bluuebunny/crossref_metadata_2025 huggingface dataset:
SLI381 (Adderall XR), a Two‐Component, Extended‐Release Formulation of Mixed Amphetamine Salts: Bioavailability of Three Test Formulations and Comparison of Fasted, Fed, and Sprinkled Administration
Authors: Tulloch Simon J. , Zhang Yuxin , McLean Angus , Wolf Kathleen N. , Mays David A.
Published: June 2004

Study Objectives. To assess the bioavailability of three test formulations of a single dose of extended‐release Adderall 20‐mg capsules compared with two doses of immediate‐release Adderall 10‐mg tablets, and to assess the bioequivalence of a single 30‐mg dose of the chosen extended‐release Adderall formulation (designated as SLI381) administered in applesauce (sprinkled) and the same dose administered as an intact capsule with or without food.

Design. Randomized, open‐label, crossover study.

Setting. Clinical research unit.

Patients. Forty‐one healthy adults.

Interventions. Study A had four treatment sequences: three test formulations (A, B, and C) of a single dose of extended‐release Adderall 20 mg, and two 10‐mg doses of Adderall given 4 hours apart. Study B had three treatment sequences: a single dose of SLI381 30 mg as an intact capsule after overnight fast, an intact capsule after a high‐fat breakfast, and the contents of a capsule sprinkled in 1 tablespoon of applesauce.

Measurements and Main Results. The 20‐mg test formulation A had comparable pharmacokinetic profiles and bioequivalence in rate and extent of drug absorption to Adderall 10 mg twice/day for both d‐ and l‐amphetamine. Formulations B and C had statistically significant differences from the reference drug in some pharmacokinetic parameters. A 30‐mg dose of SLI381 showed no significant differences in rate and extent of absorption of d‐ and l‐amphetamine for fasted or sprinkled conditions compared with the high‐fat meal condition.

Conclusion. SLI381 20 mg/day is bioequivalent to Adderall 10 mg twice/day. SLI381 30 mg administered in applesauce is bioequivalent in terms of both rate and extent of absorption to the same dose administered as an intact capsule in both fasted and fed states.
Abnormal Movements and Tardive Dyskinesia in Smokers and Nonsmokers with Schizophrenia Genotyped for Cytochrome P450 2D6
Authors: Ellingrod Vicki L. , Schultz Susan K. , Arndt Stephan
Published: June 2004

Study Objective. To investigate the relationships between cytochrome P450 (CYP) 2D6 genotype, antipsychotic drug exposure, abnormal movements and tardive dyskinesia, and cigarette smoking.

Design. Prospective, longitudinal study.

Setting. University mental health research center.

Patients. Thirty‐seven patients with schizophrenia.

Intervention. Patients were genotyped for CYP2D6*1, *3, and *4 alleles, and data were collected on their psychiatric symptoms, cigarette smoking status, and antipsychotic drug exposure. Abnormal movements were measured using the Abnormal Involuntary Movement Scale (AIMS). Presence of tardive dyskinesia was also evaluated.

Measurements and Main Results. A linear regression model used the AIMS scores as the dependent variable, and genotype, sex, smoking status, and antipsychotic drug exposure as independent variables. Antipsychotic drug exposure, genotype, and cigarette smoking interaction was significant (p<0.0212) for patients with the CYP2D6*1/*3, *4 genotype. Seventy‐eight percent of smokers with the CYP2D6*1/*3, *4 genotype had tardive dyskinesia compared with 20–33% of patients in other groups.

Conclusion. Patients with a CYP2D6*3 or *4 allele may shunt antipsychotic metabolism through other pathways that are induced by cigarette smoke. This induction may result in formation of neurotoxic metabolites, leading to increased AIMS scores and a higher frequency of tardive dyskinesia compared with patients without these alleles.
The Effect of Phytosterols on Quality of Life in the Treatment of Benign Prostatic Hyperplasia
Authors: Coleman Craig I. , Hebert John H. , Reddy Prabashni
Published: June 2004

In the United States, phytosterols are available as over‐the‐counter dietary supplements and are promoted as a safe and natural way to maintain a healthy prostate. In men with benign prostatic hyperplasia (BPH), evidence suggests that the agents improve urologic symptoms and flow measures to a greater extent than placebo and to a similar extent as finasteride. The primary goal for treating men with BPH is to reduce lower urinary tract symptoms and increase quality of life (QOL). Therefore, QOL has become an increasingly important end point in clinical trials. We reviewed all seven studies that determined the effect of phytosterols on QOL in patients with BPH. All trials assessed QOL with international prostate symptom score questions. Six studies found phytosterols to have beneficial effects on QOL; however, poor study design limits what can be learned from these evaluations. Most studies included a limited number of patients, and many were not placebo controlled. Since few of them evaluated the effect of phytosterols beyond 6 months, little evidence exists of the agents' long‐term efficacy in reducing symptomatology or increasing QOL. Finally, phytosterols have not been adequately compared with a‐blocking agents, one of the most widely administered and effective pharmacologic treatments of BPH. Larger studies comparing phytosterols with other treatments of BPH such as a‐blockers should be conducted. In addition, a consensus should be reached as to which questionnaires are best to evaluate potential changes in QOL after treatment of BPH.
Lack of Effect of Nizatidine‐Induced Elevation of Gastric pH on the Oral Bioavailability of Dapsone in Healthy Volunteers
Authors: Itokazu Gail S. , Fischer James H. , Manitpisitkul Prasarn , Hariharan Radhika , Danziger Larry H.
Published: June 2004

Study Objective. To investigate the effect of histamine2 (H2)‐receptor antagonist‐induced elevation of gastric pH on oral bioavailability of a single dose of dapsone 100 mg.

Design. Prospective, randomized, crossover, open‐label, single‐dose pharmacokinetic study.

Setting. Teaching hospital.

Patients. Sixteen men were enrolled in the study; data from 11 subjects were evaluable.

Interventions. Participants received two treatments separated by at least 14 days. Treatment A consisted of a single dose of dapsone 100 mg. Treatment B consisted of a single dose of dapsone 100 mg plus two doses of oral nizatidine 300 mg administered 3–4 hours apart to maintain gastric pH above 6.0. Plasma samples collected before and up to 120 hours after dapsone administration were analyzed for dapsone and monoacetyldapsone (MADDS) by high‐performance liquid chromatography. Pharmacokinetic parameters were determined by noncompartmental analysis.

Measurements and Main Results. Gastric pH in the first 6 hours after dapsone administration was above 6.0 for a mean ± SD of 1.1% ± 2.9% of the time in the absence of nizatidine and 69.5% ± 18.0% of the time during nizatidine therapy. The geometric mean dapsone maximum plasma concentration (Cmax) declined by 13% (p<0.01), and median time to Cmaxoccurred 2 hours later (p<0.01) with nizatidine coadministration compared with dapsone alone. Inclusion of the 90% confidence interval for the mean Cmax ratio within the equivalence interval of 0.8–1.25 demonstrated the lack of clinical significance for this modest decrease in Cmax. Neither the area under the dapsone plasma concentration‐time curve from zero to infinity nor the elimination half‐life of dapsone were significantly altered by nizatidine. No clinically significant changes were observed in the pharmacokinetics of MADDS with regard to coadministration of nizatidine.

Conclusion. Elevation of gastric pH by H2‐receptor antagonists, such as nizatidine, does not result in clinically important changes in the rate or extent of oral dapsone absorption.
Validity of Cancer‐Related Fatigue Instruments
Authors: Schwartz Amy H.
Published: June 2004

Fatigue is one of the most debilitating and common symptoms associated with hematologic and oncologic disorders and treatment strategies. Patient factors influence etiology and symptom manifestation, which in turn affect diagnosis, management, and monitoring. Fatigue instruments can assist with the identification, management, and monitoring of this difficult and debilitating process. A variety of fatigue instruments have been developed, several of which have been validated in patients with cancer. Psychometric confirmation is difficult because of the diverse nature of cancer‐related fatigue. Prospective, comparative, and combination analyses of the developed instruments are required to confirm validation and clarify use in practice.
Hormonal Interventions for Menstrual Migraines
Authors: Chavanu Kathleen J. , O'Donnell Dannielle C.
Published: June 2004

Menstrual migraines are a treatment challenge for both the migraineur and the health care professional. Although some women with menstrual migraines may respond to acute and preventive therapies for nonmenstrual migraines, others continue to suffer from refractory menstrual migraines. These women may respond to hormonal interventions, which may reduce the frequency of menstrual migraines, thereby lessening the need for abortive migraine therapies, decreasing migraine‐related disability, and improving quality of life. Menstrual migraines have a distinct pathophysiology that differs from menstrual‐related migraines. Published studies have shed light on the effectiveness of a variety of hormonal interventions, including oral contraceptives, which may be administered with an extended‐dosing strategy; estrogen replacement therapy; selective estrogen receptor modifiers; danazol; and leuprolide.
Intranasal Corticosteroids for Allergic Rhinitis
Authors: Trangsrud Amanda J. , Whitaker Amy L. , Small Ralph E.
Published: June 2004

Intranasal corticosteroids are accepted as safe and effective first‐line therapy for allergic rhinitis. Several intranasal corticosteroids are available: beclomethasone dipropionate, budesonide, flunisolide, fluticasone propionate, mometasone furoate, and triamcinolone acetonide. All are efficacious in treating seasonal allergic rhinitis and as prophylaxis for perennial allergic rhinitis. In general, they relieve nasal congestion and itching, rhinorrhea, and sneezing that occur in the early and late phases of allergic response, with studies showing almost complete prevention of late‐phase symptoms. The rationale for topical intranasal corticosteroids in the treatment of allergic rhinitis is that adequate drug concentrations can be achieved at receptor sites in the nasal mucosa. This leads to symptom control and reduces the risk of systemic adverse effects. Adverse reactions usually are limited to the nasal mucosa, such as dryness, burning and stinging, and sneezing, together with headache and epistaxis in 5–10% of patients regardless of formulation or compound. Differences among agents are limited to potency, patient preference, dosing regimens, and delivery device and vehicle.
Looking Beyond Highly Active Antiretroviral Therapy: Drug‐Related Hepatotoxicity in Patients with Human Immunodeficiency Virus Infection
Authors: Orenstein Robert , Tsogas Nickolaos
Published: June 2004

Management of human immunodeficiency virus (HIV) has become increasingly complex since the introduction of highly active antiretroviral therapy (HAART). Patients with HIV have become exposed to an increasing array of drugs to treat HIV, prevent opportunistic infections and immune dysfunction, and manage comorbid illnesses and therapeutic complications. Hepatic complications have become common and may lead to discontinuation of treatment and significant morbidity. Up to 90% of patients with acquired immunodeficiency syndrome (AIDS) receive at least one drug that can cause hepatotoxicity. Clinicians treating patients with HIV frequently face difficulty distinguishing abnormal liver transaminase levels and toxicities in patients receiving several drugs. Some potential causes of hepatic dysfunction are viral infections, alcohol and substance abuse, and hepatotoxic drugs such as HAART. Recent reports have focused on the hepatotoxicity of HAART and the role of hepatitis viruses to the exclusion of many other agents prescribed for patients with HIV. Many of the common antibiotics, antifungals, antivirals, and ancillary agents prescribed for patients with HIV are independently associated with hepatotoxicity. Clinicians should be aware of the potential non‐antiretroviral hepatotoxic agents that are frequently administered in HIV management.
Association Between Honey Consumption and Infant Botulism
Authors: Tanzi Maria G. , Gabay Michael P.
Published: June 2004

Infant botulism, a disease that results in a blockade of voluntary motor and autonomic functions, was first recognized in the United States in the late 1970s. Since then, more than 1000 cases in this country have been reported to the Centers for Disease Control and Prevention (CDC). Numerous studies have shown that the ingestion of honey is linked with infant botulism. In addition, honey samples across the United States have tested positive for Clostridium botulinum spores and toxins. Such substantial evidence led the CDC to recommend that honey not be given to infants younger than 12 months old. It is important that clinicians be familiar with this risk and should not recommend honey‐containing products or supplements or the use of honey as a flavoring agent for infants in this age group.
The Critical Care Pharmacist: An Essential Intensive Care Practitioner
Authors: Papadopoulos John , Rebuck Jill A. , Lober Cheryl , Pass Steven E. , Seidl Edward C. , Shah Rina A. , Sherman Deb S.
Published: June 2004

Clinical pharmacy services in the critical care setting have expanded dramatically and include assisting physicians in pharmacotherapy decision making, providing pharmacokinetic consultations, monitoring patients for drug efficacy and safety, providing drug information, and offering medical education to physicians, nurses, and patients. Measurable clinical effects of these services include reduced drug errors and adverse drug events, decreased morbidity and mortality rates, and a positive pharmacoeconomic impact by decreasing overall health care costs.
Clinical Pharmacist Staffing in United States Hospitals
Authors: Bond C. A. , Raehl Cynthia L. , Franke Todd
Published: June 2004

We evaluated hospital demographics (census regions, size, teaching affiliation, hospital ownership, hospital pharmacy director's degree, pharmacist location within the hospital) and clinical pharmacist staffing/occupied bed in United States hospitals. A database was constructed from the 1992 American Hospital Association's Abridged Guide to the Health Care Field and the 1992 National Clinical Pharmacy Services database. Simple statistical tests and multiple regression analysis were employed. The study population consisted of 1391 hospitals that reported information on clinical pharmacist staffing. The mean number of clinical pharmacists/100 occupied beds was 0.51 ± 0.18. Factors associated with increased clinical pharmacist staffing were west north central region (slope = 0.0029439, p=0.002), Pacific region (slope = 0.0032089, p=0.004), affiliation with pharmacy teaching hospitals (slope = 0.0025330, p=0.0001), teaching hospitals (slope = 0.0028122, p=0.001), federal government ownership (slope = 0.0029697, p=0.012), directors with Pharm.D. degrees (slope = 0.0335020, p=0.002), directors with M.S. Pharmacy degrees (slope = 0.0028622, p=0.003), pharmacists in a decentralized location (slope = 0.0035393, p=0.0001), and pharmacy technician staffing (slope = 0.0517713, p=0.0001). Statistically significant associations between demographic variables and decreased clinical pharmacist staffing/occupied bed were mid‐Atlantic region (slope = –0.0028237, p=0.002), small size(slope = –0.0028894, p=0.001), pharmacy directors with B.S. degrees (slope = –0.0019271, p = 0.023), and pharmacy administrator staffing (slope = –0.0184513, p=0.042). The R2 for this multiple regression analysis was 28.31% and adjusted R2 was 24.83%. Increased pharmacy technician staffing had the greatest association (slope = 0.0517713) with increased clinical pharmacist staffing. Significant differences were observed between clinical pharmacist staffing and hospital demographic factors. It appears that one of the most effective ways to increase clinical pharmacist staffing is to increase pharmacy technician staffing (slope). These findings will help future researchers determine specific reasons why some types of hospitals have higher and some lower levels of clinical pharmacist staffing.
Elevation of Carbamazepine‐10, 11‐Epoxide by Quetiapine
Authors: Fitzgerald Brian J. , Okos Anthony J.
Published: June 2004

A 52‐year‐old woman and a 56‐year‐old man who were receiving carbamazepine experienced markedly elevated levels of its active metabolite, carbamazepine‐10,11‐epoxide (CBZ‐E), after starting quetiapine therapy. The CBZ‐E:carbamazepine ratio increased 3–4‐fold in each patient. Levels of CBZ‐E returned to baseline after discontinuing this drug combination. The metabolite can accumulate and cause neurotoxicity. The woman experienced ataxia and agitation while receiving quetiapine, which resolved after carbamazepine was switched to oxcarbazepine. The man was asymptomatic. To our knowledge, these are the first two case reports describing this interaction. Quetiapine may inhibit epoxide hydrolase and/or glucuronidation of carbamazepine‐10,11‐trans‐diol in the same way as valproate and possibly lamotrigine do. If carbamazepine and quetiapine are administered concurrently, clinicians should consider monitoring CBZ‐E concentrations.
Seizures and Extrapyramidal Symptoms in a Patient with Tourette's Syndrome, Asperger's Syndrome, and Multiple Sclerosis Treated with Interferon β‐1a and Clomipramine
Authors: Dubisar Beth M. , Stoner Steven C. , Khan Rintu , Farrar Cynthia D.
Published: June 2004

Seizure activity is a known complication associated with multiple sclerosis; however, it may also result from side effects of the treatments for the disease. A 21‐year‐old man with Tourette's syndrome, pedophilia, Asperger's syndrome, and multiple sclerosis experienced seizures after receiving therapy with interferon (β‐1a. Adjustments in his drug regimen led to the discovery of pseudoparkinsonism and other extrapyramidal symptoms. This case report illustrates how pharmacodynamic properties of drugs can complicate the treatment of neurologic disorders. Clinicians must be aware of the delicate balance between the signs and symptoms of disease states and the effects of drugs.
Metronidazole‐Induced Pancreatitis in a Patient with Recurrent Vaginal Trichomoniasis
Authors: Feola David J. , Thornton Alice C.
Published: June 2004

Recurrent acute pancreatitis associated with metronidazole developed in a 49‐year‐old woman who was taking the drug as treatment for vaginal trichomoniasis. The lack of alternative effective therapies for trichomoniasis governed the decision to rechallenge the patient with metronidazole despite a vague history of this reaction on a previous occasion. Six reports of this reaction are found in the literature. The patient was admitted to the hospital 12 hours after taking a single dose of metronidazole. Severe epigastric pain and elevated amylase and lipase concentrations led to the diagnosis of acute pancreatitis, although results of an abdominal ultrasound were unremarkable. The patient made a full recovery. Although this reaction occurs infrequently, this case report illustrates the need to develop additional therapies for treatment of trichomoniasis.
Anaphylactoid Reaction to Enoxaparin in a Patient with Deep Venous Thrombosis
Authors: MacLaughlin Eric J. , Fitzpatrick Kevin T. , Sbar Evelyn , Jewell Coty
Published: June 2004

A 40‐year‐old Caucasian man diagnosed with right deep venous thrombosis secondary to trauma was treated with subcutaneous enoxaparin. Within minutes of administering the first dose (1 mg/kg), he experienced an apparent anaphylactoid reaction; symptoms were abdominal pruritus, severe cough, shortness of breath, anxiety, and global pruritus. Physical examination revealed an erythematous macular rash and stridor on auscultation secondary to cervical edema. No other drugs were given before the reaction occurred, and the patient's only drug therapy at home had consisted of a daily multivitamin, and acetaminophen and ibuprofen as needed. Administration of low‐molecular‐weight heparins such as enoxaparin is increasing, and clinicians must be aware of the potential for adverse drug events such as hypersensitivity reactions.
Sepsis: A Frequent, Life‐Threatening Syndrome
Authors: Jacobi Judith
Published: June 2004

Innovative treatments have enhanced the understanding of the pathophysiology of sepsis. An understanding of the underlying nature of the disorder is necessary to develop new therapies and determine their roles in treating patients with sepsis. By studying and determining the interactions among the inflammatory, coagulation, and fibrinolytic pathways, investigators have discovered exciting new areas of research into the mechanisms of tissue injury in sepsis.
Pharmacology, Clinical Efficacy, and Safety of Drotrecogin alfa (activated)
Authors: Rudis Maria I. , Fish Douglas N.
Published: June 2004

The protein C pathway, which plays an important role in maintaining normal hemostasis and is a critical link between the inflammatory and procoagulant host responses to infection, is involved in modulating the coagulation and inflammation associated with severe sepsis. Recombinant human activated protein C (APC), or drotrecogin alfa (activated), shares the intrinsic pharmacologic activity of endogenous APC. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, drotrecogin alfa (activated) decreased absolute mortality by 6% and relative risk of mortality by 19% compared with placebo. Drotrecogin alfa (activated) is an important advancement in the treatment of adult patients with severe sepsis.
Pharmacokinetics and Clinical Use of Drotrecogin alfa (activated) in Patients with Severe Sepsis
Authors: Olsen Keith M. , Martin Steven J.
Published: June 2004

Drotrecogin alfa (activated) pharmacokinetics have been reported in healthy volunteers and in patients with severe sepsis. Clearance is rapid and appears to increase with weight; consequently, drotrecogin alfa (activated) is dosed on a weight basis. Drotrecogin alfa (activated) promotes fibrinolysis and inhibits thrombin production to produce an anticoagulant effect. The primary adverse events are related to its pharmacologic activity, with serious bleeding reported in 3.5% of patients receiving the drug in a multicenter phase III trial compared with 2.0% for patients receiving placebo. Monitoring parameters correspond with bleeding and should include international normalized ratio, platelet count, hematocrit, and overt signs of bleeding. Because of the protein nature of drotrecogin alfa (activated), pharmacists should be aware of the proper preparation and stability issues in order to afford efficient, cost‐effective administration. As further data on drotrecogin alfa (activated) therapy become available, dosing and monitoring strategies may be altered to optimize the clinical benefits.
Current Issues Regarding the Use of Drotrecogin alfa (activated)
Authors: Hassan Erkan , Mann Henry J.
Published: June 2004

The key issues clinicians are facing regarding drotrecogin alfa (activated) include questions concerning the pathophysiology and appropriate patient selection for administration of this drug. In the Recombinant Human Activated Protein C Worldwide Evaluation in Severe Sepsis (PROWESS) trial, the efficacy of drotrecogin alfa (activated) was demonstrated in patients with severe sepsis. Because of this trial's strict inclusion and exclusion criteria, however, the applicability of the study criteria to different types of patients raises important issues. Coupling the data from the PROWESS trial with additional information being gained from expanding clinical experience, as well as additional studies, clinicians will be able to better understand and refine the use of activated protein C within their respective practices.
Impact of Drotrecogin alfa (activated) on Resource Use and Implications for Reimbursement
Authors: Dasta Joseph F. , Cooper Liesl M.
Published: June 2004

Selecting therapies in health care requires rigorous review of clinical and economic data. The financial implications of new clinical treatment options are an important component. The preferred method for evaluating the costs and effects of therapies is cost‐effectiveness analysis along with an estimation of utility associated with the life‐years gained. Preliminary reports suggest patients receiving drotrecogin alfa (activated) for severe sepsis have a faster resolution of cardiovascular and pulmonary dysfunction with minimal additional financial burden despite additional survivors. Furthermore, the reported cost/quality‐adjusted life‐year of $48,800 is consistent with many other common life‐saving measures. Recently approved new technology payments for hospitals treating patients with drotrecogin alfa (activated) minimize financial impact. Clinicians and administrators should work collaboratively to optimize the therapy of patients with severe sepsis, minimize the financial impact on the health care system, and maximize the utility of drotrecogin alfa (activated).
Strategies to Optimize Drotrecogin alfa (activated) Use: Guidelines and Therapeutic Controversies
Authors: Cohen Henry , Welage Lynda S.
Published: June 2004

Drotrecogin alfa (activated) is a new agent that may substantially affect the treatment of patients with severe sepsis. Despite its therapeutic promise, treatment with drotrecogin alfa (activated) represents a new challenge for many clinicians and health care centers. Specifically, optimizing the appropriate role for drotrecogin alfa (activated) requires balancing numerous issues, including its efficacy in high‐risk patients with its potential for indiscriminate administration. One common approach to minimizing indiscriminate administration of drotrecogin alfa (activated) and maximizing its efficacy while minimizing its toxicity is for hospitals to develop therapeutic guidelines that define how the agent should be used. We outline factors that should be considered when developing drotrecogin alfa (activated) therapy guidelines and address realistic questions that routinely arise in clinical practice regarding the implementation of such guidelines and the administration of this product. In general, the guidelines must facilitate optimization of drug therapy and not be viewed as hurdles to drug therapy. Developing clear guidelines that are based on evidence, outlining a specific process to facilitate optimal therapy, and educating all parties involved are paramount to ensuring that the benefits of therapy are maximized.
Pitfalls Associated with Commonly Used Methods for Pharmacoeconomic Analyses
Authors: Klepser Donald G.
Published: June 2004

Demonstrating the economic value of treatment has become an important objective of many clinical trials. Awareness of the limitations of the methods used in pharmacoeconomic studies of infectious diseases will help in understanding why improved methods are needed to adequately describe the costs associated with infectious episodes. Current analyses generally consider three levels of cost and use three methods to determine costs associated with an infectious episode. However, these costs and the methods for obtaining them may not be appropriate in all studies. Future pharmacoeconomic research needs to adhere to established principles but embrace new methodologies to improve the validity and usefulness of these studies.
The Dynamics of Health Care Resource Utilization
Authors: Klepser Michael E. , Klepser Donald G.
Published: June 2004

Many pharmacoeconomic studies suffer from issues relating to the sensitivity of data and ability to accurately determine treatment‐related costs. In addition, cost data generally are treated as static or constant variables. Our goal was to develop an approach to cost analysis that would allow us to appreciate the dynamic nature of health care resource utilization. By collecting detailed cost data on a daily basis and focusing on a narrow interval encompassing the infectious process, we were able to detect changes in resource utilization associated with management of the infectious process. This method also allowed us to assess and compare the dynamics of resource utilization among various patient groups.
Approaches to Analysis of Length of Hospital Stay Related to Antibiotic Therapy in a Randomized Clinical Trial: Linezolid versus Vancomycin for Treatment of Known or Suspected Methicillin‐Resistant Staphylococcus Species Infections
Authors: Li Jim Zhiming , Willke Richard J. , Rittenhouse Brian E. , Glick Henry A.
Published: June 2004

As length of hospital stay (LOS) represents about 70–90% of the total cost of treating serious infections, it represents a key variable in analyzing the health economic differences between treatments for hospitalized patients. In a retrospective analysis using LOS data from a multinational, randomized, phase III clinical trial, we examined two methods (the log‐logistic model and Kaplan‐Meier survival function) and three approaches (unadjusted total LOS, total LOS adjusted for nontreatment factors, and adjusted LOS based on antibiotic treatment [the antibiotic treatment LOS]) for estimating antibiotic treatment effect on LOS and determined if these approaches could reduce the variation in LOS and control for the imbalance between treatment groups. The trial enrolled patients who were hospitalized with known or suspected Staphylococcus species infections who received at least one dose of linezolid or vancomycin (intent‐to‐treat sample) and who continued taking the study drug for at least 7 days (clinically evaluable sample). In the intent‐to‐treat sample, the linezolid group had a 2‐ (unadjusted) or 4‐day (adjusted for nontreatment factors) shorter LOS at the 25th percentile; a 1‐ or 2‐day advantage, respectively, at the 50th percentile (median); and a 0.6‐ or 1.6‐day mean LOS advantage, compared with the vancomycin group. With the antibiotic treatment LOS approach, the linezolid group had mean and median LOS reductions comparable to or greater than those seen in the nontreatment‐factor‐adjusted results. Results for the clinically evaluable sample were similar to those of the intent‐to‐treat sample, but the differences between the treatment groups were greater. Linezolid‐treated patients had significant LOS reductions that otherwise would be masked without the use of more appropriate, but less commonly used, methods.
Use of Insurance Claims Data to Assess Outpatient Antimicrobial Therapy for Gram‐Positive Infections
Authors: Carmeli Yehuda , Mozaffari Essy
Published: June 2004

With the increasing frequency of antibiotic‐resistant gram‐positive infections in the United States, many patients are being treated outside the hospital setting. The majority of studies on the cost of outpatient antimicrobial therapy involve retrospective medical record review or prospective data collection. These methods tend to be expensive and time consuming, and often fail to produce a sufficiently large sample size. Analysis of insurance claims data offers a convenient approach for studying the costs associated with outpatient therapy for gram‐positive infections. To demonstrate this approach, a study of the cost of intravenous vancomycin home care therapy was conducted using claims data from a large insurance company.
Cost Perspectives for Outpatient Intravenous Antimicrobial Therapy
Authors: Tice Alan D. , Hoaglund Pam A. , Nolet Barbara , McKinnon Peggy S. , Mozaffari Essy
Published: June 2004

Intravenous antimicrobial therapy often continues after a patient is discharged from the hospital or it begins in the outpatient setting. Reimbursement for this therapy varies by payer. The United States Outpatient Parenteral Antibiotic Therapy (OPAT) Outcomes Registry is a valuable resource for quantifying cost by payer, as well as for describing practice patterns and adverse events related to intravenous antimicrobial therapy. To describe the reimbursement structure and cost of intravenous vancomycin home care therapy for four different types of payers, a survey of home infusion companies was done. Also surveyed were infusion programs participating in the OPAT Outcomes Registry, representing four different types of payers, to determine the cost of outpatient intravenous therapy. A retrospective cohort study of these infusion programs was conducted to describe practice patterns and to identify adverse events that resulted from intravenous vancomycin. We found that the cost of outpatient therapy was substantial, although nonuniform, across payer types. Alternative outpatient therapies associated with lower risks for adverse events and lower costs should be considered.
Changes in Pharmacy Practice Faculty 1995–2001: Implications for Junior Faculty Development
Authors: Raehl Cynthia L.
Published: June 2004

Objective.To compare changes in United States pharmacy practice faculty demographics from 1995–2001 and to discuss the implications for junior faculty development.

Methods.Demographic data were extracted from the American Association of Colleges of Pharmacy institutional research system for academic years 1995–1996 and 2000–2001.

Results.In 2000–2001, pharmacy practice was the largest faculty discipline, 3.8 times larger than the next three disciplines. Junior pharmacy practice faculty occupied 65% of all junior full‐time pharmacy faculty positions. Tenure track assistant professors decreased 4% from 283 to 271, and nontenure track assistant professors increased 58% from 427 to 677 (χ2= 20.0, p<0.05). In 2000–2001, 72% of all pharmacy practice assistant professors were nontenure track, up from 59% in 1995–1996. Women assistant professors in pharmacy practice outnumbered men by 2:1. Challenges faced by new faculty include balancing teaching, practice, and research demands; selecting a nontenure or tenure track and understanding its expectations; limiting teaching preparation time; developing productive writing habits; setting performance goals; managing time; and handling the mental and physical stress of academic life. Senior faculty must actively help new members appreciate the many positive aspects of academic life by sharing their strategies and success stories.

Conclusion.Schools and colleges of pharmacy relied heavily on increasing the number of nontenure track junior pharmacy practice faculty to meet increased clinical education demands.
Evaluation of Survival and Pharmacodynamic Relationships for Five Fluoroquinolones in a Neutropenic Murine Model of Pneumococcal Lung Infection
Authors: Ernst Erika J. , Klepser Michael E. , Petzold C. Rosemarie , Doern Gary V.
Published: June 2004

Study Objective. To compare the antistreptococcal activity of five fluoroquinolone antibiotics, using a neutropenic murine model of pneumococcal pulmonary infection.

Design. Animal experiment.

Setting. University‐affiliated research center.

Animals. Neutropenic and control mice weighing 24–29 g.

Intervention. After induction of neutropenia, renal failure, and infection with Streptococcus pneumoniae, the mice received one of five fluoroquinolones twice/day for 72 hours beginning 12 hours after infection. Dosages were selected to approximate 0.1 × AUC0–24 (area under the concentration‐time curve from 0–24 hours) and AUC0–24 achieved in humans. Control mice received normal saline. Survival was assessed at regular intervals for up to 10 days. At least 10 mice were included in each cohort (range 10–34).

Measurements and Main Results. Ciprofloxacin, clinafloxacin, grepafloxacin, levofloxacin, and moxifloxacin were studied at subtherapeutic and therapeutic dosages against three quinolone‐susceptible isolates of S. pneumoniae that lacked mutations in parC, parE, and gyrA. Pharmacokinetic profile of each agent and dosing regimen was determined. A composite survival curve for all fluoroquinolones and isolates was constructed. Relationships between survival rate at 72 hours and AUC: MIC (minimum inhibitory concentration), peak: MIC, time above the MIC (percentage of dosing interval) for total and free drug concentrations were fit by using a sigmoid maximal effect (Emax) model. Survival was significantly better in the higher dosage group than in the lower dosage group. Time above MIC did not display a correlation with outcome. The AUC: MIC showed a greater correlation with outcome (R2 = 0.56 total, 0.54 free) than did peak: MIC (R2 = 0.52 total, 0.51 free). With use of composite data, total AUC: MIC ratios associated with 50%, 90%, and 99% of Emax were 34:1, 56:1, and 95:1, respectively.

Conclusions. In this model, efficacy was achieved with the fluoroquinolone antibiotics at dosages yielding AUC0–24 comparable to those obtained in humans. One pharmacodynamic parameter (i.e., AUC: MIC) may be applied to various fluoroquinolones and isolates of S. pneumoniae. The AUC: MIC was more predictive of outcome than was time above the MIC or peak: MIC.
Clinical Efficacy and Pharmacoeconomics of a Continuous‐Infusion Piperacillin‐Tazobactam Program in a Large Community Teaching Hospital
Authors: Grant Edward M. , Kuti Joseph L. , Nicolau David P. , Nightingale Charles , Quintiliani Richard
Published: June 2004

Study Objective. To compare continuous versus intermittent administration of piperacillin‐tazobactam with regard to clinical, microbiologic, and economic outcomes.

Design. Prospective, open‐label controlled study.

Setting. Community teaching hospital.

Patients. Ninety‐eight hospitalized patients prescribed piperacillintazobactam.

Intervention. Substitutions were implemented so that 47 patients initially prescribed intermittent infusion of piperacillin‐tazobactam were switched to continuous infusion of this drug combination. Dosages varied in accordance with the type of infection and each patient's renal function. Fifty‐one other patients with similar demographics and types of infection received intermittent infusion with piperacillin‐tazobactam.

Measurements and Main Results. Clinical success rates were 94% for the continuous‐infusion group and 82% for the intermittent‐infusion group (p=0.081). Microbiologic success rates were 89% for the continuous‐infusion group and 73% for the intermittent‐infusion group (p=0.092). Days to normalization of fever were significantly lower (p=0.012) in the continuous‐infusion group (1.2 ± 0.8 days) than in the intermittent‐infusion group (2.4 ± 1.5 days). Level 1 and level 2 costs/patient were both reduced by continuous infusion, although the difference was statistically significant only for level 2 costs ($399.38 ± 407.22 for continuous infusion vs $523.49 ± 526.85 for intermittent infusion, p=0.028).

Conclusion. Continuous infusion of piperacillin‐tazobactam provided clinical and microbiologic outcomes equivalent to those for intermittent infusion. Compared with intermittent infusion, continuous infusion significantly shortened the time to temperature normalization, while also offering a significant reduction in level 2 expenditures.
Treatment of Sickle Cell Pain
Authors: Marlowe Karen F. , Chicella Michael F.
Published: June 2004

Sickle cell disease affects 70,000 Americans who experience an average of 0.8 painful episodes each year. The pathophysiology of sickle cell pain is not completely understood. The disease is characterized by both acute and chronic pain syndromes. Patients with sickle cell pain often encounter barriers to receiving appropriate care, including lack of continuity of care and perceived opiate addiction. Studies describing pharmacotherapy for sickle cell pain have been primarily retrospective and uncontrolled. In analyzing the available literature regarding pathophysiology, assessment, and treatment of sickle cell pain, we found a need for increased practitioner education and intervention to improve the level of care provided to patients with this disease.
Removal of Lepirudin, a Recombinant Hirudin, by Hemodialysis, Hemofiltration, or Plasmapheresis
Authors: Willey Michelle L. , de Denus Simon , Spinler Sarah A.
Published: June 2004

Lepirudin (recombinant hirudin), a direct thrombin inhibitor, is an effective alternative method of anticoagulation in patients with heparin‐induced thrombocytopenia. However, because it is eliminated by the kidneys, the half‐life of lepirudin may be substantially prolonged in patients with renal failure. Patients undergoing hemodialysis must be closely monitored, and therapy must be individualized based on each patient's ability to clear the drug. Current literature on the removal of lepirudin by dialysis or plasmapheresis is limited, but available data suggest that lepirudin can be removed with these methods. The ability of filtration systems to remove lepirudin from the blood is highly dependent on the membrane material used in the system. Understanding the effects of hemodialysis, hemofiltration, and plasmapheresis on lepirudin levels is important, especially since no antidote is available to treat elevated serum lepirudin concentrations.
Patient Perceptions of a Proton Pump Inhibitor Therapeutic Interchange Program Across the Continuum of Care
Authors: Sodorff Michelle M. , Galt Kimberly A. , Galt Michael A. , Turner Paul D. , Lambrecht Jason E.
Published: June 2004

Objective. To determine if participation in a hospital‐based proton pump inhibitor (PPI) therapeutic interchange program resulted in differences in patient perceptions related to clinical and humanistic outcomes.

Methods. A quasiexperimental repeated‐measures study compared patients' perceptions in two groups (111 patients) at hospital admission, discharge, 3–4 days after discharge, and 2–3 weeks after discharge to detect differences across the continuum of care. Patient awareness of the hospital‐based interchange also was examined. Clinical and quality‐of‐life outcomes were measured by using a condition‐specific instrument modified for use with patients. Satisfaction and expectations were measured by using extent‐of‐agreement measures. Group 1 (60 patients) was prescribed omeprazole before admission, switched to lansoprazole during hospitalization, and discharged taking omeprazole. Group 2 (51 patients) was prescribed lansoprazole before admission and continued taking lansoprazole throughout hospitalization and after discharge. Patients who were unable to communicate or who had a substantial change in severity of illness (not attributable to gastrointestinal disorders) during the study were excluded.

Results. No significant differences were found between groups 1 and 2 for clinical outcomes, quality of life, extent to which expectations were met, or satisfaction at the four time periods. Nineteen (36%) of 53 surveyed patients in group 1 were not aware that their therapy had been interchanged while in the hospital.

Conclusion. Patient‐perceived outcomes and expectations of therapy across the continuum of care were not affected by a hospital‐based PPI therapeutic interchange program.
Rabbit Syndrome Secondary to Risperidone
Authors: Hoy Jenifer S. , Alexander Bruce
Published: June 2004

After taking risperidone for 4 months, a 38‐year‐old man with a major depressive disorder experienced rabbit syndrome. This uncommon extrapyramidal side effect is characterized by rhythmic movements of the mouth and may be caused by typical antipsychotics and risperidone secondary to blockade of dopamine D2 receptors. The syndrome, whose exact mechanism is unknown, responded to anticholinergic treatment in this patient. A literature review indicated that most recent cases have occurred as reactions to the atypical antipsychotic risperidone. Changing treatment to an atypical antipsychotic other than risperidone, such as olanzapine 10 mg/day, may lead to suppression or elimination of the syndrome.
Selective Serotonin Reuptake Inhibitor‐Induced Rash: Case Report and Review of the Literature
Authors: Sannicandro Tracie J. , Farrar Martha C. , Markowitz John S.
Published: June 2004

Selective serotonin reuptake inhibitors (SSRIs) are one of the most frequently prescribed classes of drugs. Rashes induced by SSRIs seldom have been reported in the literature. Computerized MEDLINE and Current Contents searches yielded a report of two cases of rash induced specifically by paroxetine. We describe a patient who developed a rash that appeared on day 3 of treatment with oral paroxetine 20 mg/day. Her rash was morbilliform, pruritic, and generalized over the trunk and limbs, with some facial involvement. There was no palm or sole involvement. The patient reported that she had experienced a similar reaction to fluoxetine, which may suggest a drug class effect. The rash resolved within 2 days of drug discontinuation and treatment with oral diphenhydramine and topical hydrocortisone cream.
Rhinocerebral Mucormycosis in the Era of Lipid‐Based Amphotericin B: Case Report and Literature Review
Authors: Mondy Kristin E. , Haughey Bruce , Custer Philip L. , Wippold Franz J. , Ritchie David J. , Mundy Linda M.
Published: June 2004

Rhinocerebral mucormycosis (RCM) is an invasive fungal infection that necessitates, in most cases, aggressive surgical debridement and high cumulative, often nephrotoxic doses of amphotericin B. A 50‐year‐old woman with RCM was treated successfully with amphotericin B lipid complex as primary therapy. The patient previously had displayed progressive intracranial involvement and rising serum creatinine levels while receiving the conventional (nonlipid) form of amphotericin B. A literature review identified only a few cases where systemic antifungal therapy was administered, with minimal or no surgery. Our case further supports that amphotericin B lipid complex can be used as primary therapy in selected patients with RCM, without the need for surgical exenteration.
Nontraditional Dosing of Ampicillin‐Sulbactam for Multidrug‐Resistant Acinetobacter baumannii Meningitis
Authors: Cawley Michael J. , Suh Caroline , Lee Susanne , Ackerman Bruce H.
Published: June 2004

A 52‐year‐old man was admitted to a local hospital with headache, nausea, vomiting, dizziness, photophobia, and confusion after a sudden fall. Progressive changes in neurologic function were noted despite neurosurgical intervention and broad‐spectrum antimicrobial coverage. Cerebral spinal fluid (CSF) culture identified Acinetobacter baumannii that was resistant to traditionally recommended therapies of amikacin and imipenem‐cilastatin. The organism demonstrated minimum inhibitory concentrations of greater than 32 μg/ml and 8 μg/ml, respectively, for these two agents. Ampicillin 2 g‐sulbactam 1 g every 3 hours was administered based on history of therapeutic failure of traditional dosing in our thermal injury population. Repeat CSF cultures after 12 days of ampicillin‐sulbactam therapy were negative. After 35 days, the patient's A. baumannii infection was completely resolved. The patient experienced no adverse drug events or toxicity with this high‐dosage regimen.
Cerivastatin‐Induced Rhabdomyolysis: 11 Case Reports
Authors: Ravnan Susan L. , Locke Christy , Yee William P. , Haase Kelli
Published: June 2004

3‐Hydroxy‐3‐methylglutaryl coenzyme A (HMG‐CoA) reductase inhibitors are a frequently prescribed class of drugs that are generally well tolerated by most patients. A rare, yet serious side effect associated with these drugs is rhabdomyolysis. Although all HMG‐CoA reductase inhibitors can cause this adverse effect, prevalence may differ among specific agents. Over a 16‐month period, in three hospitals, 11 patients experienced cerivastatin‐induced rhabdomyolysis, but no cases of rhabdomyolysis associated with any other HMG‐CoA reductase inhibitors were reported.