bluuebunny/crossref_metadata_2025_split huggingface dataset:
Economic Issues and Antibiotic Resistance in the Community
Authors: Reed Shelby D , Laxminarayan Ramanan , Black Doug J , Sullivan Sean D 
Published: June 2003

BACKGROUND: Inappropriate antibiotic use is generally considered to be the primary cause of antibiotic resistance in the community. Multiple economic factors, at the level of physicians, patients, healthcare organizations, and pharmaceutical companies, foster poor antibiotic use. OBJECTIVE: To describe the influence of economic factors on the use and development of antibiotics and to evaluate the extent to which the cost of resistance is important in the economic evaluation of antibiotic products. DATA SOURCES: Literature identified through MEDLINE (1966–May 2001), bibliographies from relevant articles, government reports, and proceedings from conferences about antibiotic resistance. DATA SYNTHESIS: Economic factors at all levels of the healthcare system contribute to the inappropriate use of antibiotics in the community setting. Relatively little economic research has been published on antibiotic resistance, and very few cost-effectiveness analyses of antibiotic treatment alternatives have explicitly included the cost of resistance. CONCLUSIONS: A better understanding of economic factors that influence the prescribing, marketing, and development of antibiotics could lead to more successful efforts at curtailing the growth of antibiotic resistance in the community setting.
Treatment of Vitamin B12–Deficiency Anemia: Oral versus Parenteral Therapy
Authors: Lane Lenee A , Rojas-Fernandez Carlos 
Published: June 2003

OBJECTIVE: To evaluate the use of oral cyanocobalamin therapy in the treatment of cobalamin (vitamin B12)–deficient anemia. DATA SOURCES: Primary and review articles were identified by MEDLINE search (1966–May 2000) and through secondary sources. DATA SYNTHESIS: Cobalamin-deficient anemia is among the most common diagnoses in older populations. Cobalamin-deficient anemia may be diagnosed as pernicious anemia, resulting from the lack of intrinsic factor required for cobalamin absorption or as protein malabsorption from the inability to displace cobalamin from protein food sources. Several studies provide evidence that daily oral cyanocobalamin as opposed to monthly parenteral formulations may adequately treat both types of cobalamin-deficient anemias. CONCLUSIONS: Daily oral cyanocobalamin at doses of 1000–2000 μg can be used for treatment in most cobalamin-deficient patients who can tolerate oral supplementation. There are inadequate data at the present time to support the use of oral cyanocobalamin replacement in patients with severe neurologic involvement.
Effect of Hemodialysis on Leflunomide Plasma Concentrations
Authors: Beaman Jasmine M , Hackett L Peter , Luxton Grant , Illett Kenneth F 
Published: June 2003

OBJECTIVE: To report on the influence of hemodialysis on the disposition of leflunomide in a woman with end-stage renal disease. CASE SUMMARY: A 65-year-old white woman with a history of diabetes, end-stage renal disease, rheumatoid arthritis, vasculitis, and leg ulcers was admitted to the hospital with a flare in the symptoms of joint pain and vasculitis. Prior to admission, she had been treated for rheumatoid arthritis with methotrexate 7.5 mg once a week. Due to adverse effects from methotrexate and continuing painful joints, leflunomide was considered as a therapeutic alternative. A loading dose of 100 mg was followed two days later by a daily dose of 10 mg. The active metabolite of leflunomide (A771726) was measured before and after hemodialysis and between hemodialysis sessions over a period of 80 days. Pre- and post-hemodialysis concentrations were compared for 17 sessions during this time. Based on the initial measured concentrations, the leflunomide dose was increased to 20 mg/d for several weeks before being reduced to 15 mg due to elevated liver enzymes. DISCUSSION: Although renal pathways are responsible in part for excretion of A771726, the concentrations achieved in this patient at doses of 10–20 mg/d were at the low end of the range reported in the literature. It was shown that pre- and post-hemodialysis concentrations of A771726 did not differ significantly. Thus, the low concentrations of A771726 were not a result of the hemodialysis. CONCLUSIONS: Steady-state concentrations of A771726 in plasma were not affected by hemodialysis or renal impairment. Reduction of the dose of leflunomide in patients with chronic renal failure undergoing hemodialysis does not appear to be required.
Pathophysiology and First-Line Treatment of Osteoarthritis
Authors: Hogue Jesse H , Mersfelder Tracey L 
Published: June 2003

OBJECTIVE: To review the pathophysiology of osteoarthritis (OA) and the various treatment modalities, focusing specifically on acetaminophen (APAP), nonsteroidal antiinflammatory drugs (NSAIDs), and cyclooxygenase-2 (COX-2) inhibitors as the primary treatment options. DATA SOURCES: Primary literature and tertiary references were identified by a MEDLINE search (1966–March 2001) and through other secondary sources. STUDY SELECTION AND DATA EXTRACTION: After evaluating the articles and references identified from the data sources, all the information that was judged relevant by the reviewers was included in the review article. DATA SYNTHESIS: OA is the most common joint disorder worldwide. Current research suggests that factors such as inflammation and changes in subchondral bone may play a larger role in the pathophysiology than previously thought. With this research and the development of COX-2 inhibitors, selecting the medication of choice for OA has become difficult. CONCLUSIONS: More research needs to be done before the pathophysiology of OA can be clearly determined. In the meantime, treatment should be based on clinical data and patient response. Studies have shown that APAP and NSAIDs have comparable efficacy, as do traditional NSAIDs and COX-2 inhibitors. APAP is associated with fewer toxicities than are the traditional NSAIDs. Due to their mechanism of action, the new COX-2 inhibitors should result in fewer adverse effects compared with traditional NSAIDs, but evidence from clinical trials has not been conclusive. Therefore, APAP should still be considered the drug of choice for OA.
Lidocaine—Prilocaine Cream versus Tetracaine Gel for Procedural Pain in Children
Authors: Taddio Anna , Gurguis Mona GY , Koren Gideon 
Published: June 2003

OBJECTIVE: To determine the relative efficacy of lidocaine—prilocaine and tetracaine for procedural pain in children. METHODS: Systematic review was performed (MEDLINE 1990–June 2001) of all studies comparing the efficacy of these 2 modalities of pain relief in children undergoing painful cutaneous procedures. Search terms included lidocaine, prilocaine, tetracaine, and anesthesia. RESULTS: Eight studies compared lidocaine—prilocaine with tetracaine in children for 4 different procedures: intravenous cannulation, venipuncture, Port-a-Cath puncture, and laser therapy. When used as labeled (60 min for lidocaine—prilocaine, 30 min for tetracaine), the 2 modalities provided similar analgesic efficacy. When both anesthetics were applied for a similar duration of time (40 min, 60 min, 2 h), tetracaine provided superior anesthesia. Tetracaine was commonly associated with erythema, and lidocaine—prilocaine was associated with blanching of the skin. CONCLUSIONS: Lidocaine—prilocaine and tetracaine appear to be comparable for procedural pain relief when used as recommended. Tetracaine is more efficacious than lidocaine—prilocaine when both anesthetics are applied for the same amount of time.
Different Risks for NSAID-Induced Anaphylaxis
Authors: van Puijenbroek Eugène P , Egberts Antoine CG , Meyboom Ronald HB , Leufkens Hubert GM 
Published: June 2003

BACKGROUND: After drugs are marketed, spontaneous reporting systems can provide valuable information regarding the occurrence of suspected adverse drug reactions. The Netherlands Pharmacovigilance Foundation has received a substantial number of anaphylactic reaction reports related to the use of nonsteroidal antiinflammatory drugs (NSAIDs). OBJECTIVE: To investigate whether the risk of anaphylactic reactions being reported during the use of various NSAIDs is greater than with other classes of drugs and if differences among NSAIDs exist. METHODS: In a case/noncase design, reporting odds ratios (RORs) were calculated using logistic regression analysis. Cases were defined as reports in which anaphylactic or anaphylactoid reactions were reported; all other reports were considered as noncases. The index group consisted of reports in which NSAIDs were mentioned as the suspected medication; the reference group consisted of all other reports. RESULTS: Between January 1985 and November 2000, the Netherlands Pharmacovigilance Foundation Lareb received 76 cases concerning anaphylactic reactions to NSAIDs. These drugs are strongly associated with anaphylactic reactions. The ROR adjusted for age, gender, and source of the reports was 9.4 (95% CI 6.9 to 12.7). Anaphylactic reactions associated with the use of naproxen, ibuprofen, and diclofenac were reported disproportionately with respect to other drugs. The corresponding RORs from logistic regression analysis adjusted for age, gender, and reporting source for diclofenac, naproxen, and ibuprofen were 17.2 (95% CI 12.1 to 24.5), 9.1 (95% CI 5.2 to 15.9), and 5.5 (95% CI 2.5 to 11.9), respectively. CONCLUSIONS: The results of this study strengthen previous findings concerning the relative high risk of developing an anaphylactic reaction during the use of NSAIDs, particularly diclofenac, ibuprofen, and naproxen.
Correlation between Activated Clotting Time and Activated Partial Thromboplastin Times
Authors: Smythe Maureen A , Koerber John M , Nowak Sandra N , Mattson Joan C , Begle Robert L , Westley Susan J , Balasubramaniam Mamtha 
Published: June 2003

OBJECTIVE: To evaluate the correlation between clotting time tests and heparin concentration, the correlation between activated clotting time (ACT) and activated partial thromboplastin time (aPTT) results, and to compare the clinical decisions based on ACT results with those based on aPTT results. METHODS: Retrospective evaluation of a large database containing heparin concentrations, ACT results (1 device), and aPTT results (3 different instruments: 2 bedside, 1 laboratory-based). Correlations between heparin concentrations and clotting time tests and between ACT results and aPTT results were determined. Clinical decisions regarding heparin dosage adjustments based on ACT results were compared with those based on aPTT results. RESULTS: Correlations between clotting time tests and heparin concentrations were r = 0.72 for ACT and r = 0.74–0.86 for the aPTT instruments. The laboratory-based aPTT had the highest correlation to heparin concentrations. The correlation between ACT and aPTT results ranged from r = 0.64–0.67. Heparin dosage adjustment decisions based on ACT results agreed with decisions based on aPTT results 59–63% of the time. CONCLUSIONS: The laboratory-based aPTT has a stronger correlation to heparin concentration than the bedside-based aPTT and ACT. The correlation between ACT and aPTT was similar among 3 different aPTT instruments. Decisions to adjust heparin therapy based on ACT results differed from decisions based on aPTT results more than one-third of the time.
Absorption of Colesevelam Hydrochloride in Healthy Volunteers
Authors: Heller Dennis P , Burke Steven K , Davidson David M , Donovan Joanne M 
Published: June 2003

OBJECTIVE: To assess whether colesevelam hydrochloride is absorbed in healthy volunteers. METHODS: A single-center, open-label, radiolabeled study was performed with 16 healthy volunteers. Subjects were administered non-radiolabeled colesevelam hydrochloride 1.9 g twice daily for 4 weeks, followed by a single dose of [14C]-colesevelam 2.4 g (480 μCi). These subjects continued to receive non-radioactive colesevelam 1.9 g twice daily for 4 days after administration of the radiolabeled dose. Blood, urine, and feces were collected immediately prior to administration of [14C]-colesevelam and at specified intervals after administration. The whole-blood equivalent concentration of colesevelam was calculated using data collected throughout the 96 hours following radiolabeled drug administration. The proportion of [14C]-colesevelam excreted through urine or feces was calculated based on the amount of radioactivity recovered up to 216 hours after the radiolabeled dose. RESULTS: The mean cumulative total recovery of [14C]-colesevelam in urine and feces was 0.05% and 74%, respectively. Excluding 2 subjects for whom cumulative recovery was <25%, the mean cumulative fecal recovery was 82%. The mean maximum whole-blood equivalent concentration of colesevelam was 0.165 ± 0.10 μg equiv/g 72 hours after administration of [14C]-colesevelam, which was estimated to be 0.04% of the administered dose. All blood samples contained <4 × the number of background counts (dpm). CONCLUSIONS: The cumulative recovery data in urine and feces are consistent with the conclusion that colesevelam is not absorbed and is excreted entirely through the gastrointestinal system.
Effect of Colesevelam on Lovastatin Pharmacokinetics
Authors: Donovan Joanne M , Kisicki James C , Stiles Mark R , Tracewell William G , Burke Steven K 
Published: June 2003

OBJECTIVE: To assess potential interactions of colesevelam hydrochloride and lovastatin in healthy volunteers when lovastatin alone was administered with dinner, both lovastatin and colesevelam were administered with dinner, and colesevelam was administered with dinner and lovastatin was administered 4 hours later with a snack. METHODS: A single-center, open-label, 3-period, crossover drug interaction study was performed with 22 healthy volunteers. Blood samples were collected at specified intervals before and after dosing, and plasma concentrations of lovastatin and lovastatin hydroxyacid were measured using a liquid chromatography/mass spectroscopy/mass spectroscopy method. RESULTS: Maximal concentration (Cmax), AUC from time 0 to the last time point measured (AUC0-t), and AUC0-∞ values for lovastatin were 102%, 94%, and 104%, and for lovastatin hydroxyacid were 102%, 91%, and 92%, respectively, of control values when colesevelam and lovastatin were coadministered with dinner. Administration of colesevelam with dinner and lovastatin 4 hours later with a snack resulted in a decreased Cmax and AUC0-t for lovastatin (63% and 37%, respectively; p < 0.05) and an increased Cmax and AUC0-t for lovastatin hydroxyacid (61% and 50%, respectively; p < 0.05), both compared with lovastatin alone administered with dinner. CONCLUSIONS: Colesevelam had no significant effect on lovastatin pharmacokinetics when coadministered with lovastatin at dinner. A split-dosing regimen resulted in alterations in pharmacokinetic parameters for lovastatin and lovastatin hydroxyacid that are likely due to known differences in the pharmacokinetics of lovastatin when administered to patients with meals or in a fasting state.
Reimbursement Claims Analysis of Outcomes with Carvedilol and Metoprolol
Authors: Luzier Aileen B , Antell Laura A , Chang Li-Ling , Xuan Jianwei , Roth David A 
Published: June 2003

OBJECTIVE: To compare resource use and costs in heart failure (HF) patients receiving metoprolol, a selective β1-receptor blocker, with carvedilol, which blocks β1-, β2-, and α1-adrenergic receptors, by use of a retrospective reimbursement—claims analysis. METHODS: Resource use and cost data were extracted for patients diagnosed with HF and treated with carvedilol or metoprolol for 6 months after the initiation of the respective therapy, by use of claims submitted to 6 healthcare plans. A modified Charlson index was used to assess comorbidity. Stepwise logistic regression was used to measure the influence of treatment on hospitalization. RESULTS: Claims from 139 carvedilol and 106 metoprolol patients showed that carvedilol patients experienced significantly fewer total hospitalizations (36.0% vs. 62.3%, respectively; p < 0.001) and emergency department visits (23.7% vs. 42.5%, respectively; p = 0.002) and a trend for fewer HF—related (7.9% vs. 14.2%, respectively; NS) and cardiac-related hospitalizations (15.1% vs. 24.5%, respectively; NS). Treatment with carvedilol was associated with a significant decrease in the risk of any hospitalization (adjusted odds ratio 0.35, 95% CI 0.20 to 0.63; p < 0.001). Higher pharmacy costs (mean $1677 vs. $1322; p < 0.001) and lower total costs (mean $8100 vs. $14 475; p = 0.025) were observed in carvedilol-treated compared with metoprolol-treated patients, respectively. CONCLUSIONS: Compared with metoprolol, the more comprehensive adrenergic blockade achieved with carvedilol may translate into greater clinical benefits in patients with HF. Despite higher pharmacy costs, lower total costs were observed in carvedilol-treated patients.
Severe Cellulitis/Myositis Caused by Stenotrophomonas Maltophilia
Authors: Downhour Nathan P , Petersen Eskild A , Krueger Todd S , Tangella Krishnarao V , Nix David E 
Published: June 2003

OBJECTIVE: To present a case of cellulitis/myositis due to Stenotrophomonas maltophilia in the absence of trauma and to discuss a potentially novel treatment option. CASE SUMMARY: A 57-year-old white man, having undergone an allogeneic bone marrow transplant, developed myositis with S. maltophilia of the left soleus muscle; there had been no trauma. Risk factors for infection included neutropenia, prolonged hospitalization and intensive care unit stay, and broad-spectrum antibiotic exposure. The affected area of muscle was resected and the patient successfully treated with trimethoprim/sulfamethoxazole (TMP/SMX), ticarcillin/clavulanate, and aztreonam. DISCUSSION: In severe myositis/cellulitis caused by S. maltophilia, TMP/SMX is considered the drug of choice. However, bacteriostatic agents such as TMP/SMX are less than ideal in neutropenic patients. The combination of ticarcillin/clavulanate plus aztreonam has been shown to improve activity in vitro against this organism compared with TMP/SMX. This is likely due to inhibition of the 2 β-lactamases this organism produces by clavulanate and aztreonam. In our study of clinical isolates of S. maltophilia, this combination reduced the minimum inhibitory concentration at 90% by 128-fold and was synergistic against 10 of 12 isolates tested in time—kill analysis. CONCLUSIONS: S. maltophilia is emerging as an important pathogen in patients with compromised immunity, leading to severe infections that are difficult to treat. Based on in vitro synergy studied, we recommend considering ticarcillin/clavulanate plus aztreonam as a potential treatment option in immunocompromised patients with S. maltophilia infection.
Brasofensine Treatment for Parkinson's Disease in Combination with Levodopa/Carbidopa
Authors: Frackiewicz Edyta J , Jhee Stanford S , Shiovitz Thomas M , Webster Jonathan , Topham Christine , Dockens Randy C , Whigan Daisy , Salazar Daniel E , Cutler Neal R 
Published: June 2003

OBJECTIVE: To investigate the safety, tolerability, pharmacokinetic, and pharmacodynamic properties of the dopamine transporter antagonist brasofensine (BMS-204756) in patients with Parkinson's disease receiving levodopa/carbidopa treatment. METHODS: A 4-period crossover study was performed in 8 men (mean age 66 y) with moderate Parkinson's disease (Hoehn—Yahr stage II—IV). A dose escalation study was used in which each patient was given a single oral dose of brasofensine 0.5, 1, 2, or 4 mg, which was coadministered with the patient's usual dose of levodopa/carbidopa. RESULTS: The maximum concentration (Cmax) values of brasofensine observed in plasma after oral administration were 0.35, 0.82, 2.14, and 3.27 ng/mL for the 0.5-, 1-, 2-, and 4-mg doses, respectively; these concentrations occurred 4 hours (time to Cmax) after administration in all cases. Exposure to brasofensine (based on AUC0-∞) increased at a rate greater than proportional to dose. Based on the motor performance subscale of the Unified Parkinson's Disease Rating Scale, no change in patient disability was observed at any dose level. CONCLUSIONS: Brasofensine was safe and well tolerated in the patient cohort studied at daily doses of up to 4 mg. Adverse events were generally mild in intensity, and included headache, insomnia, phlebitis, dizziness, ecchymosis, and vomiting.
Development of a Pharmacist-Managed Lipid Clinic
Authors: Cording Margaret A , Engelbrecht-Zadvorny Emily B , Pettit B Jill , Eastham John H , Sandoval Rheta 
Published: June 2003

OBJECTIVE: To describe the development of a pharmacist-managed lipid clinic within a primary care medical clinic and review its results after approximately 12 months of operation. METHODS: A pharmacist-managed lipid clinic was developed at Naval Medical Center San Diego. Administrative background, treatment algorithm development, operational issues, clinical activities, and barriers to the clinic are discussed. For intermediate outcomes, data from patients who had at least 1 intervention by the pharmacist and 1 follow-up lipid panel were analyzed for medication use, changes in lipid parameters, and percent reaching the low-density-lipoprotein (LDL) target goal. Modified National Cholesterol Education Program — Adult Treatment Panel II guidelines were used to determine the LDL goal. RESULTS: Following approximately 12 months of operation, the clinic received 204 referrals and consisted of 146 active patients. A brief study was conducted to assess clinical outcomes. Of 115 patients who were seen in the clinic and met inclusion criteria, 57% were receiving treatment with a hydroxymethylglutaryl coenzyme A reductase inhibitor (statin) and 17% were receiving fibrates; 17% of the patients were not receiving lipid-lowering medications. Relative to baseline, LDL cholesterol concentrations decreased 20%, high-density-lipoprotein cholesterol increased 11%, and triglycerides decreased 19%. Overall, LDL goals were reached in 77% of the patients. LDL goals were attained by 63%, 79%, and 93% of patients with targets of <100, <130, and <160 mg/dL, respectively. Results are compared with other studies regarding lipid goal attainment. CONCLUSIONS: A pharmacist-managed lipid clinic can be developed and integrated into a primary care medical clinic. Pharmacists can effectively manage lipid-lowering therapy, helping to achieve LDL goals.
Treatment of Clostridium Difficile-Associated Diarrhea
Authors: Malnick Stephen DH , Zimhony Oren 
Published: June 2003

OBJECTIVE: To review the literature related to the treatment and infection control of Clostridium difficile-associated diarrhea (CDAD). DATA SOURCES: A MEDLINE search (1966–August 2001) of the English literature was conducted. DATA SYNTHESIS: C. difficile is a leading cause of antibiotic-related diarrhea. The clinical spectrum extends from simple diarrhea to fulminant colitis. Cessation of antibiotic therapy alone is sufficient for mild cases; however, the majority of cases require oral metronidazole as the drug of choice. Vancomycin orally is reserved for patients who have failed to respond to metronidazole, are pregnant, or are severely ill. There is an important role for infection control interventions. CONCLUSIONS: CDAD is a common infection. Appropriate antibiotic treatment and infection control policies can prevent the spread and reduce the morbidity associated with this disease.