opportunities, such as "Coordinating Centers of Excellence" to accelerate adoption of evidence-based practices in community settings.
Community Mental Health Services↗
The effect of fluvastatin on the pharmacokinetics and pharmacodynamics of ezetimibe.
OBJECTIVE: The objective of this study was to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and fluvastatin in healthy hypercholesterolemic subjects at clinically-relevant doses and to evaluate the potential for a pharmacokinetic drug interaction between ezetimibe and fluvastatin. METHODS: In a single-center, evaluator-blind, placebo-controlled, multiple-dose, parallel-group study 32 healthy subjects with hypercholesterolemia were randomized to 4 treatments administered once daily for 14 days: ezetimibe 10 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe placebo, fluvastatin 20 mg plus ezetimibe 10 mg, and ezetimibe placebo. Blood samples were collected to measure serum lipids and to determine steady-state pharmacokinetics. RESULTS: Ezetimibe 10 mg significantly (p < or = 0.01) decreased total-cholesterol and low-density lipoprotein cholesterol (LDL-C) concentrations compared to placebo at Day 14. Fluvastatin 20 mg also caused a significant (p = 0.01) reduction in total-cholesterol and a decrease in LDL-C at Day 14 compared to placebo, however, the decrease in LDL-C did not reach statistical significance (p = 0.08). The coadministration of ezetimibe 10 mg and fluvastatin 20 mg caused significantly (p < or = 0.01) greater mean percent reductions in LDL-C and total-cholesterol than fluvastatin 20 mg alone or placebo at Day 14. Fluvastatin had no clinically significant effect on the pharmacokinetics of ezetimibe. On average, ezetimibe appeared to decrease the rate and extent of fluvastatin bioavailability. CONCLUSION: Coadministration of ezetimibe and fluvastatin was safe and well tolerated and caused significant incremental reductions in LDL-C and total cholesterol compared to fluvastatin administered alone. The pharmacokinetics of ezetimibe were not affected by coadministration with fluvastatin. The apparent decrease in fluvastatin exposure on administration with ezetimibe was likely to be due to the parallel study design and two pharmacokinetic outliers and is considered of no clinical significance.
Adult↗
Pegylated IFNs for chronic hepatitis C: an update.
For over a decade, IFN-alpha(2) has been the standard treatment for chronic hepatitis C. However, the drug's rapid clearance and short half-life have led to low rates of sustained virological response. Pegylation is a well-established method of modifying the pharmacological properties of IFNs, causing significant improvements in pharmacokinetics, which in turn lead to improved efficacy. Two pegylated forms of IFN-alpha(2) have been developed: PEG-IFN-alpha(2b) and PEG-IFN-alpha(2a), and their efficacy has been established in randomised, controlled trials. However, the two differ significantly in structure, in vitro activity and pharmacological properties, and this may translate into -differences in clinical efficacy. Comparative trials have been initiated that will provide insight into relative importance of pharmacokinetics, bioactivity and dosing regimen.
Animals↗
Heroes in community psychiatry: Professor Gerald Caplan.
Explore the source record for details and available documents.
Community Psychiatry↗
Pharmacodynamic and pharmacokinetic interaction between fenofibrate and ezetimibe.
OBJECTIVE: The cholesterol absorption inhibitor, ezetimibe, significantly decreases low-density lipoprotein-cholesterol (LDL-C) levels in patients with primary hypercholesterolemia. The pharmacodynamic, pharmacokinetic, and safety profiles of ezetimibe and fenofibrate were evaluated alone and after co-administration in 32 subjects with primary hypercholesterolemia. RESEARCH DESIGN AND METHODS: This was a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study. Subjects with untreated LDL-C > or = 130 mg/dL (3.37 mmol/L) were randomized to receive one of four oral treatments each morning for 14 days: fenofibrate 200 mg + ezetimibe 10 mg, fenofibrate 200 mg, ezetimibe 10 mg, or placebo. Serum lipids were assessed before drug administration on day 1, day 7, and day 14. Pharmacokinetic parameters were assessed on day 14. MAIN OUTCOME MEASURES: The primary pharmacodynamic parameter was percentage change from baseline in LDL-C concentration following co-administration of ezetimibe and fenofibrate vs either drug alone, or placebo. A secondary outcome was the potential for a pharmacokinetic interaction between ezetimibe and fenofibrate. RESULTS: Ezetimibe and fenofibrate co-administration was well tolerated and produced statistically significant mean percentage reductions from baseline in LDL-C (p < or = 0.05 vs either drug alone or placebo), total cholesterol and triglycerides (p < or = 0.05 vs either fenofibrate or placebo), apolipoprotein C-III (p < or = 0.05 vs placebo), and LDL-III (p < or = 0.05 vs either drug alone or placebo). Ezetimibe did not significantly affect the pharmacokinetics of fenofibrate. Concomitant fenofibrate administration significantly increased the mean C(max) and AUC of total ezetimibe approximately 64% and 48%, respectively. However, based on the established safety profile and flat dose-response of ezetimibe, this effect is not considered to be clinically significant. CONCLUSION: Co-administration of ezetimibe and fenofibrate produced significantly greater reductions in LDL-C than either drug alone and greater reductions in triglycerides than fenofibrate. These effects were accompanied by improvements in the lipid/lipoprotein profile, suggesting that co-administration therapy with ezetimibe and fenofibrate may be an effective therapeutic option for patients with mixed dyslipidemia.
Adult↗
Effects of ezetimibe on the pharmacodynamics and pharmacokinetics of lovastatin.
BACKGROUND: Ezetimibe is a cholesterol absorption inhibitor which decreases low-density lipoprotein cholesterol (LDL-C) in patients with hypercholesterolemia. This study investigated the potential for pharmacodynamic and/or pharmacokinetic interactions between ezetimibe and lovastatin. METHODS: In a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study, 48 healthy men with hypercholesterolemia (screening LDL-C >or= 130 mg/dL) who were stabilized and maintained on a National Cholesterol Education Program (NCEP) Step I diet were randomized to one of the following six oral treatments once daily for 14 days: lovastatin 20 mg; lovastatin 20 mg plus ezetimibe 5, 10, or 20 mg; lovastatin 40 mg plus ezetimibe 10mg; or placebo. RESULTS: Reported adverse events were generally mild, nonspecific, and similar among treatments. There were no significant changes in safety laboratory test results, including those for enzymes indicative of muscle or liver injury. Coadministration of ezetimibe and lovastatin did not increase the plasma concentrations of lovastatin or beta-hydroxylovastatin. In this parallel comparison study there was an apparent decrease in lovastatin exposure, however, the reduction in lovastatin or beta-hydroxylovastatin concentrations was not related to the ezetimibe dose and is not considered to be clinically important. Ezetimibe 5, 10, or 20 mg combined with lovastatin 20 mg caused a significantly (p < 0.01) greater reduction in LDL-C than lovastatin 20 mg alone, with no apparent effect on HDL-C or triglycerides. LDL-C was reduced by 51.0% with ezetimibe 10 mg plus lovastatin 20 mg, 56.0% with ezetimibe 10 mg plus lovastatin 40 mg, 33.2% with lovastatin alone, and 17.3% with placebo. CONCLUSIONS: The co-administration of ezetimibe and lovastatin was well tolerated and resulted in a significantly greater percentage reduction in serum LDL-C concentrations than with lovastatin alone, with an average incremental reduction of 16-18%. Ezetimibe 10mg appears to be the optimal dose when co-administered with lovastatin 20mg once daily. Further incremental reductions in LDL-C from the co-administration of ezetimibe and lovastatin are expected only when the dose of lovastatin is increased. The co-administration of ezetimibe and lovastatin has the potential to produce clinically significant reductions in LDL-C compared to either drug alone, with favorable safety and tolerability.
Adult↗
Pharmacodynamic interaction between ezetimibe and rosuvastatin.
BACKGROUND: Ezetimibe is a lipid-lowering drug indicated for the treatment of hypercholesterolemia as co-administration with HMG-CoA reductase inhibitors (statins) or as monotherapy. The primary objectives of this study were to evaluate the pharmacodynamic effects and safety of the co-administration of ezetimibe and the new statin rosuvastatin. A secondary objective was to examine the potential for a pharmacokinetic interaction between ezetimibe and rosuvastatin. METHODS: This was a randomized, evaluator (single)-blind, placebo-controlled, parallel-group study in healthy hypercholesterolemic subjects (untreated low-density lipoprotein cholesterol [LDL-C] > or = 130 mg/dL [3.37 mmol/L]). After the outpatient screening and NCEP Step I diet stabilization periods, 40 subjects were randomized to one of the 4 following treatments: rosuvastatin 10 mg plus ezetimibe 10 mg (n = 12); rosuvastatin 10 mg plus placebo (matching ezetimibe 10 mg) (n = 12); ezetimibe 10 mg plus placebo (matching ezetimibe 10 mg) (n = 8); or placebo (2 tablets, matching ezetimibe 10 mg) (n = 8). All study treatments were administered once daily in the morning for 14 days as part of a 16-day inpatient confinement period. Fasting serum lipids were assessed pre-dose on days 1 (baseline), 7, and 14 by direct quantitative assay methods. Safety was evaluated by monitoring laboratory tests and recording adverse events. Blood samples were collected for ezetimibe and rosuvastatin pharmacokinetic evaluation prior to the first and last dose and at frequent intervals after the last dose (day 14) of study treatment. Plasma ezetimibe, total ezetimibe (ezetimibe plus ezetimibe-glucuronide) and rosuvastatin concentrations were determined by validated liquid chromatography with tandem mass spectrometric detection (LC-MS/MS) assay methods. RESULTS: All active treatments caused statistically significant (p < or = 0.02) decreases in LDL-C concentration versus placebo from baseline to day 14. The co-administration of ezetimibe and rosuvastatin caused a significantly (p < 0.01) greater reduction in LDL-C and total cholesterol than either drug alone. In this 2-week inpatient study with restricted physical activity there was no apparent effect of any treatment on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The co-administration of ezetimibe and rosuvastatin caused a significantly (p < 0.01) greater percentage reduction in mean LDL-C (-61.4%) than rosuvastatin alone (-44.9%), with a mean incremental reduction of -16.4% (95%CI -26.3 to -6.53). Reported side effects were generally mild, nonspecific, and similar among treatment groups. There were no significant increases or changes in clinical laboratory tests, particularly those assessing muscle and liver function. There was no significant pharmacokinetic drug interaction between ezetimibe and rosuvastatin. CONCLUSIONS: Co-administration of ezetimibe 10 mg with rosuvastatin 10 mg daily caused a significant incremental reduction in LDL-C compared with rosuvastatin alone. Moreover, co-administering ezetimibe and rosuvastatin was well tolerated in patients with hypercholesterolemia.
Adult↗
Temozolomide in patients with advanced cancer: phase I and pharmacokinetic study.
STUDY OBJECTIVE: To determine the maximum tolerated dose, dose-limiting toxicity, pharmacokinetics, and potential antitumor activity of temozolomide administered as a single dose every 28 days. DESIGN: Open label, phase I, dose-escalation trial. SETTING: University-affiliated cancer center. PATIENTS: Eleven patients aged 33-73 years with a documented solid tumor or lymphoma who failed therapy of proven efficacy for their disease or had a disease for which no conventional therapy was available. INTERVENTION: Temozolomide 500 mg/m2 was administered as a single oral dose every 28 days. Doses were escalated to 750 or 1000 mg/m2. No intrapatient dose escalation was allowed. At least two patients were enrolled at each dose level. Patients who did not have progressive disease and did not experience a dose-limiting toxicity, or experienced a dose-limiting toxicity but were eligible for dose reduction, were eligible to continue on the study. MEASUREMENTS AND MAIN RESULTS: Pharmacokinetic analysis was performed for temozolomide and its active metabolite, 5-(3-methyltriazeno)-imidazole-4-carboxamide (MTIC). Neutropenia and thrombocytopenia were dose limiting at 1000 mg/m2. Temozolomide was absorbed rapidly (mean time to maximum concentration 1.4 hrs) and eliminated, with average half-life and apparent oral systemic clearance values of 1.8 hours and 97 ml/minute/m2, respectively. Mean systemic exposure to MTIC was 3.7% of temozolomide. No objective responses were observed. The maximum tolerated dose of temozolomide was 750 mg/m2. CONCLUSION: Temozolomide 750 mg/m2 administered orally every 28 days was well tolerated. Alternate temozolomide dosing schedules such as continuous daily administration may enhance antitumor activity through sustained depletion of the DNA repair protein O6-alkylguanine DNA alkyltransferase.
Administration, Oral↗
Four decades of community mental health: a symphony in four movements.
The authors present a detailed chronological discussion of the evolution of community mental health care in the United States with emphasis on the period of the 40 years since the passage of the Community Mental Health Centers Construction Act of October 31, 1963.
Community Mental Health Centers↗
Pharmacodynamic interaction between the new selective cholesterol absorption inhibitor ezetimibe and simvastatin.
AIMS: The primary aims of these two single-centre, randomized, evaluator-blind, placebo/positive-controlled, parallel-group studies were to evaluate the potential for pharmacodynamic and pharmacokinetic interaction between ezetimibe 0.25, 1, or 10 mg and simvastatin 10 mg (Study 1), and a pharmacodynamic interaction between ezetimibe 10 mg and simvastatin 20 mg (Study 2). Evaluation of the tolerance of the coadministration of ezetimibe and simvastatin was a secondary objective. METHODS: Eighty-two healthy men with low-density lipoprotein cholesterol (LDL-C) >or=130 mg dl-1 received study drug once daily in the morning for 14 days. In Study 1 (n=58), five groups of 11-12 subjects received simvastatin 10 mg alone, or with ezetimibe 0.25, 1, or 10 mg or placebo. In Study 2 (n=24), three groups of eight subjects received simvastatin 20 mg alone, ezetimibe 10 mg alone, or the combination. Blood samples were collected to measure serum lipids in both studies. Steady-state pharmacokinetics of simvastatin and its beta-hydroxy metabolite were evaluated in Study 1 only. RESULTS: In both studies, reported side-effects were generally mild, nonspecific, and similar among treatment groups. In Study 1, there were no indications of pharmacokinetic interactions between simvastatin and ezetimibe. All active treatments caused statistically significant (P<0.01) decreases in LDL-C concentration vs placebo from baseline to day 14. The coadministration of ezetimibe and simvastatin caused a dose-dependent reduction in LDL-C and total cholesterol, with no apparent effect on high-density lipoprotein cholesterol (HDL-C) or triglycerides. The coadministration of ezetimibe 10 mg and simvastatin 10 mg or 20 mg caused a statistically (P<0.01) greater percentage reduction (mean -17%, 95% CI -27.7, -6.2, and -18%, -28.4, -7.4, respectively) in LDL-C than simvastatin alone. CONCLUSIONS: The coadministration of ezetimibe at doses up to 10 mg with simvastatin 10 or 20 mg daily was well tolerated and caused a significant additive reduction in LDL-C compared with simvastatin alone. Additional clinical studies to assess the efficacy and safety of coadministration of ezetimibe and simvastatin are warranted.
Administration, Oral↗