bluuebunny/crossref_metadata_2025_split huggingface dataset:
Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes Part I: Antiepileptic Drugs, Contraceptives, Smoking, and Folate
Authors: Lewis Dale P , Van Dyke Don C , Stumbo Phyllis J , Berg Mary J 
Published: March 2004

OBJECTIVE: Part I of this review examines the relationship between antiepileptic drugs (AEDs) and pregnancy outcomes. Drug-induced folate deficiency and the role of AED metabolism are emphasized. Part II will discuss periconceptional folate supplementation for prevention of birth defects. Part III will discuss the mechanism of folate's protective effect, therapeutic recommendations, compliance, and cost. DATA SOURCES: A MEDLINE search was conducted for journal articles published through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included phenytoin, carbamazepine, phenobarbital, primidone, valproic acid, oral contraceptives, clomiphene, drug-induced abnormalities, spina bifida, anencephaly, neural tube defect, folate, folic acid, and folic acid deficiency. STUDY SELECTION: Relevant animal and human studies examining the effects of AEDs, smoking, and oral contraceptives on folate status and pregnancy outcome are reviewed. DATA EXTRACTION: Studies and case reports were interpreted. Data extracted included dosing, serum and red blood cell folate concentrations, teratogenicity of anticonvulsant medications, metabolism of AEDs and folate, and genetic susceptibility to AED-induced teratogenicity. DATA SYNTHESIS: Low serum and red blood cell folate concentrations are associated with adverse pregnancy outcomes. Decreases in serum folate are seen with AEDs, oral contraceptives, and smoking. Since similar birth defects are observed with multiple AEDs, metabolism of aromatic AEDs to epoxide metabolites and genetic factors may play a role in teratogenesis. CONCLUSIONS: Adequate prepregnancy planning is essential for women who have epilepsy. Women receiving folate-lowering drugs may be at increased risk of adverse pregnancy outcomes. Therefore, epileptic women contemplating pregnancy should be treated with the minimum number of folate-lowering drugs possible and receive folic acid supplementation.
Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes Part II: Improvement with Folic Acid
Authors: Lewis Dale P , Van Dyke Don C , Stumbo Phyllis J , Berg Mary J 
Published: March 2004

OBJECTIVE: To provide a comprehensive review of periconceptional folic acid supplementation and factors affecting folate supplementation trials. DATA SOURCES: A MEDLINE search was conducted through December 1997. Additional sources were obtained from Current Contents and citations from the references obtained. Search terms included folate, folic acid, neural tube defect, spina bifida, and anencephaly. STUDY SELECTION: Relevant animal and human studies examining the effects of folate were reviewed. DATA EXTRACTION: Data collected included: type of study, folate dosing, dietary folate intake, serum and red blood cell folate concentrations, type of defect(s) studied, vitamin usage, parental risk factors, factors affecting trial results. DATA SYNTHESIS: Nine key factors have been identified that affect outcomes of folic acid supplementation trials. Daily doses of 0.8 mg decreased the occurrence and doses of 4 mg decreased the recurrence of neural tube defects in randomized clinical trials. Since lower folic acid doses were effective in nonrandomized trials, research is needed to determine the lowest effective dosage. Other benefits involving pregnancy outcome are suggested. CONCLUSIONS: Women of childbearing age should take a daily folic acid supplement to reduce the risk of pregnancies resulting in infants with a neural tube defect and other potential adverse pregnancy outcomes. Further health benefits from folic acid supplementation are reviewed in Part III of this series.
Cutaneous Ulceration: An Unusual Sign of Methotrexate Toxicity — First Report in a Patient without Psoriasis
Authors: Ben-Amitai Dan , Hodak Emmilia , David Michael 
Published: March 2004

OBJECTIVE: To describe a case of skin ulcer related to methotrexate toxicity. CASE SUMMARY: A 67-year-old white man with seronegative arthralgia developed recurrent skin ulcer concurrent with 3-year treatment with methotrexate 5 mg daily. The skin ulcer resolved on discontinuation of methotrexate. DISCUSSION: To the best of our knowledge, this is the first reported case of skin ulcer believed to be induced by methotrexate in a patient without psoriasis. CONCLUSIONS: Skin ulceration should be added to the list of possible toxic adverse effects of methotrexate, not only in psoriatic patients but also in those without psoriasis.
Interaction between Fenofibrate and Warfarin
Authors: Ascah Kathyrn J , Rock Gail A , Wells Philip S 
Published: March 2004

OBJECTIVE: To determine whether the potentiation of warfarin's anticoagulation effect, which occurred in two patients, was due to an interaction with fenofibrate. CASE SUMMARY: Two patients developed significant potentiation of the anticoagulant effect of warfarin while receiving fenofibrate. In one patient we followed published guidelines to test the potential interaction, including rechallenge twice, and measurements of factors II, V, and VII and liver enzymes to ensure the authenticity of the interaction. We confirmed the interaction by noting that the international normalized ratio (INR) increased with rechallenge, the clotting factor concentrations decreased in concert with the INR, and no other laboratory or clinical factors accounted for this potentiation of the oral anticoagulant affect DISCUSSION: We previously developed criteria specifically for determining the strength of inferred causation in reports of drug interactions with oral anticoagulants; these criteria were adapted from previously described principles of causality assessment. Our observations in two patients suggest a “highly probable” potentiating interaction between fenofibrate and warfarin. Our data do not allow us to draw definitive conclusions on a mechanism of interaction, but fenofibrate is an oral antilipemic agent, similar to clofibrate, that has been described as potentiating oral anticoagulants by affecting coagulation factor synthesis, likely by altering receptor synthesis. Our finding of lower concentrations of coagulation factors suggests a similar mechanism for fenofibrate. Recent data suggest that lipid lowering is effective for primary and secondary prevention of cardiac events. One might therefore expect to see an increase in the use of the various lipid-lowering agents in patients who receive long-term anticoagulation. Our results indicate that the potential for an exaggerated anticoagulant effect occurs within 5–10 days in patients treated with fenofibrate who are receiving long-term anticoagulation with warfarin. CONCLUSIONS: Fenofibrate potentiates the effect of warfarin. Serial monitoring of the INR, at least three times per week, is therefore strongly recommended when initiating fenofibrate therapy in patients receiving warfarin.
Evidence-Based Pharmacotherapy: Review of Basic Concepts and Applications in Clinical Practice
Authors: Etminan Mahyar , Wright James M , Carleton Bruce C 
Published: March 2004

OBJECTIVE: To introduce concepts that may assist pharmacists in the use and application of scientific evidence in clinical practice. These concepts are followed by examples of clinical trials as well as case scenarios that guide the reader through solving clinical problems using the tools discussed in the article. BACKGROUND: The introduction of evidence-based practice in the 1990s has had a positive impact on the practices of medicine and pharmacy. Part of this impact has been in the area of drug therapy. Although much literature has been published on the principles of evidence-based practice in the past few years, most of this material was intended for practicing physicians. We are not aware of any articles on the use of the evidence-based principles intended for clinical pharmacists. We are also aware that discussing all of these principles is an enormous task and thus beyond the scope of this article. Therefore, we focused this discussion on a brief summary of different study designs, factors affecting the strength of scientific evidence, and interpretation of the data. An approach in the use of these concepts is discussed through the use of case scenarios. RECOMMENDATIONS: Clinical pharmacists must use concepts in evidence-based practice when making pharmacotherapeutic decisions.
Epoprostenol in Primary Pulmonary Hypertension
Authors: Herner Sheryl J , Mauro Laurie S 
Published: March 2004

OBJECTIVE: To review briefly the epidemiology, pathophysiology, and current treatment of primary pulmonary hypertension (PPH) and review the available clinical data on epoprostenol in PPH. DATA SOURCES: A MEDLINE search (January 1966–August 1998) was used to identify case reports and clinical studies pertaining to epoprostenol in PPH. Bibliographic lists were also used. STUDY SELECTION: All English-language clinical studies of epoprostenol in PPH were included. Incomplete study descriptions (abstracts) were not included. DATA EXTRACTION: Study design, population, methods, clinical outcomes, and adverse effects were evaluated. DATA SYNTHESIS: PPH is a relatively rare disease that results in symptoms of congestive heart failure and has a five-year survival rate of 34%. Therapy has consisted of vasodilators, anticoagulation, oxygen, and ultimately lung transplantation. Epoprostenol, which has recently become available as an integral pharmacotherapeutic option, has been shown to improve hemodynamic parameters such as cardiac output, pulmonary artery pressure, and pulmonary vascular resistance. It has been shown to improve exercise parameters, New York Heart Association (NYHA) functional class, and survival. Epoprostenol is indicated for patients with severe disease (NYHA class III or IV) who do not respond to acute vasodilator challenge or chronic calcium-channel blocker therapy. Its chronic administration is challenging as it requires continuous infusion via central venous catheter and a special infusion pump. Administration is further complicated by the 48-hour expiration of reconstituted epoprostenol and the need to refrigerate the reconstituted drug. CONCLUSIONS: Epoprostenol improves hemodynamics and clinical outcome in patients with severe PPH. Epoprostenol therapy requires intensive patient education and medical monitoring, but it can improve well-being and delay the need for lung transplantation.
Torsade De Pointes Resulting from the Addition of Droperidol to an Existing Cytochrome P450 Drug Interaction
Authors: Michalets Elizabeth Landrum , Smith Laura K , Van Tassel Eric D 
Published: March 2004

OBJECTIVE: To report a case of QT prolongation associated with concomitant cyclobenzaprine and fluoxetine administration followed by torsade de pointes potentiated by droperidol. CASE SUMMARY: A 59-year-old white woman who had been receiving long-term fluoxetine and cyclobenzaprine therapy was admitted for Achilles tendon repair. Baseline QTc was prolonged at 497 msec. Prior to surgery, the patient received droperidol, an agent known to prolong the QT interval. During surgery the patient developed torsade de pointes, which progressed into ventricular fibrillation. On postoperative day 1, after cyclobenzaprine discontinuation, the QTc decreased toward normal (440 msec). DISCUSSION: Cyclobenzaprine shares anticholinergic effects, tachycardia, and dysrhythmic potential with the tricyclic antidepressants (TCAs). Fluoxetine is a known inhibitor of the CYP2D6 isoenzyme (along with CYP3A4 and CYP2C) and has been shown to increase TCA serum concentrations. The combination of cyclobenzaprine and fluoxetine resulted in significant QT prolongation in our patient that progressed to torsade de pointes after preoperative droperidol administration. Resolution of QT abnormalities after cyclobenzaprine discontinuation provided further evidence of a drug-induced etiology. Other possible medical and drug-related causes of torsade de pointes are reviewed and ruled out. CONCLUSIONS: Clinicians should be aware of the dysrhythmic potential of cyclobenzaprine and fluoxetine, monitor for other cytochrome P450 inhibitors, and avoid concomitant drugs known to prolong the QT interval.
Pharmacokinetics of Anticancer Drugs in Cerebrospinal Fluid
Authors: Morikawa Norifumi , Mori Teruaki , Kawashima Hisanori , Takeyama Masaharu , Hori Shigeaki 
Published: March 2004

OBJECTIVE: To examine the pharmacokinetics of anticancer drugs in the cerebrospinal fluid (CSF) during chemotherapy by the lumbar– ventricular (LV) and ventricular–lumbar (VL) routes. CASE SUMMARY: A 69-year-old Japanese woman with disseminated glioblastoma received two LV and four VL courses of CSF perfusion chemotherapy with methotrexate, nimustine, and cytarabine hydrochloride. Samples of CSF from the ventricles and lumbar spinal canal were obtained via Ommaya reservoirs during one LV and one VL course. Drug concentrations in the CSF were measured by fluorescence polarization immunoassay or HPLC. RESULTS: During LV CSF perfusion, the highest CSF drug concentrations in both the ventricles and the lumbar spinal canal were observed at the end of perfusion. During treatment, the concentrations of all three drugs in the lumbar spinal canal were higher than those in the ventricles. The CSF AUC of methotrexate in the ventricles was 16.1% of that in the lumbar spinal canal. During VL CSF perfusion, the highest drug concentrations were also observed at the end of perfusion. The drug concentrations in the lumbar spinal canal were initially lower than those in the ventricles. However, the concentrations of methotrexate and cytarabine in the lumbar spinal canal exceeded those in the ventricles 3 hours after perfusion. The AUC of methotrexate in the lumbar spinal canal was 174.9% of that in the ventricles. CONCLUSIONS: The pharmacokinetics of anticancer drugs in ventricular CSF differ from those in lumbar CSF during LV and VL perfusion chemotherapy.
Using Literature in Health Care: Reflections on “The Yellow Wallpaper”
Authors: Frye Carla B 
Published: March 2004

OBJECTIVE: To discuss how literature can be used to educate healthcare practitioners and students about the patient's physical and emotional response to treatment. DATA SOURCES: A MEDLINE search (January 1975-November 1997) of English-language literature pertinent to using literature in health care was performed. Additional literature was obtained from a search of the New York University Web site on medicine and humanities, biographies of Charlotte Perkins Gilman, and a search of the MLA and INFOTRAC database. SELECTION AND DATA EXTRACTION: All articles and literature were considered for possible inclusion in this article. Pertinent information, as judged by the author, was selected for discussion. SUMMARY: Literature can pose a wealth of information to the healthcare professional. The short story “The Yellow Wallpaper” is analyzed in this article as one example of how literature portrays the patient's emotional response to disease. This short story describes a 19th-century woman's “descent into madness” and the ineffective treatment attempted by her well-meaning physician husband. The author, Charlotte Perkins Gilman, loosely based the story on her own experience with the respected physician, S Weir Mitchell and his famous rest cure. Some biographical information about Mitchell and Perkins is included, as well as a commentary on the treatment of depression in the 19th century. CONCLUSIONS: Short stories such as “The Yellow Wallpaper,” novels, and other short stories can help to remind the healthcare professional of the subjective nature of even our most proven therapies. As we strive to teach and deliver pharmaceutical care, we can use literature to help us understand the emotional impact of our drug therapies.
Cost-Minimization Analysis of Piperacillin/Tazobactam versus Imipenem/Cilastatin for the Treatment of Serious Infections: A Canadian Hospital Perspective
Authors: Marra Fawziah O , Frighetto Luciana O , Marra Carlo A , Sleigh Kenna M , Stiver H Grant , Bryce Elizabeth A , Reynolds Robert P , Jewesson Peter J 
Published: March 2004

BACKGROUND: In 1998 we reported the first Canadian double-blind, randomized, clinical trial involving a comparison of piperacillin/tazobactam (P/T) with imipenem/cilastatin (I/C). The present study was conducted to determine the feasibility of replacing I/C at our institution. OBJECTIVE: To describe the outcome of a pharmacoeconomic analysis of the clinical trial from the perspective of a tertiary acutecare institution. METHODS: A total of 150 consenting adults originally prescribed I/C were randomly assigned to receive either P/T 4.5 g iv (n = 75) or I/C 500 mg iv (n = 75) every six hours. Actual direct medical resources used in relation to the treatment of bacterial infections were prospectively assessed during a clinical trial; these included cost of study and ancillary antibiotics, hospitalization, diagnostic testing (radiology, laboratory assessments), and labor, as well as treatment of adverse drug reactions, antibiotic failures, and superinfections. RESULTS: While costs for successful treatment courses were similar across treatment arms, hospitalization costs for treatment course failures were higher for P/T recipients. Direct medical costs for treatment courses associated with a superinfection were also higher in the P/T arm. Overall costs for treatment failures with either study drug were at least twofold those observed for successful treatment courses. Mean total management cost per patient in the P/T group was $15 211 ($ CDN throughout) (95% CI $11 429 to $18 993), compared with $14 232 (95% CI $11 421 to $17 043) in the I/C group (p = 0.32), resulting in a mean cost difference of $979. Sensitivity analyses revealed that the superiority of I/C over P/T for successful treatment of serious infections was sensitive to changes in the cost of hospitalization and drug efficacy for either drug. CONCLUSIONS: Based on the results of the clinical trial, P/T and I/C offer similar clinical, microbiologic, and toxicity outcomes in hospitalized patients with serious infections. Under base–case conditions, our pharmacoeconomic analysis showed that I/C was a cost-effective alternative to P/T at the dosage regimens studied. However, this finding was sensitive to plausible changes in both clinical and economic parameters.
Management of End-Stage Renal Disease in Children
Authors: Smith Pamela S 
Published: March 2004

OBJECTIVE: To review the medical literature on management of end-stage renal disease (ESRD) and its complications in the pediatric patient. DATA SOURCES AND STUDY SELECTION: MEDLINE searches (1970–1997) of the English-language literature. Clinical trials and reviews of drug therapy management were included, and bibliographies were reviewed for relevant articles. DATA SYNTHESIS: Principles of renal replacement therapy in children have been expanded to include maintenance of fluid and electrolyte balance and to manage the complications of ESRD in children. Types of renal replacement and their complications are reviewed. Complications of ESRD are reviewed with emphasis on drug therapy management of anemia of chronic renal failure, growth retardation, and hypertension. A discussion of the use of vitamins and supplements to maintain bone and mineral homeostasis is provided, and specific recommendations for vaccination of children with ESRD are given. CONCLUSIONS: Children with end-stage renal failure present a unique challenge to the pharmacist. Renal replacement therapy for children with ESRD involves some form of dialysis and an intensive medication regimen. Complications must be treated with appropriate drug therapy. Drug therapy must be monitored closely for dosage adjustment, clinical response, drug interactions, and toxicity. Patients and families must receive continuous education and follow-up to encourage compliance. The pharmacist must work closely with the healthcare team to optimize drug therapy and improve patient education and compliance.
Ambulatory Management of Chemotherapy-Induced Fever and Neutropenia in Adult Cancer Patients
Authors: Davis Diane D , Raebel Marsha A 
Published: March 2004

OBJECTIVE: To review the literature on the management of low-risk adults with chemotherapy-induced fever and neutropenia (CIFN). Included in the review are methods to identify these patients, management options, and economic impact associated with nontraditional treatment options. DATA SOURCES: A MEDLINE and bibliographic search (January 1966–December 1997) for all English-language studies evaluating the identification and treatment of adult, low-risk CIFN patients was completed. Reference lists from identified articles also served as literature sources. STUDY SELECTION AND DATA EXTRACTION: All human studies identified from the data sources were evaluated. Pertinent information, excluding pediatric studies, was selected and critically evaluated for discussion. DATA SYNTHESIS: Alterations in prominent bacterial isolates in CIFN, newer antibiotic choices, enhanced focus on patient comfort, and cost-containment directives have promoted recent research identifying adult cancer patients with low-risk CIFN. Using this information to select low-risk CIFN patients, several investigators have completed trials using antibiotic therapy applicable to the ambulatory setting. Additionally, some investigators have included the use of an oral outpatient antibiotic regimen. Limited data indicate that this approach is a reasonable treatment option for selected patients. CONCLUSIONS: A subset of adult patients with CIFN are at low risk for serious morbidity and mortality when treated with broad-spectrum antibiotics in the ambulatory setting. Managing these patients with this approach requires close patient selection, intense follow-up, data collection, and ongoing evaluation to determine efficacy and patient safety. Currently, ambulatory treatment with oral antibiotics for CIFN is not considered standard of care. Further studies of larger size designed to confirm low-risk patient characteristics and optimal antibiotic selection are required.
Isoniazid-Induced Psychosis
Authors: Alao Adekola O , Yolles Jennifer C 
Published: March 2004

OBJECTIVE: To report a suspected case of isoniazid-induced psychosis in a 31-year-old woman. CASE SUMMARY: A 31-year-old white woman without a prior psychiatric history presented with psychotic symptoms suspected to be related to prophylactic treatment with isoniazid after she tested positive to a tuberculin (purified protein derivative) test. The psychotic symptoms resolved partially after isoniazid was discontinued and completely after treatment with olanzapine was begun. The patient remained symptom-free 11 months after discharge from the hospital. DISCUSSION: Cases of isoniazid-related psychiatric disorders reported in the literature include psychosis, obsessive–compulsive neurosis, and mania. With the increasing prevalence of tuberculosis in the US, more people are expected to receive treatment for tuberculosis. Pyridoxine deficiency may play a role in the pathogenesis of isoniazid-induced psychosis. Such deficiency states may be detected indirectly by measuring urinary metabolites of tryptophan. CONCLUSIONS: Clinicians should be aware of this adverse effect of isoniazid and that it may present with a broad clinical picture.