bluuebunny/crossref_metadata_2025 huggingface dataset:
Accuracy, Clinical Correlation, and Patient Acceptance of Two Handheld Prothrombin Time Monitoring Devices in the Ambulatory Setting
Authors: Chapman Derek C , Stephens Mark A , Hamann Gale L , Bailey Lamar E , Dorko Craig S
Published: March 2004

OBJECTIVE:

To evaluate the accuracy, clinical correlation, ease of use, and patient acceptance of the Coaguchek and the ProTime Microcoagulation System as compared with standard laboratory methods for prothrombin time determination.

METHODS:

A total of 30 prothrombin times, expressed as international normalized ratios (INRs), were determined by each handheld device for comparison with standard laboratory testing. Accuracy was evaluated by calculating the absolute difference for each pair of INR values. Clinical correlation was defined as an INR obtained by the handheld monitor that would have resulted in the same therapeutic decision as the INR obtained by the standard laboratory method. Subjects were surveyed to determine which method of INR determination they preferred and their reasons for that preference.

RESULTS:

Accuracy was superior with the Coaguchek monitor. The absolute difference (mean ± SD) in the laboratory and Coaguchek INRs was 0.28 ± 0.23 (p = 0.96). The absolute difference (mean ± SD) in the laboratory and the ProTime Microcoagulation System INRs was 0.56 ± 0.34 (p < 0.001). For clinical correlation, two out of 24 (8.3%) INRs with the Coaguchek were sufficiently different from the laboratory INR to have resulted in a different therapeutic decision, compared with 12 out of 24 (50%) with the ProTime Microcoagulation System (p < 0.005). Of subjects surveyed, 77.8% preferred the finger stick method.

CONCLUSIONS:

The Coaguchek was superior to the ProTime Microcoagulation System in accuracy, clinical correlation, and ease of use. The study also showed that patients preferred capillary blood sampling by finger puncture over venipuncture for INR monitoring.
Nonprescription and Alternative Medication Use by Individuals with HIV Disease
Authors: Smith Scott R , Boyd Eddie L , Kirking Duane M
Published: March 2004

OBJECTIVE:

To examine the strength of the associations between predisposing, enabling, and need-for-care variables and the self-treatment of HIV disease; and to compare sociodemographic and illness-related factors associated with the use of vitamins, nonprescription medications, herbs, and recreational substances among HIV-infected individuals.

METHODS:

Data were derived from 7887 interviews conducted as part of the AIDS Cost and Services Utilization Survey. The conceptual framework was the Andersen Behavioral Model of Health Services Use. Factors associated with nonprescription and alternative medication use were assessed using logistic regression. Generalized estimating equations were applied to adjust variance estimates for within-person correlations of drug use over time.

RESULTS:

After adjusting for perceived health status, T cell count, and stage of disease, the results indicated that African-Americans were less likely to use nonprescription drugs (odds ratio [OR] 0.65, 95% CI 0.52 to 0.81), vitamins (OR 0.59, 95% CI 0.48 to 0.73), and herbs (OR 0.41, 95% CI 0.22 to 0.76), compared with non-Hispanic whites. Similarly, Hispanics were less likely to report use of herbs (OR 0.58, 95% CI 0.34 to 0.98) or recreational drugs (OR 0.34, 95% CI 0.15 to 0.76) than were non-Hispanic whites. Oppositely, individuals who had a college education were more likely to use vitamins (OR 1.26, 95% CI 1.05 to 1.50) and herbs (OR 2.47, 95% CI 1.56 to 3.91). Enabling variables such as insurance status and income were generally associated only with use of recreational drugs. Need-for-care variables were generally associated only with use of nonprescription drugs and vitamins.

CONCLUSIONS:

Predisposing, enabling, and need-for-care variables from the Andersen Behavioral Model were significantly associated with the use of four categories of drugs to self-treat HIV disease. However, there was not a consistent pattern across the drug categories.
The Evolving Role of Platelet Glycoprotein IIb/IIIa Inhibitors in the Management of Acute Coronary Syndromes
Authors: Stringer Kathleen A
Published: March 2004

OBJECTIVE:

To briefly discuss the pathophysiology of acute coronary syndromes (ACS) and to present the clinical data currently available regarding the use of platelet glycoprotein (GP) IIb/IIIa inhibitors in the management of ACS.

DATA SOURCES:

Literature on antithrombotic therapy in ACS was identified using a MEDLINE search (January 1988–September 1998), along with the Agency on Health Care Policy and Research guidelines for the management of unstable angina. Abstracts from recent scientific meetings were also reviewed.

STUDY SELECTION:

Review articles from the cardiology literature (pathophysiology) and randomized, controlled clinical trials of currently approved platelet GP IIb/IIIa inhibitors in ACS were evaluated. Ex vivo platelet aggregation studies and pharmacology literature were also included. Abstract data were included to illustrate specific points when published literature was not available.

DATA EXTRACTION:

Study data were evaluated based on study design, outcome parameters, and adverse drug reactions. Clinical information from review articles was evaluated based on applicability to the treatment of ACS.

DATA SYNTHESIS:

Platelet adhesion and aggregation are pivotal events in the pathophysiology of ACS. The GP IIb/IIIa inhibitors represent a new and unique class of drugs that block fibrinogen and von Willebrand factor–mediated platelet aggregation, the common end point of all biologic pathways of platelet aggregation. Three agents are currently approved by the Food and Drug Administration: abciximab, a monoclonal antibody; eptifibatide, a synthetic peptide; and tirofiban, a synthetic nonpeptide.

CONCLUSIONS:

Clinical trial data demonstrate efficacy of all three GP IIb/IIIa inhibitors in reducing the combined end point of morbidity and mortality in patients undergoing angioplasty. Eptifibatide and tirofiban also reduce the combined end point of morbidity and mortality in patients with unstable angina. These data expand the present role of platelet GP IIb/IIIa inhibitors by providing evidence for their effectiveness in the medical treatment of ACS. However, the specific role that these agents will have in the management of ACS is yet to be fully defined.
Tetravalent Rotavirus Vaccine
Authors: Wandstrat Todd L , Kaplan-Machlis Barbara , Temple Mary E , Nahata Milap C
Published: March 2004

OBJECTIVE:

To review the clinical efficacy, safety, and pharmacoeconomic data about the use of rhesus–human reassortant rotavirus tetravalent vaccine (RRV-TV) in infants and children.

DATA SOURCES:

A MEDLINE search (January 1990–December 1998) was conducted to identify all publications on the RRV-TV vaccine including pharmacology, clinical trials, adverse effects, and pharmacoeconomics in infants and children. Bibliographies of articles were also used.

STUDY SELECTION:

All randomized and placebo-controlled clinical efficacy trials were reviewed. Additionally, pharmacoeconomic studies focusing on the potential impact on healthcare costs were chosen for review.

DATA SYNTHESIS:

Rotavirus-induced gastroenteritis is a significant problem in developed and developing countries. Various forms of a rotavirus vaccine have been studied worldwide. The tetravalent vaccine appears to have similar efficacy in developed and developing countries. It seems to be most effective against the most severe forms of gastroenteritis, with an 80% overall efficacy rate. This vaccine is well tolerated; the most common adverse effect is fever after the first dose. Pharmacoeconomic studies indicate that although the vaccine may be only moderately effective against less severe gastroenteritis, over $1 billion annually could potentially be saved in the US with its universal use.

CONCLUSIONS:

The new rotavirus vaccine is effective in preventing and reducing the incidence of rotavirus-induced gastroenteritis. The morbidity, mortality, and healthcare costs from this disease may be reduced if this vaccine is provided to children worldwide.
Noncardiogenic Pulmonary Edema Immediately following Rapid Protamine Administration
Authors: Brooks Joseph C
Published: March 2004

OBJECTIVE:

To report the case of a rare, potentially preventable, immediate noncardiogenic pulmonary edema reaction to the rapid administration of protamine during coronary artery bypass graft (CABG) surgery.

CASE SUMMARY:

A 74-year-old white man was administered a 250-mg bolus of protamine sulfate toward the end of CABG surgery to reverse the heparin anticoagulation. Immediately following the administration of protamine, oxygen saturation declined, pink frothy sputum was suctioned from the trachea, and 1500 mL of serous fluid was removed from the airway. The patient was stabilized, but the surgeons were unable to close his chest because of the profound edema. Chest closure occurred on hospital day 6, with discharge from the intensive care unit on hospital day 28.

DISCUSSION:

Noncardiogenic pulmonary edema is a rare adverse event that occurs in 0.2% of cardiopulmonary bypass patients, with mortality rates approaching 30%. Complement activation or direct pharmacologic release of histamine by high concentrations of protamine is the suspected cause. High concentrations of protamine in the lungs may directly release histamine, with significant vasodilating effects.

CONCLUSIONS:

Immediate reversal of heparin anticoagulation with protamine is necessary to control bleeding; however, rapid protamine injection can be associated with life-threatening pulmonary edema. Slower, cautious administration and accurate calculation of protamine doses may prevent such an event.
Ethics in Christianity and Health Care: Can “Character” Be Defined in This Interdisciplinary Course?
Authors: Broeseker Amy E
Published: March 2004

OBJECTIVE:

To describe a unique interdisciplinary ethics course that incorporates elements of character into a decision-making model.

METHODS:

The Ethics in Christianity and Health Care course is divided into two sections: ethics in Christianity and ethics in health care. The first section comprises the initial 30% of the course, and the second portion spans the latter 70%. Character traits of ethical persons are described in the second section of the course and are then used in an adapted decision-making model. A scenario from a nontraditional Doctor of Pharmacy student is included to illustrate this decision-making process. Texts, assignments, and assessments are also discussed briefly.

This course provides a framework within which ethical relationships are described and discussed. The character traits delineated in the article offer a logical approach when solving ethical dilemmas.
Alopecia Due to Psychotropic Medications
Authors: Gautam Monica
Published: March 2004

OBJECTIVE:

To review the literature and describe the incidence and nature of psychotropic drug–related alopecia to assist clinicians in their therapeutic decisions when this adverse event occurs.

DATA SOURCES:

A MEDLINE search (December 1966–March 1998), using each drug name and the keywords alopecia or hair loss, was conducted. A database from the Clarke Institute of Psychiatry in Toronto was also searched. Additional English-language articles were identified through the bibliography of the reviewed literature. Certain pharmaceutical companies were also consulted.

STUDY SELECTION:

All published case reports and review articles were considered for study evaluation.

DATA EXTRACTION:

When possible, details regarding psychotropic drug therapy, development of alopecia, and clinical outcomes were collected for each case.

DATA SYNTHESIS:

Hair loss from the scalp, eyebrows, and pubic area was identified as a possible, yet uncommon, adverse effect of most psychotropic medications. There are few effective management options for alopecia; however, resolution was achieved on discontinuation of the offending drug in almost all of the cases reported. Alopecia was perceived to be an undesirable effect by most patients, often resulting in poor compliance and hence therapeutic failures.

CONCLUSIONS:

Due to the self-limiting nature of mild to moderate hair loss with psychotropic medications, clinicians should consider continuing therapy if there is a good clinical response and the patient agrees with this decision. If severe alopecia occurs, it is recommended to discontinue the medication and pursue therapy with another agent. This is to ensure positive therapeutic outcomes and improved patient compliance.
Use of Intravenous Valproate in Three Pediatric Patients with Nonconvulsive or Convulsive Status Epilepticus
Authors: Hovinga Collin A , Chicella Mike F , Rose Doug F , Eades Shannan K , Dalton James T , Phelps Stephanie J
Published: March 2004

OBJECTIVE:

To report the pharmacokinetics of intravenous valproate (VPA) in children with generalized convulsive status epilepticus (GCSE) or nonconvulsive status epilepticus (NCSE). To provide loading and maintenance dosing for patients with hepatic induction secondary to concurrent anticonvulsants.

CASE SUMMARY:

Two patients (10 y, 34 mo) with GCSE refractory to benzodiazepines, phenobarbital, phenytoin, and pentobarbital received intravenous VPA. Apparent volume of distribution (Vd) following a 20 mg/kg loading dose was 0.29 L/kg. Maintenance infusions of 4–6 mg/kg/h produced steady-state total concentrations of 66 mg/L and 92.4 mg/L (unbound concentration 44.6 mg/L). Clearance ranged from 63–66 mL/h/kg. An eight-year-old with NCSE received intravenous VPA (13.4 mg/kg load followed by 9 mg/kg every 8 h). Total and unbound steady-state VPA concentrations were 32.9 mg/L and 21.2 mg/L, respectively. Elimination half-life was eight hours.

DISCUSSION:

We constructed a pharmacokinetic simulation using VPA parameters from children receiving mono- or polyanticonvulsants. Our Vd and elimination half-life rates were comparable with published pediatric values. Patients on hepatic inducers had clearance rates 2.5 times those of children receiving oral anticonvulsant polytherapy. Unbound fractions (48.3% and 66%) were significantly higher than normal.

CONCLUSIONS:

A 20 mg/kg loading dose should produce a concentration after the bolus dose of approximately 75 mg/L. Initial infusion should consider hepatic induction (noninduced = 1 mg/kg/h, polyanticonvulsant therapy = 2 mg/kg/h, and high-dose pentobarbital = 4 mg/kg/h). Adjustments should be based on response and serum concentrations.
Losartan-Induced Angioedema
Authors: Rivera José O
Published: March 2004

OBJECTIVE:

To report a case of angioedema associated with losartan administration.

CASE SUMMARY:

A 45-year-old white man with a history of hypertension and gout was treated with losartan/hydrochlorothiazide, allopurinol, and colchicine. The patient experienced two episodes of angioedema within a 10-hour period. On both occasions the symptoms resolved after treatment.

DISCUSSION:

Angiotensin-converting enzyme (ACE) inhibitors are associated with a relatively high incidence of angioedema. The incidence of angioedema secondary to losartan, an angiotensin II receptor antagonist, is unknown. The patient reported in this case differs significantly from the two cases reported in the literature because he had normal renal function, no previous exposure to ACE inhibitors, the reaction was of late onset, and the symptoms recurred.

CONCLUSIONS:

This case suggests that losartan can induce late-onset angioedema in patients with normal renal function and that the reaction can recur after initial resolution of the symptoms.
Clinical Presentation, Diagnosis, and Pharmacotherapy of Patients with Primary Brain Tumors
Authors: Newton Herbert B , Turowski Robert C , Stroup Tammie J , McCoy Laura K
Published: March 2004

OBJECTIVE:

To briefly review the clinical presentation and diagnosis of patients with primary brain tumors, followed by an in-depth survey of the pertinent pharmacotherapy.

DATA SOURCES:

A detailed search of the neurologic, neurosurgical, and oncologic literature for basic science research, clinical studies, and review articles related to chemotherapy and pharmacotherapy of primary brain tumors.

STUDY SELECTION:

Relevant studies on tissue culture systems, animals, and humans examining the mechanisms of action, pharmacokinetics, clinical pharmacology, and treatment results of chemotherapeutic agents for primary brain tumors. In addition, studies of pharmacologic agents administered for supportive care and symptom control are reviewed.

DATA SYNTHESIS:

Primary brain tumors derive from cells within the intracranial cavity and generally present with headache, seizure activity, cognitive changes, and weakness. They are diagnosed most efficiently with magnetic resonance imaging. After diagnosis, the most common supportive medications include corticosteroids, gastric acid inhibitors, and anticonvulsants. Chemotherapy is adjunctive treatment for patients with malignant tumors and selected recurrent or progressive benign neoplasms. In general, the most effective chemotherapeutic drugs are alkylating agents such as the nitrosoureas, procarbazine, cisplatin, and carboplatin. Other agents used include cyclophosphamide, methotrexate, vincristine, and etoposide. Angiogenesis inhibitors and gene therapy comprise some of the novel therapeutic strategies under investigation.

CONCLUSIONS:

The efficacy of chemotherapy for primary brain tumors remains modest. Novel agents must be discovered that are more specific and attack tumor cells at the molecular level of tumorigenesis. Furthermore, strategies must be developed to counteract the pervasive problem of brain tumor chemoresistance.
Diltiazem Increases Tacrolimus Concentrations
Authors: Hebert Mary F , Lam Annie Y
Published: March 2004

OBJECTIVE:

To describe a patient with increased tacrolimus concentrations due to a diltiazem drug interaction.

CASE SUMMARY:

A 68-year-old white man, four months following orthotopic liver transplantation secondary to hepatitis C and Laënnec's cirrhosis, was admitted to the intensive care unit for diarrhea, dehydration, and atrial fibrillation. He was stabilized on oral tacrolimus 8 mg twice daily, with a whole blood tacrolimus trough concentration of 12.9 ng/mL on admission. He was started on a continuous infusion of diltiazem for one day, followed by 30 mg orally every eight hours. Three days after admission, the patient became delirious, confused, and agitated; he was found to have a whole blood tacrolimus trough concentration of 55 ng/mL. The tacrolimus was withheld and diltiazem was discontinued. The tacrolimus concentrations fell over the next three days to 6.7 ng/mL, with a corresponding improvement in his mental status. The oral tacrolimus was restarted at 3 mg twice daily and increased gradually to 5 mg twice daily over the next four days; this produced tacrolimus trough concentrations between 9 and 10 ng/mL.

DISCUSSION:

Tacrolimus is known to be a substrate for P-glycopro-tein and metabolized by CYP3A. Diltiazem inhibits CYP3A, P-glycoprotein, and tacrolimus metabolism in vitro. Although this interaction may have been predictable, this is the first detailed case report describing this clinically significant drug interaction.

CONCLUSIONS:

Diltiazem can dramatically increase tacrolimus concentrations and result in tacrolimus toxicity. Avoidance of this interaction or careful monitoring of tacrolimus concentrations along with tacrolimus dose reduction is recommended if diltiazem therapy cannot be avoided.
Propafenone Disposition during Continuous Venovenous Hemofiltration
Authors: Seto Winnie , Trope Angela E , Gow Robert M
Published: March 2004

OBJECTIVE:

To determine the extent of removal of propafenone by continuous venovenous hemofiltration (CVVH) in a critically ill pediatric patient.

CASE SUMMARY:

A three-year-old white–Japanese girl was admitted to the critical care unit following cardiac surgery. Her postoperative course was complicated by the development of junctional ectopic tachycardia, requiring propafenone; and acute renal failure, which necessitated the use of CVVH. The serum and ultrafiltrate concentrations of propafenone and its 5-hydroxy metabolite were measured to determine both total and CVVH clearance.

CONCLUSIONS:

The data from this case report showed that propafenone was not significantly removed by CVVH. Furthermore, the total clearance of propafenone was not affected by the patient's renal or liver function impairment.
Fatal Fulminant Hepatitis Associated with Bromfenac Use
Authors: Rabkin John M , Smith Megan J , Orloff Susan L , Corless Christopher L , Stenzel Peter , Olyaei Ali J
Published: March 2004

OBJECTIVE:

To report a case of fulminant hepatic failure associated with the use of bromfenac, a new analog of the phenyl acetate class of nonsteroidal antiinflammatory drugs.

CASE SUMMARY:

A 60-year-old white woman with liver failure who had no known history of chronic liver disease was transferred to the liver transplant unit for evaluation. For three months preceding her illness, the patient was treated with bromfenac 25 mg po qid for arthritic pain. Prior to the initiation of bromfenac, her liver function test results were normal. Etiologic evaluation at presentation was unremarkable. The patient's condition continued to deteriorate, with the development of hepatic encephalopathy and worsening liver function test results while awaiting liver transplantation. Progressive hepatic and renal dysfunction along with respiratory decompensation ensued, and the patient died 48 days after initial presentation.

CONCLUSIONS:

Fulminant hepatic failure associated with the prolonged use of bromfenac appears to be an idiosyncratic response consistent with experience with other agents of its class. This case along with other cases of serious hepatotoxicity associated with the use of this agent ultimately resulted in bromfenac's removal from the market.
Dose-Related Increases in Cerebrospinal Fluid Concentrations of Methotrexate in a Postoperative Patient with Glioblastoma
Authors: Morikawa Norifumi , Mori Teruaki , Kamenofuchi Yousuke , Kawashima Hisanori , Takeyama Masaharu , Hori Shigeaki
Published: March 2004

OBJECTIVE:

To investigate the postoperative pharmacokinetics of methotrexate in the plasma and cerebrospinal fluid (CSF) in the space created by tumor removal of a patient with glioblastoma during hyperosmotic disruption of the blood–brain barrier (BBB) and intraarterial chemotherapy with a stepwise increase in the methotrexate dosage.

CASE SUMMARY:

A 30-year-old Japanese woman with glioblastoma received four courses of hyperosmotic disruption of the BBB and intraarterial chemotherapy with a combination of peplomycin, vindesine, nimustine, pirarubicin, and methotrexate. The patient was initially administered mannitol; anticancer drugs were then infused into the left internal carotid artery. Following the first, second, third, and fourth courses of treatment, methotrexate 350, 700, 1000, and 1500 mg, respectively, were administered for 30 minutes. Samples of blood and CSF from the space created by tumor removal were obtained. Methotrexate concentrations were measured by fluorescence polarization immunoassay and the pharmacokinetic parameters of methotrexate in plasma and CSF were estimated.

RESULTS:

The plasma concentration of methotrexate peaked at the end of drug infusion, then decreased in a biexponential decay manner during the remainder of the treatment period. The CSF concentration of methotrexate in the space created by tumor removal peaked two hours after drug administration, then monoexponentially decreased. Although the maximal CSF concentration of methotrexate in the space created by tumor removal was lower than that in the plasma, the CSF concentration of methotrexate in the space created by tumor removal exceeded that in the plasma six hours after drug infusion. The half-life of methotrexate in the CSF exceeded that in the plasma. The AUC for the plasma and CSF methotrexate concentration increased parallel with the methotrexate dosage. The mean CSF AUC of methotrexate was 59.4% of that found in plasma.

CONCLUSIONS:

The CSF AUC of methotrexate in the space created by tumor removal increased parallel with the methotrexate dosage during hyperosmotic disruption of the BBB and intraarterial chemotherapy.
Successful Anticoagulation with Dalteparin in a Patient with Mechanical Heart Valves
Authors: Maharaj Siobhan , Bayliff Charles D , Kovacs Michael J
Published: March 2004

BACKGROUND:

Standard thromboprophylaxis of patients with mechanical heart valves is achieved using warfarin. In certain patients this may be very difficult; thus, alternative pharmacotherapy must be used.

OBJECTIVE:

To report a case of a patient who successfully used dalteparin, a low-molecular-weight heparin, for anticoagulation.

CASE SUMMARY:

A 58-year-old white woman with mechanical aortic and mitral heart valves initially received warfarin for anticoagulation. Thromboprophylaxis was very challenging. Her international normalized ratios (INRs) were erratic and occasionally responded paradoxically to changes in dose. Finally, she experienced a left hemispheric stroke when her INR was extremely subtherapeutic. Subsequently, despite best efforts, her INR again was subtherapeutic; warfarin was discontinued and dalteparin was initiated with daily self-administered subcutaneous injections of 16 000 units. No complications have arisen since initiation of the new pharmacotherapy approximately 18 months ago.

DISCUSSION:

The use of low-molecular-weight heparin for the treatment and prevention of venous thromboembolism is well described. There are few reports of its use for thromboprophylaxis of patients with mechanical heart valves. Our patient has been managed successfully with dalteparin.

CONCLUSIONS:

Dalteparin was effectively and safely used for the thromboprophylaxis of a patient with mechanical heart valves whose anticoagulation was previously difficult to manage with warfarin. Dalteparin deserves further study in patients who are unable to tolerate warfarin.
Vigabatrin: A Novel Therapy for Seizure Disorders
Authors: Gidal Barry E , Privitera Michael D , Sheth Raj D , Gilman Jamie T
Published: March 2004

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of vigabatrin and its role in the management of seizure disorders.

METHODS:

A MEDLINE search of English-language literature from January 1993 through January 1999 was conducted using vigabatrin as a search term to identify pertinent studies and review articles. Additional studies were identified from the bibliographies of reviewed literature. The manufacturer provided postmarketing surveillance data. Priority was given to randomized, double-blind, placebo-controlled studies.

FINDINGS:

Vigabatrin is a selective and irreversible inhibitor of γ-aminobutyric acid transaminase. In controlled clinical trials of vigabatrin add-on therapy in patients with uncontrolled partial seizures, 24–67% of patients achieved a ≤50% reduction in seizure frequency. Data from two comparative trials with carbamazepine monotherapy indicate that vigabatrin monotherapy reduces the frequency of partial seizures in patients with newly diagnosed epilepsy. Vigabatrin also controls infantile spasms, particularly those associated with tuberous sclerosis. Vigabatrin is more effective in patients with partial seizures than in those with generalized seizures. The drug is generally well tolerated. Headache and drowsiness were the most common adverse effects observed in controlled clinical trials; visual field defects, psychiatric reactions, and hyperactivity also have been reported. There are no known clinically significant drug interactions.

CONCLUSIONS:

Vigabatrin improves seizure control as add-on therapy for refractory partial seizures and may produce therapeutic benefits in the treatment of infantile spasms. Vigabatrin is generally well tolerated, with a convenient administration schedule, a lack of known significant drug interactions, and no need for routine monitoring of plasma concentrations.
Procainamide-Induced Psychosis: A Case Report and Review of the Literature
Authors: Bizjak Eric D , Nolan Paul E , Brody Eric A , Galloway James M
Published: March 2004

OBJECTIVE:

To describe a case of procainamide-induced psychosis in an adult treated for atrial fibrillation.

CASE SUMMARY:

A 45-year-old Native American woman developed acute psychosis within 72 hours of initiating procainamide for atrial fibrillation. Symptoms abated within 24 hours of discontinuing procainamide. Serum procainamide/ N-acetylprocainamide concentrations were therapeutic throughout treatment. Sotalol was started without recurrence of symptoms.

DISCUSSION:

Psychosis is a rare complication of treatment with procainamide, but the exact mechanism for this adverse event is not fully understood. Seven cases implicating procainamide as the cause of acute psychosis are reported in the literature. Cases of psychosis involving other antiarrhythmic agents have also been reported.

CONCLUSIONS:

Healthcare personnel should be aware of this adverse event related to procainamide and other antiarrhythmic agents.
Study of Cardiovascular Risk Intervention by Pharmacists (SCRIP): A Randomized Trial Design of the Effect of a Community Pharmacist Intervention Program on Serum Cholesterol Risk
Authors: Tsuyuki Ross T , Johnson Jeffrey A , Teo Koon K , Ackman Margaret L , Biggs Rosemarie S , Cave Andrew , Chang Wei-Ching , Dzavik Vladimir , Farris Karen B , Galvin Donna , Semchuk William , Simpson Scot H , Taylor Jeff G
Published: March 2004

OBJECTIVE:

To determine the efficacy of a program of intervention by pharmacists on lipid risk management in patients at high risk for cardiovascular events.

METHODS:

Randomized, multicenter (44 sites in Alberta and Saskatchewan) study of community pharmacist intervention versus usual care in 1000 patients. Patients are those at high risk of vascular events (existing atherosclerotic vascular disease, or diabetes with ≥1 other risk factor). After obtaining consent, the pharmacist calls the Project Office to randomize. Patients allocated to intervention receive a brochure and education about cardiovascular risk factors. Pharmacists also complete a physician contact form, which lists the patient's risk factors, medications, and any recommendations. A point-of-care cholesterol test is performed, the result is discussed with the patient, and it is entered on the contact form. If appropriate, the patient is asked to see his or her primary care physician for further assessment and/or treatment, and the form is faxed to the physician. Patients are followed up at two, four, eight, 12, and 16 weeks. During follow-up visits, pharmacists provide educational reinforcement and check for primary end point occurrence. Patients allocated to usual care receive the brochure only, with minimal follow-up. The primary end point is a composite of measurement of a complete lipid panel by the physician, or addition or modification of lipid-lowering drug therapy. Substudies will evaluate economics (third-party payer and pharmacy manager perspective), patient satisfaction, and quality of life.

CONCLUSIONS:

SCRIP (Study of Cardiovascular Risk Intervention by Pharmacists) is a unique ongoing trial that is evaluating a community pharmacist intervention designed to optimize cholesterol risk management in patients at high risk for cardiovascular events.
Lamotrigine Overdose Presenting as Anticonvulsant Hypersensitivity Syndrome
Authors: Mylonakis Eleftherios , Vittorio Carmela C , Hollik Deborah A , Rounds Sharon
Published: March 2004

OBJECTIVE:

To describe the laboratory and physical manifestations of lamotrigine toxicity presenting as anticonvulsant hypersensitivity syndrome.

CASE SUMMARY:

A 49-year-old white man presented to our institution with a two-day history of low-grade fever, erythema, and edema involving the periorbital area. Five days earlier, he had been placed on lamotrigine treatment for bipolar disorder. He inadvertently received four daily doses of lamotrigine 2700 mg each. Physical examination was significant for periorbital edema and discrete and confluent blanching red macules and papules involving the face, trunk, and extremities. Laboratory tests revealed leukocytosis, hepatitis, and acute renal failure. With normalization of the laboratory results, the eruptions and edema gradually resolved.

DISCUSSION:

Lamotrigine toxicity can lead to periorbital edema, rash, and multiorgan system abnormalities. This presentation has clinical and laboratory similarities with anticonvulsant hypersensitivity syndrome, which suggests that at some threshold concentration the amount of lamotrigine may overwhelm the body's ability to metabolize the drug, leading to a similar hypersensitivity reaction. Lamotrigine is a relatively new agent, and this report may provide useful insights on evaluating the clinical toxicology of this agent.

CONCLUSIONS:

Healthcare providers should be aware that lamotrigine overdose may present with multiorgan involvement, similar to anticonvulsant hypersensitivity syndrome.
Oxacillin-Induced Tissue Necrosis
Authors: Fromm Laurie A , Graham Diane L
Published: March 2004

OBJECTIVE:

To report a case of oxacillin-induced tissue necrosis in which recommended concentration guidelines for dilution and administration were used. Oxacillin concentration data, potential risk factors, and treatment options for extravasation injuries are also briefly reviewed.

CASE SUMMARY:

Oxacillin was infused peripherally by infusion pump in a 79-year-old white woman as prophylactic antibiotic coverage for permanent pacemaker placement. Oxacillin extravasation occurred after the second postoperative dose. A dimesized area of necrosis was noted at the heparinlock insertion site.

DISCUSSION:

Only one case of oxacillin-induced necrosis has been reported. The degree of damage and concentration of drug used were not specifically described. Concentration may play a role in the appearance or absence of tissue damage after an antibiotic extravasation and should be taken into consideration when evaluating a drug's tissue toxicity potential.

CONCLUSIONS:

The potential exists for oxacillin 50 mg/mL to cause tissue damage in humans if an extravasation occurs. This reaction may be avoided with use of a less-concentrated preparation, avoidance of infusion pump administration, and identification of high-risk patients.
Evaluation of a Computer-Assisted Antibiotic-Dose Monitor
Authors: Evans R Scott , Pestotnik Stanley L , Classen David C , Burke John P
Published: March 2004

OBJECTIVE:

To examine the effect of a computer-assisted antibiotic-dose monitor used to reduce the number of days that patients receive excessive dosages of antibiotics and the number of adverse drug events (ADEs) secondary to antibiotics.

DESIGN:

Descriptive epidemiologic study of a two-year preintervention period and one-year intervention period.

SETTING:

The LDS Hospital, a tertiary care center in Salt Lake City, UT.

PATIENTS:

All patients aged • 18 years, admitted to LDS Hospital from April 1, 1993, to March 31, 1996, who received at least one of five targeted antibiotics (vancomycin, gentamicin, imipenem, cefazolin, cefuroxime), who had a serum creatinine or a urine creatinine clearance test result before antibiotic therapy, and who were never admitted or transferred to the shock/trauma/respiratory intensive care unit.

METHODS:

Each morning during the 12-month intervention period, the antibiotic-dose monitor checked the renal function of all patients who were receiving any of the five antibiotics. Pharmacists received a computer listing of patients who may have been receiving excessive dosages. The antibiotic-dose monitor suggested an alternate dosage and a pharmacikst contacted the patient's physician if the suggested change in the dosage was appropriate.

RESULTS:

During the intervention period, 4483 patients received at least one of the five study antibiotics and 1974 (44%) were identified as receiving an excessive dosage, compared with 4494 (50%) of 8901 patients during the preintervention period (p < 0.001). The patients receiving excessive dosages received an excessive dosage for an average of 2.9 days during the intervention period, compared with 4.7 days (p < 0.001) during the preintervention period. In addition, these same patients during the intervention period received fewer doses of antibiotics (10.9 vs. 13.4; p < 0.001), fewer grams of antibiotics (10.4 vs. 12.0; p < 0.02), at less cost ($98 vs. $128; p < 0.004) than the patients during the preintervention period. Moreover, there were 14 ADEs (0.3%) secondary to the five study antibiotics during the intervention period, compared with 82 (0.9%; p < 0.001) for the two-year preintervention period. The study also found that significantly more patients identified as receiving excessive dosages had experienced decreases in renal function, compared with patients who were not identified as receiving excessive dosages (25% vs. 12% during preintervention period and 23% vs. 16% during intervention period; p < 0.001).

CONCLUSIONS:

Many patients experience decreases in renal function after antibiotics are ordered. The use of the computer-assisted antibiotic-dose monitor appears to be a promising method to help reduce the excessive use and cost of antibiotic therapy and reduce the number of ADEs secondary to antibiotics.
Interaction between Ciprofloxacin and Rifampin
Authors: Temple Mary E , Nahata Milap C
Published: March 2004

OBJECTIVE:

To discuss the necessity of dose adjustment for ciprofloxacin or rifampin during their concurrent use.

DATA SOURCES:

A MEDLINE search (1966–December 1998) was completed using key terms rifampin and fluoroquinolone. English-language journals were considered.

DATA SYNTHESIS:

Studies in elderly patients after 14 days of therapy with oral ciprofloxacin and rifampin did not demonstrate significant differences in the pharmacokinetics of ciprofloxacin as compared with those in patients receiving ciprofloxacin alone. Similar results were found in intravenous drug abusers. In comparison to the pharmacokinetics of both ciprofloxacin and rifampin when given alone, the serum bactericidal activity of rifampin, when given with ciprofloxacin in healthy elderly volunteers, was reduced but still evident. Ciprofloxacin pharmacodynamics were not significantly altered. Serum bacterial titers of ciprofloxacin and pefloxacin increased twofold when given with rifampin, although their clinical significance is unknown.

RECOMMENDATION:

No strong evidence of a significant interaction exists to support dose adjustment for ciprofloxacin or rifampin during their concurrent use.
Prevention of Suboptimal β-Blocker Treatment in Patients with Myocardial Infarction
Authors: White C Michael
Published: March 2004

OBJECTIVE:

To review the published data and clinical guidelines on the use of β-blockers in myocardial infarctions (MIs) and contrast that with actual clinical practice.

DATA SOURCES:

A MEDLINE search (January 1970–June 1999) was performed to identify all relevant articles. References from these articles were also evaluated for review if deemed important.

DATA SYNTHESIS:

Intravenous and oral β-blockers have been proven to improve outcomes in patients with MIs in numerous clinical trials. In current clinical practice, only 15% of MI patients receive intravenous β-blockers and long-term β-blocker therapy is used in <40% of patients without contraindications. However, they could be safely administered to 40% and 70% of these patients, respectively. Furthermore, most of these patients are receiving doses far below those found beneficial in clinical trials. Many of the real and perceived contraindications to β-blockers are reviewed to allow the practitioner to identify patients who are incorrectly excluded from β-blocker therapy. Also discussed are special clinical situations in which the benefits observed during clinical trials may not apply.

CONCLUSIONS:

β-blockers are valuable drugs in the treatment of peri-and post-MI. In clinical practice, most patients are not treated or are inadequately treated with β-blockers. Pharmacists should ensure that such patients actually have an absolute contraindication or unusual situation where therapy is not firmly indicated. Patients without absolute contraindications warrant titration to specific target doses or a target heart rate of 55–60 beats/min.
Metabolic Acidosis and Coma following a Severe Acetaminophen Overdose
Authors: Koulouris Zoë , Tierney Michael G , Jones Gwynne
Published: March 2004

OBJECTIVE:

To report a case of metabolic acidosis and coma in a severe acetaminophen overdose.

CASE SUMMARY:

A 29-year-old white woman was admitted to the emergency department with a diminished level of consciousness and metabolic acidosis. The toxicology screen revealed a serum acetaminophen concentration of 1072 μg/mL, and she was consequently treated with intravenous acetylcysteine. Despite the elevated concentration, the patient did not manifest signs of hepatotoxicity.

DISCUSSION:

Metabolic acidosis and coma are rare manifestations in acetaminophen overdoses. In published case reports, severe acetaminophen ingestion independently causes metabolic acidosis and coma in the absence of hepatotoxicity. The mechanism by which metabolic acidosis occurs is not clearly defined. Studies conducted on animals demonstrated that in severe overdoses, acetaminophen may cause lactic acidosis by inhibiting mitochondrial respiration. The mechanism by which acetaminophen can cause coma is still unknown.

CONCLUSIONS:

Severe acetaminophen overdoses can independently cause metabolic acidosis and coma in the absence of hepatotoxicity.
Oxaprozin-Induced Symptomatic Hepatotoxicity
Authors: Kethu Sripathi R , Rukkannagari Sireesha , Lansford Charles L
Published: March 2004

OBJECTIVE:

To describe a case of symptomatic hepatotoxicity attributed to oxaprozin use.

CASE SUMMARY:

A 41-year-old white woman was admitted to the hospital with malaise, anorexia, and right upper quadrant pain. The patient was found to have severe jaundice with liver enzyme elevation. Laboratory test results for potential etiologies were negative, except for the use of oxaprozin for the preceding six weeks. Diagnosis of drug-induced hepatotoxicity was made by liver biopsy. The patient's symptoms resolved and liver enzymes normalized after oxaprozin was discontinued.

DISCUSSION:

Symptomatic hepatic effects attributable to most nonsteroidal antiinflammatory drugs (NSAIDs) are rare and usually mild. Oxaprozin has been shown to cause mild elevation of liver enzymes in clinical studies. This is the second reported case of presumed oxaprozin-induced icteric hepatitis. The mechanism of oxaprozin-induced hepatotoxicity is unclear, but is thought to be due to metabolic idiosyncrasy. Most NSAID reactions are hepatocellular and occur because of individual susceptibility (idiosyncrasy). In general, people aged >40 years and women are more predisposed to NSAID-induced liver injury.

CONCLUSIONS:

Although this toxicity is rare, clinicians should be aware of the potential for oxaprozin to cause hepatotoxicity and use caution when prescribing this medication. This case also stresses the importance of careful inquiry regarding drug or toxin exposure in cases of unexplained hepatitis.
Impact of Osteoarthritis and Analgesic Treatment on Quality of Life of an Elderly Population
Authors: Briggs Andrea , Scott Eileen , Steele Keith
Published: March 2004

OBJECTIVE:

To determine the quality of life of elderly patients with osteoarthritis (OA) compared with that of their peers with no chronic illnesses and to investigate the associations between analgesic use and quality of life.

SUBJECTS:

Patients >65 years of age with OA taking analgesics with (n = 33) and without (n = 26) comorbidities, and control patients with no chronic illness and not taking analgesics (n = 37).

METHODS:

Quality of life was assessed by the SF-36 and level of pain was measured by a visual analog scale. Multiple regression analysis was used to determine the medication characteristics and additional patient factors significantly associated with SF-36 scores.

RESULTS:

OA patients had significantly (p < 0.05) lower scores than control patients in all quality-of-life domains. OA patient scores were lowest for the domains of role-physical, bodily pain, and physical functioning. OA patients with comorbidities also had poorer general and mental health. Pain- and analgesic-related factors were significantly (p < 0.05) associated with physical health status, reduced vitality, general health, and social functioning. A better quality of life was associated with noncompliance, fewer visits to the physician, and taking oral nonsteroidal antiinflammatory agents. Presence of adverse drug reactions and sleep disturbance did not influence SF-36 scores significantly.

CONCLUSIONS:

Quality of life of elderly OA patients with and without additional comorbidities was significantly poorer than that of their healthy peers, particularly in the domains associated with physical status, but also affecting vitality, social functioning, and general health. Level of pain suffered and perceived effectiveness of analgesic medication in pain control were important factors associated with quality of life.
The Cyclooxygenase-2 Inhibitors: Safety and Effectiveness
Authors: Kaplan-Machlis Barbara , Klostermeyer Barbara Storyk
Published: March 2004

OBJECTIVE:

To review the development of cyclooxygenase-2 (COX-2) inhibitors and discuss specific agents that are currently under investigation or have been marketed.

DATA SOURCES:

Primary literature on selective COX inhibitors was identified from a comprehensive MEDLINE, English-literature search from January 1966 through September 1998, with additional studies selected by review of the references. Abstracts from recent meetings and package insert literature from approved agents were also used as source material. Indexing terms included COX-2 inhibitors, meloxicam, celecoxib, rofecoxib, flosulide, SC-58635, and MK-966.

STUDY SELECTION:

Human clinical, pharmacokinetic, and dose-ranging trials performed in Europe and the US and randomized comparative trials were reviewed.

DATA SYNTHESIS:

With the discovery of at least two COX isoforms, a better understanding of the mechanism of action and gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs) has been realized. While COX-1 is involved in physiologic maintenance, COX-2 seems to be involved in inflammation, mitogenesis, and specialized signal transductions. Selective COX-2 inhibitors may allow maximum antiinflammatory activity while improving the safety profile associated with NSAID therapy. Celecoxib and rofecoxib have been approved by the Food and Drug Administration for the treatment of osteo- and rheumatoid arthritis; meloxicam is undergoing Phase III clinical trials. Preliminary data indicate that the selective COX-2 inhibitors provide analgesic and antiinflammatory efficacy comparable with older NSAIDs, with fewer adverse gastrointestinal effects.

CONCLUSIONS:

Specific COX-2 inhibitors offer promising benefits over older NSAIDs with regard to gastrointestinal safety while maintaining analgesic and antiinflammatory efficacy. Further study is required to determine long-term efficacy and safety in clinical use.