bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacy Continuing Education Available on the Internet
Authors: Trinkle Randy
Published: May 2004

Access to interesting and pertinent continuing education material would be expected to encourage pharmacists to pursue postgraduate professional development. The Internet is one means of providing accessible and timely instructional material. Twenty‐nine Internet sources of continuing education available for pharmacists were identified. Criteria for inclusion included free educational credit and accreditation by a recognized body. Evaluation criteria were currency of the offerings, author and sponsor identification, software requirements in addition to a browser, and methods for submitting examination answers and receiving certificates of credit.
Correlation of Activated Clotting Time and Activated Partial Thromboplastin Time to Plasma Heparin Concentration
Authors: Koerber John M. , Smythe Maureen A. , Begle Robert L. , Mattson Joan C. , Kershaw Beverly P. , Westley Susan J.
Published: May 2004

Study Objective. To determine the correlation between activated clotting time (ACT) or activated partial thromboplastin time (aPTT) and plasma heparin concentration.

Design. Two‐phase prospective study.

Setting. University‐affiliated community hospital.

Patients. Thirty patients receiving continuous‐infusion intravenous heparin.

Interventions. Measurement of ACT, aPTT and plasma heparin concentrations.

Measurements and Main Results. Linear and log linear correlations were determined between clotting time tests and heparin concentrations. Linear correlations yielded r values of 0.58 for ACT (p=0.008) and 0.89 for aPTT (p=0.0001). Log linear correlations yielded r values of 0.60 for ACT (p=0.005) and 0.88 for aPTT (p=0.0001). A decision analysis was performed to determine possible consequences of dosage adjustments based on either test in relationship to the decision based on plasma heparin concentration. The decision analysis based on ACT disagreed with corresponding decisions based on plasma heparin concentration in 15 of 30 patients; 13 disagreements may have increased the risk of bleeding, and the other 2 may have increased the risk of thrombosis. Decisions based on aPTT disagreed with corresponding decisions based on plasma heparin concentration in 13 of 30 patients; 2 disagreements may have increased the risk of bleeding, and the other 11 may have increased the risk of thrombosis.

Conclusion. There are significant statistical linear and log linear correlations between both clotting time tests and plasma heparin concentrations, with aPTT showing stronger correlation than ACT. However, decisions regarding heparin therapy based on ACT may increase a patient's risk of bleeding, whereas decisions based on aPTT may increase the risk of thrombus progression or rethrombosis.
Abacavir: Absolute Bioavailability, Bioequivalence of Three Oral Formulations, and Effect of Food
Authors: Chittick Gregory E. , Gillotin Catherine , McDowell James A. , Lou Yu , Edwards Kathleen D. , Prince William T. , Stein Daniel S.
Published: May 2004

Study Objectives. Study A: to determine the absolute bioavailability of a single 300‐mg abacavir hemisulfate tablet. Study B: to determine the bioequivalence of two oral abacavir formulations (300‐mg hemisulfate tablet, 100‐mg succinate caplet), the effect of food on the bioavailability of the 300‐mg hemisulfate tablet, and the bioavailability of the hemisulfate tablet relative to the hemisulfate solution.

Design. Phase I, randomized, open‐label, balanced two‐ (study A) and three‐or four‐period (study B), crossover studies.

Setting. Two clinical research centers.

Subjects. Six men infected with the human immunodeficiency virus (HIV), aged 27–39 years (study A), and 18 HIV‐infected men and women, aged 21–50 years (study B).

Interventions. In study A, all subjects received a single, oral 300‐mg tablet of abacavir hemisulfate or a single, intravenous infusion of abacavir hemisulfate 150 mg over 60 minutes. In study B, all subjects received each of three single‐dose treatments: three 100‐mg abacavir succinate caplets in a fasted state, one 300‐mg abacavir hemisulfate tablet in a fasted state, and one 300‐mg abacavir hemisulfate tablet with a high‐fat breakfast. Twelve subjects in study B also received a fourth treatment of abacavir hemisulfate 300 mg as an oral solution in a fasted state. Plasma samples collected for 24 hours (study A) or 12 hours (study B), and urine samples collected for 12 hours (study A) were analyzed by validated high‐performance liquid chromatographic methods.

Measurements and Main Results. Abacavir pharmacokinetic parameters were calculated using standard, noncompartmental methods. In study A, the geometric least square (GLS) mean absolute bioavailability of oral abacavir was 83% (range 65–107%). In study B, the hemisulfate tablet was bioequivalent to the succinate caplet, but its time to maximum concentration (Tmax) occurred 30 minutes earlier. Administration of the abacavir hemisulfate tablet with food had no effect on area under the curve from time zero to infinity (AUC0–∞), decreased maximum concentration (Cmax) by 26%, and delayed Tmax by 38 minutes. The relative bioavailability (GLS mean AUC0–∞ ratio) of the 300‐mg abacavir hemisulfate tablet to solution was 101%, Cmax was 11% lower, and Tmax was unchanged. The most common drug‐related adverse events associated with abacavir were nausea, vomiting, abdominal pain, and headache, all of which were mild.

Conclusion. Based on our results, abacavir is safe and well tolerated and can be administered with or without meals.
Comparison of Iothalamate Clearance Methods for Measuring GFR
Authors: Dowling Thomas C. , Frye Reginald F. , Fraley Donald S. , Matzke Gary R.
Published: May 2004

Study Objective. To evaluate the bias and precision of three methods of measuring glomerular filtration rate (GFR) relative to a standard method.

Design. Prospective, outpatient study.

Setting. University‐affiliated general clinical research center.

Patients. Twenty‐six patients with various degrees of renal function (GFR range 25–151 ml/min/1.73 m2).

Interventions. Each patient received iothalamate twice during the study visit, first as a bolus injection and then as a priming dose followed by a constant‐rate infusion for 2.5 hours.

Measurements and Main Results. Plasma (ClpIVB) and renal clearances (ClrIVB) after bolus injection and plasma clearance during constant‐rate infusion (ClpINF) were compared with standard renal clearance during constant‐rate infusion (ClrINF). All three measures were highly correlated with ClrINF (r>0.90, p<0.001). The mean ClrIVB was not significantly different from ClrINF (106.3 ± 30.4 vs 104.2 ± 28.5 ml/min/1.73 m2) and provided a precise (8.8%, 95% CI 6.5–11.1%) and unbiased measure of GFR. Both ClpIVB and ClpINF were positively biased; values exceeded ClrINF by 11.8 ± 11.1 (p=0.0001) and 10.5 ± 12.5 ml/min/1.73 m2 (p=0.0003), respectively. Use of a nonrenal correction factor of 9.8 and 10.5 ml/min/1.73 m2 for infusion and bolus plasma clearance values, respectively, eliminated bias and improved the precision of these methods.

Conclusions. Iothalamate renal clearance after bolus injection is a simple, accurate, and precise measurement of GFR and may be a useful alternative to the standard infusion method in clinical investigations. The corrected plasma clearance provides a simple index of GFR for clinical practice.
Testosterone and Andropause: The Feasibility of Testosterone Replacement Therapy in Elderly Men
Authors: Lund Brian C. , Bever‐Stille Kristine A. , Perry Paul J.
Published: May 2004

Andropause, a syndrome in aging men, consists of physical, sexual, and psychologic symptoms that include weakness, fatigue, reduced muscle and bone mass, impaired hematopoiesis, oligospermia, sexual dysfunction, depression, anxiety, irritability, insomnia, memory impairment, and reduced cognitive function. Free testosterone levels begin to decline at a rate of 1% per year after age 40 years. It is estimated that 20% of men aged 60–80 years have levels below the lower limit of normal. Although the causal relationship between declining testosterone levels and development of andropause symptoms is not firmly established, administration of testosterone to this population resulted in improvements in many areas. Most studies to date focused on physical benefits of testosterone replacement and failed to assess psychologic symptoms rigorously. Preliminary data suggest that therapy may benefit elderly men with new‐onset depression. Testosterone administration is not without problems, the most worrisome being the potential for increased prostate cancer risk. Despite this concern, a limited number of studies administered the hormone weekly for up to 2 years, with only mild increases in prostate‐specific antigen over control values. Currently, insufficient evidence, primarily regarding psychologic safety and efficacy, exists to warrant general administration of testosterone to elderly hypogonadal men. Further clinical investigations of this therapy in men with low testosterone levels and andropause symptoms are justified and necessary.
Migraine: A Comprehensive Review of New Treatment Options
Authors: Weitzel Kristin W. , Thomas Michele L. , Small Ralph E. , Goode Jean‐Venable R.
Published: May 2004

Headaches are among the most common complaints reported to health care professionals and are classified by the International Headache Society as migraine, tension‐type, or cluster, with additional subtypes. Classification and etiology of headache should be determined after thorough review of the patient's history. Once diagnosed, migraine can be treated by preventive or abortive measures. Recent developments add new options, including availability of drugs for intranasal administration (sumatriptan, dihydroergotamine) and 5‐HT1B/1D agonists (rizatriptan, zolmitriptan, naratriptan, eletriptan). Although placebo‐controlled trials are available, few comparative clinical trials of these agents have been conducted; however, important pharmacologic, pharmacokinetic, and clinical differences exist among the drugs.
β‐Adrenergic‐Blocking Agents in Bronchospastic Diseases: A Therapeutic Dilemma
Authors: Tafreshi Mohammad J. , Weinacker Ann B.
Published: May 2004

Cardioselective (β‐blockers should be administered starting with a low dosage under direct medical observation. Bronchodilators should be readily available or may be coadministered. Because of several advantages, agents such as metoprolol, atenolol, and, in some cases, esmolol should be the first agents considered. In contrast to noncardioselective agents, if bronchospasm occurs, the effect of cardioselective agents is believed to be easier to reverse. Clinicians should avoid noncardioselective β‐blockers in asthmatics, even in small doses, such as those administered as eye drops. For asthmatic patients who are intolerant to noncardioselective β‐blockers, switching to a cardioselective β‐blocker might be a safe alternative. The significance of β2‐blockade usually varies with the patient's ventilatory condition, with more serious consequences being anticipated in patients with more severe asthma.
Intracellular Phosphorylation of Zidovudine in an In Vitro Hollow Fiber Model
Authors: Rana Khurram Z. , Dudley Michael N.
Published: May 2004

Combination antiretroviral therapy that includes zidovudine has proved much better in treating human immunodeficiency virus infection than monotherapy. Diminished responses to zidovudine, especially when it was given alone, was likely due to factors including interpatient variability in pharmacokinetics, nonadherence, emergence of resistant mutants, and reduced cellular enzymatic processes to phosphorylate the drug. This study evaluated the intracellular metabolism of zidovudine up to 6 weeks using a hollow fiber cellular model system that simulated exposure of cells to steady‐state concentrations achieved in humans. The CEM‐T4 lymphocytes were exposed to simulated 200‐, 600‐, and 1200‐mg daily doses of zidovudine. Samples were analyzed for monophosphate, diphosphate, and triphosphate metabolites of zidovudine by high‐performance liquid chromatography separation and radiochemical detection. The monophosphate metabolite increased as simulated doses increased, but no corresponding increases in the active triphosphate metabolite occurred. In addition, intracellular metabolism of zidovudine did not change after exposure for 6 weeks. These results suggest that the active triphosphate metabolite of zidovudine does not change much when doses are increased or when exposed for at least 6 weeks. Hollow fiber models may be used effectively to investigate intracellular metabolism of antiviral agents and for some duration of time.
Diurnal Variation in Plasma Norepinephrine in Patients with Heart Failure
Authors: Bleske Barry E. , Chung Hui‐San , DiMagno Matthew , Nicklas John M.
Published: May 2004

Diurnal variation in plasma norepinephrine (PNE) levels is well documented in healthy individuals but not in patients with heart failure. Therefore, we attempted to determine variations in PNE levels over 24 hours, measured hourly, in six patients with an ejection fraction below 40% and a history of heart failure of longer than 3 months. Three controls without a history of heart failure also were evaluated. Both patients and controls had diurnal variations in PNE, with highest levels occurring during the day and lowest at night. When data in patients were evaluated by 6‐hour time intervals the mean value for 6:00 A.M.–12:00 noon was approximately twice as high as 12:00 midnight–6:00 A.M. (689 ± 329 vs 338 ± 166 pg/ml, p<0.05, respectively). Patients also had significant peak to trough variation in PNE levels compared with controls (959 ± 396 vs 386 ± 84 pg/ml, p<0.02, respectively). These results suggest that significant intrapatient variations in PNE occur over 24 hours in patients with heart failure. These variations may have to be accounted for when evaluating and treating patients with heart failure.
Successful Rechallenge with Etoposide Phosphate after an Acute Hypersensitivity Reaction to Etoposide
Authors: Bernstein Bridget J. , Troner Michael B.
Published: May 2004

Hypersensitivity reactions to etoposide are reported infrequently and consist of hypotension, hypertension, flushing, diaphoresis, dyspnea, bronchospasm, and loss of consciousness. A 23‐year‐old woman experienced acute bronchospasm, tachycardia, hypoxia, and moderate hypertension minutes after an infusion of etoposide was begun. Symptoms resolved within an hour after administration of intravenous fluids, methylprednisolone, diphenhydramine, and oxygen. Subsequently, the patient was given etoposide phosphate without incident. To our knowledge, this is the first report of successful rechallenge with etoposide phosphate after an acute hypersensitivity reaction to etoposide.
Vinorelbine Tartrate‐Induced Pulmonary Edema Confirmed on Rechallenge
Authors: Cattan Christine E. , Oberg Kristin C.
Published: May 2004

A 67‐year‐old woman with metastatic breast cancer experienced sudden and profound pulmonary edema within 45 minutes after completion of intravenous administration of vinorelbine tartrate on two occasions. Both times the drug was discontinued and the patient was treated aggressively with oxygen, intravenous furosemide, and a vasodilator. The patient suffered no lasting medical complications due to the reaction. Until clear documentation and the mechanism for occurrence of this reaction are known, patients receiving vinorelbine should be monitored closely, particularly in the first few hours after intravenous administration.
Phaeohyphomycosis from Exophiala jeanselmei with Concomitant Nocardia asteroides Infection in a Renal Transplant Recipient: Case Report and Review of the Literature
Authors: Sartoris Kathleen E. , Baillie G. Mark , Tiernan Rosemary , Rajagopalan P. R.
Published: May 2004

A 59‐year‐old black man who received a cadaveric renal transplant 15 months earlier developed subcutaneous nodules on his right upper extremity that were identified as phaeohyphomycosis caused by Exophiala jeanselmei. The man was admitted 4 weeks later with a swollen left arm and had Nocardia asteroides in this area and in the apex of his left lung. He was treated with surgical excision, and itraconazole, imipenem‐cilastatin, and trimethoprimsulfamethoxazole. With the potential presence of more than one microorganism in an immunocompromised patient, it is important to identify and differentiate them correctly to direct appropriate therapy.
Antimicrobial Resistance in Gram‐Positive Bacteria: The Myth of the MIC
Authors: Rapp Robert P.
Published: May 2004

Although much progress has occurred in the fight to treat infection, resistant bacteria increasingly are becoming problematic. The minimum inhibitory concentration is easily determined, yet its definition, clinical application, and relevance are confusing. In addition, errors can occur during in vitro susceptibility testing. The mechanism of resistance for different organisms is discussed as are the pitfalls of susceptibility testing and the prescription of antimicrobial agents.
Successful Interventions for Gram‐Negative Resistance to Extended‐Spectrum β‐Lactam Antibiotics
Authors: Rice Louis B.
Published: May 2004

Antibiotic resistance among nosocomial pathogens in this country's hospitals adds significantly to patient morbidity and mortality and the cost of health care. Optimism for identifying antimicrobial agents that would “solve the problem” of resistance has been replaced by a much more guarded and realistic view of the battle between humans and pathogenic microorganisms. Efforts now are more appropriately directed toward limiting, rather than completely eliminating, resistance, generally by either infection control or antibiotic control measures, and sometime combinations of the two. Methicillin‐oxacillin resistance in Staphylococcus aureus (MRSA) results from the expression of an acquired penicillin‐binding protein (PBP 2a) that is not transferable in vitro. In most hospitals, even those with high percentages of MRSA, relatively few resistant clones are identified, suggesting transmission of individual strains throughout the hospital population. Because person‐to‐person spread is so important in transmission of MRSA, strategies aimed at preventing transmission of the resistant strains are remarkably effective when strictly enforced. Ceftazidime resistance in Enterobacteriaceae results from point mutations within genes that encode widely prevalent and often transferable plasmid‐mediated enzymes. In addition, mutations of these genes that allow hydrolysis of cephalosporins usually result in decreased activity against other drugs, including the penicillins and β‐lactamase inhibitors. Effective measures to control ceftazidime‐resistant Enterobacteriaceae have as their cornerstone limiting administration of antibiotics that select for the emergence and spread of these mutations, especially ceftazidime. The importance of infection‐control techniques in limiting the prevalence of ceftazidime‐resistant Enterobacteriaceae is less well established. Methods that are informed by a detailed understanding of the molecular mechanisms of resistance and resistance spread offer the best hope for limiting dissemination of antibiotic‐resistant bacteria in a cost‐effective manner.
Decreased Antimicrobial Resistance after Changes in Antibiotic Use
Authors: Smith David W.
Published: May 2004

Vancomycin‐resistant enterococci (VRE) and methicillin‐oxacillin–resistant Staphylococcus aureus (MRSA) originally predominated in large medical centers; however, these isolates are now common in community hospitals and community clinics. No simple answer is available regarding control of antimicrobial‐resistant bacteria, especially VRE and MRSA, as their numbers increase and pose a more serious threat to patient care. The source of colonization is often difficult to identify because of transport of patients among different locations on the continuum of care (e.g., hospital to extended care facility to home and back). At one hospital, control strategies greatly reduced the occurrence of gram‐negative bacteria such as VRE. Since 1994, VRE declined from 16% to 5%. Similarly, the number of MRSA isolates declined from 35% to 23%. These declines are attributed to a cohesive working relationship among pharmacists, microbiologists, and infectious disease physicians and personnel, and to a decision to decrease administration of cephalosporins in favor of piperacillin‐tazobactam.
Low‐Molecular‐Weight Heparins in Pregnancy
Authors: Ensom Mary H. H. , Stephenson Mary D.
Published: May 2004

We conducted a systematic review, with MEDLINE and Cochrane Library data base searches and bibliographic reviews, of English‐language reports describing therapy with low‐molecular‐weight heparin (LMWH) in pregnancy. Altogether 40 citations, excluding abstracts, were identified. When the quality of evidence was categorized according to the method outlined by the U.S. Preventive Services Task Force, 2 articles were level I, 3 were level II‐1, 3 were level II‐2, 4 were level II‐3, 9 were level III, and the remaining 19 were classified as other (i.e., below level III). Of the 728 pregnant women and 1 postpartum woman described in the 40 citations, 340 (47%) received dalteparin, 192 (26%) enoxaparin, 108 (15%) certoparin, 54 (7%) nadroparin, 30 (4%) other LMWH, and 6 (< 1%) unspecified. The indication for LMWH in most patients (606 pregnancies, 83%) was for thromboprophylaxis. Daily doses ranged from 2500–22,000 U for dalteparin, 20 mg (2000 U)–80 mg (8000 U) for enoxaparin, 3000 U for certoparin, and 2050–15,000 U for nadroparin. Regimens included fixed dosages, increasing dosages as pregnancy progressed, dosages based on body weight, and dosages titrated according to anti‐Xa levels. Duration of therapy ranged from a single dose to 476 days. Maternal anti‐Xa levels were reported for 255 pregnancies. Target anti‐Xa levels ranged from 0.1–0.6 U/ml and measured values from 0.0–0.7 U/ml. Major maternal findings were 18 local and generalized skin reactions, 27 bleeding complications, 9 thromboembolic events, 8 deep vein thromboses, 1 bilateral renal vein thrombosis, 4 pulmonary emboli, 1 hepatic infarction, 4 cases of thrombophlebitis, 12 cases of preeclampsia, 1 placental abruption, and 2 osteoporotic vertebral fractures. A major fetal finding was lack of anti‐Xa activity in fetal or cord blood. Published experience suggests that LMWHs are generally safe and effective when administered for thromboprophylaxis during pregnancy. Until prospective, randomized, controlled trials comparing them with unfractionated heparin are performed, their benefits in pregnancy will remain inconclusive.
Effectively Treating Common Infections in Residents of Long‐Term Care Facilities
Authors: Ernst Michael E. , Ernst Erika J.
Published: May 2004

Clinicians involved in caring for institutionalized elderly frequently must treat common infections endemic to the setting. Numerous factors specific to these patients make accurate diagnosis and management more difficult than in healthy ambulatory adults. Three infections are commonly encountered in residents of long‐term care facilities: bacterial pneumonia, urinary tract infections, and skin and soft tissue infections. More antimicrobial agents are available now than ever before; therefore, judicious administration of drugs and familiarity with current treatment recommendations are imperative.
Enteral Nutrition in Patients with Pancreatitis
Authors: Kale‐Pradhan Pramodini B. , Elnabtity Manal H. , Park Nancy J. , Laus Mark
Published: May 2004

Nutritional support in the form of total parenteral nutrition (TPN) or enteral nutrition (EN) is successfully used in patients with pancreatitis, in whom the goal is to provide optimal nutrition while minimizing pancreatic exocrine activity. Controversy continues as to whether TPN or EN is more appropriate. Although TPN is traditionally preferred in acute pancreatitis, EN offers some advantages, being more physiologic, safer, and more cost‐effective. A review of available animal and human studies suggests that elemental diets may be effective in patients with mild acute pancreatitis. In patients who have no clinical indication for restricting the gastrointestinal tract, EN may be preferred.
The Effects of Peracetic Acid‐Hydrogen Peroxide Reprocessing on Dialyzer Solute and Water Permeability
Authors: Scott Meri K. , Mueller Bruce A. , Sowinski Kevin M.
Published: May 2004

We characterized the effects of peracetic acid‐hydrogen peroxide (PAHP) reprocessing on hemodialyzer permeability to water and solutes of various molecular weights and compared these effects within and between dialyzers. An aqueous‐based solution containing urea, creatinine, vancomycin, inulin, myoglobin, and albumin was dialyzed for 60 minutes with a hemodialyzer after undergoing 0, 1, 5, 10, and 15 reuse cycles. Solute clearance, sieving coefficient (SC), and ultrafiltration coefficient were determined. We found that PAHP reprocessing significantly decreased water and solute removal (urea, creatinine, vancomycin, inulin) by cellulose triacetate dialyzers (CT190) over 15 reuses (p<0.05) but did not affect the permeability of polysulfone dialyzers (F80A). Inulin removal was significantly lower for F80A than for CT190 (p<0.0001 and p<0.001 for clearance and SC values, respectively). Myoglobin and albumin removal by CT190 significantly decreased over 15 reuses (p<0.05), but no protein was detected in dialysate or ultrafiltrate at any reuse number for F80A. Reprocessing with PAHP alters dialyzer permeability; the effect is more pronounced for the CT190 dialyzer, but removal of solutes with molecular weight above 1500 Da is significantly lower with F80A dialyzers than with CT190. These changes in dialyzer permeability should be considered when determining optimal reuse procedures.
Atovaquone Suspension in HIV‐Infected Volunteers: Pharmacokinetics, Pharmacodynamics, and TMP‐SMX Interaction Study
Authors: Falloon Judith , Sargent Susie , Piscitelli Stephen C. , Bechtel Christine , LaFon Stephen W. , Sadler Brian , Walker Robert E. , Kovacs Joseph A. , Polis Michael A. , Davey Richard T. , Lane H. Clifford , Masur Henry
Published: May 2004

Study Objective. To evaluate the pharmacokinetics and safety of atovaquone suspension in volunteers infected with the human immunodeficiency virus ((HIV).

Design. Open‐label, nonrandomized study.

Setting. Two clinical research centers.

Patients. Twenty‐two HIV‐infected volunteers with a median CD4 cell count of 37 cells/mm3.

Interventions. Patients received atovaquone suspension fasting or fed for 2‐week periods with crossover at dosages of 500 mg/day, and randomization to fasting or fed at dosages of 750 and 1000 mg/day. A subset of patients also received 750 mg twice/day with food, and a subset of those who received 1000 mg/day fasting also received 1000 mg with food. During a long‐term dosing phase, a subset of subjects were evaluated for an interaction between atovaquone and trimethoprim‐sulfamethoxazole (TMP‐SMX).

Measurements and Main Results. Average steady‐state atovaquone concentrations at 500 mg were 6.7 ± 3.2 μg/ml fasted and 11.3 ± 5.0 μg/ml with food; at 750 mg, 9.9 ± 7.1 μg/ml fasted and 12.5 ± 5.9 μg/ml with food; at 1000 mg, 9.7 ± 4.3 μg/ml fasted and 13.6 ± 5.0 μg/ml with food; and at 1500 mg, 21.1 ± 5.0 μg/ml with food. Thus, plasma concentrations were not proportional to dose. Concomitant food ingestion resulted in a 1.3‐ to 1.7‐fold increase in values. Average steady‐state concentrations were less than 10 μg/ml in 21% and more than 15 μg/ml in 36% of patients at 1000 mg/day with food; at 750 mg twice/day, all five patients had levels above 15 μg/ml. Atovaquone suspension was well tolerated; diarrhea, nausea, fatigue, and rash were the most common adverse events. Concomitant administration of TMP‐SMX did not change atovaquone concentrations and resulted in small decreases in concentrations of TMP (16%) and SMX (10%).

Conclusion. Plasma concentrations are significantly higher when atovaquone suspension is administered with food compared with fasting. Total doses of 1500 mg/day are likely to achieve concentrations effective for prophylaxis of Pneumocystis carinii pneumonia.
CYP2D6 Mutations and Therapeutic Outcome in Schizophrenic Patients
Authors: Hamelin Bettina A. , Dorson Peter G. , Pabis Dennis , Still Daniel , Bouchard Roch‐H. , Pourcher Emmanuel , Rail Jimmy , Turgeon Jacques , Crismon M. Lynn
Published: May 2004

Study Objective. To investigate whether a relationship exists between the most common known cytochrome P450 (CYP) isozyme 2D6 mutations and schizophrenia. Because most antipsychotic and antidepressant agents interact with CYP2D6, we also investigated clinical outcomes in schizophrenic poor metabolizers (PMs) and extensive metabolizers (EMs).

Design. Prospective, observational study.

Setting. Two psychiatric hospitals and a university‐affiliated nonpsychiatric hospital.

Subjects. Thirty‐nine consecutive schizophrenic patients (POP 1), 89 schizophrenics of French Canadian origin (POP 2), and 384 healthy French Canadians (POP 3).

Intervention. All study subjects were genotyped for CYP2D6 mutant alleles. POP 1 patients were evaluated before and after 21 or more days of treatment with antipsychotic drugs metabolized at least in part by CYP2D6.

Measurements and Main Results. Whole blood was collected to determine CYP2D6 alleles *1, *3, *4, *5, *6, and *7 using standard restriction fragment length polymorphisms and polymerase chain reaction techniques. In comparison, CYP2D6 genotypes were determined in POP 2 and POP 3. Twenty‐three (59.0%) of 39 patients in POP 1 were genotypically EM homozygotes, 15 (38.4%) were EM heterozygotes, and 1 (2.6%) was a PM. Similar genotype distributions were determined in POP 2 and in POP 3. Genotype distributions for all three populations were in Hardy‐Weinberg equilibrium (p>0.05), and there was no significant difference among them (p=0.857). In POP 1, no differences were seen among genotypes in disease symptom severity, number and severity of adverse drug effects, or attitudes toward drug treatment at baseline and at the end of the study. In fact, all patients improved significantly during their hospital stay (all p<0.05), although independent of the CYP2D6 genotype.

Conclusion. Common CYP2D6 mutant alleles were not associated with schizophrenia or with disease symptoms, antipsychotic‐related adverse effects, or attitudes toward treatment.
Clinical and Economic Effectiveness of an Inpatient Anticoagulation Service
Authors: Mamdani Muhammad M. , Racine Eric , McCreadie Scott , Zimmerman Chris , O'Sullivan Tami L. , Jensen Gail , Ragatzki Paul , Stevenson James G.
Published: May 2004

We conducted a prospective cohort study to evaluate clinical and economic end points achieved by a pharmacist‐managed anticoagulation service compared with usual care (50 patients/group). The primary therapeutic end point was the time between starting heparin therapy and surpassing the activated partial thromboplastin time therapeutic threshold. The primary economic end point was the direct variable cost of hospitalization from admission to discharge. No significant differences between groups were noted for the primary therapeutic end point. Total hospital costs were significantly lower for patients receiving pharmacist‐managed care than for those receiving usual care ($1594 and $2014, respectively, 1997 dollars, p=0.04). Earlier start of warfarin (p=0.05) and shorter hospital stay (5 and 7 days, p=0.05) were associated with the pharmacist‐managed group.
Effect of the Moderate Consumption of Olestra in P Receiving Long‐term Warfarin Therapy
Authors: Beckey Nick P. , Korman Lisa B. , Parra David
Published: May 2004

We conducted a prospective, randomized, double‐blind, placebo‐controlled, parallel‐group trial to evaluate the effect of the moderate consumption of snacks containing olestra on the international normalized ratio (INR) in 40 patients receiving long‐term warfarin therapy. Patients continued their warfarin regimen and were assigned to receive 1.5 servings/day (42 g) for 2 weeks of Pringles Original Flavor Fat Free Potato Crisps with Olean (12 g olestra/1.5 servings) or Pringles Original Flavor Potato Crisps (placebo group). Patients' INRs were measured weekly for 2 weeks. Thirty‐six patients completed the first week of the trial. After 1 week, the mean change in the INR from baseline increased by 0.02 ± 0.5 in the olestra group and by 0.17 ± 0.4 in the placebo group (p=0.327). Ten patients in the olestra group and 12 in the placebo group completed the second week of the study. Mean change in the INR from baseline was similar at week 2, −0.18 ± 0.38 and 0.09 ± 0.53 (p=0.193), respectively. Gastrointestinal side effects (diarrhea, gas, bloating) occurred in three patients in the olestra group and five in the placebo group (p=0.3). Moderate consumption of snacks containing olestra did not significantly affect the INR (> 0.3 U) at 1 week in patients receiving long‐term anticoagulation with warfarin. It does not appear that moderate consumption of these snacks would affect the INR after 2 weeks, but this must be confirmed in a larger sample with adequate power at 2 weeks.
Evaluation of Acinetobacter baumannii Infection and Colonization, and Antimicrobial Treatment Patterns in an Urban Teaching Hospital
Authors: Weingarten Cindy M. , Rybak Michael J. , Jahns Brian E. , Stevenson James G. , Brown William J. , Levine Donald P.
Published: May 2004

In 1990 there was a sudden increase in the incidence of colonization and infection due to Acinetobacter baumannii (AB) in our intensive care units (ICUs). The isolates were multiply resistant to β‐lactam and aminoglycoside antibiotics, but remained susceptible to imipenem, amikacin, and ampicillin‐sulbactam. We examined the frequency of infection and colonization with AB and the effects of increased imipenem and amikacin therapy on Pseudomonas aeruginosa. We also used disease‐matched controls to determine the clinical and financial impacts of treating colonization. All patients with at least one AB isolate from January—December 1992 were identified retrospectively and classified as infected or colonized based on published Centers for Disease Control criteria; the control group was selected from a computerized medical records data base matching primary diagnostic codes (102 patients both groups). The 102 patients yielded 140 isolates, 124 resistant AB and 16 sensitive AB. Thirty three patients were infected, 69 colonized. Mortality correlated with APACHE II scores. Patients acquired the organism approximately 2 weeks after admission; they had a mean ICU stay of 27.35 days, compared with 5.53 days for controls. Patients with positive AB cultures required significantly more use of ventilators than those with negative AB cultures. They also had significantly longer hospital stay, more bed transfers, greater duration and number of antibiotics, and higher hospital and pharmacy charges. Unnecessary treatment for colonization with either imipenem or amikacin resulted in a substantial decrease of P. aeruginosa susceptibility to each agent. The financial impact of treating colonization was significant and is a potential area for cost avoidance. Our results emphasize the need to extubate and move patients to non‐ICU beds as soon as possible to decrease the risk of nosocomial infection. It also highlights the need to avoid treating colonization, thus avoiding unnecessary antibiotic therapy.
Analysis of Number Needed to Treat and Cost of Platelet Glycoprotein IIb/IIIa Inhibitors in Percutaneous Coronary Interventions and Acute Coronary Syndromes
Authors: Bell Dawn M.
Published: May 2004

This retrospective review and analysis of pivotal clinical trials compared acquisition costs and outcomes of platelet glycoprotein IIb/IIIa inhibitors. Absolute reduction in the number of deaths and nonfatal myocardial infarctions at 30 days, number of patients that need to be treated to prevent one event, and drug costs expended to prevent one event were assessed. In patients undergoing percutaneous coronary intervention (PCI), abciximab is the better value, especially in high‐risk patients. In those with unstable angina and non‐Q wave myocardial infarction, costs of eptifibatide and tirofiban were not significantly different, but the cost of tirofiban was more variable. These agents have the potential to be cost‐effective if administered to populations at high risk for adverse outcomes of acute coronary syndromes or PCI. Prospective methods to identify these high‐risk patients are being developed.
Intravenous Immunoglobulin as Adjunctive Treatment for Streptococcal Toxic Shock Syndrome Associated with Necrotizing Fasciitis: Case Report and Review
Authors: Cawley Michael J. , Briggs Michael , Haith Linwood R. , Reilly Kathleen J. , Guilday Robert E. , Braxton Gayna R. , Patton Mary Lou
Published: May 2004

Streptococcal toxic shock syndrome (STSS) is caused by infection with a toxicogenic strain of Streptococcus pyogenes. Clinical manifestations may be those of a mild illness, characterized by malaise, fever, and muscle pain, to severe sepsis and multisystem organ failure. The syndrome may be associated with several invasive infections including necrotizing fasciitis. Treatment is primarily surgical debridement of infected tissue with supportive care, antibiotics, and hemodynamic monitoring. Intravenous immunoglobulin (IVIG) is reported to have beneficial effects in the management of STSS associated with necrotizing fasciitis. The agent was successful in conjunction with surgical excision and antibiotics in a patient with necrotizing fasciitis, toxic shock, and multisystem organ failure. On the basis of this experience and a thorough literature review, we concur that IVIG may be a useful adjunct in the treatment of STSS associated with necrotizing fasciitis.
Elevated Serum Triglycerides with Clozapine Resolved with Risperidone in Four Patients
Authors: Dufresne Robert L. , Ghaeli Padideh
Published: May 2004

Serum triglyceride levels of four patients with psychotic disorders were decreased after switching therapy from clozapine to risperidone. In two patients clozapine was reinstated after risperidone was discontinued; serum triglyceride levels increased. This increase when clozapine was switched to risperidone and vice versa is consistent with our previous report of elevated serum triglyceride levels in clozapine‐treated patients. Other reports show increases with the atypical antipsychotics, olanzapine and quetiapine. We believe serum triglyceride levels should be monitored in patients who have other cardiac risk factors and are receiving clozapine.
Shaking, Chills, and Rigors with Once‐Daily Gentamicin
Authors: Lucas Kristy H. , Schliesser Shelley H. , O'Neil Michael G.
Published: May 2004

A patient receiving once‐daily gentamicin experienced shaking, chills, and rigors. This adverse reaction has occurred in patients around the country at many different institutions. Although the etiology is thought to be mediated by higher than normal endotoxin levels in one product, other possibilities must be explored.
Emergence of Low‐Molecular‐Weight Heparins in Cardiology
Authors: Stringer Kathleen A.
Published: May 2004

Drug therapy for the management of acute coronary syndromes is rapidly expanding. Over the past few years, a number of new antithrombotic agents have been introduced, including low‐molecular‐weight heparins. The epidemiology and pathophysiology of acute coronary syndromes are discussed, with a historical perspective on the use of antithrombotic therapy.
Clinical Trials of Low‐Molecular‐Weight Heparins in Cardiology
Authors: Spinler Sarah A.
Published: May 2004

Our understanding of the pathophysiology of acute coronary syndromes is evolving as the role of prognostic coagulation markers and the different effects unfractionated heparin and low‐molecular‐weight heparins have on these coagulation markers are investigated. The results of recent clinical trials of low‐molecular‐weight heparins in acute coronary syndromes are summarized, and an economic evaluation of enoxaparin for these indications is reviewed.
Low‐Molecular‐Weight Heparins for Acute Coronary Syndromes: An Emergency Medicine Perspective
Authors: Gonzalez Edgar R.
Published: May 2004

Patients with chest pain represent one of the largest and most challenging populations for emergency departments to treat. Diagnostic and treatment modalities implemented in the emergency department are associated with significant clinical outcomes and financial implications. Critical pathways are being developed to increase the speed and efficiency with which these patients are managed. Of particular importance is the evolving role of low‐molecular‐weight heparins, which have both clinical and economic advantages over unfractionated heparins in treating unstable angina and non‐Q wave myocardial infarction.
Clinical Pharmacy Services and Hospital Mortality Rates
Authors: Bond C. A. , Raehl Cynthia L. , Franke Todd
Published: May 2004

We evaluated the associations between clinical pharmacy services and mortality rates in 1029 United States hospitals. A data base was constructed from Medicare mortality rates from the Health Care Financing Administration and the National Clinical Pharmacy Services data base. A multivariate regression analysis, controlling for severity of illness, was employed to determine the associations. Four clinical pharmacy services were associated with lower mortality rates: clinical research (p<0.0001), drug information (p=0.043), drug admission histories (p=0.005), and participation on a cardiopulmonary resuscitation (CPR) team (p=0.039). The actual number of deaths (lower) associated with the presence of these four services were clinical research 21,125 deaths in 108 hospitals, drug information 10,463 deaths in 237 hospitals, drug admission histories 3843 deaths in 30 hospitals, and CPR team participation 5047 deaths in 282 hospitals. This is the first study to indicate that both centrally based and patient‐specific clinical pharmacy services are associated with reduced hospital mortality rates. This suggests that these services save a significant number of lives in our nation's hospitals.
Gabapentin: A Review of Published Experience in the Treatment of Bipolar Disorder and Other Psychiatric Conditions
Authors: Letterman Laura , Markowitz John S.
Published: May 2004

Successful therapy with valproate and carbamazepine in patients with psychiatric disorders led to investigation of other anticonvulsants for similar indications. Gabapentin is a relatively new anticonvulsant being investigated for potential use in the treatment of bipolar disorder (BD), anxiety disorders, behavioral dyscontrol, and substance use disorders. Its favorable side effect profile, absence of the need for therapeutic drug monitoring, and minimal drug interactions give gabapentin a potential role in these indications. Computer searches of the biomedical literature were undertaken to identify all pertinent case reports, case series, and studies of the drug as monotherapy or adjunctive therapy for BD; 10 reports were retrieved. In the treatment of various anxiety disorders, one study, one case report, and one case series were identified. At least one case series described gabapentin therapy for alcohol withdrawal and one case report of the drug for agitation associated with dementia. Published, well‐designed studies evaluating the agent's effectiveness as monotherapy for BD are lacking. Its benefit as an adjunctive treatment with other mood stabilizers is also unestablished. Data regarding its efficacy in the treatment of anxiety disorders or manifestations of substance abuse are limited. These areas may deserve further investigation.
The Impact of First‐Line Antihypertensive Drugs on Erectile Dysfunction
Authors: Barksdale John D. , Gardner Stephanie F.
Published: May 2004

Erectile dysfunction, a problem estimated to affect up to 30 million American men, is associated with a number of systemic illnesses and drugs. Age is not thought to be an independent risk factor for the disorder, but accompanying illnesses and their treatments may contribute to its onset. Newer classes of antihypertensive agents are less frequently associated with sexual dysfunction than diuretics or (β‐blockers. However, nearly every first‐line antihypertensive drug has been reported to cause some degree of erectile dysfunction. Management options include lifestyle modification, dosage reduction, discontinuation of the offending agent, switching to an alternative drug, and pharmacologic therapy.
The Role of Dehydroepiandrosterone in Diabetes Mellitus
Authors: Wellman Melinda , Shane‐McWhorter Laura , Orlando Patricia L. , Jennings J. Phillip
Published: May 2004

Much has been written in the lay literature regarding potential benefits of dehydroepiandrosterone (DHEA). Although it was removed from the over‐the‐counter market in 1985, the Dietary Supplement Health Education Act of 1994 allowed the drug to be marketed as a food supplement. Because DHEA no longer falls under the scrutiny of the Food and Drug Administration, many unverified claims have been put forth in the press espousing its therapeutic value. This barrage of “infomercials” has left the average American consumer (and health care professional) curious about DHEA and its possible therapeutic utility. One focus of recent research is to define the role of DHEA in diabetes mellitus. Although it has been claimed that decreased levels of endogenous DHEA are associated with diabetes, impaired glucose tolerance, hyperglycemia, and insulin resistance, much of the information is based on cross‐sectional studies. Other claims correlate decreased endogenous DHEA levels with adverse cardiovascular effects. Some information is contradictory and indicates high doses of exogenous DHEA may produce adverse cardiovascular effects, an undesirable outcome in patients with diabetes mellitus. At this time, its administration in patients with diabetes is not warranted. Long‐term trials evaluating the role of exogenous DHEA and its effect on patients with diabetes should be conducted.
Prophylactic Antibiotics for Severe Acute Pancreatitis: The Beginning of an Era
Authors: Kramer Katherine M. , Levy Howard
Published: May 2004

Death from acute severe pancreatitis results from infection and multiple organ system failure occurring late in the course of illness. Patients with necrotizing pancreatitis involving at least one‐third of the organ are at highest risk of secondary infection and death. We conducted a MEDLINE search to identify human trials of prophylactic antibiotics in acute pancreatitis. Results of early studies of prophylactic ampicillin to avoid secondary infection and death were negative, but the studies included patients with mild disease who are at low risk for infection. Antibiotics were beneficial in four recently completed studies: imipenem significantly reduced pancreatic and nonpancreatic sepsis (p≤ 0.01); cefuroxime reduced all infectious complications (p< 0.01) and deaths (p= 0.0284); a regimen of ceftazidime, amikacin, and metronidazole reduced all infectious complications (p< 0.03); and protocol use of imipenem significantly reduced pancreatic infection compared with nonprotocol antibiotics (p= 0.04) and no antibiotics (p< 0.001). Based on these results, we suggest early antibiotic prophylaxis in patients with necrotizing pancreatitis, but the best drug and duration of therapy are unknown.
Itraconazole in Cyclodextrin Solution
Authors: Stevens David A.
Published: May 2004

Itraconazole, a water‐insoluble oral triazole antifungal, has been formulated in cyclodextrin as a solution. Cyclodextrin is a ring of glucose molecules that can accept a lipophilic guest molecule within the ring. This enables solubilization and delivery to the lipid interface of the gut lumen, resulting in absorption of the guest molecule without absorption of the ring. This new system enhances the absorption of itraconazole. Improved blood and tissue levels of itraconazole and topical effect in mucosal disease should result in greater efficacy for a variety of indications, particularly patients with gastroenteropathy in whom absorption of earlier preparations was sometimes problematic.