bluuebunny/crossref_metadata_2025 huggingface dataset:
Combined Network Design and Multiperiod Pricing: Modeling, Solution Techniques, and Computation
Authors: Bienstock Daniel , Raskina Olga , Saniee Iraj , Wang Qiong
Published: March 2006

In this paper we describe an efficient algorithm for solving novel optimization models arising in the context of multiperiod capacity expansion of optical networks. We assume that the network operator must make investment decisions over a multiperiod planning horizon while facing rapid changes in transmission technology, as evidenced by a steadily decreasing per-unit cost of capacity. We deviate from traditional and monopolistic models in which demands are given as input parameters, and the objective is to minimize capacity deployment costs. Instead, we assume that the carrier sets end-to-end prices of bandwidth at each period of the planning horizon. These prices determine the demands that are to be met, using a plausible and explicit price-demand relationship; the resulting demands must then be routed, requiring an investment in capacity. The objective of the optimization is now to simultaneously select end-to-end prices of bandwidth and network capacities at each period of the planning horizon, so as to maximize the overall net present value of expanding and operating the network. In the case of typical large-scale optical networks with protection requirements, the resulting optimization problems pose significant challenges to standard optimization techniques. The complexity of the model, its nonlinear nature, and the large size of realistic problem instances motivates the development of efficient and scalable solution techniques. We show that while general-purpose nonlinear solvers are typically not adequate for the task, a specialized decomposition scheme is able to handle large-scale instances of this problem in reasonable time, producing solutions whose net present value is within a small tolerance of the optimum.
Tracking a Financial Benchmark Using a Few Assets
Authors: Yao David D. , Zhang Shuzhong , Zhou Xun Yu
Published: March 2006

We study the problem of tracking a financial benchmark—a continuously compounded growth rate or a stock market index—by dynamically managing a portfolio consisting of a small number of traded stocks in the market. In either case, we formulate the tracking problem as an instance of the stochastic linear quadratic control (SLQ), involving indefinite cost matrices. As the SLQ formulation involves a discounted objective over an infinite horizon, we first address the issue of stabilizability. We then use semidefinite programming (SDP) as a computational tool to generate the optimal feedback control. We present numerical examples involving stocks traded at the Hong Kong and New York Stock Exchanges to illustrate the various features of the model and its performance.
A New Linear Programming Approach to Radiation Therapy Treatment Planning Problems
Authors: Romeijn H. Edwin , Ahuja Ravindra K. , Dempsey James F. , Kumar Arvind
Published: March 2006

We consider the problem of radiation therapy treatment planning for cancer patients. During radiation therapy, beams of radiation pass through a patient, killing both cancerous and normal cells. Thus, the radiation therapy must be carefully planned so that a clinically prescribed dose is delivered to targets containing cancerous cells, while nearby organs and tissues are spared. Currently, a technique called intensity-modulated radiation therapy (IMRT) is considered to be the most effective radiation therapy for many forms of cancer. In IMRT, the patient is irradiated from several beams, each of which is decomposed into hundreds of small beamlets, the intensities of which can be controlled individually. In this paper, we consider the problem of designing a treatment plan for IMRT when the orientations of the beams are given. We propose a new model that has the potential to achieve most of the goals with respect to the quality of a treatment plan that have been considered to date. However, in contrast with established mixed-integer and nonlinear programming formulations, we do so while retaining linearity of the optimization problem, which substantially improves the tractability of the optimization problem. Furthermore, we discuss how several additional quality and practical aspects of the problem that have been ignored to date can be incorporated into our linear model. We demonstrate the effectiveness of our approach on clinical data.
Effective Heuristics for Multiproduct Partial Shipment Models
Authors: Dawande Milind , Gavirneni Srinagesh , Tayur Sridhar
Published: March 2006

Motivated by real applications, we consider the problem of shipping products to multiple customers from limited inventory. After formulating the optimization problems under different restrictions on partial shipments, we find that commercially available packages, applied directly, are unsatisfactory, as are simple greedy approaches. We develop a scheme of heuristics that enables the user to select a good balance between computation time and effectiveness. A detailed computational study of one- and two-period industrial-sized problems indicates that these heuristics are computationally practical and generate solutions that are, on average, within 3%–4% of the optimum.
Optimal Selection of a Connected Reserve Network
Authors: Önal Hayri , Briers Robert A.
Published: March 2006

Spatial considerations are important in conservation reserve design. A particularly important spatial requirement is the connectivity of selected sites. Direct connections between reserve sites increase the likelihood of species persistence by allowing dispersal and colonization of other areas within the network without species having to leave the reserve. The conventional set-covering and maximal-covering formulations of the reserve selection problem assume that species representation is the only criterion in site selection. This approach usually results in a small but highly fragmented reserve, which may not be desirable. We present a linear integer programming framework incorporating spatial contiguity as an additional site selection criterion. An empirical application to a data set on the occurrence of breeding birds in Berkshire, United Kingdom, demonstrates that site connectivity requires a significantly larger reserve. Incorporation of spatial criteria increases the computational complexity of the problem. To overcome this, we use a two-stage procedure where the original sites are aggregated first and an optimum solution is determined for the aggregate sites. Then, site selection is restricted to original sites included in the aggregate solution and a connected reserve is determined. In this particular application the above procedure generated a significantly more efficient reserve than a heuristic selection.
Effect of Glucosamine on Glucose Control
Authors: Stumpf Janice L , Lin Shu-Wen
Published: March 2006

Objective:

To review the literature regarding the effect of glucosamine on glucose control.

Data Sources:

English-language articles on the effects of administration of exogenous glucosamine on glucose control were identified through a search of MEDLINE (1966–March 2006), EMBASE (1988–March 2006), and International Pharmaceutical Abstracts (1970–March 2006) databases using the search terms glucosamine, blood glucose, and diabetes mellitus. Abstracts of articles were then reviewed to determine relevance to the topic. Bibliographies of selected articles were screened for other pertinent references.

Data Synthesis:

Theoretically, glucosamine may alter glucose metabolism. Insulin resistance has been noted following intravenous administration of glucosamine in animal studies; however, these findings have not been confirmed in humans. Alterations in glucose control have not been documented in long-term efficacy studies using oral glucosamine for osteoarthritis or in trials of short duration conducted in healthy or diabetic subjects. The long-term effects of glucosamine in patients with diabetes have yet to be established in well-controlled trials.

Conclusions:

Small, short-term studies suggest that glucosamine may be used in selected patients without affecting glucose control; however, data in patients with diabetes mellitus are limited, and close monitoring for potential changes in glucose control is recommended.
Development and Validation of the Medication-Based Disease Burden Index
Authors: George Johnson , Vuong Tam , Bailey Michael J , Kong David CM , Marriott Jennifer L , Stewart Kay
Published: March 2006

Background:

Medication lists offer an alternative source of data on comorbidities and disease burden.

Objective:

To develop and validate the Medication-Based Disease Burden Index (MDBI).

Methods:

A list of medications corresponding to the leading causes of global death was pilot tested and finalized by an expert panel. The resulting index was tested on drug regimens of patients at risk of medication misadventure. Criterion validity of the index was established against Charlson's index and Chronic Disease Score (CDS). Sensitivity, specificity, predictive validity, convergent and discriminant validity, and interrater and test–retest reliabilities of the index were also assessed.

Results:

The MDBI consisting of specific medications for 20 chronic medical conditions and corresponding disability weightings was developed. The MDBI was tested on 317 patients with mean ± SD Charlson's index scores of 2.8 ± 2.2 and CDS scores of 7.3 ± 2.8. Mean MDBI scores (0.33 ± 0.28) demonstrated significant correlations with Charlson's index scores (r = 0.31; p < 0.001) and CDS (r = 0.53; p < 0.001). MDBI had satisfactory sensitivity and high specificity. Age of the patients and number of medications had significant correlation with the MDBI scores, but the MDBI scores were not significantly different in males and females. MDBI scores could successfully predict death and planned or unplanned readmissions (OR = 4.7, 95% CI 1.4 to 15.5; p = 0.01). MDBI demonstrated high inter-rater (intraclass correlation coefficient [ICC] = 0.99) and test–retest reliabilities (ICC = 0.98).

Conclusions:

Initial testing suggests that MDBI could offer an alternative low-cost and convenient method for quantifying disease burden and predicting health outcomes.
Recent Advances in Neonatal Pharmacotherapy
Authors: Calhoun Darlene A , Murthy S Narasimha , Bryant Bobby G , Luedtke Sherry A , Bhatt-Mehta Varsha
Published: March 2006

Objective:

To provide commentary and reviews and brief discussions in controversial or innovative recent advances in neonatal pharmacotherapy. To discuss cutting edge drug delivery systems that may become useful in neonatal drug delivery in the future.

Data Sources:

Articles were identified through searches of MEDLINE (1990–October 2005), key articles in the authors' files, and in some cases, through data generated and/or published by the author of a particular topic.

Data Selection:

Article selection and relevance to the topics under discussion was determined by individual authors.

Data Synthesis:

Therapeutic strategies addressed in this review include the use of hematopoietic growth factors including a simulated amniotic fluid preparation containing these growth factors for neonates with selected gastrointestinal problems, erythropoietin for neuroprotection following perinatal asphyxia, drug therapy advances in treatment of patent ductus arteriosus (PDA), evaluation of advances in transdermal drug delivery, and its potential application to neonates and advances in the treatment of persistent pulmonary hypertension (PPHN) of the newborn.

Conclusions:

Despite being over 30 years old, the practice of neonatology is as much of an art as a science. Advances in the basic science research have improved our understanding of use of pharmacologic agents in the premature and full-term neonate including drug disposition pathways. Expanding our knowledge on issues such as physiology of hematopoietic factors, the pharmacologic responses of conditions such as PDA and PPHN, and newer technologies for drug administration, as well as other pharmacologic reponses in the neonate are vital in the development of safe and efficacious treatments for neonates. Many questions remain unanswered, and every clinician must make an effort to contribute to the knowledge and understanding of pharmacotherapy in this patient population.
Safety of Angiotensin-Converting Enzyme Inhibitors in Patients with Insect Venom Allergies
Authors: Stumpf Janice L , Shehab Nadine , Patel Anish C
Published: March 2006

Objective:

To review the literature with respect to the safety of angiotensin-converting enzyme (ACE) inhibitors in patients allergic to insect venom and those undergoing venom immunotherapy (VIT).

Data Sources:

A MEDLINE search was conducted (1966–March 2006) using the following search terms: bee sting, venom, insect stings, ACE inhibitors, angiotensin II receptor blockers, immunotherapy, and desensitization. The bibliographies of qualifying articles were also searched for relevant references.

Data Synthesis:

Several case reports have described severe allergic reactions, including anaphylaxis, in patients taking ACE inhibitors subsequent to being stung or receiving VIT. Exacerbation of the allergic response by ACE inhibitors is thought to be related to accumulation of bradykinin and inhibition of the formation of angiotensin II. Similar reactions have not been described with angiotensin-receptor blockers, but are theoretically possible.

Conclusions:

ACE inhibitors may exacerbate the response to insect venom, resulting in potentially life-threatening allergic reactions to insect stings or VIT. Although this risk is difficult to quantify based only on data from case reports, it seems prudent that patients with documented allergic reactions to insect venom avoid ACE inhibitor therapy, if possible. If, after careful consideration of the risks and benefits, ACE inhibitor therapy is deemed warranted, education regarding measures to minimize exposure to insect stings and training on self-administration of epinephrine should be provided, as with any person with venom allergy. In patients in whom VIT is appropriate, temporary discontinuation of the ACE inhibitor prior to each venom injection may prevent subsequent adverse reactions.
Argatroban Dosing of Patients with Heparin-Induced Thrombocytopenia and an Elevated aPTT Due to Antiphospholipid Antibody Syndrome
Authors: Pendleton Robert , Wheeler Michelle M , Rodgers George M
Published: March 2006

Objective:

To describe the clinical characteristics, management, and outcomes of patients with heparin-induced thrombocytopenia with thrombosis (HITTS) or without thrombosis (HIT) who also had an elevated baseline activated partial thromboplastin time (aPTT) due to antiphospholipid antibody syndrome (APS).

Case Summary:

Four patients with HIT/HITTS and an elevated baseline aPTT due to APS were identified. Two patients had venous thrombosis, 1 had limb ischemia, and 1 had isolated HIT. All 4 were managed with a weight-based fixed dose of argatroban without laboratory monitoring. None of the patients had thrombotic or bleeding complications once therapy was initiated.

Discussion:

Management of patients with HIT/HITTS and an abnormal baseline aPTT due to APS is problematic. We review alternative management strategies, such as monitoring direct thrombin inhibitors with the ecarin clotting time or thrombin inhibition time or using an alternative anticoagulant, such as fondaparinux. As of March 13, 2006, none of these management strategies has been evaluated in a clinical trial for this patient population. We report the successful use of weight-based, fixed-dose argatroban without laboratory monitoring in patients with APS.

Conclusions:

Use of a fixed-dose argatroban regimen without laboratory monitoring is a potential management strategy for patients with HIT/HITTS and an elevated baseline aPTT due to APS.
Acute Dystonia with Low-Dosage Aripiprazole in Tourette's Disorder
Authors: Fountoulakis Konstantinos N , Siamouli Melina , Kantartzis Sotiris , Panagiotidis Panagiotis , lacovides Apostolos , Kaprinis George St
Published: March 2006

Objective:

To report a case of an acute dystonic episode in a patient with Tourette's disorder (TD) treated with the partial dopamine agonist aripiprazole.

Case Summary:

An 18-year-old male with TD was prescribed aripiprazole 10 mg orally daily, which produced a significant improvement in his symptoms. However, after 3 days of treatment, he experienced an acute episode of dystonia with facial muscle spasm, oculogyric crisis, and torticolis. All symptoms resolved after a single intramuscular injection of Dipendine 5 mg. The Naranjo probability scale indicated that the adverse events were probably caused by aripiprazole.

Discussion:

To our knowledge, as of this writing, this is the first report concerning an aripiprazole-induced dystonic episode in an adult, and it is especially notable because it occurred at low dosage. Aripiprazole is a dopamine partial agonist and a serotonin2A antagonist with a favorable adverse effect profile. Short-term clinical trials reported a very low incidence of extrapyramidal symptoms, with akathisia being the most common, although there have been reports of severe extrapyramidal symptoms in a 3-year-old child and in an adolescent with a previous history of such symptoms.

Conclusions:

Acute dystonic phenomena may be caused by aripiprazole, although the drug's suggested mode of action largely precludes them.
Risperidone Treatment of Bipolar Mania
Authors: Nguyen Lisa N , Guthrie Sally K
Published: March 2006

Objective:

To review clinical trial evidence regarding the efficacy and safety of risperidone for the treatment of bipolar mania.

Data Sources:

Articles were identified through searches of PubMed (1950–August 2005), EMBASE (1988–August 2005 week 37), and International Pharmaceutical Abstracts (1970–August 2005) databases using the key words risperidone, atypical antipsychotics, and bipolar mania. Additional references were found through review of bibliographies of identified articles. PubMed searches for efficacy and safety were limited to clinical trials.

Study Selection and Data Extraction:

Six randomized trials and 6 observational studies of risperidone monotherapy or combination therapy for bipolar mania in adults were selected.

Data Synthesis:

Randomized, placebo-controlled and observational trials reported that risperidone monotherapy decreases manic symptoms in patients with a moderate severity of mania, as determined by change in Young Mania Rating Scale (YMRS) scores. Adverse effects observed in monotherapy trials included somnolence, extrapyramidal symptoms (EPS), and weight gain. Clinical trials of risperidone in combination with other mood stabilizers (ie, lithium, valproate, carbamazepine, topiramate) also reported decreases in YMRS scores in patients with moderate and severe manic symptoms.

Conclusions:

Risperidone monotherapy or adjunctive therapy with other first-line mood stabilizers may be effective for the treatment of acute bipolar mania in adults with moderate severity of mania. The use of risperidone as monotherapy in severe mania or in maintenance treatment remains to be elucidated.
Pantoprazole-lnduced Thrombocytopenia
Authors: Watson Tracy D , Stark Jennifer E , Vesta Kimi S
Published: March 2006

Objective:

To report 2 cases of thrombocytopenia associated with pantoprazole treatment and discuss existing reports on this drug-induced adverse event.

Case Summaries:

This paper describes the course of thrombocytopenia associated with pantoprazole 40 mg in 2 hospitalized patients. In both cases, thrombocytopenia appeared after the initiation of pantoprazole and rapidly improved after discontinuation of pantoprazole, although complete resolution of thrombocytopenia occurred in only one patient prior to discharge from the hospital.

Discussion:

The mechanism of drug-induced thrombocytopenia is often poorly understood, and proton-pump inhibitors are generally not strongly suspected as a cause of thrombocytopenia. However, an objective causality assessment using the Naranjo probability scale revealed a probable relationship between thrombocytopenia and pantoprazole in both of the cases. It is unknown whether this is a class effect.

Conclusions:

Although drug-induced thrombocytopenia with pantoprazole appears to be rare, it represents a potentially severe adverse effect. This supports the judicious prescribing of pantoprazole and possibly other proton-pump inhibitors.
Critical Care
Authors: Dasta Joseph F
Published: March 2006

2006 marks the 40th year of publication for The Annals. Over that time, The Annals has been an important contributor to the development of clinical pharmacy. Throughout 2006, we are publishing articles reflecting on the history of clinical pharmacy through the eyes of practitioners, including those pioneering clinical pharmacy, as well as those who have more recently entered the profession and a well-established specialty. In addition, we are also presenting articles and editorials from the early history of The Annals that have given direction and shape to the practice of clinical pharmacy (see pages 740 and 742).
Depressive Symptoms in Coronary Artery Disease Patients After Hypertension Treatment
Authors: Ried L Douglas , Tueth Michael J , Taylor Michael D , Sauer Brian C , Lopez Larry M , Pepine Carl J
Published: March 2006

Background:

Depression is highly prevalent and frequently recurs in patients with coronary artery disease (CAD) and hypertension. Certain medications used to treat hypertension are alleged to be associated with higher risk of depression.

Objective:

To compare depressive symptoms before and during treatment with 2 equivalent hypertension treatment strategies in patients with CAD stratified according to a self-reported history of physician-diagnosed depression.

Methods:

Patients enrolled in a randomized hypertension treatment study were mailed baseline and one year follow-up surveys and stratified according to a self-reported history of depression. Patients (N = 1152) were 50 years old or older with hypertension and clinically stable CAD. Depressive symptoms were measured using the Center for Epidemiologic Studies—Depression (CES-D). High risk of depression was defined as a history of physician-diagnosed depression reported by patients on the baseline survey. Depressive symptoms were compared for verapamil sustained-release (SR)– and atenolol-based hypertension treatment.

Results:

Among patients with a previous history of depression, depressive symptoms improved over the one year follow-up period for patients assigned to both treatment regimens. Depressive symptoms improved for patients with no depression history in the verapamil SR group (p < 0.001) and were unchanged in the atenolol group (p = 0.52). Patients assigned to the atenolol-based strategy without prior history of depression were more likely to worsen 5 or more points on the CES-D.

Conclusions:

When antihypertensive treatment options are clinically equivalent, prescribers may first consider using a verapamil SR–based strategy, especially in patients with CAD who have no history of depression.
Dutasteride: A Dual 5-α Reductase Inhibitor for the Treatment of Symptomatic Benign Prostatic Hyperplasia
Authors: Dolder Christian R
Published: March 2006

Objective:

To review the pharmacology, pharmacokinetics, efficacy, safety, drug interactions, and dosing recommendations of dutasteride, a 5-α reductase inhibitor for benign prostatic hyperplasia (BPH).

Data Sources:

A MEDLINE search (1966–February 2006) was conducted to extract human research data in the English language on dutasteride. Search terms included benign prostatic hyperplasia, dutasteride, and finasteride. The reference lists of articles identified through this search process, the manufacturer's Web site, and dutasteride prescribing information were also examined.

Study Selection and Data Extraction:

All published studies and clinical data from the manufacturer were included, with emphasis placed on randomized, controlled trials.

Data Synthesis:

Dutasteride is approved for the treatment of symptomatic BPH in men with an enlarged prostate to improve urinary symptoms, reduce the risk of acute urinary retention, and reduce the need for BPH-related surgical interventions. Compared with placebo, dutasteride has been shown to significantly improve BPH symptoms, reduce the incidence of acute urinary retention and BPH-related surgery, and improve BPH-related quality of life. Few published data exist comparing dutasteride with finasteride. The most common adverse effects of dutasteride include ear, nose, and throat infection; malaise; headache; dizziness; and musculoskeletal pain.

Conclusions:

Clinical trials, sponsored primarily by the manufacturer, have shown dutasteride to be an effective treatment of BPH compared with placebo and to likely possess efficacy similar to that of finasteride. Further studies are needed to gain a more clear understanding of any clinically significant differences between dutasteride and finasteride.
Atypical Antipsychotic–Induced Akathisia with Depression: Therapeutic Role of Mirtazapine
Authors: Ranjan Sanjeev , Chandra Prabha S , Chaturvedi Santosh K , Prabhu Santosh C , Gupta Arun
Published: March 2006

Objective:

To investigate the efficacy of mirtazapine in treating akathisia caused by risperidone and olanzapine, as well as its use in alleviating comorbid depressive disorder.

Case Summaries:

Five patients with diagnoses varying from schizophrenia, delusional disorder, and bipolar disorder developed akathisia while on treatment with olanzapine and risperidone. The likelihood that risperidone and olanzapine had induced akathisia in all patients was rated probable according to the Naranjo probability scale. Four of these patients were also found to be depressed. The akathisia was successfully treated with mirtazapine, and 3 of the 4 depressed patients improved with mirtazapine treatment. Use of mirtazapine did not result in any adverse effect.

Discussion:

Mirtazapine is a potent antagonist of central α2 auto- and hetero-adrenergic receptors, as well as an antagonist of 5-HT2A/2C, 5-HT3, and histaminergic H1 postsynaptic receptors. The efficacy of mirtazapine in treatment of akathisia may result from its antagonist property at the H1 receptors and its dopaminergic activity in frontal cortex. The use of mirtazapine offers advantages over other antiakathisia drugs in its better adverse effect profile, as well as its ability to treat coexisting depression.

Conclusions:

Mirtazapine is efficacious in treating atypical antipsychotic–induced akathisia. It may be a good option, particularly in patients with coexisting depression.
Naturalistic Impact of Second-Generation Antipsychotics on Weight Gain
Authors: Brixner Diana I , Said Qayyim , Corey-Lisle Patricia K , Tuomari A Vickie , L'italien Gilbert J , Stockdale William , Oderda Gary M
Published: March 2006

Background:

While second-generation antipsychotics (SGAs) have had benefits over earlier antipsychotic treatments, their use has been associated with reports of weight gain. Body mass index (BMI) has been studied in clinical trials with limited comparison between drugs.

Objective:

To investigate the impact of each SGA on the risk of weight increase in an adult population.

Methods:

Using a national electronic medical records database, a naturalistic impact of SGAs on BMI was evaluated. Patients (aged ≥ 18 y) receiving a prescription for an antipsychotic drug between January 1995 and March 2004 were identified. An adverse event was defined as at least a 7% increase in BMI from baseline within one year of antipsychotic prescription and a post-increase BMI of at least 25 kg/m2.

Results:

A total of 9394 patients were identified, with 1514 cases of increased BMI after initial prescription. Risperidone (OR 1.39; 95% CI 1.16 to 1.66), quetiapine (OR 1.36; 95% CI 1.13 to 1.64), and olanzapine (OR 1.76; 95% CI 1.50 to 2.07)were significantly more likely to cause BMI increase compared with first-generation antipsychotics (FGAs). Aripiprazole (OR 0.72; 95% CI 0.36 to 1.46), ziprasidone (OR 0.68; 95% CI 0.39 to 1.18), and clozapine (OR 1.01; 95% CI 0.56 to 1.81) were less likely to induce weight gain compared with FGAs.

Conclusions:

This study provides a foundation for understanding how SGAs impact weight gain in a naturalistic, as opposed to a clinical trial, setting and provides evidence that there are differential risks of weight gain between SGAs. Because of negative long-term health effects of weight gain, physicians need to take all factors into consideration when recommending pharmaceutical therapy for patients with severe mental illness.
Critical Care Pharmacy Services in United States Hospitals
Authors: MacLaren Robert , Devlin John W , Martin Steven J , Dasta Joseph F , Rudis Maria I , Bond CA
Published: March 2006

Background:

Critical care pharmacy activities have been described as fundamental, desirable, and optimal, but actual services provided have not been evaluated.

Objective:

To characterize the type and level of pharmacy services provided to intensive care units (ICUs).

Methods:

A 38 question survey was sent in 2 consecutive mailings to all US institutions (N = 3238) with an ICU. Questions were categorized according to clinical, educational, administrative, and scholarly activities, with levels of services stratified as fundamental, desirable, or optimal.

Results:

Completed surveys were received from 382 (11.8%) institutions encompassing 1034 ICUs. Direct clinical pharmacy activities were provided at 62.2% of ICUs. The pharmacists in those programs attended rounds 4.4 ± 1.5 days/wk, mean ± SD, and had a workweek that consisted of patient care (43% of hours worked), drug distribution (26.2%), administration (12.6%), education (10.9%), and scholarly activities (7.3%). Fundamental clinical activities performed during at least 75% of patient ICU days were providing drug information, drug therapy evaluation, drug therapy intervention, and pharmacokinetic monitoring. Conducting inservices (92.8%), a fundamental service, was the only educational activity frequently provided. Most respondents were involved with at least one multidisciplinary committee, and 45.5% conducted scholarly activities. Desirable or optimal activities were not frequently provided across all service categories.

Conclusions:

Clinical pharmacists are directly involved as caregivers in nearly two-thirds of ICUs in the US. Although they provide a range of clinical and administrative services, involvement in educational and scholarly activities is variable. The level of services provided is consistent with the criteria deemed fundamental for improving patient care. Higher-order services are far less likely to be provided.
Comparative Absorption Profiles of Divalproex Sodium Delayed-Release Versus Extended-Release Tablets—Clinical Implications
Authors: Dutta Sandeep , Reed Ronald C , O'dea Robert F
Published: March 2006

Background:

The distinct absorption characteristics of the conventional enteric-coated, delayed-release (DR) and the novel extended-release (ER) divalproex sodium formulations are not well recognized.

Objective:

To quantitatively and qualitatively differentiate the absorption characteristics of divalproex-DR and -ER formulations.

Methods:

Healthy volunteers (N = 28) received single 1000 mg doses of divalproex-DR and divalproex-ER tablets in a crossover fashion. Noncompartmental and compartmental analyses were used to estimate valproic acid (VPA) pharmacokinetics from the plasma concentration–time profiles determined from intensive blood sampling over 48 hours.

Results:

VPA was not absorbed from divalproex-DR in the first 2 hours (absorption lag-time) after dosing. After VPA release in the intestine, approximately 63% of the dose was absorbed in less than 1 hour, that is, 2.9 hours (mean absorption time) from dosing. Maximum concentration (Cmax) was achieved approximately 4 hours after dosing. VPA absorption was complete (~93% of dose) within 3 absorption half-lives (~4.5 h) post-absorption lag-time, that is, 6–7 hours from dosing. In contrast, VPA absorption from divalproex-ER starts immediately after administration, initially at a modest rate, followed by slow and extended absorption at a constant rate for more than 20 hours; VPA concentrations at 1 and 2 hours were 28% and 40% of Cmax. Approximately 53% of the dose was absorbed within 12 hours (mean absorption time); complete absorption occurred over more than 20 hours without any dose dumping.

Conclusions:

When antihypertensive treatment options are clinically equivalent, prescribers may first consider using a verapamil SR–based strategy, especially in patients with CAD who have no history of depression. VPA absorption from enteric-coated divalproex-DR is rapid following a lag-time of approximately 2 hours and is complete within 6–7 hours of dosing. In contrast, VPA absorption from divalproex-ER starts immediately after administration, but occurs at a slow, approximately constant rate over more than 20 hours.
Book Reviews
Authors: Williams Ruth M.
Published: March 2006

Oxford guide to behavioural experiments in cognitive therapy Edited by J. Bennett‐Levy, G. Butler, M. Fennell, A. Hackmann, M. Mueller & D. Westbrook

Oxford, UK: Oxford University Press, 2004, Pp. 461, £29.95, ISBN 0‐19‐8529155/8529163
Book Reviews
Authors: Cox Sally G.
Published: March 2006

Neuropsychological assessment (4th edn) Edited by Muriel D. Lezak, Diane B. Howieson, David W. Loring (with H. Julia Hannay and Jill S. Fischer) New York: Oxford University Press. 2004, Pp. 1016, $89.50 hardback, ISBN: 0‐19‐511121‐4
Book Reviews
Authors: Wild Jennifer
Published: March 2006

Special issue: Mental imagery and memory in psychopathology Edited by Emily A. Holmes and Ann Hackmann Memory, 12(4), 2004
Book Reviews
Authors: Dudley Robert
Published: March 2006

Paranoia: The psychology of persecutory delusions

ByFreeman D. and Garety P. A. Hove: Psychology Press 2004. Maudsley Monographs 45, Pp.208, Hardback £24.95, ISBN 184169522X
Stabilization of Axon Branch Dynamics by Synaptic Maturation
Authors: Ruthazer Edward S. , Li Jianli , Cline Hollis T.
Published: March 2006

The developmental refinement of topographic projections in the brain is reflected in the dynamic sculpting of axonal arbors that takes place as connections between CNS structures form and mature. To examine the role of synaptogenesis and synaptic maturation in the structural development of axonal projections during the formation of the topographic retinotectal projection, we coexpressed cytosolic fluorescent protein (FP) and FP-tagged synaptophysin (SYP) in small numbers of retinal ganglion cells in living albinoXenopuslaevistadpoles to reveal the distribution and dynamics of presynaptic sites within labeled retinotectal axons. Two-photon time-lapse observations followed by quantitative analysis of tagged SYP levels at individual synapses demonstrated the time course of synaptogenesis: increases in presynaptic punctum intensity are detectable within minutes of punctum emergence and continue over many hours. Puncta lifetimes correlate with their intensities. Furthermore, we found that axon arbor dynamics are affected by synaptic contacts. Axon branches retract past faintly labeled puncta but are locally stabilized at intensely labeled SYP puncta. Visual stimulation for 4 h enhanced the stability of the arbor at intense presynaptic puncta while concurrently inducing the retraction of exploratory branches with only faintly labeled or no synaptic sites.
Evidence fromIn VivoImaging That Synaptogenesis Guides the Growth and Branching of Axonal Arbors by Two Distinct Mechanisms
Authors: Meyer Martin P. , Smith Stephen J
Published: March 2006

To explore the relationship between axon arbor growth and synaptogenesis, developing retinal ganglion cell (RGC) axon arbors in zebrafish optic tectum were imagedin vivoat high temporal and spatial resolution using two-photon microscopy. Individual RGC axons were dually labeled by expression of a cytosolic red fluorescent protein (DsRed Express) to mark arbor structure and a fusion of the synaptic vesicle protein synaptophysin with green fluorescent protein (Syp:GFP) to mark presynaptic vesicles. Analysis of time-lapse sequences acquired at 10 min intervals revealed unexpectedly rapid kinetics of both axon branch and vesicle cluster turnover. Nascent axonal branches exhibited short average lifetimes of 19 min, and only 17% of newly extended axonal processes persisted for periods exceeding 3 h. The majority (70%) of Syp:GFP puncta formed on newly extended axonal processes. Syp:GFP puncta also exhibited short average lifetimes of 30 min, and only 34% of puncta were stabilized for periods exceeding 3 h. Moreover, strongly correlated dynamics of Syp:GFP puncta and branch structure suggest that synaptogenesis exerts strong influences on both the extension and the selective stabilization of nascent branches. First, new branches form almost exclusively at newly formed Syp:GFP puncta. Second, stabilized nascent branches invariably bear Syp:GFP puncta, and the detailed dynamics of branch retraction suggest strongly that nascent synapses can act at branch tips to arrest retraction. These observations thus provide evidence that synaptogenesis guides axon arbor growth by first promoting initial branch extension and second by selective branch stabilization.
Synergistic Control of Protein Kinase Cγ Activity by Ionotropic and Metabotropic Glutamate Receptor Inputs in Hippocampal Neurons
Authors: Codazzi Franca , Di Cesare Alessandra , Chiulli Nino , Albanese Alberto , Meyer Tobias , Zacchetti Daniele , Grohovaz Fabio
Published: March 2006

Conventional protein kinase C (PKC) isoforms are abundant neuronal signaling proteins with important roles in regulating synaptic plasticity and other neuronal processes. Here, we investigate the role of ionotropic and metabotropic glutamate receptor (iGluR and mGluR, respectively) activation on the generation of Ca2+and diacylglycerol (DAG) signals and the subsequent activation of the neuron-specific PKCγ isoform in hippocampal neurons. By combining Ca2+imaging with total internal reflection microscopy analysis of specific biosensors, we show that elevation of both Ca2+and DAG is necessary for sustained translocation and activation of EGFP (enhanced green fluorescent protein)-PKCγ. Both DAG production and PKCγ translocation were localized processes, typically observed within discrete microdomains along the dendritic branches. Markedly, intermediate-strength NMDA receptor (NMDAR) activation or moderate electrical stimulation generated Ca2+but no DAG signals, whereas mGluR activation generated DAG but no Ca2+signals. Both receptors were needed for PKCγ activation. This suggests that a coincidence detection process exists between iGluRs and mGluRs that relies on a molecular coincidence detection process based on the corequirement of Ca2+and DAG for PKCγ activation. Nevertheless, the requirement for costimulation with mGluRs could be overcome for maximal NMDAR stimulation through a direct production of DAG via activation of the Ca2+-sensitive PLCδ (phospholipase Cδ) isoform. In a second important exception, mGluRs were sufficient for PKCγ activation in neurons in which Ca2+stores were loaded by previous electrical activity. Together, the dual activation requirement for PKCγ provides a plausible molecular interpretation for different synergistic contributions of mGluRs to long-term potentiation and other synaptic plasticity processes.
Nuclear Factor κB Deficiency Is Associated with Auditory Nerve Degeneration and Increased Noise-Induced Hearing Loss
Authors: Lang Hainan , Schulte Bradley A. , Zhou Daohong , Smythe Nancy , Spicer Samuel S. , Schmiedt Richard A.
Published: March 2006

Degeneration of the spiral ganglion neurons (SGNs) of the auditory nerve occurs with age and in response to acoustic injury. Histopathological observations suggest that the neural degeneration often begins with an excitotoxic process affecting the afferent dendrites under the inner hair cells (IHCs), however, little is known about the sequence of cellular or molecular events mediating this excitotoxicity. Nuclear factor κB (NFκB) is a transcription factor involved in regulating inflammatory responses and apoptosis in many cell types. NFκB is also associated with intracellular calcium regulation, an important factor in neuronal excitotoxicity. Here, we provide evidence that NFκB can play a central role in the degeneration of SGNs. Mice lacking the p50 subunit of NFκB (p50−/−mice) showed an accelerated hearing loss with age that was highly associated with an exacerbated excitotoxic-like damage in afferent dendrites under IHCs and an accelerated loss of SGNs. Also, as evidenced by immunostaining intensity, calcium-buffering proteins were significantly elevated in SGNs of the p50−/−mice. Finally, the knock-out mice exhibited an increased sensitivity to low-level noise exposure. The accelerated hearing loss and neural degeneration with age in the p50−/−mice occurred in the absence of concomitant hair cell loss and decline of the endocochlear potential. These results indicate that NFκB activity plays an important role in protecting the primary auditory neurons from excitotoxic damage and age-related degeneration. A possible mechanism underlying this protection is that the NFκB activity may help to maintain calcium homeostasis in SGNs.
A 3-Synapse Positive Feedback Loop Regulates the Excitability of an Interneuron Critical for Sensitization in the Leech
Authors: Crisp Kevin M. , Muller Kenneth J.
Published: March 2006

Sensitization of reflexive shortening in the leech has been linked to serotonin (5-HT)-induced changes in the excitability of a single interneuron, the S cell. This neuron is necessary for sensitization and complete dishabituation of reflexive shortening, during which it contributes to the sensory-motor reflex. The S cell does not contain 5-HT, which is released primarily from the Retzius (R) cells, whose firing enhances S-cell excitability. Here, we show that the S cell excites the R cells, mainly via a fast disynaptic pathway in which the first synapse is the electrical junction between the S cell and the coupling interneurons, and the second synapse is a glutamatergic synapse of the coupling interneurons onto the R cells. The S cell-triggered excitatory postsynaptic potential in the R cell diminishes and nearly disappears in elevated concentrations of divalent cations because the coupling interneurons become inexcitable under these conditions. Serotonin released from the R cells feeds back on the S cell and increases its excitability by activating a 5-HT7-like receptor; 5-methoxytryptamine (5-MeOT; 10 μm) mimics the effects of 5-HT on S cell excitability, and effects of both 5-HT and 5-MeOT are blocked by pimozide (10 μm) and SB-269970 [(R)-3-(2-(2-(4-methylpiperidin-1-yl)-ethyl)pyrrolidine-1-sulfonyl)phenol] (5 μm). This feedback loop may be critical for the full expression of sensitization of reflexive shortening.
The Different Effects on Recognition Memory of Perirhinal Kainate and NMDA Glutamate Receptor Antagonism: Implications for Underlying Plasticity Mechanisms
Authors: Barker Gareth R. I. , Warburton E. Clea , Koder Timothy , Dolman Nigel P. , More Julia C. A. , Aggleton John P. , Bashir Zafar I. , Auberson Yves P. , Jane David E. , Brown Malcolm W.
Published: March 2006

To investigate the involvement of different types of glutamate receptors in recognition memory, selective antagonists of NMDA and kainate receptors were locally infused into the perirhinal cortex of the rat temporal lobe. Such infusion of a selective kainate receptor antagonist produced an unusual pattern of recognition memory impairment: amnesia after a short (20 min) but not a long (24 h) delay. In contrast, antagonism of perirhinal NMDA glutamate receptors by locally infused AP-5 (2-amino-5-phosphonopentanoic acid) impaired recognition memory after the long but not the short delay. For both drugs, impairment was found when the drug was present during acquisition but not when it was present during retrieval. Experimentsin vitroindicate that selective antagonism of NMDA receptors containing NR2A subunits blocks perirhinal long-term potentiation (LTP), whereas antagonism of NMDA receptors containing NR2B subunits blocks long-term depression (LTD). However, recognition memory after a 24 h delay was impaired only when both an NR2A and an NR2B antagonist were infused together, not when either was infused separately. These results establish that kainate receptors have a role in recognition memory that is distinct from that of NMDA receptors, that there must be at least two independent underlying memory mechanisms in the infused region, that this region and no other is necessary for both short-term and long-term familiarity discrimination, and that perirhinal-dependent long-term recognition memory does not rely solely on processes used in NMDA-dependent LTP or LTD (although it might be independently supported by components of each type of process with one substituting for the other).
Early and Simultaneous Emergence of Multiple Hippocampal Biomarkers of Aging Is Mediated by Ca2+-Induced Ca2+Release
Authors: Gant John C. , Sama Michelle M. , Landfield Philip W. , Thibault Olivier
Published: March 2006

Age-dependent changes in multiple Ca2+-related electrophysiological processes in the hippocampus appear to be consistent biomarkers of aging, and several also correlate with cognitive decline. These findings have led to the hypothesis that a common mechanism of Ca2+dyshomeostasis underlies aspects of aging-dependent brain impairment. However, some key predictions of this view remain untested, including that multiple Ca2+-related biomarkers should emerge concurrently during aging and their onset should also precede/coincide with initial signs of cognitive decline. Moreover, blocking a putative common source of dysregulated Ca2+should eliminate aging differences. Here, we tested these predictions using combined electrophysiological, imaging, and pharmacological approaches in CA1 neurons to determine the ages of onset (across 4-, 10-, 12-, 14-, and 23-month-old F344 rats) of several established biomarkers, including the increases in the slow afterhyperpolarization, spike accommodation, and [Ca2+]irise during repetitive synaptic stimulation. In addition, we tested the hypothesis that altered Ca2+-induced Ca2+release (CICR) from ryanodine receptors, which can be triggered by L-type Ca2+channels, provides a common source of dysregulated Ca2+in aging. Results showed that multiple aging biomarkers were first detectable at about the same age (12 months of age; approximately midlife), sufficiently early to influence initial cognitive decline. Furthermore, selectively blocking CICR with ryanodine slowed the Ca2+rise during synaptic stimulation more in aged rat neurons and, notably, reduced or eliminated aging differences in the biomarkers. Thus, this study provides the first evidence that altered CICR plays a role in driving the early and simultaneous emergence in hippocampus of multiple Ca2+-related biomarkers of aging.
B-Ephrin Reverse Signaling Is Required for NMDA-Independent Long-Term Potentiation of Mossy Fibers in the Hippocampus
Authors: Armstrong John N. , Saganich Michael J. , Xu Nan-Jie , Henkemeyer Mark , Heinemann Stephen F. , Contractor Anis
Published: March 2006

The mossy fiber to CA3 pyramidal neuron synapse in the hippocampus displays an atypical form of NMDA receptor-independent long-term potentiation (LTP). Plasticity at this synapse is expressed in the presynaptic terminal as an elevated probability of neurotransmitter release. However, evidence indicates that postsynaptic mechanisms and trans-synaptic signaling through an association between postsynaptic EphB receptors and presynaptic B-ephrins are necessary for the induction of LTP. Here we show that ephrin-B3 protein is highly expressed in mossy fiber axons and terminals. There are specific deficits in mossy fiber LTP in mice in which the cytoplasmic C-terminal signaling domain of the ephrin-B3 protein is replaced with β-galactosidase. These deficits are not observed in ephrin-B3 null mutant mice because of functional redundancy by virtue of other B-ephrins. These results indicate that B-ephrin reverse signaling into the presynaptic mossy fiber bouton is required for the induction of NMDA receptor-independent LTP at this synapse.