bluuebunny/crossref_metadata_2025 huggingface dataset:
Menlo Worldwide Forwarding Optimizes Its Network Routing
Authors: Prior Robert C. , Slavens Rob L. , Trimarco Jerry , Akgun Vedat , Feitzinger Edward G. , Hong Chyi-Fu
Published: March 2004

Since 2000, Menlo Worldwide Forwarding (formerly Emery Worldwide) has faced a particularly challenging business environment that has been exacerbated by a weakened economy, the events of September 11, and a decreasing demand for airfreight. To meet these challenges, the company and Menlo Worldwide Technologies developed a network-routing-optimization model to optimize Menlo Worldwide Forwarding$s North American transportation network. The project team and senior managers have repeatedly identified and applied low cost solutions to meet the changing and complex network-routing requirements. By maximizing its use of network capacity, the company has increased profitability and reduced operating costs while maintaining high service levels. In 2002 alone, Menlo Worldwide Forwarding reduced operating costs by 21 percent, increased operating margin by 41 percent, and improved financial results by $80 million in the North American aircraft transportation operation. Moreover, management used the optimization model to facilitate Menlo$s transition from a heavily asset-based, integrated airfreight company to an asset-light, freight-forwarding business. This created a flexible operating environment and a competitive advantage for future operations.
UPS Optimizes Its Air Network
Authors: Armacost Andrew P. , Barnhart Cynthia , Ware Keith A. , Wilson Alysia M.
Published: March 2004

Operations research specialists at UPS and the Massachusetts Institute of Technology (MIT) created a system to optimize the design of service networks for delivering express packages. The system simultaneously determines aircraft routes, fleet assignments, and package routings to ensure overnight delivery at minimal cost. It has become central to the UPS planning process, fundamentally transforming the process and the underlying planning assumptions. Planners now use the system’s solutions and insights to improve plans. UPS management credits the system with identifying operational changes that have saved over $87 million between 2000 and 2002. Anticipated future savings are expected to be in the hundreds of millions of dollars.
Opti-Money at Bank Hapoalim: A Model-Based Investment Decision-Support System for Individual Customers
Authors: Avriel Mordecai , Pri-Zan Hanna , Meiri Ronit , Peretz Avi
Published: March 2004

Opti-Money is a decision-support system for allocating assets that was developed at Bank Hapoalim, Israel's largest bank. Based on customer- and market-specific inputs, we solve a modified Markowitz-type nonlinear programming problem to produce optimal tailor-made investment portfolios in terms of asset classes. In its five years of operation, this mature system has provided excellent quantifiable results for the bank and its customers. In 2002, we held some 133,000 consultation sessions with 63,000 customers in which we used Opti-Money. Apart from the considerable prestige the system gained through its track record and uniqueness in the Israeli banking sector, it obtained net income 88 percent higher in customer accounts that used Opti-Money than in those that did not. The annual earnings over and above benchmarks to customers who follow the investment advice provided by the system total US$244 million. In 2002, the annual income for the bank directly attributed to Opti-Money exceeded US$31 million.
Separation Algorithms for Classes of STSP Inequalities Arising from a New STSP Relaxation
Authors: Carr Robert
Published: March 2004

The problem of separating a class of inequalities that are valid for the symmetric traveling salesman problem (STSP) consists of devising an efficient method that, given a fractional point x *. for a relaxation of the STSP, either finds an inequality in the given class of STSP inequalities that is violated by x *. or determines that there are no such violated inequalities. We can define important classes of STSP inequalities by performing Naddef's and Rinaldi's (1993) node-lifting operation on STSP inequalities defined on small graphs.

We present efficient methods for exactly separating large classes of STSP inequalities that arise from an STSP relaxation related to node lifting. In particular, we show how to find efficiently the most-violated inequality in the class of STSP inequalities having a backbone set with a constant number k of vertices, and thus separate in polynomial time the class of all STSP inequalities whose backbone set has at most k vertices.
Interior Gradient and Epsilon-Subgradient Descent Methods for Constrained Convex Minimization
Authors: Auslender A. , Teboulle M.
Published: March 2004

We extend epsilon-subgradient descent methods for unconstrained nonsmooth convex minimization to constrained problems over polyhedral sets, in particular over ℝp+. This is done by replacing the usual squared quadratic regularization term used in subgradient schemes by the logarithmic-quadratic distancelike function recently introduced by the authors. We then obtain interior ε-subgradient descent methods, which allow us to provide a natural extension of bundle methods and Polyak's subgradient projection methods for nonsmooth convex minimization. Furthermore, similar extensions are considered for smooth constrained minimization to produce interior gradient descent methods. Global convergence as well as an improved global efficiency estimate are established for these methods within a unifying principle and minimal assumptions on the problem's data.
Hamiltonian Cycles and Singularly Perturbed Markov Chains
Authors: Ejov Vladimir , Filar Jerzy A. , Nguyen Minh-Tuan
Published: March 2004

We consider the Hamiltonian cycle problem embedded in a singularly perturbed Markov decision process. We also consider a functional on the space of deterministic policies of the process that consists of the (1,1)-entry of the fundamental matrices of the Markov chains induced by the same policies. We show that when the perturbation parameter, ε, is less than or equal to 1/N2, the Hamiltonian cycles of the directed graph are precisely the minimizers of our functional over the space of deterministic policies. In the process, we derive analytical expressions for the possible N distinct values of the functional over the, typically, much larger space of deterministic policies.
On the Sequential Quadratically Constrained Quadratic Programming Methods
Authors: Solodov M. V.
Published: March 2004

An iteration of the sequential quadratically constrained quadratic programming method (SQCQP) consists of minimizing a quadratic approximation of the objective function subject to quadratic approximation of the constraints, followed by a line search in the obtained direction. Methods of this class are receiving attention due to the development of efficient interior point techniques for solving subproblems with this structure, via formulating them as second-order cone programs. Recently, Fukushima et al. (2003) proposed a SQCQP method for convex minimization with twice continuously differentiable data. Their method possesses global and locally quadratic convergence, and it is free of the Maratos effect. The feasibility of subproblems in their method is enforced by switching between the linear and quadratic approximations of the constraints. This strategy requires computing a strictly feasible point, as well as choosing some further parameters. We propose a SQCQP method where feasibility of subproblems is ensured by introducing a slack variable and, hence, is automatic. In addition, we do not assume convexity of the objective function or twice differentiability of the problem data. While our method has all the desirable convergence properties, it is easier to implement. Among other things, it does not require computing a strictly feasible point, which is a nontrivial task. In addition, its global convergence requires weaker assumptions.
Index Policies for Stochastic Search in a Forest with an Application to R&D Project Management
Authors: Denardo Eric V. , Rothblum Uriel G. , Van der Heyden Ludo
Published: March 2004

This paper concerns a stochastic search problem in a forest. As motivation, consider the issue of investing in a research-and-development project. Each activity that could be undertaken in the project is represented as an edge in a forest. Each edge has a cost of being attempted and a probability of success. An edge can be attempted if each of its predecessors has been attempted, and if each of those attempts has succeeded. The overall project succeeds if a path is found from a stem to a leaf of the forest all of whose edges are successful. Overall success yields an economic benefit. The problem is to find an investment strategy that maximizes expected utility, either with a linear or an exponential utility function. This problem will be shown to have a simple solution. Each edge will be assigned an index such that expected utility is maximized by attempting, at each opportunity, an edge whose index is most positive, terminating the search when no edges remain whose indices are positive. These indices are nested in a way that makes them quick to compute.
An Analysis of the EM Algorithm and Entropy-Like Proximal Point Methods
Authors: Tseng Paul
Published: March 2004

The EM algorithm is a popular method for maximum likelihood estimation from incomplete data. This method may be viewed as a proximal point method for maximizing the log-likelihood function using an integral form of the Kullback-Leibler distance function. Motivated by this interpretation, we consider a proximal point method using an integral form of entropy-like distance function. We give a convergence analysis of the resulting proximal point method in the case where the cluster points lie in the interior of the objective function domain. This result is applied to a normal/independent example and a Gaussian mixture example to establish convergence of the EM algorithm on these examples. Further convergence analysis of the method for maximization over an orthant is given in low dimensions. Sublinear convergence and schemes for accelerating convergence are also discussed.
Characterizations of Error Bounds for Convex Multifunctions on Banach Spaces
Authors: Ng Kung Fu , Zheng Xi Yin
Published: March 2004

In terms of various derivatives such as contingent derivative and Dini-derivative, we give a series of characterizations of error bounds for convex multifunctions defined on Banach spaces, extending Lewis and Pang's result on a characterization of the existence of global error bounds for approximate solutions of convex inequalities in Euclidean spaces. Applications are given not only to improve some known results but also to provide new results on the existence of error bounds for not necessarily lower semicontinuous convex functions.
Do CT scans aid assessment of distal tibial physeal fractures?
Authors: Cutler L. , Molloy A. , Dhukuram V. , Bass A.
Published: March 2004

Distal tibial physeal fractures are the second most common growth plate injury and the most common cause of growth arrest and deformity. This study assesses the accuracy of pre-operative planning for placement of the screws in these fractures using either standard radiographs or CT scans.

We studied 62 consecutive physeal fractures over a period of four years. An outline of a single cut of the CT scan was used for each patient. An ideal position for the screw was determined as being perpendicular to and at the midpoint of the fracture. The difference in entry point and direction of the screw between the ideal and the observers’ assessments were compared using the paired Student’s t-test. There was a statistically significant improvement (p < 0.0001) in the accuracy of the point of insertion and the direction of the screw on the pre-operative plan when CT scans were used rather than plain radiographs.

We would, therefore, recommend that CT scans are routinely used in the pre-operative assessment and treatment of distal tibial physeal fractures.
Treatment of supracondylar fracture of the humerus in children by skeletal traction in a brace
Authors: Matsuzaki K. , Nakatani N. , Harada M. , Tamaki T.
Published: March 2004

In 1980, we developed a specially designed brace for treating supracondylar fractures of the humerus in children, along with an easy and safe technique of reduction by skeletal traction. This method, which takes into consideration only the medial tilting and anterior angulation of the distal fragment, achieves complete reduction, ignoring any lateral, posterior and minor rotational displacements of the fragment. Skeletal traction is applied through a screw inserted into the olecranon and the angulation at the fracture site is reduced regardless of the anatomical position without manipulation.

We treated 193 children with displaced supracondylar fractures of the humerus using this method between 1980 and 2001. Only four children (2%) developed cubitus varus. The majority obtained an excellent range of movement at the elbow; one had a 25° limitation of flexion. This technique is an effective and easy method of treating supracondylar fractures of the humerus in children.
Sagittal gait patterns in spastic diplegia
Authors: Rodda J. M. , Graham H. K. , Carson L. , Galea M. P. , Wolfe R.
Published: March 2004

Classifications of gait patterns in spastic diplegia have been either qualitative, based on clinical recognition, or quantitative, based on cluster analysis of kinematic data. Qualitative classifications have been much more widely used but concerns have been raised about the validity of classifications, which are not based on quantitative data.

We have carried out a cross-sectional study of 187 children with spastic diplegia who attended our gait laboratory and devised a simple classification of sagittal gait patterns based on a combination of pattern recognition and kinematic data. We then studied the evolution of gait patterns in a longitudinal study of 34 children who were followed for more than one year and demonstrated the reliability of our classification.
Infection in total joint replacements
Authors: Mohanty S. S. , Kay P. R.
Published: March 2004

A retrospective review of MRSA screening showed that of a total of 8911 patients screened pre-operatively between May 1996 and February 2001, 83 (0.9%) had MRSA isolated from one source or another. During the same period, 115 (13.6%) of 844 positive tissue samples taken during surgery grew Staphylococcus aureus. Of these only 1 (0.01%) was reported to be methicillin-resistant (MRSA). However, a total of 366 (43.4%) isolates from tissue samples were reported as coagulase-negative staphylococci (C-NS). Of these, 312 samples were tested for methicillin sensitivity, of which 172 (55.1%) were found to be resistant.

Staphylococcus epidermidis is the most prevalent and persistent species found on most skin and mucous membranes, constituting 65% to 90% of all staphylococci. Most isolates in tissue samples were found to be methicillin-resistant coagulase-negative staphylococcus (55.1%). Hence, it may be appropriate to undertake screening for methicillin-resistant Staphylococcus epidermidis in addition to that for MRSA.
Rotation of the spinal cord in idiopathic scoliosis
Authors: Maruta T. , Minami S. , Kitahara H. , Isobe K. , Otsuka Y. , Nakata Y. , Moriya H.
Published: March 2004

We undertook a radiographic analysis with pre-operative computed tomographic myelography in 78 patients with idiopathic scoliosis in order to analyse rotation of the spinal cord and to investigate its clinical significance. The angle of rotation of the cord had a statistically significant relationship to both that of the apical vertebra and the size of the primary curve. The relationship between the rotation of the cord and that of the apical vertebra was divided into three types. The cord rotated in the same direction as the apical vertebra in 55 patients and rotated in the opposite direction in the remaining 23 patients. In the first group, the angle of rotation of the cord was more than that of the vertebra in six patients, but less than it in 49 patients. These results suggest that the neuraxis in idiopathic scoliosis may be under tension in the axial dimension.
Arthrodiastasis in Perthes’ disease
Authors: Maxwell S. L. , Lappin K. J. , Kealey W. D. , McDowell B. C. , Cosgrove A. P.
Published: March 2004

We have examined the effect of arthrodiastasis on the preservation of the femoral head in older children with Perthes’ disease. We carried out a prospective trial in boys over the age of eight years and girls over seven years at the time of the onset of symptoms. The patients had minimal epiphyseal collapse and were compared with a conventionally treated, consecutive, historical control group. Arthrodiastasis was applied for approximately four months. The primary outcome measure was the extent of epiphyseal collapse at the end of the fragmentation phase. One of the 15 treated hips and nine of the 30 control hips showed a loss of height of 50% or more of the lateral epiphyseal column on the anteroposterior radiographs (Herring grade-C classification). On a Lauenstein view, one of the treated hips and 19 of the control hips showed at least a loss of height of 50% of the anterior epiphyseal column. The complications of arthrodiastasis included pin-site infection in most hips, transient joint stiffness in two, and breakage of a pin in two. The final outcome will be known when all the patients and the control group reach skeletal maturity.
Hydroxyapatite-coated, cementless total knee replacement in patients aged 75 years and over
Authors: Dixon P. , Parish E. N. , Chan B. , Chitnavis J. , Cross M. J.
Published: March 2004

We have carried out a prospective study comparing the results at five years in patients older than 75 years of age undergoing hydroxyapatite-coated, cementless total knee replacement (TKR) with those who were younger. The Knee Society clinical rating scores were recorded before and after operation. Of 559 patients undergoing TKR, 135 were in the elderly age group. The knee scores at five years or more showed comparable results, with patients under 75 years of age reaching a score of 183 and those aged 75 years or over reaching 174. These differences were predominantly due to the functional component of the score. We conclude that elderly patients do just as well as the younger group using this prosthesis.
Bilateral, uncemented total hip arthroplasty in osteopetrosis
Authors: Jones D. P. Gwynne , Hodgson B. F. , Hung N. A.
Published: March 2004

Bilateral, uncemented hip replacements were performed on a 45-year-old woman with autosomal dominant osteopetrosis. The hips showed degenerative changes and protrusio acetabuli. Difficulties were encountered especially during preparation of the femoral canal. At ten-year follow-up she has an excellent clinical and radiological result with no sign of osteolysis. Uncemented hip replacement, while technically demanding, can be successful in the intermediate term for patients with this condition.
Roentgen stereophotogrammetric analysis of the Birmingham hip resurfacing arthroplasty
Authors: Glyn-Jones S. , Gill H. S. , McLardy-Smith P. , Murray D. W.
Published: March 2004

The Birmingham hip resurfacing (BHR) arthroplasty is a metal-on-metal prosthesis for which no medium- or long-term results have been published. Despite this, it is increasing in popularity as an alternative to stemmed prostheses for younger patients. Since the fixation of the socket is conventional, the major concern is long-term failure of the femoral component. This can be predicted by the use of roentgen stereophotogrammetric analysis (RSA). We have therefore undertaken such a study of the BHR femoral component over a period of two years.

Twenty patients (22 hips) underwent a standard BHR procedure. Migration of the femoral component was measured by RSA at intervals of three, six, 12 and 24 months. At 24 months the total three-dimensional migration of the head was 0.2 mm. This was not statistically significant. Previous studies have shown that implants which loosen quickly have rapid early migration. Our results therefore suggest that the BHR femoral component is an inherently stable device which is likely to perform well in the long term.
Limb lengthening and correction of deformity in the lower limbs of children with osteogenesis imperfecta
Authors: Saldanha K. A. N. , Saleh M. , Bell M. J. , Fernandes J. A.
Published: March 2004

We performed limb lengthening and correction of deformity of nine long bones of the lower limb in six children (mean age, 14.7 years) with osteogenesis imperfecta (OI). All had femoral lengthening and three also had ipsilateral tibial lengthening. Angular deformities were corrected simultaneously. Five limb segments were treated using a monolateral external fixator and four with the Ilizarov frame. In three children, lengthening was done over previously inserted femoral intramedullary rods.

The mean lengthening achieved was 6.26 cm (mean healing index, 33.25 days/cm). Significant complications included one deep infection, one fracture of the femur and one anterior angulation deformity of the tibia. The abnormal bone of OI tolerated the external fixators throughout the period of lengthening without any episodes of migration of wires or pins through the soft bone. The regenerate bone formed within the time which is normally expected in limb-lengthening procedures performed for other conditions.

We conclude that despite the abnormal bone characteristics, distraction osteogenesis to correct limb-length discrepancy and angular deformity can be performed safely in children with OI.
The effects of a combination of hyaluronic and amniotic membrane on the formation of peritendinous adhesions after flexor tendon surgery in chickens
Authors: Özgenel G. Y.
Published: March 2004

We have investigated the effects of the intra-operative application of a combination of hyaluronic acid and amniotic membrane on adhesions in the flexor tendons of a chicken model. We used 144 tendons which were partially divided and then repaired by a modified Kessler technique. There were four test groups: group 1, simple tendon repair, group 2, repair site wrapped with amniotic membrane, group 3, hyaluronic acid injected around the repair site, and group 4, repair site wrapped with amniotic membrane and hyaluronic acid injected within it.

At three and six weeks, the extent of the adhesions and the healing of the tendon were evaluated macroscopically and histologically. The range of movement of the toe and tensile strength of the repaired tendons were measured at 20 weeks. The least adhesions were observed in group 4 but no significant difference was found in the healing of the tendons. Overall, the intra-operative application of a combination of hyaluronic acid and amniotic membrane appears to be effective in preventing adhesions of the flexor tendon.
Synovectomy reduces stromal-cell-derived factor-1 (SDF-1) which is involved in the destruction of cartilage in osteoarthritis and rheumatoid arthritis
Authors: Kanbe K. , Takemura T. , Takeuchi K. , Chen Q. , Takagishi K. , Inoue K.
Published: March 2004

We have compared the concentrations of stromal-cell-derived factor-1 (SDF-1), matrix metalloproteinase-1 (MMP-1), MMP-9 and MMP-13 in serum before and after synovectomy or total knee replacement (TKR). We confirmed the presence of SDF-1 and its receptor CXCR4 in the synovium and articular cartilage by immunohistochemistry. We established chondrocytes by using mutant CXCR4 to block the release of MMPs.

The level of SDF-1 was decreased 5.1- and 6.7-fold in the serum of patients with OA and RA respectively, after synovectomy compared with that before surgery. MMP-9 and MMP-13 were decreased in patients with OA and RA after synovectomy. We detected SDF-1 in the synovium and the bone marrow but not in cartilage. CXCR4 was detected in articular cartilage. SDF-1 increased the release of MMP-9 and MMP-13 from chondrocytes in a dose-dependent manner. The mutant CXCR4 blocked the release of MMP-9 and MMP-13 from chondrocytes by retrovirus vector.

Synovectomy is effective in patients with OA or RA because SDF-1, which can regulate the release of MMP-9 and MMP-13 from articular chondrocytes for breakdown of cartilage, is removed by the operation.
Outcome after primary hemiarthroplasty for fracture of the head of the humerus
Authors: Kralinger F. , Schwaiger R. , Wambacher M. , Farrell E. , Menth-Chiari W. , Lajtai G. , Hübner C. , Resch H.
Published: March 2004

We have examined 167 patients who had a hemiarthroplasty for three- and four-part fractures and fracture-dislocations of the head of the humerus in a multicentre study involving 12 Austrian hospitals. All patients were followed for more than a year.

Anatomical healing of the tuberosity significantly influenced the outcome as measured by the Constant score and subjective patient satisfaction. With regard to pain, the outcome was generally satisfactory but only 41.9% of patients were able to flex the shoulder above 90°. The age of the patient and the type of prosthesis significantly influenced the healing of the tuberosity, but bone grafting did not. Achievement of healing of the tuberosity was inferior in institutions at which less than 15 hemiarthroplasties had been performed (Mann-Witney U test, p = 0.0001).
Changes in the ratio of type-I and type-II collagen expression during monolayer culture of human chondrocytes
Authors: Marlovits S. , Hombauer M. , Truppe M. , Vècsei V. , Schlegel W.
Published: March 2004

We compared the changes in the ratio of type-I and type-II collagen in monolayer cultures of human articular chondrocytes (HAC). HAC were isolated from samples of cartilage from normal joints and cultivated in monolayer for up to 46 days. Expression of collagen type-I and type-II was determined by immunocytochemistry, Western blotting, and the nested reverse transcription polymerase chain reaction (RT-PCR), and quantified by real-time PCR.

The transition from a spherical morphology to the flattened morphology of an anchorage-dependent culture was accompanied by a rapid change in the collagen phenotype with the replacement of collagen type II by collagen type I. This was confirmed by immunocytochemistry and Western blotting between days 21 and 28. Using techniques for the analysis of gene transcription (nested RT-PCR and real-time PCR), a complete switch of collagen gene expression was not observed. Expression of collagen type I increased 100-fold during the culture time. That of collagen type II was found during the entire period and decreased more than 100-fold.

The main finding was that expression of the genes encoding collagen type I and II was highly time-dependent and the ratio of collagen type II to I (CII/CI), defined as an index of cell differentiation, was significantly higher (215- to 480-fold) at the beginning of the culture. At the end of the experimental culture time, ratios between 0.1 and 1 were reached.
Intraperitoneal Thrombolytic Therapy for Peritoneal Dialysis–Associated Peritonitis
Authors: Worland Melinda A , Radabaugh Rhonda S , Mueller Bruce A
Published: March 2004

OBJECTIVE:

To review the literature pertaining to the use of adjunctive thrombolytic therapy for the treatment of peritoneal dialysis–associated peritonitis (PDAP).

DATA SOURCES:

A MEDLINE search was conducted (January 1966– December 1997) to find articles using the terms peritonitis, peritoneal dialysis, and each thrombolytic drug. References from these articles were then reviewed to identify further sources.

DATA EXTRACTION:

Representative case reports and clinical trials are summarized in this report. Information regarding thrombolytic dosing, administration techniques, and reported efficacy rates are included from both case reports and clinical trials.

DISCUSSION:

Thrombolytic agents administered intraperitoneally appear to facilitate antibiotic penetration into the biofilm formed by certain bacteria. Numerous case reports of intraperitoneal thrombolytic adjunctive therapy for recurrent or persistent PDAP have indicated that these agents may have a role in the treatment of selected patients. Urokinase and streptokinase are the only thrombolytics that have been studied. They appear to have similar efficacy, but the adverse drug event rate with streptokinase is unacceptably high. The efficacy of therapy with urokinase is probably inferior to removal of the peritoneal dialysis catheter, but, if successful, allows for the continuation of peritoneal dialysis therapy.

CONCLUSIONS:

In conjunction with appropriate antibiotic therapy, intraperitoneal instillation of urokinase should be reserved for patients who develop two or more episodes of recurrent or persistent PDAP in the absence of poor compliance and in whom dialysis catheter removal should be avoided (i.e., they cannot tolerate hemodialysis).
Pharmacoeconomic Analysis of Using Sinemet CR over Standard Sinemet in Parkinsonian Patients with Motor Fluctuations
Authors: Hempel Alan G , Wagner Mary L , Maaty Mohamed A , Sage Jacob I
Published: March 2004

OBJECTIVE:

To compare the costs of pharmacotherapy in patients with Parkinson's disease before and after converting from standard Sinemet to extended-release Sinemet CR.

DESIGN:

Investigators retrospectively reviewed records of patients converting from Sinemet to Sinemet CR for efficacy and total drug costs. Cost-effectiveness was evaluated retrospectively from data collected in prospective Sinemet CR efficacy trials.

SETTING:

Parkinson's disease clinic at a tertiary care university teaching hospital.

PATIENTS:

100 patients with motor fluctuations who had undergone an initial 6-month course of Sinemet therapy, followed by a 6-month course of Sinemet CR.

MAIN OUTCOME MEASURES:

Total cost was measured as the cost of Sinemet formulations plus the costs of other antiparkinson medications. Differences in pre- and postconversion costs were compared by using the paired, two-tailed Student's t-test. A substudy of 39 patients on the cost-effectiveness of conversion measured the ratio of daily medication costs to the daily hours “on” without chorea.

RESULTS:

While total daily medication costs after conversion increased by 21%, patients experienced either a comparable or an improved degree of disease control with Sinemet CR. Patients who were also taking selegiline were able to decrease selegiline expense by 20%. The costs of other adjunctive medications did not differ significantly after conversion. The cost-effectiveness analysis revealed an increase in postconversion on time by 2.2 hours (p = 0.0001), accompanied by a $2.85 decrease in total cost per hour on without chorea (p = 0.11).

CONCLUSIONS:

Although Sinemet CR is more costly, it may be more cost-effective in patients with motor fluctuations. Some patients may be able to reduce adjunctive medications.
Low-Molecular-Weight Heparins in the Treatment of Deep-Vein Thrombosis
Authors: Martineau Pierre , Tawil Nadine
Published: March 2004

OBJECTIVE:

To compare the characteristics and clinical efficacy of low-molecular-weight heparins (LMWHs) and unfractionated heparin (UFH) in the treatment of deep-vein thrombosis (DVT). Adverse effects, dosing, and cost issues are also discussed.

DATA SOURCES:

A MEDLINE search (January 1984–October 1997) was used to identify pertinent French and English literature, including clinical trials and reviews on LMWHs and their use in DVT.

STUDY SELECTION:

Trials comparing dalteparin, enoxaparin, tinzaparin, and nadroparin with UFH were selected. As studies were numerous, only randomized trials including more than 50 patients were reviewed. Moreover, all patients studied had a first episode of symptomatic DVT confirmed by objective tests (i.e., venography, duplex ultrasonography, impedance plethysmography). Clinical efficacy and safety of LMWHs were assessed in these trials.

DATA EXTRACTION:

Results pertaining to venographic assessment, recurrent thromboembolism, total mortality, and bleeding complications were extracted from the selected studies.

DATA SYNTHESIS:

Compared with UFH, LMWHs have a longer plasma half-life, better subcutaneous bioavailability, more predictable anticoagulant response, and require less intense laboratory monitoring. Most trials demonstrate comparable effects on thrombus extension and incidence of recurrent thromboembolism. Compared with UFH, LMWHs do not alter total mortality. Although animal trials predict a lower hemorrhagic potential for LMWHs, the incidence of bleeding complications is generally similar to that observed with UFH. Outpatient management of DVT with LMWHs has shown comparable safety and efficacy with inpatient UFH use but a shorter hospital stay.

CONCLUSIONS:

Because LMWHs are as safe and as effective as UFH, and because of their more convenient method of administration, they can be considered valuable alternatives for the treatment of DVT. Savings generated by less intensive laboratory monitoring and the possibility of early hospital discharge and outpatient therapy may outweigh the higher acquisition cost of LMWHs.
Pressure Ulcer Management in the Geriatric Patient
Authors: Orlando Patricia L
Published: March 2004

OBJECTIVE:

To increase the understanding of pharmacists and other health-system clinicians regarding pharmaceutical applications of pressure ulcer prevention and treatment in geriatric patients.

DATA SOURCES:

An extensive MEDLINE retrieval was conducted which encompassed the years 1967–1998; the search terms used included pressure sore, pressure ulcer, decubitus ulcer, and geriatrics.

DATA SUMMARY:

Pressure ulcers affect populations with limited mobility, reduced cognition, and less-independent activities of daily living, such as the elderly. Identification of the high-risk patient is required for successful prevention outcomes. For existing lesions, a variety of treatment modalities exist, not all of which have demonstrated therapeutic benefit. Given these options, clinicians are faced with treatment selection challenges that should be based on the clinical setting, available scientific evidence, and individualized patient care needs.

CONCLUSIONS:

Prevention of pressure ulcerations is imperative to reduce patient morbidity, mortality, and overall healthcare costs. Given the number of treatment options available, pharmacists can assist in the treatment selection process. Education of the patient and family regarding pressure ulcer prevention and treatment requires early and ongoing involvement by the interdisciplinary team.
Dapsone-Induced Methemoglobinemia
Authors: Ward Kristina E , McCarthy Michelle W
Published: March 2004

OBJECTIVE:

To report a case of methemoglobinemia in a patient receiving dapsone for prophylaxis of Pneumocystis carinii pneumonia (PCP).

CASE SUMMARY:

A 69-year-old white woman was hospitalized to rule out sepsis. Two years prior to this admission, the patient received an orthotopic liver transplant after which she required hemodialysis three times weekly. Because of intolerance to trimethoprim/ sulfamethoxazole and aerosolized pentamidine, she was prescribed dapsone therapy on hospital day 13, that was continued for 11 days. On hospital day 45 the patient received a cadaveric kidney transplant, and dialysis treatments were scheduled only as needed. One week after the transplant, dapsone therapy was resumed. Nine days into this course of dapsone, the patient developed dyspnea and oxygen desaturation of unknown etiology. The patient was evaluated for and diagnosed with methemoglobinemia. She received two doses of intravenous methylene blue and one dose of oral activated charcoal due to fluctuating methemoglobin concentrations.

DISCUSSION:

The elimination of dapsone is not completely understood. Several case reports of dapsone-induced methemoglobinemia are present in the literature. Most have occurred in patients who have accidentally or deliberately overdosed. Cases of methemoglobinemia in patients receiving therapeutic doses of dapsone are discussed.

CONCLUSIONS:

The growing numbers of immunosuppressed patients due to transplantation or HIV may result in increased dapsone use for the prevention of PCP. Clinicians should be aware of the adverse effects associated with dapsone therapy, and patients with dyspnea and hypoxemia of unclear etiology should be evaluated for methemoglobinemia.
Vitamin E in the Treatment of Tardive Dyskinesia
Authors: Boomershine Kellie H , Shelton Penny S , Boomershine Jason E
Published: March 2004

OBJECTIVE:

To review the efficacy of vitamin E in the treatment of tardive dyskinesia (TD).

DATA SOURCES:

Published articles and abstracts in English were identified from January 1986 to March 1999 by MEDLINE and International Pharmaceutical Abstracts searches using the terms vitamin E, α-tocopherol, and tardive dyskinesia. Additional articles were identified from the references of the retrieved articles and cross- referencing selected articles.

DATA EXTRACTION:

All clinical trials evaluating the use of vitamin E in human subjects with TD were reviewed. Selected articles also included those considered to be helpful in providing a basic introduction to TD pathophysiology and management.

DATA SYNTHESIS:

TD occurs in approximately 20% of patients treated with neuroleptics. The resulting dyskinesias can be irreversible and are often psychologically and physically debilitating. Recent research suggests that TD may be a result of neuronal damage inflicted by free radicals generated from increased neurotransmitter turnover and metabolism. Vitamin E as a naturally occurring free radical scavenger has been evaluated in the treatment of TD. Eighteen completed trials are available either in completed or abstract form. Twelve of these trials have produced positive results with vitamin E in the treatment of TD. Patients who have had TD for less than five years appear to respond better than patients with long-standing TD.

CONCLUSIONS:

Research suggests that vitamin E offers benefit in the management of a subgroup of patients with TD. Further investigation is needed to ascertain continued efficacy with long-term use as well as the role of vitamin E in TD prophylaxis.
Primary Induction with Mycophenolate Mofetil and Corticosteroids in a Liver Transplant Recipient with Hepatorenal Syndrome
Authors: Carr Roxane R , Yoshida Eric M , Chung Stephen W , Partovi Nilufar
Published: March 2004

OBJECTIVE

To report the use of mycophenolate mofetil for primary induction in a liver transplant recipient to avoid the nephrotoxicity of cyclosporine/tacrolimus.

CASE SUMMARY:

A 47-year-old white man in hepatic coma with anuric hepatorenal syndrome received a liver transplant, and was given mycophenolate mofetil and corticosteroids as primary induction immunosuppression with the addition of low-dose cyclosporine 13 days later. His renal function improved and he remains rejection-free after 13 months of follow-up.

CONCLUSIONS

This case suggests that mycophenolate mofetil may be used as a primary induction agent in liver transplant recipients with renal failure to avoid the additional nephrotoxicity of the standard immunosuppressants, cyclosporine and tacrolimus. Low-dose cyclosporine/tacrolimus may be introduced later as the renal function improves.

OBJETIVO

Se reporta el uso de micofenolato mofetíl como indución primaria en un recipiente con transplante hepático con el propósito de evitar la nefrotoxicidad debido a ciclosporina y tacrolimus.

RESUMEN DEL CASO

Un hombre de 47 años de edad en coma hepático y con síndrome hepáticorenal anúrico recibió un transplante de hígado y tratamiento con micofenolato mofetíl y corticosteroides como inducción inmunosupresiva primaria más la adición subsecuente de dosis bajas de ciclosporina después de 13 días. La función renal se mejoró y el paciente permaneció sin síntomas de rechazo después de 4 meses de observacions continuas.

CONCLUSIONES

La presentación de este caso sugiere que micofenolato mofétil puede ser usado como un agente inductivo primario en recipientes de transplantes hepáticos e insuficiencia renal con el fín de evitar la nefrotoxicidad adicional debido a los medicamentos inmunosupresivos estandar de ciclosporina y tacrolimus. Dosis bajas de ciclosporina y tacrolimus pueden ser añadidas en el futuro después de una mejoría en la función renal.
Pharmacologic Management of Alzheimer Disease Part III: Nonsteroidal Antiinflammatory Drugs — Emerging Protective Evidence?
Authors: Flynn Barbara L , Theesen Karen A
Published: March 2004

OBJECTIVE:

To provide information about research evaluating the role of nonsteroidal antiinflammatory drugs (NSAIDs) in the prevention, or delay in the onset of, Alzheimer disease (AD).

DATA SOURCES:

Studies, review articles, and editorials identified from MEDLINE searches (January 1990–December 1996) and bibliographies of identified articles. The addendum lists articles from 1996 to June 1999.

STUDY SELECTION:

Studies, review articles, and editorials addressing NSAIDs and AD pharmacotherapy research.

DATA EXTRACTION:

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

DATA SYNTHESIS:

AD is a complex disorder and there are numerous factors involved in the process. The pathology of AD is characterized by the development of amyloid plaques and neurofibrillary tangles. In addition, more than 40 immunoprotective proteins that are not unique to AD are found at autopsy that are normally absent, or present in very low concentrations, in normal brain. These findings suggest that AD may involve an inflammatory process. Preliminary results from studies investigating the incidence and onset of AD in patients with arthritis who have taken NSAIDs suggest that NSAIDs may have a protective effect. Studies evaluating the possible association between arthritis, NSAIDs, and AD are reviewed.

CONCLUSIONS:

Preliminary evidence suggests that NSAIDs may have a protective effect against the development of AD. Further prospective, double-blind, placebo-controlled studies are needed to determine the role of NSAIDs in AD. These dose-finding studies should focus on specific agents and identify the dosage and duration of therapy necessary for a protective or therapeutic effect. Additionally, not all elderly patients are candidates for NSAIDs. Determining the definitive mechanism of action of NSAIDs in AD may suggest alternative agents that have similar pharmacologic activity, but are associated with fewer adverse effects.
Beyond Benzodiazepines: Alternative Pharmacologic Agents for the Treatment of Insomnia
Authors: Wagner Judy , Wagner Mary L , Hening Wayne A
Published: March 2004

OBJECTIVE:

To review the epidemiology, etiology, and classification of insomnia and provide an overview of the pharmacologic therapy of insomnia. Novel nonbenzodiazepine hypnotics including zolpidem, zopiclone, and zaleplon, as well as nonprescription products such as valerian and melatonin, are reviewed in detail.

DATA SOURCES:

A MEDLINE search was performed to identify relevant clinical studies, case reports, abstracts, and review articles published between April 1992 and December 1997. Key search terms included insomnia, benzodiazepines, zolpidem, zopiclone, zaleplon, Cl 284,846, melatonin, and valerian. Additional references were obtained from the lists of review articles and textbooks.

DATA EXTRACTION AND SYNTHESIS:

Data concerning the safety and efficacy of the hypnotic agents were extracted from all available clinical trials and abstracts. Background information regarding insomnia, benzodiazepines, and other hypnotics was extracted from the most current literature, including review articles and textbooks.

CONCLUSIONS:

New developments in benzodiazepine receptor pharmacology have introduced novel nonbenzodiazepine hypnotics that provide comparable efficacy to benzodiazepines. Although they may possess theoretical advantages over benzodiazepines based on their unique pharmacologic profiles, they offer few, if any, significant advantages in terms of adverse effects. Over-the-counter agents such as valerian and melatonin may be useful in alleviating mild, short-term insomnia, but further clinical trials are required to fully evaluate their safety and efficacy.
Lack of Pharmacokinetic Interaction between Mexiletine and Omeprazole
Authors: Kusumoto Masaaki , Ueno Kazuyuki , Tanaka Kazuhiko , Takeda Kazuya , Mashimo Kohji , Kameda Takaya , Fujimura Yasuo , Shibakawa Masahiko
Published: March 2004

OBJECTIVE:

To investigate the effect of omeprazole on the pharmacokinetics of mexiletine.

METHODS:

Nine healthy male Japanese volunteers participated in a crossover study. On day 1, the subjects received mexiletine 200 mg. On days 2–7, they received omeprazole 40 mg, and on day 8 they received mexiletine 200 mg and omeprazole 40 mg concomitantly. Serum concentrations of mexiletine were determined just before drug administration and at 1, 2, 3, 4, 6, 8, 12, and 24 hours on day 1 and day 8.

RESULTS:

No differences in mexiletine concentrations were observed between the two phases of the study. The mean AUCs after administration of mexiletine alone and in combination with omeprazole 40 mg/d were 6.26 and 6.20 ng·h/L, respectively.

CONCLUSIONS:

These findings suggest that omeprazole does not affect mexiletine metabolism.

OBJETIVO:

Investigar el efecto de omeprazole en la farmacocinética de mexiletine.

MÉTODOS:

Nueve hombres japoneses saludables participaron en forma voluntaria en un estudio cruzado. En el primer día, los voluntarios recibieron mexiletine 200 mg solamente. Desde el segundo al séptimo día, los sujetos recibieron omeprazole, y en el octavo día recibieron mexiletine y omeprazole 40 mg concomitantemente. Los concentracions séricas de mexiletine fueron tomadas justo antes de la administración del medicamento en la 1, 2, 3, 4, 6, 8, 12, y 24 hora después de la administración del medicamento en el día 1 y en el día 8.

RESULTADOS:

En las concentraciones de mexiletine no fueron observadas diferencias entre los dos fases del estudio. El área promedio bajo la curva de concentración versus tiempo despues de la administración de mexiletine solo y en combinación con omeprazole 40 mg/día fueron 6.26 y 6.20 ng·h/L, respectivamente.

CONCLUSIONES:

Los hallazgos sugieren que omeprazole no afecta el metabolismo de mexiletine.

OBJECTIF:

Évaluer l'influence de l'oméprazole sur la pharmacocinétique de la mexilétine.

MÉTHODES:

Neuf volontaires sains ont participé à cette étude. Tous les individus étaient d'origine Japonaise et de sexe masculin. Dans un premier temps, les individus ont reçu une dose unique de 200 mg de mexilétine. Puis ils ont reçu 40 mg d'oméprazole pendant 6 jours. La huitième journée de l'étude, on leur a administré 40 mg d'oméprazole accompagné de 200 mg de mexilétine. Des prélèvements sanguins ont été effectués immédiatement avant l'administration de mexilétine et après 1, 2, 3, 4, 6, 8, 12, et 24 heures. Les concentrations de mexilétine étaient mesurées par chromatographie liquide haute performance.

RÉSULTATS:

Aucune différence n'a été noté entre les concentrations de mexilétine au jour 1 et celles au jour 8. Les surfaces sous la courbe moyennes étaient de 6.26 et 6.20 ng · h/L, respectivement.

CONCLUSIONS:

Les résultats suggérent que l'oméprazole n'affecte pas le métabolisme de la mexilétine.