bluuebunny/crossref_metadata_2025 huggingface dataset:
Quality-of-Life Assessment in an Outpatient Parenteral Antibiotic Program
Authors: Goodfellow Alan F , Wai Amy O , Frighetto Luciana , Marra Carlo A , Ferreira Barbara M , Chase M Lynn , Nicol Ruth E , Leong Carole A , Tomlinson Sally , Jewesson Peter J
Published: June 2003

OBJECTIVE:

To measure changes and to identify predictors of change of health-related quality of life (HRQoL) for enrollees into an outpatient parenteral antibiotic therapy (OPAT) program.

METHODS:

A multidisciplinary, single-center, prospective investigation was conducted at a 1000-bed Canadian adult tertiary-care teaching hospital. Over a 15-month study period, consenting patients who were enrolled in the OPAT program completed paired Short Form-36 (SF-36) questionnaires within 48 hours prior to discharge from the hospital and again 26–30 days after discharge. Sociodemographic data and clinical variables were also collected for the purpose of determining potential predictors of change in quality of life.

RESULTS:

During the study period, 134 patients were enrolled in the OPAT program and 82 completed the paired SF-36 questionnaires. Study participants experienced a significant improvement in 3 SF-36 domains (physical functioning, bodily pain, role emotional) and the mental component summary scale (MCS) scores when they were transferred from the hospital to home setting. The SF-36 scores for all domains and summary scales were lower than the Canadian population average (all p < 0.001). Multiple linear-regression analysis revealed that infectious disease diagnosis and baseline physical component summary scale (PCS) scores were predictors of the change in the PCS score when patients transferred from the hospital to the home setting. Length of hospital stay and baseline MCS scores were predictors of the change in MCS scores when patients transferred from the hospital to the home setting.

CONCLUSIONS:

This study reveals that some domains in HRQoL appear to improve 4 weeks after discharge for adults enrolled in an OPAT program and that there are different predictors for changes in physical and mental health.
Niacin-ER and Lovastatin Treatment of Hypercholesterolemia and Mixed Dyslipidemia
Authors: Yim Barbara T , Chong Pang H
Published: June 2003

OBJECTIVE

To review the currently available information on the once-daily combination of niacin extended-release (ER)/lovastatin in the treatment of patients with hypercholesterolemia and mixed dyslipidemia at high risk for cardiovascular events.

DATA SOURCES

MEDLINE (1966–July 2002) was searched for primary and review articles. Data from the manufacturer were also included.

STUDY SELECTION/DATA EXTRACTION

All articles and product labeling deemed relevant to the combination of niacin and statins (i.e., lovastatin) were included for review. English-language studies selected for inclusion were limited to those with human subjects.

DATA SYNTHESIS

The Food and Drug Administration approved a new fixed-dose combination of niacin-ER/lovastatin, which is administered once daily. The efficacy and safety of the combined agent have been proven to be similar to either component used alone or in combination for management of hyperlipidemia and mixed dyslipidemia.

CONCLUSIONS

Elevated low-density lipoprotein cholesterol (LDL-C) is independently associated with a higher risk for cardiovascular events. Lowering of elevated LDL-C concentrations with statin monotherapy may be insufficient in patients at high risk for cardiovascular events. In fact, consideration of elevated triglycerides (TGs) and/or low concentrations of high-density lipoprotein cholesterol (HDL-C) in patients with elevated LDL-C places them at greater risk. The addition of niacin may enhance or improve the lipid profile of those who require a further decrease of TGs and/or increase of HDL-C even after stable statin therapy. Niacin-ER offers efficacy similar to that of immediate-release niacin, but minimal myopathy and hepatotoxicity (compared with sustained-release niacin). Although no clinical outcomes are available, current evidence shows that the combination product offers adequate lowering of LDL-C and TGs and increasing HDL-C. The data suggest that therapy with the niacin-ER and lovastatin combination product is safe and does not increase the incidence of adverse effects. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-003-H01
Fluoroquinolone Treatment of Community-Acquired Pneumonia: A Meta-Analysis
Authors: Salkind Alan R , Cuddy Paul G , Foxworth John W
Published: June 2003

OBJECTIVE:

To determine the role of newer fluoroquinolones (FQs) for adults with community-acquired pneumonia (CAP) whose level of illness allows treatment with an oral antibiotic.

METHODS:

Meta-analysis of randomized controlled trials comparing a macrolide, β-lactam, or doxycycline antibiotic with a newer oral FQ for the treatment of CAP.

RESULTS:

Patients (5118), most of whom were <60 years of age and free of coexisting diseases, were enrolled in 13 studies comparing an oral macrolide or β-lactam antibiotic with an FQ for the treatment of CAP. No previous study compared doxycycline with an FQ. In the intention-to-treat (ITT) population, no trial demonstrated significant differences between FQs or alternative therapies. Summary estimates showed a statistically significant advantage in favor of the FQs in both the ITT (OR 1.22; 95% CI 1.02 to 1.47; p = 0.03) and evaluable populations (OR 1.37; 95% CI 1.11 to 1.68; p = 0.003). The number needed to treat for an FQ advantage was 33 (95% CI 17 to 362) in the ITT population and 37 (95% CI 22 to 121) in the evaluable population. Treatment failures represented slow symptom resolution; no deaths were reported.

CONCLUSIONS:

The newer oral FQs showed modest therapeutic benefit compared with the studied alternative antibiotics in adults with CAP. Based on the number needed to treat from the ITT population as a measure of treatment effect, clinicians must decide whether treating 33 patients with an FQ to prevent a single therapeutic failure with another studied antibiotic warrants use of an agent from that class for an illness with a generally favorable outcome regardless of antibiotic selection, and at a time when FQ resistance may be increasing.
Fluorouracil for Allergic Reactions to Capecitabine
Authors: Liu Chin Y
Published: June 2003

OBJECTIVE:

To report the safe use of fluorouracil in a patient with breast cancer who had allergic reactions to capecitabine.

CASE SUMMARY:

A 42-year-old African American woman with metastatic breast cancer developed progressive disease. Capecitabine 1500 mg taken by mouth twice daily was prescribed as the salvage chemotherapy. She developed a generalized rash and itching, sore throat, and dizziness approximately 4 hours after the first dose of capecitabine. These reactions recurred immediately after the second dose. Capecitabine was discontinued and the allergic reactions resolved after the woman took diphenhydramine for 1 week. In view of limited therapeutic options for her progressive disease, a trial of fluorouracil 300 mg/m2/d continuous intravenous infusion over 5 days was initiated without any premedications. She did not experience any reactions. The dose of fluorouracil in the second cycle was increased to 400 mg/m2/d continuous infusion over 5 days.

DISCUSSION:

Capecitabine is not intrinsically cytotoxic, but is converted to fluorouracil in tumor tissues via a 3-step enzymatic pathway. Capecitabine reaches peak blood concentrations in about 1.5 hours, with peak fluorouracil concentrations occurring at 2 hours. The elimination half-life of both drugs is 0.5–0.7 hours. The patient tolerated the rechallenge with fluorouracil without complications. Objective causality assessment revealed that the adverse event was probably drug induced. It was postulated that the allergic reaction was most likely caused by capecitabine or the intermediate metabolites based on the immediate reappearance of symptoms from the rechallenge, pharmacokinetic data, and well-tolerance of fluorouracil.

CONCLUSIONS:

The use of fluorouracil treatment with careful monitoring can be considered in a patient with mild allergic reactions to capecitabine.
Fulminant Liver Failure Associated with Clarithromycin
Authors: Tietz Andreas , Heim Markus H , Eriksson Urs , Marsch Stephan , Terracciano Luigi , Krähenbühl Stephan
Published: June 2003

OBJECTIVE

To report a patient developing fulminant liver failure while being treated with clarithromycin for pneumonia.

CASE SUMMARY

A 58-year-old white woman developed fulminant liver failure while being treated with the macrolide antibiotic clarithromycin for pneumonia. Comedication included N-acetylcysteine, atenolol, and isradipine. Other causes of liver failure, such as viral hepatitis, autoimmune hepatitis, toxins, and heart failure, were excluded by appropriate diagnostic means. All drugs were stopped, and the patient was transferred to another hospital for liver transplantation. She recovered spontaneously within several days, making transplantation unnecessary. A liver biopsy obtained 10 days after the initial presentation revealed centroacinar necrosis and beginning fibrous reorganization, compatible with recent centroacinar damage.

DISCUSSION

Since no other cause could be identified, liver injury was considered to be drug related. Fulminant liver failure has not previously been described with concomitant use of atenolol and N-acetylcysteine. Although isradipine has been associated with hepatocellular injury, there are no reports of fulminant liver failure with this agent, and our patient had been treated for >2 years without signs of toxicity. The most likely cause of liver failure in this patient was, therefore, clarithromycin, which undergoes hepatic metabolism and has been reported to cause fulminant hepatic failure. A second possibility is an interaction between clarithromycin and isradipine, potentially increasing the hepatic toxicity of isradipine.

CONCLUSIONS

Clarithromycin may be a cause of fulminant liver failure either alone or by inhibiting the metabolism of other drugs.
Safety of Selegiline with Cold Medications
Authors: Jacob Jeena E , Wagner Mary L , Sage Jacob I
Published: June 2003

OBJECTIVE:

To evaluate the safety of the coadministration of selegiline with cold medications.

DATA SOURCES:

Clinical literature accessed through MEDLINE(1965–September 2002), IPA database, and Drug-Reax System. The following search terms were used: selegiline, pseudoephedrine, dextromethorphan, MAOI, and drug interactions. Somerset Pharmaceuticals, the marketers of Eldepryl (selegiline HCI), were also contacted.

DATA SYNTHESIS:

Despite a warning against its concomitant use with pseudoephedrine and dextromethorphan, interactions with selegiline have not been reported. However, there have been reports of patients experiencing adverse events with related agents.

CONCLUSIONS:

Patients taking selegiline should try to avoid pseudoephedrine and dextromethorphan or use drugs without interaction potential. If selegiline is used with these medications, watch for adverse events or replace selegiline with another drug.
Lactic Acidemia Associated with Metformin
Authors: Khan Jamshed K , Pallaki Muralidhar , Tolbert Sandra R , Hornick Thomas R
Published: June 2003

OBJECTIVE

To report 2 cases of lactic acidemia associated with the use of metformin in patients with normal renal function.

CASE SUMMARY

An 82-year-old African American man and a 76-year-old white man developed an elevated serum lactic acid concentration a few weeks after initiation of metformin therapy for type 2 diabetes. After the patients discontinued metformin, the serum lactic acid concentration normalized in both cases. An objective causality assessment revealed that the adverse drug event was probably related to the use of metformin.

DISCUSSION

Metformin interferes with the production and elimination of lactic acid by a variety of mechanisms that are not well understood. Few systematic data are available on changes in plasma lactic acid concentrations in patients with type 2 diabetes and normal renal function. Clinical significance of a high serum lactic acid concentration needs clarification.

CONCLUSIONS

Metformin therapy can be associated with subclinical elevation of lactic acid concentration in the absence of renal insufficiency or other contraindications to using this agent in patients with type 2 diabetes. Periodic monitoring of basic metabolic panels may prevent this potentially serious complication of metformin therapy.
Adverse Reaction to a Dietary Supplement in an Elderly Patient
Authors: Sleeper Rebecca B , Kennedy Shalyn M
Published: June 2003

OBJECTIVE

To describe the case of an elderly patient who experienced hepatic enzyme elevations and symptoms of hepatitis associated with the administration of a dietary supplement.

CASE SUMMARY

A 92-year-old white woman with no history of hepatic disease developed jaundice and increased confusion associated with increased hepatic enzymes. The hepatitis panel, abdominal ultrasound, and antinuclear antibody screen indicated no abnormalities. A drug regimen review revealed that the patient was receiving a dietary supplement, Nutrilite Double X Multivitamin–Multimineral. Following discontinuation of the supplement, the patient's symptoms resolved and the hepatic enzymes decreased or returned to the reference range at evaluations occurring 1 week and 1 month after intervention. An objective causality assessment revealed this to be a probable adverse drug event.

DISCUSSION

While the association of certain herbal preparations with hepatotoxicity has been demonstrated, the potential for this adverse effect is easily overlooked. In this patient, infectious or autoimmune causes of acute hepatitis were ruled out, and drug-induced causes were considered. The resolution of symptoms and laboratory values following discontinuation of the supplement support a relationship between the dietary supplement and this episode of hepatitis.

CONCLUSIONS

Our case indicates that there was a probable relationship between the dietary supplement Nutrilite Double X Multivitamin–Multimineral and the development of acute hepatitis. Due to the multiingredient formulation of the product, as well as lack of data describing manufacturing procedures, it is difficult to determine which component may be associated with this effect. Over-the-counter supplements should be considered as a part of the differential diagnosis in patients presenting with increased liver enzymes and related symptoms.
Olmesartan Medoxomil: The Seventh Angiotensin Receptor Antagonist
Authors: Gardner Stephanie F , Franks Amy M
Published: June 2003

OBJECTIVE

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of olmesartan medoxomil, an angiotensin II receptor antagonist for the treatment of hypertension.

DATA SOURCES

Information was obtained from MEDLINE searches (1996–April 2002) of English-language medical literature. Search terms included CS-866, olmesartan, olmesartan medoxomil, RNH-6270 (active metabolite of olmesartan), Benicar, angiotensin receptors, and antihypertensive agents. In addition, references from relevant articles were reviewed for additional citations. The authors independently reviewed literature identified in the searches. Studies evaluating olmesartan (i.e., abstracts, clinical trials, data on file with manufacturer) were considered for inclusion.

STUDY SELECTION

All articles identified from data sources with pertinent information regarding olmesartan medoxomil were evaluated, and all information deemed relevant was included in this review.

DATA SYNTHESIS

Olmesartan medoxomil is a competitively priced addition to the class of angiotensin II receptor antagonists. Monotherapy with olmesartan medoxomil in once-daily doses of 20–40 mg has produced significant reductions in systolic and diastolic blood pressure in hypertensive patients. Adverse effects have been minimal with olmesartan medoxomil, with dizziness being the only adverse effect occurring more often than with placebo in clinical trials. Additionally, animal studies indicate that olmesartan medoxomil may prove to be useful treatment for diabetic nephropathy, as well as atherosclerosis.

CONCLUSIONS

Olmesartan medoxomil has a favorable safety and efficacy profile, with blood pressure–lowering effects comparable to those of other angiotensin receptor blockers (i.e., losartan, valsartan, irbesartan). At this time, formulary decisions will be driven primarily by economic issues. Theoretical benefits of olmesartan medoxomil in reducing atherogenesis and lowering angiotensin II concentrations better than the alternative agents will be determined only with more extensive research. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-002-H01
Aztreonam Treatment of Pasteurella Multocida Cellulitis and Bacteremia
Authors: Winner Jamie S , Gentry Chris A , Machado Linda J , Cornea Paul
Published: June 2003

OBJECTIVE:

To report a case of Pasteurella multocida cellulitis and bacteremia treated successfully with aztreonam.

CASE SUMMARY:

An 81-year-old white man with multiple antibiotic allergies was admitted with severe cellulitis of the left arm and bacteremia due to P. multocida. The patient was treated for 14 days with aztreonam and had complete resolution of the infection.

DISCUSSION:

To our knowledge, this is the first published case describing successful treatment of P. multocida cellulitis and bacteremia with aztreonam. Antimicrobials recommended for use in P. multocida infections include penicillin, ampicillin, amoxicillin, second- and third-generation cephalosporins, tetracyclines, fluoroquinolones, and trimethoprim/sulfamethoxazole. There is very little information in the current literature regarding the activity of aztreonam toward P. multocida.

CONCLUSIONS:

This case demonstrates the potential use of aztreonam for P. multocida cellulitis and bacteremia in those instances where antibiotics of choice cannot be given.
Warfarin and Amoxicillin/Clavulanate Drug Interaction
Authors: Davydov Liya , Yermolnik Marina , Cuni Lewis J
Published: June 2003

OBJECTIVE:

To report a case of warfarin–amoxicillin/clavulanate potassium (AM/CL) interaction resulting in an elevated international normalized ratio (INR) and hematuria.

CASE SUMMARY:

A 58-year-old Hawaiian/Asian/European woman developed an elevated INR and microscopic hematuria as a result of a drug–drug interaction between warfarin and AM/CL.

DISCUSSION:

Our report of an increased INR with bleeding complications as a result of an interaction between warfarin and AM/CL is consistent with those in the literature. Although the mechanism for this interaction is not fully known, it is suspected that a decrease in vitamin K–producing gut flora with resulting vitamin K deficiency would be the most likely contributing factor. An objective causality assessment revealed that this adverse drug event as a result of the warfarin and AM/CL interaction was possible.

CONCLUSIONS:

An increased INR secondary to warfarin interactions with various antibacterial agents is a known phenomenon. An increased awareness of warfarin–AM/CL interaction and appropriate monitoring are essential to control the INR levels and prevent bleeding complications.
Intrapleural Alteplase in a Patient with Complicated Pleural Effusion
Authors: Walker Charlotte A , Shirk Mary Beth , Tschampel Marva M , Visconti James A
Published: June 2003

OBJECTIVE:

To report the intrapleural use of alteplase in a patient diagnosed with complicated pleural effusion (CPE).

CASE SUMMARY:

A 62-year-old white woman admitted with respiratory distress and hypotension developed a right-sided multi-loculated pleural effusion. Thoracentesis and chest tube drainage were not successful in resolving the effusion. In an attempt to increase the drainage of the pleural effusion, alteplase 16 mg was administered into the pleural cavity via the chest tube on 6 consecutive days. As a result, the volume drained from the patient's chest tube increased, there was improvement on the chest X-ray, and she did not require surgical intervention.

DISCUSSION:

While streptokinase and urokinase have been shown to be useful adjuncts to chest tube drainage in the treatment of complicated pleural effusion and empyema, there have been no reports on the use of intrapleural alteplase. This report demonstrates that intrapleural administration of alteplase is a useful adjunct to tube drainage in resolving CPE.

CONCLUSIONS:

This patient's CPE resolved when intrapleural alteplase was used as an adjunct to chest tube drainage and antibiotics. Controlled trials need to be conducted to investigate fully the efficacy, dosing, and safety of intrapleural alteplase in the treatment of patients with CPE and empyema.
Hemodynamic and Electrocardiographic Effects of Short-Term Ginkgo Biloba
Authors: Kalus James S , Piotrowski Alexandria A , Fortier Christopher R , Liu Xinhcun , Kluger Jeffrey , White C Michael
Published: June 2003

OBJECTIVE:

To evaluate the immediate and short-term hemodynamic and electrocardiographic effects of Ginkgo biloba (ginkgo).

METHODS:

Healthy volunteers were randomized to receive ginkgo 120 mg or placebo twice daily for 7 days in this prospective, double blind trial. After at least a 7-day washout period, subjects were crossed over to an additional 7 days of alternate therapy. Blood pressure, heart rate, and 12-lead electrocardiograms were evaluated immediately before (baseline), and at 1, 3, and 5 hours after observed ingestion of study drug on days 1 and 7 of therapy. Electrocardiographic parameters (P wave and QRS complex duration; PR, QT, and QTc intervals) were measured in lead II by a blinded investigator.

RESULTS:

Ginkgo had no effect on any of the evaluated electrocardiographic parameters at any time point on days 1 or 7. Additionally, no changes in heart rate or systolic and diastolic blood pressure were found between the groups at any time point on any evaluative day.

CONCLUSIONS:

Commonly used doses of Ginkgo biloba do not have any immediate or short-term effects on blood pressure, heart rate, or electrocardiographic variables in young, healthy volunteers.
Bosentan for the Treatment of Pulmonary Arterial Hypertension
Authors: Kenyon Kenneth W , Nappi Jean M
Published: June 2003

OBJECTIVE:

To describe the pharmacology, pharmacokinetics, efficacy, and safety of bosentan in the treatment of pulmonary arterial hypertension (PAH).

DATA SOURCES:

A MEDLINE and Current Contents search (1966–June 2002) of the English-language literature was conducted to identify published dose-ranging, pharmacokinetic, pivotal efficacy trials and review articles of bosentan and endothelin antagonists. Additional references were identified from the bibliographies of the retrieved articles.

DATA SYNTHESIS:

Bosentan is the first orally active, nonpeptide endothelin receptor antagonist approved by the Food and Drug Administration for use in patients with World Health Organization (WHO) functional class III and IV PAH. Titrated to a dose of 125 mg twice daily, bosentan produces pulmonary vasodilation, improving cardiopulmonary hemodynamics leading to better outcomes for patients. It is metabolized primarily by the hepatic system via the cytochrome P450 enzyme pathway and eliminated by biliary excretion. Bosentan is an inducer of the isoenzymes CYP3A4 and 2C9. It possesses a unique pharmacokinetic profile with a terminal elimination half-life of approximately 5 hours, yet steady-state plasma concentrations are not achieved for 3–5 days as a result of enhanced drug clearance and autoinduction following multiple daily dosing. The major adverse effects of bosentan are the potential for birth defects and hepatotoxicity.

CONCLUSIONS:

The use of bosentan in patients with WHO functional class III and IV PAH is associated with improved exercise tolerance, cardiopulmonary hemodynamics, and increased time to clinical worsening when compared with placebo. It offers significant advantage in ease of administration and quality of life compared with epoprostenol therapy, with similar efficacy.
Voriconazole: A New Triazole Antifungal Agent
Authors: Pearson Margaret M , Rogers P David , Cleary John D , Chapman Stanley W
Published: June 2003

OBJECTIVE:

To review the pharmacology, in vitro susceptibility, pharmacokinetics, clinical efficacy, and adverse effects of voriconazole, a triazole antifungal agent.

DATA SOURCES:

A MEDLINE search, restricted to English language, was conducted from 1990 to June 2002. Supplementary sources included program abstracts from the Interscience Conference on Antimicrobial Agents and Chemotherapy and the Infectious Diseases Society of America from 1996 to 2001 and manufacturer information available through the Food and Drug Administration's Web site.

DATA EXTRACTION:

All published and unpublished trials and abstracts citing voriconazole were selected.

DATA SYNTHESIS:

Voriconazole has shown in vitro activity against many yeasts and a variety of mold and dermatophyte isolates. Voriconazole can be administered either orally or parenterally. It exhibits good oral bioavailability, wide tissue distribution including distribution into the central nervous system, and hepatic metabolism. Drug interactions occur through inhibition of the CYP2C9, CYP2C19, and CYP3A4 isoenzymes, resulting in alterations in kinetic parameters of either voriconazole or the interacting agent. Efficacy has been illustrated in open, noncomparative studies of aspergillosis in immunocompromised patients. Human case reports describe successful treatment of rare fungal pathogens. The most commonly reported adverse events include visual disturbances and elevations in liver function tests.

CONCLUSIONS:

Voriconazole is at least as effective as amphotericin B in the treatment of acute invasive aspergillosis in immunocompromised patients. It has similar efficacy as fluconazole in treatment of esophageal candidiasis. Voriconazole did not achieve statistical non-inferiority to liposomal amphotericin B for empirical therapy in patients with neutropenia and persistent fever, diminishing enthusiasm for use in this indication until additional trials are completed. Based on case reports and in vitro efficacy, voriconazole may prove to be a clinically useful agent in the treatment of other fungal disease.
Effect of Cyclooxygenase-2 Inhibitors on Blood Pressure
Authors: Johnson Deanna L , Hisel Tina M , Phillips Beth Bryles
Published: June 2003

OBJECTIVE:

To evaluate the effect of cyclooxygenase-2 selective inhibitors (CSIs) on blood pressure.

DATA SOURCES:

Clinical literature accessed through MEDLINE (1966–May 2002). Key search terms included COX-2 selective inhibitors; anti-inflammatory agents, nonsteroidal; celecoxib; rofecoxib; and hypertension.

DATA SYNTHESIS:

Data from prospective studies on the effects of CSIs on blood pressure are conflicting. Several studies have reported increased blood pressure as an adverse effect of CSIs.

CONCLUSIONS:

Additional studies are needed to evaluate the effects of CSIs on blood pressure. CSIs should be used with caution in hypertensive patients and blood pressure monitored closely if a CSI is indicated.
CANCER Resistance Surveillance Program: Initial Results from Hematology–Oncology Centers in North America
Authors: Mutnick Alan H , Kirby Jeffrey T , Jones Ronald N ,   The CANCER Study Group
Published: June 2003

OBJECTIVE

The CANCER (Chemotherapy Alliance for Neutropenics and the Control of Emerging Resistance) surveillance program was initiated to collect culture data on antimicrobial and antifungal agents in hospitals treating neutropenic patients in North America, as a means to monitor the development of microbial resistance.

METHODS

A total of 2042 isolates from bloodstream, respiratory, urinary, and cutaneous infections in 2000–2001 were submitted by 33 oncology centers, clinics, and hospitals in North America, sent to a central laboratory, and tested by National Committee for Clinical Laboratory Standards methods against 42 different antimicrobials.

RESULTS

Staphylococcus aureus, Escherichia coli, coagulase-negative staphylococci, Enterococcus spp., and Klebsiella spp. represented the most frequently isolated pathogens during the initial benchmark year. The incidence of extended-spectrum β-lactamase–producing phenotypes ranged from 1.6% to 4.6% among E. coli and Klebsiella spp. Amikacin, tobramycin, polymyxin B, and piperacillin/tazobactam provided the highest susceptibility rates against Pseudomonas aeruginosa isolates. Yeast bloodstream isolates demonstrated complete susceptibility to amphotericin B, but 14% of strains were considered to have high-level fluconazole resistance.

CONCLUSIONS

Elevated resistance rates when compared to general hospital strains were not observed in the CANCER program during the baseline year of this novel longitudinal, resistance surveillance program. The prevalence of gram-positive pathogens, although representing more than 50% of all bacterial isolates, was slightly lower than that reported previously by other investigators. Continued evaluation for antimicrobial resistance as well as changes in the prevalence of gram-positive pathogens requires the use of longitudinal surveillance programs such as the CANCER program. Such initiatives allow the development of therapeutic strategies for coping with changes in resistance and pathogen prevalence in this dynamic at-risk patient environment.
Diagnosis and Treatment of Graves Disease
Authors: Streetman Darcie D , Khanderia Ujjaini
Published: June 2003

OBJECTIVE:

To review the etiology, diagnosis, and clinical presentation of Graves disease and provide an overview of the standard and adjunctive treatments. Specifically, antithyroid drugs, β-blockers, inorganic iodide, lithium, and radioactive iodine are discussed, focusing on current controversies.

DATA SOURCES:

Primary articles were identified through a MEDLINE search (1966–July 2000). Key word searches included β-blockers, Graves disease, inorganic iodide, lithium, methimazole, and propylthiouracil. Additional articles from these sources and endocrinology textbooks were also identified. We agreed to include articles that would highlight the most relevant points, as well as current areas of controversy.

DATA SYNTHESIS:

Graves disease is the most common cause of hyperthyroidism. The 3 main treatment options for patients with Graves hyperthyroidism include antithyroid drugs, radioactive iodine, and surgery. Although the antithyroid drugs propylthiouracil (PTU) and methimazole (MMI) have similar efficacy, there are situations when 1 agent is preferred. MMI has a longer half-life than PTU, allowing once-daily dosing that can improve patient adherence to treatment. PTU has historically been the drug of choice for treating pregnant and breast-feeding women because of its limited transfer into the placenta and breast milk. Adjuvant therapies for Graves disease include β-blockers, inorganic iodide, and lithium. β-Blockers are used to decrease the symptoms of hyperthyroidism. Inorganic iodide is primarily used to prepare patients for thyroid surgery because of its ability to decrease the vascularity of the thyroid gland. Lithium, which acts in a manner similar to iodine, is not routinely used due to its transient effect and the risk of potentially serious adverse effects. In the US, radioiodine therapy has become the preferred treatment for adults with Graves disease. It is easy to administer, safe, effective, and more affordable than long-term treatment with antithyroid drugs. Hypothyroidism is an inevitable consequence of radioiodine therapy. Radioiodine is contraindicated in pregnant women because it can damage the fetal thyroid gland, resulting in fetal hypothyroidism. Bilateral subtotal thyroidectomy, which was once the only treatment available, is now performed only in special circumstances. In addition to the normal risks associated with surgery, laryngeal nerve damage, hypoparathyroidism, and hypothyroidism can occur following that procedure.

CONCLUSIONS:

Despite extensive experience with medical management, controversy prevails regarding choosing among the various drugs for treatment of Graves disease. None of the treatment options, including antithyroid drugs, radioiodine, and surgery, is ideal. Each has risks and benefits, and selection should be tailored to the individual patient.
Pramlintide for the Treatment of Diabetes Mellitus
Authors: Kleppinger Erika L , Vivian Eva M
Published: June 2003

OBJECTIVE:

To provide an overview of the role of amylin, as well as that of pramlintide, a synthetic analog of amylin, in maintaining glucose homeostasis; and discuss the pharmacology, pharmacokinetics, efficacy, adverse effects, and role of pramlintide in the control of postprandial hyperglycemia.

DATA SOURCES:

The data presented in this review were obtained from published literature, abstracts presented at scientific meetings, and information on file with the manufacturer. MEDLINE searches (1986–March 2003) using the search terms pramlintide and amylin were conducted to identify clinical trials and review articles. Additionally, the bibliographies of the identified articles were reviewed.

DATA SYNTHESIS:

Clinical trials have demonstrated that amylin in combination with insulin controls postprandial glucose levels by decreasing food intake, slowing gastric emptying, and suppressing glucagon secretion. Clinical trials also showed significant decreases in mean plasma glucose levels and glycosylated hemoglobin, as well as the added benefits of weight loss and reduction in insulin doses. The most commonly reported adverse effects associated with pramlintide in clinical trials were gastrointestinal complaints and hypoglycemia, which occurred most frequently during initiation of therapy.

CONCLUSIONS:

The administration of insulin alone often does not result in optimal metabolic control. The treatment of amylin deficiency, in addition to insulin deficiency, may be warranted in order to obtain glucose homeostasis. The role of pramlintide, an amylin analog, will become clearer as more clinical data become available.
Bosentan and Warfarin Interaction
Authors: Murphey Lisa M , Hood Elizabeth H
Published: June 2003

OBJECTIVE:

To report a case of decreased international normalized ratio (INR) in a patient receiving warfarin and bosentan.

CASE SUMMARY:

A 35-year-old African American woman with a history of primary pulmonary hypertension managed with warfarin, diltiazem, and hydrochlorothiazide was initiated on bosentan therapy. The patient's INR had been stable and within therapeutic range (goal 2.0–3.0) for the previous 3 months with warfarin 27.5 mg/wk, but became subtherapeutic after 10 days of bosentan therapy. Addition of over-the-counter medications, herbal products, vitamins, or dietary changes was denied. The INR remained subtherapeutic for 5 weeks despite weekly warfarin dose increases. After these 5 weeks of dosage increases, the INR became supratherapeutic for 3 weeks, resulting in a subsequent dosage decrease. The resultant warfarin dose required to maintain a therapeutic INR was 45 mg/wk, a 63.6% dosage increase after the initiation of bosentan.

DISCUSSION:

This case shows that a clinically significant interaction between bosentan and warfarin may exist. An objective causality assessment revealed that the interaction was probable. Although the possibility of this interaction has been noted, no previously documented occurrence of this interaction has been identified.

CONCLUSIONS:

Bosentan may significantly decrease the anticoagulant properties of warfarin. The INR should be monitored more frequently when bosentan is initiated, adjusted, or discontinued in patients taking warfarin.
Isotretinoin and Psychiatric Illness in Adolescents and Young Adults
Authors: Enders Shelly J , Enders Jason M
Published: June 2003

OBJECTIVE:

To evaluate the relationship between isotretinoin and psychiatric illness in adolescents and young adults.

DATA SOURCES:

Primary literature located via MEDLINE (1966–December 2002). Key terms were isotretinoin, depression, psychosis, suicide, and adolescents.

DATA SYNTHESIS:

Information regarding depression was added to isotretinoin labeling in 1998 following a series of case reports and submitted to the MedWatch system.

CONCLUSIONS:

Although a causal relationship may exist between isotretinoin and psychiatric illness in adolescents and young adults, this has not been demonstrated in the literature. Until evidence establishes a presence or lack of causality, prescribers should exercise caution when treating adolescents and young adults with isotretinoin.
Melatonin for the Treatment of Tardive Dyskinesia
Authors: Nelson Leigh Anne , McGuire J Michael , Hausafus Sarah N
Published: June 2003

OBJECTIVE:

To review the available literature regarding the use of melatonin in the treatment of tardive dyskinesia (TD).

DATA SOURCES:

Literature was identified through MEDLINE (1966–September 2002), PsycINFO (1967–September 2002), and references of relevant articles. Review articles, case reports/series, and animal and human studies were reviewed.

DATA SYNTHESIS:

Melatonin has been investigated in TD based on its antioxidant properties. Animal studies and several human case series describe an association between melatonin and TD. Two recent, controlled studies evaluated the role of melatonin in the treatment of TD.

CONCLUSIONS:

There is a paucity of data evaluating the use of melatonin in TD. Both of the controlled studies evaluating its use are limited by methodologic issues. Although the most recent trial did report a statistically significant improvement in TD with melatonin, these results are not considered to be clinically significant. There are inadequate data at the present time to support the use of melatonin in patients with TD.
Simvastatin–Fluconazole Causing Rhabdomyolysis
Authors: Shaukat Aasma , Benekli Mustafa , Vladutiu Georgirene D , Slack James L , Wetzler Meir , Baer Maria R
Published: June 2003

OBJECTIVE:

To report a case of rhabdomyolysis after concomitant use of simvastatin, a commonly used hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, and fluconazole, an azole antifungal agent.

CASE SUMMARY:

An 83-year-old white man with a history of congestive heart failure and hyperlipidemia presented to the hospital 1 week following the addition of fluconazole to a medication regimen that included simvastatin 40 mg once daily. The patient had severe muscle weakness and a markedly elevated serum creatine kinase activity, which resolved following discontinuation of simvastatin and fluconazole.

DISCUSSION:

Rhabdomyolysis is a recognized adverse effect of HMG-CoA reductase inhibitors (statins), commonly caused by their interaction with other drugs, such as azole antifungals, that inhibit the cytochrome P450 isoenzyme family. An objective causality assessment revealed that the adverse drug event was probable. Although drug interactions have been described for combinations of other HMG-CoA reductase inhibitors and azole antifungals, rhabdomyolysis likely caused by the interaction between simvastatin and fluconazole has not yet been reported. This case reinforces the importance of being vigilant for drug interactions, particularly in connection with commonly prescribed medications such as statins.

CONCLUSIONS:

Patients receiving statins who have cancer may receive azole antifungals and other drugs that inhibit CYP3A4 during treatment, predisposing them to toxicity. These patients should therefore be monitored closely for drug interactions.
Anaphylactoid Reaction to Ciprofloxacin
Authors: Ho Dora Y , Song Jessica C , Wang Clifford C
Published: June 2003

OBJECTIVE:

To report a case of anaphylactoid reaction in an HIV-negative patient associated with the administration of intravenous ciprofloxacin.

CASE SUMMARY:

A 79-year-old Armenian man developed an anaphylactoid reaction following a first-time exposure to intravenous ciprofloxacin. This reaction was characterized by severe hypotension, wheezing, tachypnea, tachycardia, and pruritus. The patient had complete recovery once ciprofloxacin treatment was terminated and supportive care was provided.

DISCUSSION:

Fluoroquinolones are important therapeutic agents in the management of infectious diseases and are generally safe and well tolerated. Anaphylactoid and anaphylactic reactions have been documented as adverse effects of ciprofloxacin, ofloxacin, norfloxacin, levofloxacin, and moxifloxacin. To date, >33 cases have been reported with ciprofloxacin, of which at least 10 occurred in HIV-positive patients. In Europe, 15 cases of anaphylactoid reactions to ofloxacin have been reported and, more recently, with moxifloxacin. Since anaphylactoid reactions are potentially life threatening, the administration of fluoroquinolones to patients who have experienced a prior reaction to any of these agents should be avoided, unless tolerance has been confirmed by oral challenge tests.

CONCLUSIONS:

The anaphylactoid reaction in our patient was probably induced by ciprofloxacin as validated by the Naranjo probability scale. Although anaphylactoid/anaphylactic reactions are rare adverse effects of ciprofloxacin and other fluoroquinolones, clinicians should be aware of this potentially fatal event.
Experience with an Adverse Drug Reaction Reporting Program in a Neurology Specialty Clinic
Authors: Ryan Melody , Gora-Harper Mary Lea , Caldwell Frank
Published: June 2003

OBJECTIVE:

To describe an adverse drug reaction (ADR) reporting program that was developed in a university-affiliated neurology specialty clinic.

METHODS:

Reportable ADRs were identified through 3 mechanisms: by clinicians through routine visits, by patients who were encouraged to follow up with the pharmacist in the clinic, and by the pharmacist who contacted high-risk patients. Patient demographics, the suspected drug(s), elements to define probability, and outcomes were documented, collated, and analyzed for trends and opportunities for continuous quality-improvement efforts. Information was shared with clinic administrators and clinicians. Serious ADRs were reported to the Food and Drug Administration.

RESULTS:

The experience during a 1-year period, during which 40 ADRs were reported, is described. Medications by frequency of report and types of reactions are reported. None of the ADRs required admission to the hospital. Pharmacy personnel reported the majority of ADRs (92.5%).

CONCLUSIONS:

This program is successfully incorporated within daily practice and is an integral part of quality-improvement efforts.
Health Survey Data on Potentially Inappropriate Geriatric Drug Use
Authors: Laurier Claudine , Moride Yola , Kennedy Wendy A
Published: June 2003

BACKGROUND:

Studies have suggested that elderly patients do not always use medications appropriately. Investigations that have relied on prescription claim databases or clinical records focus on acquisition or prescription, and hypotheses must be made to assess actual consumption. Population survey data constitute an alternative way to study inappropriate use.

OBJECTIVE:

To estimate the prevalence of potentially inappropriate use of medications in elderly patients in Québec based on self-reported use.

METHODS:

Using a cross-sectional, general population, health survey in which self-reported medication use in the 2 days prior to the survey was recorded, we estimated the prevalence of inappropriate medication use in elderly patients (≥65 y old) who responded. Two sets of published criteria were used to define inappropriate use: one to assess use of inappropriate drugs, and another to assess concomitant duplications and potential interactions.

RESULTS:

Of the 3400 patients surveyed, 6.5% had used ≥1 inappropriate drugs, 2.5% had ≥1 occurrences of potentially inappropriate duplication of medications, and 2.7% had ≥1 potential medication interactions. Concomitant use of at least 2 benzodiazepines was reported by 8.5% of respondents using these drugs. Use of ≥1 long-acting benzodiazepines was reported by 4.2% of the sample.

CONCLUSIONS:

Population health surveys are a useful tool for detecting potentially inappropriate medication use in the elderly. In particular, the high prevalence of inappropriate use of benzodiazepines signals a need for improved detection and intervention in this group.

TRANSFONDO:

Existen estudios que demuestran que los ciudadanos viejos no siempre usan sus medicamentos adecuadamente. Estudios basados en los bancos de datos de los reclamos de prescripción o expedientes clínicos se hacen a base de la adquisición o prescripción de medicamentos. De estos se crean hipótesis para estimar el consumo real de medicamentos. Una manera alterna de realizar estudios sobre el uso inapropiado de medicamentos lo es a través de datos obtenidos de encuestas poblacionales.
The Depression Anxiety Stress Scales (DASS): Normative data and latent structure in a large non‐clinical sample
Authors: Crawford John R. , Henry Julie D.
Published: June 2003

Objectives: To provide UK normative data for the Depression Anxiety and Stress Scale (DASS) and test its convergent, discriminant and construct validity.

Design: Cross‐sectional, correlational and confirmatory factor analysis (CFA).

Methods: The DASS was administered to a non‐clinical sample, broadly representative of the general adult UK population (N = 1,771) in terms of demographic variables. Competing models of the latent structure of the DASS were derived from theoretical and empirical sources and evaluated using confirmatory factor analysis. Correlational analysis was used to determine the influence of demographic variables on DASS scores. The convergent and discriminant validity of the measure was examined through correlating the measure with two other measures of depression and anxiety (the HADS and the sAD), and a measure of positive and negative affectivity (the PANAS).

Results: The best fitting model (CFI = .93) of the latent structure of the DASS consisted of three correlated factors corresponding to the depression, anxiety and stress scales with correlated error permitted between items comprising the DASS subscales. Demographic variables had only very modest influences on DASS scores. The reliability of the DASS was excellent, and the measure possessed adequate convergent and discriminant validity.

Conclusions: The DASS is a reliable and valid measure of the constructs it was intended to assess. The utility of this measure for UK clinicians is enhanced by the provision of large sample normative data.
Outcomes of patients completing and not completing cognitive therapy for depression
Authors: Cahill Jane , Barkham Michael , Hardy Gillian , Rees Anne , Shapiro David A. , Stiles William B. , Macaskill Norman
Published: June 2003

Objectives: The aims of this study were to use symptom intensity measures collected at each session (1) to describe the outcomes of clients who received cognitive therapy (CT) for depression in a clinically representative sample, and (2) to compare the outcomes of clients who completed the agreed number of sessions with those who did not.

Design and method: Clients (N = 58) contracted to attend between 12 and 20 sessions of CT completed the Beck Depression Inventory (BDI) immediately prior to each therapy session. The BDI and other measures were collected at intake and, for those who completed therapy, at a post‐therapy assessment.

Results: Completers' BDI scores improved significantly from intake to post‐treatment and significantly more from intake to their final session than did those of non‐completers. However, when non‐completers' final session scores were matched with scores of randomly selected completers at the corresponding session, the difference in improvemen was not significant. A significantly higher proportion of clients who completed the agreed number of sessions achieved reliable and clinically significant change (71.4%, 25/35), compared with just 13% (3/23) of clients who did not.

Conclusions: (1) CT for depression can be effective in a clinically representative population. (2) Attrition from clinical trials may bias estimates of treatment effectiveness.