bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of a non-homogeneous sphere on a rigid surface
Authors: Carré M J , James D M , Haake S J
Published: March 2004

This paper examines the impact behaviour of a non-homogenous sphere (in this case a cricket ball with a rolled core construction) with a rigid surface. Experiments were carried out to measure the force-deflection behaviour of a cricket ball during a normal impact in two orientations (impacting on the seam and perpendicular to the seam). For the two orientations of impact, a disparity was found in terms of the force-deflection behaviour. Greater deformation was found for impacts landing on the seam, compared to those landing perpendicular to the seam. Comparisons with quasi-static test data suggested that only the bottom third of the ball may have been compressed during impact.

The dynamic force-deflection behaviour was modelled using a mass attached to a Hertzian spring in parallel with a damper whose damping coefficient varied with the contact area. The coefficients in the model could be described using the velocity before impact alone. The model was found to be in good agreement with the experimental data.

The model was then extended to predict oblique impacts by incorporating a measured coefficient of friction. This performed well in predicting the rebound velocity, angle and spin of a cricket ball after oblique impact with a cricket pitch. Inconsistencies in the results were attributed to deformation in the pitch surface.
A comparative study of dynamic mesh updating methods used in the simulation of fluid-structure interaction problems with a non-linear free surface
Authors: Sudharsan N M , Ajaykumar R , Murali K , Kumar K
Published: March 2004

This paper compares the performance of three mesh movement algorithms: Laplacian smoothing, linear spring analogy and torsion spring analogy for a fluid mesh update in staggered fluid-structure interaction (FSI) simulations with a non-linear free surface. The mesh updating schemes are applied to simulate three representative cases of the above-stated dual moving boundary problem. The performances of the algorithms are gauged on the basis of their ability to delay the initiation of a complete remesh of the fluid domain while maintaining solution accuracy. To satisfy this dual objective, the mesh-updating algorithm should not only prevent mesh failure but should also maintain well-shaped triangles. The reasons for the failure of different schemes are explained and suitable modifications are suggested/implemented to enhance thier performance. It is shown that these modifications prove to be very successful in improving the effectiveness of the algorithms.
A mathematical solution to the design and manufacturing problems of ball-end cutters having a cutting edge with constant angle to the axis
Authors: Chen W-F
Published: March 2004

This paper considers two of the major problems associated with the design and manufacture of ball-end cutters whose cutting edge lies at a constant angle to the axis. The first problem involves the inability to solve the mathematical description of the cutting edge at the top of the ball-end cutter, while the second problem relates to the tendency of the grinding wheel feeding speed description to approach infinity in the same region. Mathematical models are developed to overcome these problems. These models provide a valuable reference for the future design and manufacture of cutters of this type.
A fluid film model for finite element analysis of structures with linear hydrostatic bearings
Authors: Jeon S Y , Kim K H
Published: March 2004

Linear hydrostatic bearings are well known for their high motion guide accuracy, low friction and wear, high stiffness and high load-carrying capacity. It is very useful to predict the behaviour of a structure with linear hydrostatic bearings in the design stage. In this work, a finite element model is suggested to represent fluid films between bearing blocks and rails. The model can be used to capture the deformation of the bearing structure as well as the varying properties of the fluid film. With this model incorporated into the commercial finite element code ABAQUS, static and quasi-static analyses of the structures containing hydrostatic bearings can be performed efficiently. Comparisons with known experimental data are presented.
Acceleration of coagulation of particles in oil utilizing an a.c. electric field
Authors: Yanada H , Nishimura N , Imagawa T
Published: March 2004

This paper describes an experimental investigation of the coagulation of particles in oil accelerated by the action of an a.c. electric field. The ultimate goal of the investigation is to develop a high-performance electrostatic filter for insulating liquids. In order to reveal the coagulation mechanism and find out the mechanical conditions suitable for the coagulation, the effects of various factors on the coagulation are investigated using spherical silica particles of 2, 4 and 6 μm in diameter. The coagulating state of the silica particles in oil is observed using a video-microscope with a CCD (charge coupled device) camera under various conditions. It is shown that the coagulation is better promoted with larger particles and that the particles having a small diameter are not easily coagulated. It is also shown that the oscillation amplitude relative to the double-layer thickness dominates the coagulation phenomenon. The experimental results suggest that when the surface charge on a particle and the charge in the surrounding double layer are appropriately polarized by the influence of the a.c. electric field, the coagulation is accelerated by virtue of a (relatively) strong attractive force acting between two-particle-double-layer pairs.
A new idea to improve tooth profile precision of involute spur gears manufactured by hob cutters
Authors: Chang S-L
Published: March 2004

Theoretically, hob cutters with a straight-sided cutting edge can generate a perfect involute tooth profile. However, due to an unbalanced cutting force, there will be deviation between the actual and the theoretical tooth profile. In this paper, an involute tooth profile manufactured by a hob cutter has been developed based on the theory of even contact. The concept of a shifted cutter was used to correct the tooth profile deviation of involute spur gears.
Implementation of a virtual tennis entertainment system with haptic behaviour
Authors: Hsu K-S , Cheng M-Y , Her M-G
Published: March 2004

For most of the virtual reality system, one of the major aims is to provide a vivid interaction platform between the human operators and the haptic devices. Through the user interface, a skilful operator can control the haptic devices to accomplish relatively complicated jobs in real-time. Generally, the main components of a virtual reality system include dynamic simulations, haptic devices and the user interface, which is composed of virtual environments and visual equipment. This study focuses on developing a virtual tennis entertainment system with haptic behaviour. A parallel-type robot and a serial-type robot are employed as the haptic device handlers in this study, in which they are controlled directly by the operator's arm through the user interface. The operator can sense the change in virtual environment provided by dynamic simulations. In addition, the human operator can ‘see’ the change of environment during operation in real-time through the screen. A virtual spring model and a virtual damper model were constructed to simulate the process of tennis playing in this study. Experimental results verify the feasibility of the proposed virtual tennis entertainment system.
A Decision Analysis Method for Evaluating Computer Intrusion Detection Systems
Authors: Ulvila Jacob W. , Gaffney John E.
Published: March 2004

This paper presents a decision analysis method for evaluating computer intrusion detection systems. The method integrates and extends receiver operating characteristic (ROC) and cost analysis methods to provide an expected cost metric. We demonstrate that both the ROC analysis and cost analysis methods are incomplete. Furthermore, we demonstrate how a decision tree can combine and extend the ROC and cost analysis methods to provide an expected cost metric that reflects the intrusion detection system's ROC curve, costs, and assessments of the hostility of the environment as summarized by the prior probability of intrusion. We further demonstrate how this method can be used to decide the optimal operating point on an intrusion detector's ROC curve, choose the best intrusion detection system, compare the value of one intrusion detection system with another's, determine the value of an intrusion detector over no detector, and determine how to adjust the operation of an intrusion detector to respond to changes in its environment. General results are given and the method is illustrated in several numerical examples that involve both hypothetical and real intrusion detection systems. We demonstrate that, contrary to common advice, the value of an intrusion detection system depends not only on its ROC curve, but also on various costs (such as those associated with making incorrect decisions about detection) and the hostility of the operating environment. Conclusions are drawn about the design and evaluation of intrusion detection systems and the role for decision analysis in that design and evaluation.
Clinical Applications in the Decision Analysis Literature
Authors: Cantor Scott B.
Published: March 2004

The author provides a comment to the companion literature review, focusing on clinical applications of decision analysis. The theory and application of clinical decision analysis has decreased in the management science and operations research literature, but has become a field in and of itself, with contributions to the medical and analytical communities. Decision scientists should be aware of methodological contributions in the health decision science literature.
Reversing the Perspective on the Applications of Decision Analysis
Authors: Hämäläinen Raimo P.
Published: March 2004

This paper looks into the strengths, weaknesses, opportunities, and threats (SWOT) of the field of the applications based on DA techniques; focusing especially on MAVT. The need for best practices and bias-resistant analysis procedures is pointed out. In most application papers there are no reports on the verification or testing of the procedures used. The Internet provides great opportunities in the delivery of DA software and e-learning material. Public sites such as Decisionarium ( www.decisionarium.hut.fi ) provide encouragement and a low entry level to try value tree analysis in new applications. There are also great opportunities in reaching out the other MCDA communities such as AHP practitioners. Today the need and demand for decision support is perhaps growing most rapidly in environmental problems. A clear trend is also the integration of DA into GIS and other models. Many of the applications are now published in non-OR/MS subject area journals.
The Filtered Nearest Neighbor Method for Generating Low-Discrepancy Sequences
Authors: Bennett Mihoko V. , Willemain Thomas R.
Published: March 2004

We introduce the filtered nearest neighbor method for generating low-discrepancy random-number sequences. Simulations show that these sequences have lower discrepancy than either pseudo random or quasi random numbers when used to generate small samples (N ≤ 300) in high dimensions (p ≥ 24). They are therefore useful for approximating high-dimensional expectation integrals when function evaluation is expensive.
A Hybrid Genetic/Optimization Algorithm for Finite-Horizon, Partially Observed Markov Decision Processes
Authors: Lin Zong-Zhi , Bean James C. , White Chelsea C.
Published: March 2004

The partially observed Markov decision process (POMDP) is a generalization of a Markov decision process that allows for noise-corrupted and costly observations of the underlying system state. The value function of the infinite horizon POMDP is known to be piecewise affine and convex in the probability mass vector over the state space. Such a function can be represented by a finite set of affine functions.

In this paper, we develop and evaluate an exact algorithm, GAMIP, which combines a genetic algorithm and a mixed integer program to construct the minimal set of affine functions that describes the value function. Numerical results indicate that GAMIP takes up to 60% less time to construct the minimal set than does the most efficient linear programming-based exact solution method in the literature.
Generating Cutting Planes for Mixed Integer Programming Problems in a Parallel Computing Environment
Authors: Lee Eva K.
Published: March 2004

A parallel implementation of a disjunctive cutting-plane algorithm in a distributed memory environment is described. Guided by a selection of difficult instances from MIPLIB and real instances obtained from brain-tumor research, various strategies of cut synchronization are considered, and their influence on speedup, communication overhead, load balance, and effectiveness in closing the integrality gap are studied. The parallel cutting-plane algorithm is coupled with an LP-based heuristic to assist in returning a good quality integer feasible solution upon termination of the parallel process. The parallel implementation is sufficiently coarse-grained to yield an average of less than 6% of the total time performing tasks associated with communication overhead, and it provides reasonable speedup when executing in parallel. Noticeable differences in load-balance scores are observed, depending on the number of processors used, the synchronization scheme used, and the structure of the MIP problem instance. Nevertheless, the synergism of the combined collection of cuts generated locally on each processor is effective in closing the integrality gap in all cases, and there is minimal variability in the amount of the gap closed as the number of processors varies. In particular, the degree of decentralization, as governed by the synchronization schemes, has little effect on the overall quality of the cuts generated.
Accelerating the Profitability of Hewlett-Packard's Supply Chains
Authors: Billington Corey , Callioni Gianpaolo , Crane Barrett , Ruark John D. , Rapp Julie Unruh , White Trace , Willems Sean P.
Published: March 2004

Hewlett-Packard (HP) developed a standard and common process for analysis coupled with advancement in inventory optimization techniques to invent a new and robust way to design supply-chain networks. This new methodology piloted by HP's Digital Imaging division has received sponsorship from HP's Executive Supply- Chain Council and is now being deployed across the entire company. As of May 2003, a dozen product lines have been exposed to this methodology, with four product lines already integrating this process into both the configuration of their new-product supply chains and the improvement of existing-product supply chains. The team will highlight the application of these new capabilities within HP's Digital Camera and Inkjet Supplies businesses. The realized savings from these first two projects exceeds $130 million.
The Canadian Pacific Railway Transforms Operations by Using Models to Develop Its Operating Plans
Authors: Ireland Phil , Case Rod , Fallis John , Dyke Carl Van , Kuehn Jason , Meketon Marc
Published: March 2004

North American railways have traditionally practiced tonnage-based dispatching, running trains only when they have enough freight. As a result, their customer service and their use of crews, fixed assets, locomotives, and railcars are poor. Canadian Pacific Railway is using new decision-support tools developed in-house and by MultiModal Applied Systems to create a scheduled railway. These tools use operations research approaches, such as an optimal block-sequencing algorithm, a heuristic algorithm for block design, (very fast) simulation, and time-space network algorithms for planning locomotive use and distributing empty cars. This implementation has saved $300 million Canadian (US$170 million) from mid-1999 through autumn 2000. We estimate it has saved at least an additional $210 million Canadian during 2001 and 2002 in fuel and labor costs alone. Labor productivity, locomotive productivity, fuel consumption, and railcar velocity have improved by 40, 35, 17, and 41 percent, respectively. Furthermore, Canadian Pacific Railway now provides its customers with reliable delivery times and has received many customer and shipping association awards for its improvement in service.
2003 Franz Edelman Award for Achievement in Operations Research and the Management Sciences
Authors: Spencer Thomas , Graves Stephen C.
Published: March 2004

This special issue of Interfaces presents the finalists and winners of the 32nd annual competition for the Franz Edelman Award for Achievement in Operations Research and the Management Sciences, the profession's prestigious award for the practice of operations research and the management sciences. Thomas Spencer III, chairman of the competition, and Stephen C. Graves, editor of the special issue, provide an overview of the competition and introduce the finalists and winners.
Contract Optimization at Texas Children's Hospital
Authors: Born Chris , Carbajal Monica , Smith Pat , Wallace Mark , Abbott Kirk , Adyanthaya Surain , Boyd E. Andrew , Keller Curtis , Liu Jin , New Wayne , Rieger Tom , Winemiller Bert , Woestemeyer Ron
Published: March 2004

In 1998, faced with mounting financial pressure, Texas Children's Hospital found its mission in jeopardy. Payors sought to reduce expenditures, while physicians wanted to provide the highest quality patient care, research, and teaching. Working with PROS Revenue Management, the hospital spearheaded an initiative to bring greater analytic capabilities to administrative operations, initially focusing on optimizing the performance of contracts with insurers because of the potential revenue leverage. It did so by (1) quantifying expected future demand through forecasting, (2) establishing risk as an important means of measuring contract performance, and (3) embedding the underlying Bayesian forecasting and nonlinear optimization models in a software system that supports the daily activities of contract negotiators. Direct benefits include revenue improvements of up to $17 million annually on contracts renegotiated with use of the PROS technology. The project's initial success has spawned efforts to improve the hospital's planning and operational activities. With a system designed for transfer to other hospital settings and possible enhancement of the diagnosis-related group (DRG) classification system through the use of patient pathways, the health-care optimization technology has the potential for broad impact in the industry.
Random Walks and Voting Theory
Authors: Vieille Nicolas
Published: March 2004

Voters' preferences depend on available information. Following Case-Based Decision Theory, we assume that this information is processed additively. We prove that the collective preferences deduced from the individual ones through majority vote cannot be arbitrary, as soon as a winning quota is required. The proof is based on a new result on random walks.
A Long-Range Dependent Workload Model for Packet Data Traffic
Authors: Çağlar M.
Published: March 2004

We consider a probabilistic model for workload input into a telecommunication system. It captures the dynamics of packet generation in data traffic as well as accounting for long-range dependence and self-similarity exhibited by real traces. The workload is found by aggregating the number of packets, or their sizes, generated by the arriving sessions. The arrival time, duration, and packet-generation process of a session are all governed by a Poisson random measure. We consider Pareto-distributed session holding times where the packets are generated according to a compound Poisson process. For this particular model, we show that the workload process is long-range dependent and fractional Brownian motion is obtained as a heavy-traffic limit. This yields a fast synthesis algorithm for generating packet data traffic as well as approximating fractional Brownian motion.
Quadratic Hedging and Mean-Variance Portfolio Selection with Random Parameters in an Incomplete Market
Authors: Lim Andrew E. B.
Published: March 2004

This paper concerns the problems of quadratic hedging and pricing, and mean-variance portfolio selection in an incomplete market setting with continuous trading, multiple assets, and Brownian information. In particular, we assume throughout that the parameters describing the market model may be random processes. We approach these problems from the perspective of linear-quadratic (LQ) optimal control and backward stochastic differential equations (BSDEs); that is, we focus on the so-called stochastic Riccati equation (SRE) associated with the problem. Excepting certain special cases, solvability of the SRE remains an open question. Our primary theoretical contribution is a proof of existence and uniqueness of solutions of the SRE associated with the quadratic hedging and mean-variance problems. In addition, we derive closed-form expressions for the optimal portfolios and efficient frontier in terms of the solution of the SRE. A generalization of the Mutual Fund Theorem is also obtained.
The Mean Number-in-System Vector Range for Multiclass Queueing Networks
Authors: Eaves B. Curtis , Glynn Peter W. , Rothblum Uriel G.
Published: March 2004

In a multiclass network of queues, natural sufficient conditions are given for the mean number-in-system vector to cover the nonnegative orthant as the arrival rate vector varies over the stable domain.
Pharmacologic Management of Alzheimer Disease Part I: Hormonal and Emerging Investigational Drug Therapies
Authors: Flynn Barbara L
Published: March 2004

OBJECTIVE:

To provide information about current genetic research in Alzheimer disease (AD) and potential pharmacologic interventions. Investigational pharmacologic management of AD, including serenics, hormonal therapy, neurotransmitter augmentation, neurobiologic agents, nootropics, and ampakines are also reviewed.

DATA SOURCES:

Studies, review articles, and editorials identified from MEDLINE searches (from January 1993 to December 1996), and bibliographies of identified articles.

STUDY SELECTION:

Studies, review articles, and editorials addressing current areas of AD pharmacotherapy research, including hormonal therapy and select investigational agents.

DATA EXTRACTION:

Pertinent information was selected and the data were synthesized into a review format.

DATA SYNTHESIS:

AD is a devastating disease characterized by progressive memory loss, cognitive decline, and behavioral disturbances. The behavioral problems associated with AD can present a difficult clinical challenge. Many patients with AD are intolerant of traditional pharmacologic management, including antipsychotics, antidepressants, and anxiolytics. Hormonal agents, including estrogen, medroxyprogesterone, and cyproterone acetate, may be efficacious therapeutic alternatives in the management of sexual behavioral disturbances in men. Research regarding estrogen's role in AD prevention and effect on cognitive function and behavioral symptoms in women with AD are evaluated. Studies evaluating neurotransmitter augmentation and neurobiologic agents in AD are reviewed.

CONCLUSIONS:

Environmental, genetic, neurobiologic, hormonal, and neurotransmitter influences, and their respective roles in AD pathology, are being investigated. Researchers concur that it is imperative to recognize the correlation of these factors in the etiology of AD to design effective prevention and treatment strategies. Additional studies are essential to elucidate the most efficacious treatments for AD and the attendant behavioral disturbances.
Management of Patients with Type 2 Diabetes by Pharmacists in Primary Care Clinics
Authors: Coast-Senior Elizabeth A , Kroner Beverly A , Kelley Catherine L , Trilli Lauren E
Published: March 2004

OBJECTIVE:

To determine the impact of clinical pharmacists involved in direct patient care on the glycemic control of patients with type 2 diabetes mellitus.

DESIGN:

Eligible patients included those with type 2 diabetes who received insulin or were initiated on insulin therapy by the pharmacists and were willing to perform self-monitoring of blood glucose. The pharmacists provided diabetes education, medication counseling, monitoring, and insulin initiation and/or adjustments. All initial patient interactions with the pharmacists were face-to-face. Thereafter, patient–pharmacist interactions were either face-to-face or telephone contacts.

SETTING:

Two primary care clinics in a university-affiliated Veterans Affairs Medical Center.

PARTICIPANTS:

Study subjects were patients with type 2 diabetes who were referred to the pharmacists by their primary care providers for better glycemic control.

OUTCOME MEASURES:

Primary outcome variables were changes from baseline in glycosylated hemoglobin, fasting blood glucose, and random blood glucose measurements. Secondary outcomes were the number and severity of symptomatic episodes of hypoglycemia, and the number of emergency room visits or hospitalizations related to diabetes. Twenty-three veterans aged 65 ± 9.4 years completed the study. Fifteen (65%) patients were initiated on insulin by the pharmacists; 8 (35%) were already using insulin. Patients were followed for a mean ± SD of 27 ± 10 weeks. Glycosylated hemoglobin, fasting blood glucose concentrations, and random blood glucose concentrations significantly decreased from baseline by 2.2% (p = 0.00004), 65 mg/dL (p < 0.01), and 82 mg/dL (p = 0.00001), respectively. Symptomatic hypoglycemic episodes occurred in 35% of patients. None of these episodes required physician intervention.

CONCLUSIONS:

This study demonstrates that pharmacists working as members of interdisciplinary primary care teams can positively impact glycemic control in patients with type 2 diabetes requiring insulin.
Pharmacologic Management of Alzheimer Disease Part II: Antioxidants, Antihypertensives, and Ergoloid Derivatives
Authors: Flynn Barbara L , Ranno Anthony E
Published: March 2004

OBJECTIVE:

To provide information about research evaluating antioxidants in Alzheimer disease (AD) and to discuss the potential role of β-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD therapy.

DATA SOURCES:

Studies, review articles, and editorials identified from MEDLINE searches (from 1989 to 1997) and bibliographies of identified articles.

STUDY SELECTION:

Studies and review articles addressing antioxidant, antihypertensive, and ergoloid derivative pharmacotherapy research.

DATA EXTRACTION:

Pertinent information was selected and the data synthesized into a review format.

DATA SYNTHESIS:

AD is a progressive neuropsychiatric disorder of unknown etiology. Studies evaluating the possible association between a free radical mechanism in AD and the potential role of antioxidants are reviewed. Additionally, the role of β-blockers, angiotensin-converting enzyme inhibitors, clonidine, guanfacine, nimodipine, and ergoloid derivatives in AD management are discussed.

CONCLUSIONS:

Preliminary evidence suggests that antioxidants may have a protective effect against the development of AD. Additional prospective, double-blind, placebo-controlled studies are needed to determine the role of antioxidants in the prevention and management of AD. Understanding the role of antioxidants in AD may suggest alternative agents that have similar pharmacologic activity. β-Blockers may be an option to control agitation in AD patients for whom anxiolytics or antipsychotics are ineffective or are contraindicated because of their adverse effect profiles. Other agents that may have a role in AD therapy include angiotensin-converting enzyme inhibitors, nimodipine, and ergoloid derivatives. Clonidine and guanfacine have thus far shown little promise in improving cognitive function in AD. Further prospective, double-blind, placebo-controlled trials will be necessary to elucidate the role of these agents in AD management.
Local Therapy for Cytomegalovirus Retinitis
Authors: Smith Curtis L
Published: March 2004

OBJECTIVE:

To examine the role of intraocular therapy in the management of cytomegalovirus (CMV) retinitis associated with AIDS.

DATA SOURCES:

A MEDLINE search was conducted for the years 1980–1997. In addition, relevant articles were cross-referenced to screen for additional information. The AIDS/HIV Treatment Directory was searched for information on ongoing studies.

STUDY SELECTION/DATA EXTRACTION:

Data regarding the use of local antiviral therapy for CMV retinitis are cited. Emphasis was placed on randomized, controlled trials, but descriptive studies are also included.

DATA SYNTHESIS:

Intraocular drug administration is an alternative therapy for CMV retinitis that avoids some of the disadvantages associated with systemic treatment. Intravitreal ganciclovir 200–2000 μg once weekly has been studied in a number of nonrandomized studies. Although initially effective, intravitreal ganciclovir is associated with a significant relapse rate and development of contralateral CMV retinitis. Intraocular ganciclovir implants offer the advantage of less frequent interventions and constant drug concentrations in the vitreous. Time to progression is significantly longer in patients receiving implants versus intravenous therapy; however, there is a higher incidence of contralateral eye retinitis and extraocular CMV disease with the implants. Currently, the intraocular implant is being studied in combination with oral ganciclovir to decrease the incidence of systemic CMV disease. Foscarnet and cidofovir have also been administered intravitreally for CMV retinitis. Cidofovir may offer the advantage of a long intracellular half-life, which would allow infrequent dosing; however, further study is needed to determine a safe and effective intraocular dosage.

CONCLUSIONS:

Systemic therapy continues as standard management for CMV retinitis. Local therapy has some advantages and disadvantages, but larger, randomized, controlled trials comparing systemic therapy with local therapy must be completed to define its exact role. Data from an ongoing trial of local plus oral therapy will better define this role.
Atypical Antipsychotics: Part II Adverse Effects, Drug Interactions, and Costs
Authors: Brown Candace S , Markowitz John S , Moore Thea R , Parker Nicole G
Published: March 2004

OBJECTIVE:

To compare the adverse effects, drug interactions, and costs of conventional and atypical agents, and to provide a summary of therapeutic guidelines. Part I compared the pharmacology, pharmacokinetics, and efficacy of atypical and conventional agents.

DATA SOURCES:

Information was retrieved from a MEDLINE English-language literature search from June 1986 to June 1998 and by review of references. Indexing terms included atypical antipsychotics, neuroleptics, clozapine, risperidone, olanzapine, sertindole, quetiapine, and ziprasidone.

STUDY SELECTION:

Comparative studies were selected when possible; placebo-controlled studies were included when data were limited on newer atypical antipsychotics.

DATA EXTRACTION:

Emphasis was placed on properly designed clinical trials that assessed dosage, expanded efficacy, enhanced adverse effect profile, and cost.

DATA SYNTHESIS:

Significant adverse effects are agranulocytosis with clozapine, dose-dependent extrapyramidal side effects (EPS) with risperidone, and neuroleptic malignant syndrome with clozapine and risperidone. Clinically relevant drug interactions may occur with clozapine–lorazepam, clozapine–fluvoxamine, and sertindole– quinidine. Newer atypical agents have high acquisition costs but may reduce noncompliance and rehospitalization rates.

CONCLUSIONS:

Risperidone or olanzapine are recommended as first-line agents for schizophrenia due to accumulating controlled trials and clinical experience. Quetiapine should be considered with partial response or if EPS develop, and clozapine is an option with treatment-refractory patients. Atypical agents may contribute to a better quality of life, but conventional neuroleptics are the first choice for strictly cost considerations.
Ranitidine Bismuth Citrate in the Treatment of Helicobacter Pylori Infection and Duodenal Ulcer
Authors: Vondracek Thomas G
Published: March 2004

OBJECTIVE:

To review the clinical pharmacology of ranitidine bismuth citrate in the treatment of Helicobacter pylori (HP) Infection and Duodenal Ulcer.

DATA SOURCES:

A MEDLINE search of the English-language literature from 1992 to January 1997 was conducted using the key terms Tritec, ranitidine, and bismuth. References of articles pertaining to treatment of duodenal ulcer or HP were extensively searched for relevant sources.

DATA EXTRACTION:

All articles pertaining to ranitidine bismuth citrate were considered for inclusion, with emphasis placed on randomized, double-blind trials. Priority was placed on data pertaining to regimens that are currently approved by the Food and Drug Administration for the treatment of duodenal ulcer in conjunction with HP.

DATA SYNTHESIS:

Each tablet of ranitidine bismuth citrate 400 mg contains 162 mg of ranitidine base, 128 mg of trivalent bismuth, and 110 mg of citrate. It uses the acid-suppressive actions of ranitidine and the antimicrobial and mucosal protective effects of bismuth to eradicate HP. Ranitidine bismuth citrate in conjunction with clarithromycin represents one of four treatment regimens currently approved in the US for duodenal ulcer associated with HP infection. In four double-blind, randomized trials, this agent has achieved HP eradication rates of 73–94% and duodenal ulcer healing rates of 73–89%. It is given twice daily for 28 days, and is associated with very low rates of adverse effects.

CONCLUSIONS:

Relative to some therapeutic alternatives, ranitidine bismuth citrate plus clarithromycin may be simpler to take and have less adverse effects, but may be more expensive. Compared with omeprazole plus clarithromycin, it is less expensive, may have lower ulcer healing rates, but may be more effective in eradicating HP. The role of ranitidine bismuth citrate will continue to evolve as more patients are treated, and other regimens continue to be tested for duodenal ulcer healing and HP eradication.
Pharmacotherapeutic Issues for Women of Childbearing Age with Epilepsy
Authors: Chang Shu-Ing , McAuley James W
Published: March 2004

James W McAuley

BSPharm PhD, Assistant Professor of Pharmacy Practice and Administration and Neurology, Colleges of Pharmacy and Medicine, The Ohio State University

OBJECTIVE:

To provide an overview of key pharmacotherapeutic issues in epilepsy for the woman of childbearing potential.

DATA SOURCES:

A MEDLINE search (1966–1997) was done to identify pertinent literature. Chapters in epilepsy textbooks, pregnancy registries, and their respective bibliographies were also evaluated.

STUDY SELECTION AND DATA EXTRACTION:

All identifiable sources written in English were evaluated.

DATA SYNTHESIS:

Epilepsy is a common neurologic disorder. It is estimated that nearly 1 million American women of childbearing age have epilepsy. There are many women's health issues in epilepsy. These include menstrual cycle influences on seizure activity, contraceptive–antiepileptic drug interactions, pharmacokinetic changes during pregnancy, teratogenicity of antiepileptic drugs, breast-feeding, and quality of life. These issues challenge both the woman with epilepsy and the many healthcare providers involved in her care. This article reviews these issues and makes recommendations. It addresses both the first-generation antiepileptic drugs (phenobarbital, phenytoin, carbamazepine, valproic acid) and the newer or second-generation agents (felbamate, gabapentin, lamotrigine, topiramate, tiagabine).

CONCLUSIONS/RECOMMENDATIONS:

Drug interactions between enzyme-inducing antiepileptic drugs and contraceptives are well documented. Higher doses of oral contraceptives or a second contraceptive method are suggested if epileptic women use an enzyme-inducing antiepileptic drug. Planned pregnancy is highly recommended and counseling before conception is crucial. Prepregnancy counseling should include, but is not limited to, folic acid supplementation, optimal control of seizure activity, monotherapy with the lowest effective antiepileptic drug dose, and medication adherence. Patient information should be provided about the risk of teratogenicity and the importance of prenatal care. Antiepileptic drug dosage adjustments may be necessary and should be based on clinical symptoms, not solely on serum drug concentrations. While the future holds promise for many aforementioned women's issues in epilepsy, many questions remain to be answered.
Update on Drug Interactions with Azole Antifungal Agents
Authors: Lomaestro Ben M , Piatek Michelle Ann
Published: March 2004

OBJECTIVE:

T o review and update the incidence, mechanism, and clinical relevance of drug interactions with itraconazole, ketoconazole, and fluconazole.

DATA SOURCES:

Literature was identified by MEDLINE search (from January 1990 to May 1997) using the name of each antifungal and the term “interaction” as MeSH headings. Abstracts were identified by literature citation and by review of Interscience Conference on Antimicrobial Agents and Chemotherapy from 1995 to 1996.

STUDY SELECTION:

Randomized, controlled, double-blind studies were emphasized; however, uncontrolled studies and case reports were also included. In vitro data were selected from literature review and citations.

DATA EXTRACTION:

Data were evaluated with respect to study design, clinical relevance, magnitude of interaction, and recommendations provided.

DATA SYNTHESIS:

The incidence of fungal infections and consequent azole antifungal usage continues to increase. By virtue of their antifungal mechanism (i.e., inhibition of cytochrome P450 fungal enzyme systems), azoles have been investigated and implicated in several drug interactions. The magnitude of interactions can vary from trivial to potentially fatal, and also vary with specific azole and interactant.

CONCLUSIONS:

The azole antifungal agents represent a commonly used class of agents with a broad range of potential interactions. Recent data have increased our understanding of drug-drug interactions with azoles. Pharmacists are in a unique position to identify these interactions and to intervene to decrease their morbidity and improve patient care.
Syndrome of Inappropriate Antidiuretic Hormone Associated with Vinorelbine Therapy
Authors: Garrett Clifford A , Simpson Thomas A
Published: March 2004

OBJECTIVE:

To describe onset of syndrome of inappropriate antidiuretic hormone (SIADH) associated with vinorelbine therapy for advanced breast cancer.

CASE SUMMARY:

A 50-year-old white woman with a history of advanced breast cancer refractory to other treatment modalities was receiving vinorelbine. Blood chemistries revealed severely depleted sodium and potassium concentrations from a normal baseline within a 7-day period. A recheck of blood chemistries confirmed hyponatremia. The patient was admitted to the hospital and treated for SIADH. After successful treatment, she was given demeclocycline prophylactically and rechallenged with vinorelbine without recurrence of the syndrome.

DISCUSSION:

SIADH has been reported as a complication of treatment with vinca alkaloids. To our knowledge, this is the first report of this syndrome related to vinorelbine therapy.

CONCLUSIONS:

Because of its structural similarity to the other vinca alkaloids, vinorelbine is believed to be responsible for SIADH in our patient. Clinicians should be aware of the possibility that vinorelbine may cause SIADH and possibly hypokalemia.
Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes Part I: Antiepileptic Drugs, Contraceptives, Smoking, and Folate
Authors: Lewis Dale P , Van Dyke Don C , Stumbo Phyllis J , Berg Mary J
Published: March 2004

OBJECTIVE:

Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost.

DATA SOURCES:

A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency.

STUDY SELECTION:

Relevant animal and human studies examining the effects of AEDs, smoking, and oral contraceptives on folate status and pregnancy outcome are reviewed.

DATA EXTRACTION:

Studies and case reports were interpreted. Data extracted included dosing, serum and red blood cell folate concentrations, teratogenicity of anticonvulsant medications, metabolism of AEDs and folate, and genetic susceptibility to AED-induced teratogenicity.

DATA SYNTHESIS:

Low serum and red blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis.

CONCLUSIONS:

Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation.
Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes Part II: Improvement with Folic Acid
Authors: Lewis Dale P , Van Dyke Don C , Stumbo Phyllis J , Berg Mary J
Published: March 2004

OBJECTIVE:

To provide a comprehensive review of periconceptional folic acid supplementation and factors affecting folate supplementation trials.

DATA SOURCES:

A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, spina bifida, and anencephaly.

STUDY SELECTION:

Relevant animal and human studies examining the effects of folate were reviewed.

DATA EXTRACTION:

Data collected included: type of study, folate dosing, dietary folate intake, serum and red blood cell folate concentrations, type of defect(s) studied, vitamin usage, parental risk factors, factors affecting trial results.

DATA SYNTHESIS:

Nine key factors have been identified that affect outcomes of folic acid supplementation trials. Daily doses of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of neural tube defects in randomized clinical trials. Since lower folic acid doses were effective in nonrandomized trials, research is needed to determine the lowest effective dosage. Other benefits involving pregnancy outcome are suggested.

CONCLUSIONS:

Women of childbearing age should take a daily folic acid supplement to reduce the risk of pregnancies resulting in infants with a neural tube defect and other potential adverse pregnancy outcomes. Further health benefits from folic acid supplementation are reviewed in Part III of this series.
Cutaneous Ulceration: An Unusual Sign of Methotrexate Toxicity — First Report in a Patient without Psoriasis
Authors: Ben-Amitai Dan , Hodak Emmilia , David Michael
Published: March 2004

OBJECTIVE:

To describe a case of skin ulcer related to methotrexate toxicity.

CASE SUMMARY:

A 67-year-old white man with seronegative arthralgia developed recurrent skin ulcer concurrent with 3-year treatment with methotrexate 5 mg daily. The skin ulcer resolved on discontinuation of methotrexate.

DISCUSSION:

To the best of our knowledge, this is the first reported case of skin ulcer believed to be induced by methotrexate in a patient without psoriasis.

CONCLUSIONS:

Skin ulceration should be added to the list of possible toxic adverse effects of methotrexate, not only in psoriatic patients but also in those without psoriasis.
Interaction between Fenofibrate and Warfarin
Authors: Ascah Kathyrn J , Rock Gail A , Wells Philip S
Published: March 2004

OBJECTIVE:

To determine whether the potentiation of warfarin's anticoagulation effect, which occurred in two patients, was due to an interaction with fenofibrate.

CASE SUMMARY:

Two patients developed significant potentiation of the anticoagulant effect of warfarin while receiving fenofibrate. In one patient we followed published guidelines to test the potential interaction, including rechallenge twice, and measurements of factors II, V, and VII and liver enzymes to ensure the authenticity of the interaction. We confirmed the interaction by noting that the international normalized ratio (INR) increased with rechallenge, the clotting factor concentrations decreased in concert with the INR, and no other laboratory or clinical factors accounted for this potentiation of the oral anticoagulant affect

DISCUSSION:

We previously developed criteria specifically for determining the strength of inferred causation in reports of drug interactions with oral anticoagulants; these criteria were adapted from previously described principles of causality assessment. Our observations in two patients suggest a “highly probable” potentiating interaction between fenofibrate and warfarin. Our data do not allow us to draw definitive conclusions on a mechanism of interaction, but fenofibrate is an oral antilipemic agent, similar to clofibrate, that has been described as potentiating oral anticoagulants by affecting coagulation factor synthesis, likely by altering receptor synthesis. Our finding of lower concentrations of coagulation factors suggests a similar mechanism for fenofibrate. Recent data suggest that lipid lowering is effective for primary and secondary prevention of cardiac events. One might therefore expect to see an increase in the use of the various lipid-lowering agents in patients who receive long-term anticoagulation. Our results indicate that the potential for an exaggerated anticoagulant effect occurs within 5–10 days in patients treated with fenofibrate who are receiving long-term anticoagulation with warfarin.

CONCLUSIONS:

Fenofibrate potentiates the effect of warfarin. Serial monitoring of the INR, at least three times per week, is therefore strongly recommended when initiating fenofibrate therapy in patients receiving warfarin.
Evidence-Based Pharmacotherapy: Review of Basic Concepts and Applications in Clinical Practice
Authors: Etminan Mahyar , Wright James M , Carleton Bruce C
Published: March 2004

OBJECTIVE:

To introduce concepts that may assist pharmacists in the use and application of scientific evidence in clinical practice. These concepts are followed by examples of clinical trials as well as case scenarios that guide the reader through solving clinical problems using the tools discussed in the article.

BACKGROUND:

The introduction of evidence-based practice in the 1990s has had a positive impact on the practices of medicine and pharmacy. Part of this impact has been in the area of drug therapy. Although much literature has been published on the principles of evidence-based practice in the past few years, most of this material was intended for practicing physicians. We are not aware of any articles on the use of the evidence-based principles intended for clinical pharmacists. We are also aware that discussing all of these principles is an enormous task and thus beyond the scope of this article. Therefore, we focused this discussion on a brief summary of different study designs, factors affecting the strength of scientific evidence, and interpretation of the data. An approach in the use of these concepts is discussed through the use of case scenarios.

RECOMMENDATIONS:

Clinical pharmacists must use concepts in evidence-based practice when making pharmacotherapeutic decisions.