bluuebunny/crossref_metadata_2025 huggingface dataset:
Evaluation of a Spawning Habitat Enhancement Site for Chinook Salmon in a Regulated California River
Authors: Merz Joseph E. , Setka Jose D.
Published: June 2004

An evaluation of the effectiveness of a project to enhance spawning habitat for Chinook salmon Oncorhynchus tshawytscha was conducted in the Mokelumne River, a regulated stream in California's Central Valley. Approximately 976 m3 of clean river gravel (25–150 mm) was placed in berm and gravel bar configurations along the 45-m enhancement site. Physical measurements taken before and after gravel placement indicate that the project significantly increased channel water velocities, intergravel permeability, and dissolved oxygen; reduced channel depths; and equilibrated intergravel and ambient river temperatures. These positive benefits remained throughout the 30-month monitoring period. Adult Chinook salmon began spawning at the previously unused site within 2 months after gravel placement and continued to use the site during the three spawning seasons encompassed by the study. Bed material movement was documented by channel bathymetry surveys over two water years. Topographical channel surveys provide a useful tool for monitoring bed material transport and layering redd locations on contour maps. Although its usefulness in restoring salmon populations is poorly understood, gravel enhancement can be an effective means for improving salmon spawning habitat in rivers where upstream dams have effected low gravel recruitment.
Genetic Stock Identification of Steelhead in the Columbia River Basin: An Evaluation of Different Molecular Markers
Authors: Winans Gary A. , Paquin Melanie M. , Van Doornik Donald M. , Baker Bruce M. , Thornton Perry , Rawding Dan , Marshall Anne , Moran Paul , Kalinowski Steven
Published: June 2004

Protein genetic markers (allozymes) have been used during the last decade in a genetic stock identification (GSI) program by state and federal management agencies to monitor stocks of steelhead Oncorhynchus mykiss in the Columbia River basin. In this paper we report new data for five microsatellite and three intron loci from 32 steelhead populations in the three upriver evolutionarily significant units (ESUs) and compare the performance of allozyme, microsatellite, and intron markers for use in GSI mixture analyses. As expected, microsatellites and introns had high total heterozygosity (HT) values; but there was little difference among marker classes in the magnitude of population differentiation as estimated by Wright's fixation index (FST), which ranged from 0.041 (microsatellite loci) to 0.047 (allozyme loci) and 0.050 (intron loci). For allozyme and microsatellite loci, the relationships among populations followed the patterns of geographic proximity. In computer-simulated mixture analyses, GSI estimates were more than 85% correct to the reporting group, the exact percentage depending on the marker data set and target group. Microsatellite loci provided the most accurate estimate (83%) in the 100% upper Columbia River ESU simulation, whereas simulation estimates for the 32-locus allozyme baseline were 93–94% for the 100% middle Columbia River ESU and two Snake River management groups. The simulations also showed that the estimates improved substantially up to a sample size of 50 fish per population. Technical advances will concomitantly increase the number of useful microsatellite loci and the rate of laboratory throughput, making this class of molecular marker more valuable for GSI mixture analyses in the near future. In the meantime, we recommend that steelhead management in the Columbia River rely on both allozyme and microsatellite data for GSI procedures.
Age Estimation for Shovelnose Sturgeon: A Cautionary Note Based on Annulus Formation in Pectoral Fin Rays
Authors: Whiteman Kasey W. , Travnichek Vincent H. , Wildhaber Mark L. , DeLonay Aaron , Papoulias Diana , Tillett Donald
Published: June 2004

Numerous studies have examined the age and growth of shovelnose sturgeon Scaphirhynchus platorynchus, but only one study attempted to validate age estimation techniques. Therefore, our objective was to use marginal increment analysis to validate annulus formation in pectoral fin rays of shovelnose sturgeon collected from the Missouri River. We also compared the precision of age estimates between two different readers. Marginal increment distance indicated that for most of the populations an opaque band was laid down in pectoral fin rays during the summer. However, opaque bands were formed throughout the year in some individuals, which could be problematic when using fin rays for age estimation. The agreement of age estimates by two readers for shovelnose sturgeon was only 18%, and differences in ages between the two readers increased for older fish. The presence of split annuli, false annuli, spawning bands, imbedded rays, and deteriorating sections made individual growth rings difficult to separate. Our findings verified that opaque bands are formed annually during the summer in the pectoral fin rays of most shovelnose sturgeon, but some individuals form opaque bands during other times. Pectoral fin rays will probably continue to be the most practical method of age estimation in shovelnose sturgeon, but ages estimated by this method should be used with caution.
Autumn-to-Spring Energetic and Diet Changes among Kokanee from North Idaho Lakes with and without Mysis relicta
Authors: Clarke Lance R. , Letizia Paul S. , Bennett David H.
Published: June 2004

Changes in the Pend Oreille Lake, Idaho, zooplankton community during spring and autumn have been attributed to planktivory by the opossum shrimp Mysis relicta. To examine how the altered zooplankton community affects kokanee Oncorhynchus nerka, we compared seasonal body lipids and feeding patterns of age-0 and age-1 individuals from Pend Oreille Lake with those of kokanee from Coeur d'Alene and Spirit lakes, Idaho, which did not contain M. relicta. We also contrasted our feeding pattern analysis with results of a similar study conducted in Pend Oreille Lake before M. relicta introduction. Age-0 Pend Oreille Lake kokanee showed no evidence of malnourishment, as body lipids and feeding patterns were generally similar among the three lakes. Age-1 Pend Oreille Lake kokanee had lower body lipids and stomach fullness than age-1 kokanee in the other lakes, suggesting that zooplankton community changes might affect older kokanee. We saw no evidence of direct starvation mortality in either Pend Oreille Lake year-class, since body lipids were higher than prior studies have reported for starving individuals. Seasonal kokanee feeding patterns were similar between age-classes but differed among lakes, Pend Oreille Lake individuals consuming a lower proportion of Daphnia during autumn compared with Coeur d'Alene Lake and Spirit Lake fish. Kokanee fed upon small copepod species during spring in all three lakes. Before M. relicta establishment in Pend Oreille Lake, kokanee in autumn ate a higher proportion of cladocerans, consumed a greater total prey biomass, and had fewer empty stomachs, but spring feeding patterns were more similar to those we observed. Our results show that seasonal changes in zooplankton availability in Pend Oreille Lake have probably changed age-1 kokanee foraging and energy accumulation patterns, particularly in autumn, although we cannot exclude the possibility that recent changes in predation intensity may also explain our results.
Health‐Related Quality of Life for Adults with Cystic Fibrosis: A Regression Approach to Assessing the Impact of Recombinant Human DNase
Authors: Johnson Jeffrey A. , Connolly Melinda , Zuberbuhler Peter , Brown Neil E.
Published: June 2004

Study Objectives. To examine the general health‐related quality of life (HRQOL) of adults with cystic fibrosis (CF) using available generic instruments, and to determine important predictors of change in HRQOL, including therapy with recombinant human Dnase (rhDNase).

Design. Prospective, observational study.

Patients. Fifty‐nine adults with CF.

Intervention. The Medical Outcomes Study Short‐Form 36 (SF‐36) and the EuroQol (EQ‐5D) were mailed to patients; follow‐up surveys were mailed 1 year later.

Measurements and Main Results. Multivariate regression analyses assessed the relationships between clinical and demographic variables and change in health status. The 39 respondents reported lower HRQOL scores compared with general population norms for generic instruments. Regression analyses indicated that age (p=0.010), percentage predicted forced expiratory volume in 1 second (p=0.005), hospital admission (p=0.023), and rhDNase therapy (p=0.026) were positively associated 1998 EQ‐5D index scores, whereas body mass index was negatively associated (p=0.025) with 1998 EQ‐5D index scores after controlling for baseline 1997 scores. The size of the regression coefficients indicated that only 1997 scores and hospital admission in the year were quantitatively importantly associated with 1998 scores. Baseline HRQOL assessments showed that adults with CF reported important decrements in health status and functioning. An interesting relationship between functional status and total household income was observed.

Conclusion. Although a statistically significant association between rhDNase and 1‐year change in HRQOL was found on multivariate regression analysis, the magnitude of this relationship may not be clinically important.
Outcomes of Weight‐Based Heparin Dosing Based on Literature Guidelines and Institution Individualization
Authors: Davydov Liya , Dietz Patrick A. , Lewis Patricia , Twichell Martha L. , Bertino Joseph S.
Published: June 2004

Study Objective. To determine whether unfractionated heparin is optimally dosed using published weight‐based guidelines.

Design. Six‐month, prospective study.

Setting. University hospital.

Patients. Ninety‐six patients in the weight‐based unfractionated heparin‐dosing group 1 (WBHD1; 37 men; mean age 66.9 ± 15.1 years; mean weight 80.1 ± 20.6 kg) and 68 patients in the WBHD2 (25 men; mean age 68.2 ± 15.6 years; mean weight 82.0 ± 19.6 kg).

Interventions. The WBHD1 received a 100‐U/kg intravenous bolus followed by an 18‐U/kg/hour continuous intravenous infusion. After 3 months, the protocol was modified, and the WBHD2 received a 90‐U/kg bolus followed by a 16‐U/kg/hour continuous infusion for 3 months.

Measurements and Main Results. Activated partial thromboplastin times (aPTTs), frequency of bleeding episodes that required blood transfusions, and the number of recurrent thromboembolic events were collected from both groups after 3 months on the study. In the WBHD1, 24 hours after starting heparin, 38.5% of patients had therapeutic aPTTs, and at 48 hours, 54.3% were therapeutic. In the WBHD2, 42.6% and 51.4% of patients had therapeutic aPTTs at 24 and 48 hours, respectively. There was no statistical difference between the WBHD1 and WBHD2 in the percentage of patients with therapeutic aPTTs.

Conclusions. Weight‐based heparin dosing resulted in low percentages of patients with therapeutic aPTTs. The use of weight alone to dose heparin may not be adequate to optimize therapy.
Pharmacokinetics of Gemcitabine and 2′,2′‐Difluorodeoxyuridine in a Patient with Ascites
Authors: Delauter Brian J. , Ramanathan Ramesh K. , Egorin Merrill J. , Stover Lori L. , Zuhowski Eleanor G. , Plunkett William , Zamboni William C.
Published: June 2004

Gemcitabine (dFdC) is a prodrug that undergoes metabolism by cytidine deaminase to form an inactive metabolite, 2′,2′‐difluorodeoxyuridine (dFdU). The pharmacokinetics of dFdC and dFdU have been studied; however, their disposition has never been evaluated in a patient with ascites. A patient with pancreatic cancer and malignant ascites was treated with dFdC 1500 mg/m2 over 150 minutes weekly for 3 weeks, repeated every 4 weeks. Serial plasma and ascites samples were obtained on weeks 1 and 2 of cycle 2. High‐pressure liquid chromatography was used to quantify dFdC and dFdU in plasma and ascites. The systemic dispositions of dFdC and dFdU were similar to those reported in patients without ascites. The concentration of dFdC in ascites approached 1 mg/ml. Ascitic fluid did not serve as a depot for dFdC, and the agent's concentration in ascites approached that at which its phosphorylation is saturated.
Intravenous Ribavirin and Hyperammonemia in an Immunocompromised Patient Infected with Adenovirus
Authors: Bertrand Pablo , Faro Albert , Cantwell Patricia , Tzakis Andres
Published: June 2004

Ribavirin is a synthetic guanosine analog with activity against DNA and RNA viruses. It was studied in human trials, and no marked adverse effect was reported beyond the potential for teratogenicity and reversible mild anemia. An 8‐year‐old girl received a multivisceral transplant and developed adenoviral pneumonia. She was treated with intravenous ribavirin and became hyperammonemic. Discontinuation of ribavirin led to a decrease in ammonia levels. This pattern was repeated when the drug was restarted and discontinued. We hypothesize that in a toxic environment the interaction of ribavirin with hepatocellular mitochondrial enzymes may lead to hyperammonemia.
Evolution and Pathophysiology of Chronic Systolic Heart Failure
Authors: Bleske Barry E.
Published: June 2004

Understanding of the pathophysiology of chronic systolic heart failure evolved from a purely mechanical model to one in which a cascade of neurohormones and biologically active molecules are thought to be critical in the development, maintenance, and progression of the disease. Two important neurohormonal systems are the sympathetic nervous and renin‐angiotensin‐aldosterone systems. Initially, increases in norepinephrine concentrations from the sympathetic nervous system and in angiotensin II and aldosterone are beneficial in the short term to maintain cardiac output after an insult to the myocardium. However, long‐term exposure to these neurohormones causes alterations of myocytes and interstitial make‐up of the heart. These alterations in myocardium lead to progression of heart failure and, eventually, death.
β‐Blocker Therapy: A Standard of Care for Heart Failure
Authors: Munger Mark A. , Cheang Kai Ian
Published: June 2004

β‐Adrenergic‐blocking agents underwent extensive research over the past 2 decades and emerged as a proven state‐of‐art therapy for the failing human heart. Through blockade of chronically elevated cardiac adrenergic stimulation, selective and nonselective agents with vasodilating properties prevent progression of myocardial dysfunction and cardiac remodeling. Most important, β‐adrenergic blockers added to conventional therapy of vasodilators and diuretics significantly increase survival to a 5‐year rate similar to that of cardiac transplantation. The agents also significantly reduce hospitalizations, improve quality of life, and are well tolerated in clinical trials. The challenge in treating heart failure is to ensure that every eligible patient receives these life‐saving drugs.
Developing Clinical Practice Guidelines for Heart Failure: Creative Process and Practice Implications
Authors: Adams Kirkwood F.
Published: June 2004

The rapid growth of medical knowledge has created many advances in therapeutics related to chronic disease. Translation of these advances into everyday care of patients with chronic disease has proven problematic. Guideline development offers a principal strategy to improve use of new and existing therapeutic modalities of proven benefit. To be effective, practice guidelines must not only deal with which therapies are efficacious but attempt to consider the many practical aspects necessary in the actual care of patients. In this way both the art and science of medicine can be employed to obtain optimal patient outcomes in many chronic diseases that have been associated with severe mortality, morbidity, and poor quality of life. The logical process of guideline development and its use in one specific chronic disease, heart failure, is examined.
Practical Issues in the Treatment of Patients with Heart Failure
Authors: Gattis Wendy A.
Published: June 2004

The management of heart failure is complex. Initiating and maintaining drug therapy in patients with heart failure can be challenging. Many factors influence the heart failure syndrome and are important to account for when evaluating these patients. Concomitant diseases such as ischemic heart disease and hypertension may contribute to worsening heart failure, and treatment strategies addressing these conditions should be implemented in affected patients. Concomitant drugs also must be considered. The heart failure population is at risk for drug interactions, both pharmacokinetic and pharmacodynamic, because these patients often take many drugs at the same time. Proactively recognizing potential interactions and modifying a patient's regimen to minimize or avoid adverse effects are important. Many agents are contraindicated in heart failure; thus, avoiding such therapies may significantly affect a patient's outcome. The successful treatment of a patient with heart failure requires careful consideration of many factors, including other diseases, drugs, and social issues. Addressing these factors when treating patients translates into improved pharmaceutical care.
The Use of Fluoroquinolones as Antiinfective Transition‐Therapy Agents in Community‐Acquired Pneumonia
Authors: Press Robert A.
Published: June 2004

The newer quinolone antibiotics, including levofloxacin, moxifloxacin, and gatifloxacin, offer coverage of the likely pathogens in community‐acquired pneumonia (CAP) and have been shown to be safe and effective treatments for CAP. Two of these agents, levofloxacin and gatifloxacin, have pharmacokinetic and antibacterial properties that are similar in both oral and intravenous formulations. As such, they may be excellent candidates for transition therapy involving early switch from intravenous to oral therapy followed by early hospital discharge for patients with CAP.
Antifungal Pharmacodynamics: Concentration‐Effect Relationships in Vitro and in Vivo
Authors: Groll Andreas H. , Piscitelli Stephen C. , Walsh Thomas J.
Published: June 2004

The pharmacodynamics of antifungal compounds involve relationships among drug concentrations, time, and antimicrobial effects in vitro and in vivo. Beyond better understanding of a drug's mode of action, characterization of these relationships has important implications for setting susceptibility breakpoints, establishing rational dosing regimens, and facilitating drug development. Important advances have been made in the experimental investigation of pharmacokinetics and pharmacodynamics of antifungal drugs; however, much remains to be learned about specific pathogens and specific sites of infection. Increased incorporation of pharmacokinetic and pharmacodynamic principles in experimental and clinical studies with antifungal agents is an important objective that will benefit the treatment and prophylaxis of life‐threatening invasive fungal infections in immunocompromised patients.
Investigational Antifungal Agents
Authors: Ernst Erika J.
Published: June 2004

Several new antifungal agents, including novel compounds in familiar classes and entirely new classes targeting previously untapped mechanisms, are in various stages of the drug development process. Many new triazole antifungal agents are being studied, including voriconazole, posaconazole, and ravuconazole. The echinocandin antifungals, which represent a new class of antifungal agents, possess activity against a variety of fungal pathogens. The sodarin derivatives and nikkomycins are two additional classes of antifungals in early stages of development; future studies will determine their therapeutic usefulness.
A Clinical Perspective for the Management of Invasive Fungal Infections: Focus on IDSA Guidelines
Authors: Kontoyiannis Dimitrios P.
Published: June 2004

Invasive fungal infections, especially candidiasis and aspergillosis, are a major cause of morbidity and mortality. Many controversies surround the management of these infections. A critical overview of the recent Infectious Diseases Society of America practice guidelines is provided, as are comments on both the conundrums and future perspectives in medical mycology.
Markers for Progression of Coronary Disease
Authors: Bell Dawn M.
Published: June 2004

Endothelial cells play numerous physiologic roles including regulation of vascular tone, regulation of hemostasis and fibrinolysis, regulation of inflammatory processes, and maintenance of a permeability barrier to provide for exchange and active transport of substances into the artery wall. Pathophysiologic stimuli can result in localized alterations in endothelial activity. These changes include increased permeability to plasma lipoproteins, imbalances in local thrombogenic substances causing a prothrombotic state, and release of vasoactive compounds resulting in vasoconstriction. Loss of endothelium‐dependent vasodilatation is thought to be an early physiologic event in the development of arteriosclerosis, occurring before morphologic changes in the endothelium can be detected. Much of the effects of healthy endothelium appear to be produced by nitric oxide. Decreased bioavailability of nitric oxide results in endothelial dysfunction, which is the first step in the atherosclerotic process. Risk factor modification and pharmacologic interventions that can reverse endothelial dysfunction have the potential to decrease cardiovascular events in patients at risk.
Management of Coronary Heart Disease Risk Factors and Progression with Calcium Channel Blockers
Authors: Pieper John A.
Published: June 2004

The death rate from coronary heart disease (CHD) declined by 25% in the United States during 1987–1997, but the actual number of deaths fell by only 9%. Modifiable risk factors for CHD include hypertension, elevated low‐density lipoprotein cholesterol, reduced high‐density lipoprotein cholesterol, cigarette smoking, and diabetes. Several randomized clinical trials demonstrated that calcium channel blockers reduce the frequency of strokes in patients with hypertension, with particular benefit observed in patients with both hypertension and diabetes. Results of a meta‐analysis suggest that calcium channel blockers are similar to β‐blockers in preventing death or myocardial infarction and in improving exercise tolerance among patients with established CHD. In addition, amlodipine, a long‐acting dihydropyridine, was reported to reduce nonfatal vascular events and major vascular procedures in patients with angina. Ongoing clinical trials are comparing amlodipine with an angiotensin‐converting enzyme inhibitor for slowing the onset and progression of coronary artery plaque and cardiovascular events.
Impact of the Cost of Prescription Drugs on Clinical Outcomes in Indigent Patients with Heart Disease
Authors: Schoen Marieke D. , DiDomenico Robert J. , Connor Sharon E. , Dischler Jill E. , Bauman Jerry L.
Published: June 2004

Study Objective. To measure the impact that economic relief for prescription drugs to indigent patients with cardiovascular disease has on indicators of disease control.

Design. Prospective cohort study.

Setting. University inner‐city outpatient clinic.

Patients. One hundred sixty‐three indigent patients with heart disease who were uninsured or whose insurance plan did not provide prescription drug coverage and who had baseline data.

Intervention. Patients were assisted in obtaining prescription drugs, free of charge, in an attempt to improve adherence to their drug regimens.

Measurements and Main Results. The primary end point was to determine if cardiovascular outcome measures (i.e., international normalized ratio [INR], blood pressure, low‐density lipoprotein [LDL] cholesterol, and hospitalizations) and drug adherence improved in all patients after 6 months of prescription assistance compared with a 6‐month baseline period. In patients receiving warfarin, mean INR increased from 2.44 ± 0.64 at baseline to 2.61 ± 0.53 at 6 months (p<0.05). In patients with hypertension, mean blood pressure decreased from 138 ± 20/80 ± 11 mm Hg at baseline to 138 ± 19/78 ± 12 mm Hg at 6 months (p<0.05 for diastolic blood pressure only). The mean LDL level for patients on lipid‐lowering drugs significantly decreased from 126 ± 39 mg/dl at baseline to 108 ± 38 mg/dl at 6 months (p<0.001). For each disease measure, the improved disease control seen at 6 months persisted throughout 24 months of follow‐up. Hospitalizations for the entire cohort decreased from 85 at baseline to 49 at 6 months. Patient drug adherence improved from 48.5% at baseline to 72.7% at 6 months (p<0.001).

Conclusions. Drug adherence and clinical outcomes improved, and the number of hospitalizations declined when cardiovascular drugs were obtained for patients who could not afford to pay for them. Health care insurance plans that do not provide coverage for cardiovascular prescription drugs may be more costly secondary to poor disease control and increased hospitalizations.
Adherence to Oral Montelukast and Inhaled Fluticasone in Children with Persistent Asthma
Authors: Sherman James , Patel Parul , Hutson Alan , Chesrown Sarah , Hendeles Leslie
Published: June 2004

Study Objective. To evaluate adherence to oral montelukast and inhaled fluticasone in children with persistent asthma and to determine if age, monotherapy, and duration of therapy affect adherence.

Design. Retrospective analysis.

Setting. Pediatric pulmonary clinic.

Patients. One hundred seventy‐one children with asthma who required continuous treatment with a controller agent year‐round and in whom montelukast and/or fluticasone had been prescribed for at least 90 days.

Intervention. Montelukast monotherapy had been prescribed for 54 patients, fluticasone monotherapy for 48 patients, and combination therapy for 69 patients.

Measurements and Main Results. Prescription refill histories were obtained from pharmacies identified by the parents or from Medicaid pharmacy reimbursement records. The maximum possible adherence was calculated as [(no. of doses refilled)/(no. of doses prescribed)] × 100, for a mean observation period of 203 days (range 84–365 days) for montelukast and 314 days (range 97–365 days) for fluticasone. Median adherence rates were 59% (95% confidence interval [CI] 48–65%) for montelukast and 44% (90% CI 35–50%) for fluticasone. Adherence did not significantly correlate with age, length of observation period, or whether the patient was receiving monotherapy or combination therapy. The odds ratio for very poor adherence (< 50%) was 2.0 (95% CI 1.3–3.2) for fluticasone relative to montelukast.

Conclusions. Adherence to both drugs was suboptimal. However, these data indicate that our patients were likely to take montelukast more consistently than fluticasone. Whether this translates into better asthma control requires further study.
Manuscript Peer Review—A Guide for Health Care Professionals
Authors: Sylvia Lynne M. , Herbel Jo L.
Published: June 2004

Peer review, in which peer experts assess the value of a manuscript submitted to a professional journal, is regarded as a crucial step in publication. It is generally agreed that its usefulness is highly dependent on the preparedness of each reviewer and quality of each assessment. With sustained growth in biomedical publications, more and more health professionals are being called on to serve as peer reviewers. An instructional framework should assist pharmacists and other health care professionals in conducting high‐quality manuscript reviews.
Individualized Pharmacokinetic Monitoring Results in Less Aminoglycoside‐Associated Nephrotoxicity and Fewer Associated Costs
Authors: Streetman Daniel S. , Nafziger Anne N. , Destache Christopher J. , Bertino Joseph S.
Published: June 2004

Study Objective. To examine the impact of individualized pharmacokinetic monitoring (IPM) on the development of aminoglycoside‐associated nephrotoxicity (AAN).

Design. Retrospective case‐control study.

Setting. Two teaching hospitals.

Subjects. Two thousand four hundred five patients who received aminoglycosides.

Intervention. Aminoglycoside therapy dosed by either IPM or physicians' directions.

Measurements and Main Results. Patients receiving IPM were significantly less likely to develop AAN by both univariate (7.9% vs 13.2%, p=0.02) and multivariate methods (odds ratio 0.42, p=0.002). Female sex was protective against AAN. Age 50 years and above, high initial aminoglycoside trough, long duration of therapy, and concurrent piperacillin, clindamycin, or vancomycin increased risk of AAN. We estimated that IPM decreased AAN costs by $90,995/100 patients.

Conclusion. Individualized pharmacokinetic monitoring significantly decreased the frequency of AAN and its associated economic costs.
Vasopressin and Blood Pressure Support for Pancreatitis‐Induced Systemic Inflammatory Response Syndrome with Circulatory Shock
Authors: Lamarre Patrice , Perreault Brigitte , Lesur Olivier
Published: June 2004

A 54‐year‐old patient, admitted to the intensive care unit with a diagnosis of severe pancreatitis, developed circulatory shock that failed to respond to standard vasopressor treatment: epinephrine and norepinephrine. Addition of vasopressin helped reduce standard catecholamine need while maintaining adequate arterial blood pressure. Vasopressin appears to be a promising agent for maintaining arterial pressure during septic shock or systemic inflammatory response syndrome, but due to limited data and potential side effects, its use as first‐line treatment for these indications is not recommended.
Can the Frequency and Risks of Fatal Adverse Drug Events Be Determined?
Authors: Kelly William N.
Published: June 2004

Death is the ultimate adverse drug event. Despite its importance, the frequency of fatal adverse drug events is unknown. Estimates in the United States are as high as 140,000/year, although this number is heavily disputed. Potential reasons and risks for fatal adverse drug events, as well as epidemiologic designs for studying this important public health issue, are discussed and issues are raised to promote further thought.
Fludarabine Pharmacokinetics after Subcutaneous and Intravenous Administration in Patients with Lupus Nephritis
Authors: Kuo Grace M. , Boumpas Dimitrios T. , Illei Gabor G. , Yarboro Cheryl , Pucino Frank , Burstein Aaron H.
Published: June 2004

Study Objective. To compare the pharmacokinetics of subcutaneous and intravenous fludarabine in patients with lupus nephritis.

Design. Open‐label, randomized, crossover trial conducted with a phase I‐II trial.

Setting. Government research hospital.

Patients. Five patients with lupus nephritis.

Intervention. Fludarabine 30 mg/m2/day was administered either subcutaneously or as a 0.5‐hour intravenous infusion for 3 consecutive days. All patients received oral cyclophosphamide 0.5 g/m2 on the first day of each cycle.

Measurements and Main Results. Plasma samples were collected before and 0.5, 1, 1.5, 2, 4, 8, and 24 hours after the first dose. Urine was collected at 6‐hour intervals for 24 hours. Plasma and urine were analyzed for fluoro‐arabinofuranosyladenine (F‐ara‐A), fludarabine's main metabolite, using high‐performance liquid chromatography. Compartmental techniques were used to determine the pharmacokinetics of F‐ara‐A; a linear two‐compartment model best described them. Comparison of the pharmacokinetics between subcutaneous and intravenous administration was done by using a Wilcoxon signed rank test. No significant differences were found between subcutaneous and intravenous administration in median (interquartile range) maximum concentrations of 0.51 (0.38‐0.56) and 0.75 (0.52‐0.91) mg/L, respectively, or in fitted area under the concentration‐time curves from 0–24 hours of 4.65 (4.17‐4.98) and 4.55 (3.5‐4.94) mg•hour/L, respectively. Bioavailability of F‐ara‐A after subcutaneous dosing was approximately 105% of the bioavailability after intravenous administration. Differences in renal clearance and percentage of dose excreted in urine for subcutaneous and intravenous administration were nonsignificant. No injection site reactions were seen with subcutaneous dosing.

Conclusion. Subcutaneous and intravenous administration of fludarabine appear to have similar pharmacokinetics in patients with lupus nephritis. Subcutaneous injection may offer a convenient alternative to intravenous administration.
In Vitro Characteristics of Tobramycin Aerosol from Ultrasonic and Jet Nebulizers
Authors: Asmus Michael J. , Milavetz Gary , Tice Angela L. , Teresi Mary E.
Published: June 2004

Study Objective. To compare the in vitro performance of an ultrasonic nebulizer and a jet nebulizer in producing a respirable aerosol of tobramycin solution for injection.

Design. In vitro observational study.

Devices. Ultrasonic and jet nebulizers.

Intervention. Output was determined by measuring the difference in nebulizer weight before and after nebulizing 3 ml of tobramycin injection solution. Mass median aerodynamic diameter (MMAD) and respirable mass were determined by sampling tobramycin aerosol into a cascade impactor.

Measurements and Main Results. Mean (SD) output was 1.14 (0.09) ml/minute for the ultrasonic nebulizer and 0.64 (0.08) ml/minute (p<0.001) for the jet nebulizer. Mean MMAD for the jet nebulizer (2.31 [0.10] μm) was less than that of the ultrasonic nebulizer (2.81 [0.17] μm, p<0.001). The majority of tobramycin aerosol produced was in the respirable range for both the ultrasonic (65.1% [4.10%]) and jet (60.6% [0.73%], p=0.008) nebulizers.

Conclusion. Despite small, clinically unimportant differences in aerosol size and respirable fraction, either device would be acceptable to administer tobramycin injection solution.
Impact of Antiemetic Selection on Postoperative Nausea and Vomiting and Patient Satisfaction
Authors: Darkow Theodore , Gora‐Harper Mary Lea , Goulson Daniel T. , Record Kenneth E.
Published: June 2004

Study Objective. To determine the impact of antiemetic selection on postoperative nausea and vomiting (PONV) and patient satisfaction after ambulatory surgery.

Design. Prospective, observational study.

Setting. Ambulatory surgery center in an academic medical center.

Patients. Five hundred fifty‐four consecutive patients undergoing ambulatory surgical procedures of any kind.

Intervention. Data on antiemetic utilization, occurrence of PONV, and patient satisfaction were collected perioperatively. Multiple regression analyses for antiemetic choice were performed.

Measurements and Main Results. Prophylactic antiemetic therapy was administered to 292 (52.7%) patients, most often with droperidol (200 patients), metoclopramide (134), or dexamethasone (55). Forty‐one (7.4%) patients had an episode of emesis in the postanesthesia care unit. Choice of antiemetic was not a significant predictor of PONV. Patient satisfaction for all patients was 9.5 on a 10‐point scale, with no agent more or less successful than any other.

Conclusion. As choice of antiemetic drug given for prophylaxis had little impact on clinical outcome or patient satisfaction, traditional agents should form the core of antiemetics used for PONV prophylaxis in ambulatory surgery patients.
Cost‐Effectiveness of Ceftazidime by Continuous Infusion versus Intermittent Infusion for Nosocomial Pneumonia
Authors: McNabb JoCarol J. , Nightingale Charles H. , Quintiliani Richard , Nicolau David P.
Published: June 2004

Study Objective. To determine if continuous‐infusion ceftazidime is more cost‐effective and efficacious than intermittent infusion in patients with nosocomial pneumonia.

Design. Prospective, open‐label, randomized trial.

Setting. Large, community teaching hospital.

Patients. Intensive care unit (ICU) patients with nosocomial pneumonia.

Interventions. Ceftazidime 3 g/day was administered as a continuous infusion or as 2 g 3 times/day by intermittent infusion to treat nosocomial pneumonia in the ICU. Patients also received tobramycin 7 mg/kg once/day.

Measurements and Main Results. Thirty‐five patients were evaluable; 17 received continuous infusion and 18 intermittent infusion. Clinical efficacy (94% and 83% successful outcomes with continuous and intermittent infusion, respectively), adverse events, and length of stay did not vary significantly between groups. Costs associated with continuous infusion, $627 ± 388, were significantly lower (p≤0.001) than with intermittent infusion, $1007 ± 430.

Conclusions. Continuous infusion of ceftazidime is a cost‐effective alternative to intermittent infusion for nosocomial pneumonia in the ICU.
Role of Antiarrhythmic Therapy in Patients at Risk for Sudden Cardiac Death: An Evidence‐Based Review
Authors: Hilleman Daniel E. , Bauman Jerry L.
Published: June 2004

Sudden cardiac death (SCD) accounts for more than half of all cardiac deaths occurring each year in the United States. Although it has several causes, patients at greatest risk are those with coronary artery disease and impaired left ventricular function, heart failure secondary to ischemia or idiopathic dilated cardiomyopathy, hypertrophic cardiomyopathy, documented sustained ventricular tachycardia or ventricular fibrillation, and survivors of cardiac arrest. The presence of asymptomatic ventricular arrhythmias, positive signal‐averaged electrocardiogram (ECG), low heart rate variability index, or inducible ventricular tachycardia or ventricular fibrillation increases the risk. In primary prevention trials in patients with ischemic heart disease, β‐blockers reduced both total mortality and SCD, whereas class I antiarrhythmic drugs, especially class IC, increased mortality. Among class III agents, d, l‐sotalol and dofetilide have a neutral effect on mortality, whereas d‐sotalol increases mortality. Amiodarone has a neutral effect on total and cardiac mortality but does reduce the risk of arrhythmic death and cardiac arrest. Three primary prevention trials in patients with ischemic heart disease were conducted with implantable cardioverter‐defibrillators (ICDs). Patients with low ejection fractions (EFs), asymptomatic ventricular arrhythmias, and inducible ventricular tachycardia or ventricular fibrillation had significant reductions in total, cardiac, and arrhythmic death with ICDs compared with either no drug therapy or conventional antiarrhythmic agents. The ICDs did not reduce mortality in patients with low EFs and a positive signal‐averaged ECG undergoing coronary bypass graft. In those with heart failure, b̀‐blockers reduced total and SCD mortality, but dofetilide and amiodarone had a neutral effect on mortality. In the secondary prevention of SCD, antiarrhythmic drugs alone generally are not thought to improve survival. In three trials in patients with documented sustained ventricular tachycardia or ventricular fibrillation, or survivors of SCD, ICDs reduced cardiac and arrhythmic mortality. Total mortality, however, was significantly reduced in only one of these trials. The role of antiarrhythmic drugs in secondary prevention of SCD is limited to patients in whom ICD is inappropriate or in combination with ICD. Antiarrhythmics can be given selectively with ICDs to decrease episodes of ventricular tachycardia or fibrillation to reduce ICD discharges, to suppress episodes of nonsustained ventricular tachycardia that trigger ICD discharges, to slow the rate of ventricular tachycardia to increase hemodynamic stability, to allow effective antitachycardia pacing, or to suppress supraventricular arrhythmias.
Poor Adherence with Hypolipidemic Drugs: A Lost Opportunity
Authors: Tsuyuki Ross T. , Bungard Tammy J.
Published: June 2004

All articles assessing adherence to hypolipidemic drugs were reviewed and categorized by patient population (clinical trial, unselected) and reported as rates of nonadherence and discontinuation. Overall, levels of discontinuation reported in clinical trials (6–31%) and lipid clinics (2–38%) are similar, with unselected populations consistently reporting higher rates (15–78%). Rates of nonadherence in clinical trials and lipid clinics also are comparable, with unselected populations having the highest rates. Across all settings, rates of discontinuation and nonadherence are consistently reported to be poorer with resins and niacin than with hydroxy‐6‐methylglutamate coenzyme A reductase inhibitors. Adherence to hypolipidemic agents appears to decrease in parallel with level of follow‐up. Data evaluating mechanisms of poor adherence are limited. While the search for new, efficacious therapies must continue, efforts focused on improving adherence to proven therapy may have a greater overall impact on health than any single new agent.
Inflammation and Cystic Fibrosis Pulmonary Disease
Authors: Kennedy Mary Jayne
Published: June 2004

Inflammation plays a primary role in the pathogenesis of cystic fibrosis (CF)‐related lung disease. Controlling the inflammatory process with antiinflammatory therapy may slow the progression of pulmonary disease and thereby decrease morbidity. Despite potential benefits of antiinflammatory therapy, both the decision to treat and selection of the most appropriate therapeutic agent are controversial. Although oral corticosteroids are associated with reduced progression of pulmonary disease, the risk of clinically significant adverse effects limits long‐term therapy. Clinical studies with inhaled corticosteroids failed to report positive effects on reducing airway inflammation. Based on available clinical data, routine therapy with these agents should be limited to patients with asthma or steroid‐responsive wheezing. High‐dosage ibuprofen has a beneficial effect on reducing the annual rate of decline in pulmonary function in patients with mild lung disease. Whereas initial results are encouraging, they do not support routine ibuprofen therapy in all patients with CF. However, as advocated by the Cystic Fibrosis Foundation, high‐dosage ibuprofen may be considered in children 5–12 years of age with a baseline forced expiratory volume of 60% predicted or greater.
Pharmacists' Assessment of Dispensing Errors: Risk Factors, Practice Sites, Professional Functions, and Satisfaction
Authors: Bond C. A. , Raehl Cynthia L.
Published: June 2004

Certain demographic, practice, staffing, and pharmacist satisfaction variables may contribute to dispensing errors. A survey was randomly mailed to 7298 (50%) Texas pharmacists, of which 2862 were returned (39% response rate). Responders were 2437 pharmacists who indicated that they were in practice. Of these, 535 (23%) reported no risk to patients for dispensing errors and 793 (34%) reported at least one patient/week was at risk for such an error. There was a positive relationship between number of prescription orders filled/hour and the estimated risk of dispensing errors (rs=0.285, p<0.001). Pharmacists practicing in mail service pharmacies (risk score = 1.85 ± 1.32), traditional chain store pharmacies (1.66 ± 1.18), and hospital pharmacies (1.61 ± 1.09) reported a higher risk than other groups. Pharmacists practicing in independent community pharmacies (0.75 ± 0.84), home health care (0.83 ± 0.99), grocery chain store pharmacies (1.30 ± 0.96), and mass merchandise chain store pharmacies (1.30 ± 1.08) reported a lower risk (H=260, df=8, p<0.001). Nine job satisfaction variables were strongly associated with the risk of dispensing errors (rs = between −0.3 and −0.422, p<0.001), as were prescription volume, practice site, staffing, training, pharmacist functions, and professional organization membership. The results of this survey should help pharmacists and management develop specific plans for reducing the risks of dispensing errors. These data should be useful for more in‐depth study of such errors.
Use of Bupropion SR in a Pharmacist‐Managed Outpatient Smoking‐Cessation Program
Authors: Roth Mary T. , Westman Eric C.
Published: June 2004

We administered bupropion sustained‐release (SR) in a pharmacist‐managed outpatient smoking‐cessation program. Patients were referred to the program by their primary care physician. All patients completed initial visit questionnaires, received behavioral counseling by a clinical pharmacist, and were provided educational materials on smoking cessation. Seventy‐one patients received bupropion SR for treatment of nicotine dependence and were followed for 6 months. Point prevalence abstinence rates were 28.2% and 25.4% at 8 weeks and 6 months, respectively. The trend was toward lower cessation rates in patients with a documented psychiatric diagnosis at 6 months (p=0.064). Bupropion SR was fairly well tolerated, with the most common adverse effects being dry mouth and bad taste. The agent appears to have better success for smoking cessation in patients free of psychiatric comorbidities, but further research is required to support this finding.
An Evaluation of the Hemostatic Effects of Hydrophilic, Alcohol, and Lipophilic Extracts of Notoginseng
Authors: White C. Michael , Fan Chengde , Song Jessica , Tsikouris James P. , Chow Moses
Published: June 2004

Study Objective. To compare the hemostatic effects of hydrophilic, alcohol, or lipophilic extract of notoginseng with those of the control and placebo.

Design. Hemorrhagic rat model.

Setting. Hartford Hospital, Hartford, Connecticut; animals were housed at the Hartford Hospital animal facility.

Animals. Sixty‐two male Wistar rats.

Intervention. Administration of placebo (wheat flour), and alcohol, hydrophilic (water), and lipophilic (hexane) extracts of notoginseng.

Methods. Rats were divided into five groups, and their tails were transected 5 mm from the tip. Group 1 received no treatment (control), group 2 received placebo, group 3 received alcohol extract, group 4 received hydrophilic extract, and group 5 received lipophilic extract. Total bleeding time was determined and compared among the groups.

Main Results. Bleeding time was shorter for the placebo group than the control group (p=0.035). The alcohol extract group had the shortest bleeding time, which was significantly shorter than that of the control (p<0.0001), placebo (p=0.0124), and lipophilic extract groups (p=0.002). The hydrophilic extract group had a shorter bleeding time than the control group (p=0.0058) and showed a trend toward shorter bleeding time than the lipophilic extract group (p=0.068).

Conclusions. The alcohol extract of notoginseng results in the shortest bleeding time and provides better hemostatic effects than no treatment, placebo treatment, and treatment with lipophilic extract.
Role of Coenzyme Q10 in Chronic Heart Failure, Angina, and Hypertension
Authors: Tran Mongthuong T. , Mitchell Tina M. , Kennedy Daniel T. , Giles Joel T.
Published: June 2004

Purpose. Coenzyme Q10 (CoQ10) has a pathophysiologic role in many disease states. The purpose of this review is to provide recommendations regarding the safety, efficacy, and dosing of CoQ10 in the management of chronic heart failure (CHF), angina, and hypertension.

Data Sources. Literature pertaining to the safety and efficacy of CoQ10 specifically in cardiovascular indications was reviewed. We used relevant clinical trials, articles, reviews, and letters that were selected from a literature search of the MEDLINE database (1974–2000), Micromedex Healthcare Series, and the Natural Medicines Comprehensive Database.

Findings. Coenzyme Q10 administered orally has favorable actions in the described cardiovascular conditions and appears to be safe and well tolerated in the adult population. Issues concerning optimum target dosages, potential interactions, monitoring parameters, and the role of CoQ10 as a monotherapeutic agent need to be investigated further. Favorable effects of CoQ10 on ejection fraction, exercise tolerance, cardiac output, and stroke volume are demonstrated in the literature; thus, the use of CoQ10 as adjuvant therapy in patients with CHF may be supported.

Conclusions. Coenzyme Q10 therapy in angina and hypertension cannot be substantiated until additional clinical trials demonstrate consistent beneficial effects. However, CoQ10 may be recommended as adjuvant therapy in selected patients with CHF. At this time, CoQ10 should not be recommended as monotherapy or first‐line therapy in any disease state.