bluuebunny/crossref_metadata_2025 huggingface dataset:
Thrombolytic Therapy: A Review of Its Use in Acute Myocardial Infarction
Authors: Bizjak Eric D , Mauro Vincent F
Published: March 2004

OBJECTIVE:

To review the literature on the use of thrombolytic agents in the pharmacotherapeutic management of acute myocardial infarction (AMI).

DATA SOURCE:

English-language clinical trials, reviews, and editorials derived from MEDLINE (January 1966–September 1997) and/or cross-referencing of selected articles.

STUDY SELECTION:

Articles that were selected best represent the clinical trials researching the role for thrombolytics in the therapy of AMI to improve morbidity and mortality.

DATA SYNTHESIS:

AMI is one of the leading causes of mortality in the US. Following supportive data that the most common cause of an AMI is an intracoronary thrombus, clinical investigation has demonstrated that intravenous thrombolytic agents improve survival rates in patients who experience an AMI. Several clinical trials have been conducted to determine whether one thrombolytic agent is superior to others with respect to improving mortality. At present, only the first Global Use of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries (GUSTO-I) trial has reported any statistically significant difference in mortality rate. In this trial, “front-loaded” alteplase induced a statistically significant (p < 0.001) 1% absolute reduction in 30-day and 1-year mortality compared with streptokinase. This has led to alteplase being the preferred thrombolytic at many US institutions. However, the results of GUSTO-I have been questioned by some on the basis of either study design or clinical significance.

CONCLUSIONS:

Thrombolytic agents have secured a place in the treatment of AMI due to their well-proven reduction in mortality rates. In general, comparative trials have demonstrated minimal differences in efficacy among these agents. Probably just as important as choosing which thrombolytic agent to use is ensuring that a patient experiencing an AMI is administered thrombolytic therapy unless a contraindication to receive such therapy exists in the patient and/or the patient is a candidate to receive an emergent intracoronary procedure. Trials also indicate that the sooner thrombolytics can be administered, the greater the benefit to the patient.
State Pharmacy Regulators' Opinions on Regulating Pharmaceutical Care Outcomes
Authors: Nau David P , Brushwood David B
Published: March 2004

OBJECTIVE:

To examine the opinions of state pharmacy regulators regarding responsibility for the outcomes of drug therapy, and approaches that might be taken to regulate for pharmaceutical care outcomes.

DESIGN:

Surveys were sent to the executive secretaries of state pharmacy boards. The executive secretaries were encouraged to seek input from other board staff and board members in formulating a response. Reminder postcards were sent to all subjects 1 week after the initial mailing.

MEASURES:

The survey instrument was divided into three sections. The first section identified 10 approaches that state boards could use to regulate for outcomes and asked subjects to indicate the utility of each. The second and third sections asked the subjects to determine the extent to which pharmacies and pharmacists, respectively, should be responsible for outcomes potentially related to pharmaceutical care.

RESULTS:

Forty-one usable surveys were returned. All approaches to regulation were viewed as potentially useful, and scores for three approaches indicated that they would be consistently helpful for effective regulation of pharmaceutical care outcomes. The pharmacy was viewed as solely responsible for poor outcomes related to systems deficiencies, a lack of self-assessment, inadequate references, equipment, and technician support. Pharmacists were assigned greatest responsibility for outcomes related to prescription filling, and less responsibility for outcomes related to patient care. However, there was considerable variation in responses to many of the items, reflecting the diverse opinions of pharmacy regulators on these issues.

CONCLUSIONS:

While pharmacy regulators appear open to some outcomes-oriented approaches to regulation, there is no clear consensus on responsibility for pharmaceutical care outcomes.
Glimepiride: Role of a New Sulfonylurea in the Treatment of Type 2 Diabetes Mellitus
Authors: Campbell R Keith
Published: March 2004

OBJECTIVE:

To review the clinical pharmacology data regarding the sulfonylurea glimepiride, and to summarize the clinical trials of glimepiride efficacy and safety alone and in combination with insulin for the treatment of type 2 diabetes mellitus.

DATA SOURCES:

A MEDLINE database search (English language, January 1985–April 1997) was performed to identify relevant published articles, including reviews and abstracts; the manufacturer (Hoechst Marion Roussel, Kansas City, MO) provided unpublished data.

STUDY SELECTION:

Pharmacology information was taken from representative original research articles. Eight clinical studies were selected for analysis on the basis of large enrollment, appropriate study design, and publication of results.

DATA EXTRACTION:

All clinical trials, published and unpublished, were reviewed.

DATA SYNTHESIS:

Glimepiride is a sulfonylurea that is pharmacologically distinct from other sulfonylureas because of differences in receptor-binding properties and potentially selective effects on ATP-sensitive K+ channels. The pharmacokinetic and pharmacodynamic profile of glimepiride makes it suitable for once-daily dosing. The safety and efficacy of glimepiride have been confirmed in studies involving more than 5000 patients with type 2 diabetes. In one study, once-daily doses of 1–8 mg reduced fasting plasma glucose from baseline by 43–74 mg/dL more than did placebo (p < 0.001), and hemoglobin (Hb) A1C values decreased by 1.2–1.9% more than with placebo (p < 0.001). Two-thirds of patients achieved tight control (i.e., HbA1C ≤ 7.2%). Glimepiride was as effective as second-generation sulfonylureas. The most common adverse events were dizziness and headache, but no single adverse event occurred in more than 2% of patients.

CONCLUSIONS:

Glimepiride appears to be a useful option for patients with type 2 diabetes not controlled by diet and exercise and who want to achieve tight glucose control. Glimepiride can be used alone, in combination with other antihyperglycemic agents, or in patients with secondary sulfonylurea failure, as an adjunct to insulin therapy.
Role of Propofol in Refractory Status Epilepticus
Authors: Brown Leigh Anne , Levin Gary M
Published: March 2004

OBJECTIVE:

To provide a review of the proposed mechanism of action, clinical efficacy, adverse effects, and therapeutic considerations associated with the use of propofol in the management of patients with refractory status epilepticus.

DATA SOURCES:

A MEDLINE database (January 1966–April 1998) was searched for literature pertaining to status epilepticus and propofol. Additional literature was obtained from the references of selected articles identified in the search. Information from all articles published in English was considered for inclusion in the article.

DATA SYNTHESIS:

Propofol is a unique, nonbarbiturate, anesthetic agent possessing anticonvulsant properties, although the exact anticonvulsant mechanism is unknown. Several case reports and two small, open, uncontrolled studies have described the efficacy of propofol in refractory status epilepticus. Most of these clinical reports discuss the utility of propofol after traditional treatment regimens have failed or are not tolerated. Initiation of propofol usually resulted in termination of seizure activity and/or electroencephalographic burst suppression within seconds that was sustained during the drug's use. Additionally, propofol was well tolerated. Advantages of propofol compared with traditional barbiturate anesthetic agents include better cardiovascular tolerability and a more favorable pharmacokinetic profile, allowing for rapid assessment of efficacy and neurologic assessment upon drug withdrawal. Propofol has been associated with a variety of neuroexcitatory adverse events such as opisthotonos, muscle rigidity, and choreoathetoid movements. Additionally, although the data are inconclusive, propofol has also been reported to cause seizures.

CONCLUSIONS:

Propofol has shown promising results in the management of refractory status epilepticus when traditional therapies have failed or were not tolerated; however, controlled clinical trials are needed to better assess the comparative efficacy, neurologic adverse effects, and clinical outcome to better define its role in refractory status epilepticus.
A Critical Review of Selected Pharmacoeconomic Analyses of Antidepressant Therapy
Authors: Conner Therese M , Crismon M Lynn , Still Daniel J
Published: March 2004

OBJECTIVE:

To evaluate the pharmacoeconomic benefits of treating depression and compare the available therapies by reviewing the current literature on economic analyses of depression.

DATA SOURCES:

A MEDLINE search (January 1966–June 1998) of English-language literature relating to economic analyses of depression was conducted. Key search terms included depression, antidepressant, economics, pharmacoeconomics, outcomes, and costs. Additional literature was collected from reference lists of articles found through the MEDLINE search.

STUDY SELECTION AND DATA EXTRACTION:

A MEDLINE search was performed using the above key words. Search and evaluation were limited to pharmacoeconomic evaluations of major depressive disorder. All available studies were considered for inclusion in the review.

DATA SYNTHESIS:

The advent of newer, brand-name antidepressants as well as increased concern regarding healthcare costs has raised interest in the costs associated with treating depression. Although the selective serotonin-reuptake inhibitors (SSRIs) and other newer antidepressants have higher acquisition costs, both modeling and naturalistic studies have shown that the total cost of treating depression is no higher with SSRIs than with the tricyclic antidepressants. These differences are primarily due to increased patient adherence with the newer agents and lower costs secondary to physician visits, laboratory monitoring, and hospitalization.

CONCLUSIONS:

The economic aspects of treating depression are becoming more frequently evaluated as newer antidepressant medications become available and as healthcare entities attempt to address increasing costs. In general, most pharmacoeconomic research on depression has been conducted on one of the SSRIs in comparison with various tricyclic antidepressants. These studies frequently use simulation techniques and rely heavily on data from clinical trials. Few studies have compared the newer antidepressants, and no clear evidence exists that any one of these agents is more cost-effective than others. Even fewer studies have addressed the pharmacoeconomics of medication management of depression in various healthcare environments (e.g., public mental health care vs. private psychiatry vs. primary care).
Nicotine Replacement Therapy
Authors: Thompson Gwendolyn H , Hunter Dee A
Published: March 2004

OBJECTIVE:

To review the literature on nicotine dependence, nicotine pharmacology, health consequences associated with the use of nicotine, and nicotine replacement therapies used to aid smokers who are nicotine dependent.

DATA SOURCES:

A review of articles, book bibliographies, and published studies identified by a search of the MEDLINE database from 1982 to 1996 on nicotine dependence, nicotine addiction, nicotine withdrawal, smoking, smoking cessation, smoking intervention, nicotine pharmacology, nicotine pharmacokinetics, nicotine pharmacodynamics, and nicotine replacement therapies.

STUDY SELECTION AND DATA EXTRACTION:

Inclusion criteria were published randomized, double-blind trials of at least 12 weeks' duration, meta-analyses, and panel consensus guidelines.

DATA SYNTHESIS:

Cigarette smoking and tobacco use have met the surgeon general's primary criteria as well as additional criteria for drug dependence. Drug dependence requires that the drug produce psychoactive effects. Nicotine has been identified as the cause of tobacco dependence. First, nicotine provides positive reinforcement by stimulating nicotinic receptors to promote high self-administration rates. Second, nicotine causes a negative reinforcement in the form of withdrawal symptoms when nicotine is withheld after chronic use. Nicotine replacement therapy reduces the severity of withdrawal symptoms in smokers abstaining from tobacco. Nicotine replacement therapy allows the smoker to focus on psychosocial aspects of tobacco abstinence while receiving relief from withdrawal symptoms. The long-term effectiveness and health benefits of nicotine replacement therapy coupled with nonpharmacologic approaches have been clearly established. Smoking cessation has received wide attention from the public and medical communities; it is complex and has several interwoven factors to be considered. The psychological, behavioral, and physical components have to be understood before designing a treatment plan. The most successful approaches to smoking cessation involve multicomponent, multisession behavioral treatment programs as a foundation coupled with pharmacologic intervention. Pharmacists can play a key role in initiating behavior change and ensuring the safe and proper use of nicotine replacement in order to produce the desired outcome.

CONCLUSIONS:

The optimum choice in nicotine replacement depends on the individual's needs and coping abilities. Individualized nicotine replacement coupled with nonpharmacologic interventions produces the highest rate of success for abstinence from nicotine.
Seizure Associated with Olanzapine
Authors: Lee Jerry W , Crismon M Lynn , Dorson Peter G
Published: March 2004

OBJECTIVE:

To report a case of seizures in a patient who started receiving olanzapine, and to review seizure risk associated with antipsychotic use.

CASE SUMMARY:

A 31-year-old African-American woman with multiple psychiatric and medical disorders, including generalized seizure disorder, experienced seizure activity when switched from haloperidol to olanzapine. Olanzapine was discontinued, haloperidol was quickly titrated to the previous dose, and the patient was started on oral phenytoin with no further seizure activity noted. The patient remained seizure free and phenytoin was discontinued without complications.

DISCUSSION:

Determining causality in this case is complicated by the number of confounding factors that may have contributed to the occurrence of seizures in this patient. These factors include: (1) diagnosis of generalized seizure disorder, (2) diagnosis of organic mental disorder, (3) concurrent pharmacotherapy with medications implicated in lowering the seizure threshold, and (4) abrupt change in pharmacotherapy. The likelihood that a significant drug interaction precipitated seizure activity is doubtful.

CONCLUSIONS:

Considering all factors related to causality, the likelihood that olanzapine was responsible for precipitating seizure activity in this patient was judged possible. Although premarketing studies have indicated that olanzapine may be associated with minimal seizure liability, this case serves as a reminder that postmarketing surveillance of newly released medications is essential.
ACE Inhibitor—Versus Angiotensin II Blocker–Induced Cough and Angioedema
Authors: Pylypchuk George B
Published: March 2004

OBJECTIVE:

To compare the tolerability of angiotensin-converting enzyme (ACE) inhibitors with that of angiotensin II (AII)-receptor blockers and the incidence of cough and angioedema associated with their use through review of published data.

DATA SOURCES:

References were identified through a MEDLINE search of articles published between January 1975 and April 1997. Bibliographies of pertinent references were also reviewed.

RESULTS:

Results of placebo-controlled and comparative trials of the AII blockers demonstrate that they are at least as effective as ACE inhibitors for hypertension, but exhibit an incidence of cough and absent or rare angioedema like that of placebo.

CONCLUSIONS:

In the 10 comparative trials described, all reported a lower incidence of cough with AII blockers than with ACE inhibitors. Angioedema was not reported in the comparative trials described.
Compatibility and Stability of Paclitaxel Combined with Doxorubicin Hydrochloride in Infusion Solutions
Authors: Trissel Lawrence A , Xu Quanyun A , Gilbert Doward L
Published: March 2004

OBJECTIVE:

To evaluate the physical compatibility and chemical stability of paclitaxel at concentrations of 300 and 1200 μg/mL with doxorubicin hydrochloride 200 μg/mL in NaCl 0.9% injection and dextrose 5% injection over 7 days at 4, 23, and 32 °C.

DESIGN:

The test samples were prepared in polyolefin bags of the infusion solutions at the required drug concentrations. Evaluations were performed initially and after 4 hours, and 1, 3, 5, and 7 days of storage at 4, 23, and 32 °C for physical and chemical stability. Physical stability was assessed by using visual observation in normal fluorescent light and a high-intensity monodirectional light beam. In addition, turbidity and particle content were measured electronically. Chemical stability of the two drugs was evaluated by using two stability-indicating HPLC analytic techniques.

RESULTS:

All samples were physically stable through 1 day. However, microcrystalline precipitation of paclitaxel occurred within 3 days in some samples and within 5 days in all samples. Paclitaxel concentrations remained at more than 97% in all samples throughout the study. Doxorubicin hydrochloride also was stable throughout the study period, remaining above 90% in all samples at all storage temperatures.

CONCLUSIONS:

Admixtures of paclitaxel 300 and 1200 μg/mL with doxorubicin hydrochloride are limited in their utility time by paclitaxel microcrystalline precipitation. All combinations were physically and chemically stable for at least 24 hours at 4, 23, and 32 °C.
Novel Antipsychotics and Patient Care in State Hospitals
Authors: Buckley Peter F
Published: March 2004

OBJECTIVE:

To review and highlight the opportunities and challenges of pharmacologic advances in the use of antipsychotics for the state hospital system.

METHODS:

A critical review was performed of studies published either as articles or abstracts, on the use of novel antipsychotics, particularly as they relate to the patient population within the state mental hospital system.

FINDINGS:

The recent availability of new antipsychotic medications within state facilities has resulted in more progressive treatment, reduced recidivism (and consequently cost savings), and preliminary evidence of preferential and superior treatment response in specific patient subgroups (e.g., those with aggression). At the same time, inpatient pharmacy budget increases and uncertainty in guiding the use of novel antipsychotics have influenced the availability of these agents in state hospitals.

CONCLUSIONS:

State hospital services have, by and large, embraced the developments in pharmacotherapy of schizophrenia. Optimal use of these new agents in this population requires additional information on their relative efficacy in specific patient subgroups.
Successful Vancomycin Desensitization in a Patient with End-Stage Renal Disease and Anaphylactic Shock to Vancomycin
Authors: Sorensen Suellyn J , Wise Steven L , Al-Tawfiq Jaffar A , Robb Jon L , Cushing Herbert E
Published: March 2004

OBJECTIVE:

To report successful desensitization in a patient with a history of end-stage renal disease (ESRD) and anaphylactic shock after receiving vancomycin.

CASE SUMMARY:

A 47-year-old white woman with a history of ESRD was admitted to the hospital reporting persistent nausea, vomiting, and diffuse abdominal pain. She had developed anaphylactic shock after exposure to vancomycin 3 years prior to this hospitalization. The patient's hospital course was complicated by septic shock and positive blood cultures for methicillin-resistant Staphylococcus epidermidis. The patient tolerated vancomycin desensitization and received intravenous vancomycin 100 mg/d for 21 days.

DISCUSSION:

The desensitization protocol used in this report allows for gradual increases in vancomycin serum concentrations, avoiding peak and trough concentrations that occur with intravenous boluses. Maintaining the desensitized state is dependent on the continuous presence of the antigen with a return of clinical sensitivity after drug discontinuation. The vancomycin desensitization protocol and subsequent dosing strategy was used to ensure the continuous presence of vancomycin at steady-state concentrations to prevent the return of anaphylactic sensitivity.

CONCLUSIONS:

Desensitization was successful in a patient with ESRD and history of anaphylactic shock to vancomycin.
The Medication Information Line for the Elderly: An 8-Year Cumulative Analysis
Authors: Grymonpre Ruby E , Steele John W
Published: March 2004

OBJECTIVE:

To present an 8-year (1985–1992) cumulative analysis of the 12 743 calls received by the Medication Information Line for the Elderly (MILE), a consumer-oriented drug information service.

DESIGN:

Data on all calls received by MILE were documented using a standard format. Certain calls were selected by the pharmacist for follow-up based on the nature and predicted severity of the inquiry.

SETTING:

MILE is located within the Faculty of Pharmacy of the University of Manitoba and staffed by experienced, practicing pharmacists. Calls were received from the elderly and their care providers. Calls were initially taken on a local Winnipeg line, although in 1987 a toll-free number was made available to rural Manitoba residents.

RESULTS:

The majority of the calls received by MILE were from women aged 65 years or older who accessed MILE on their own initiative. Ninety-one percent of the calls were rated as not serious. Only 6% of calls were from outside Winnipeg. Although 94% of the older consumers reported having a regular pharmacist, they commonly never thought of using their pharmacist for inquiries. The drugs cited most often by consumers, nurses, physicians, and dentists were the nonsteroidal antiinflammatory agents, cardiac drugs, diuretics, antihypertensives, benzodiazepines, and antidepressants. The types of inquiries most frequently involved adverse drug reactions, drug interactions, and therapeutic use. The drugs cited and inquiries made by pharmacist callers were more diverse than those of consumers and other healthcare professionals.

CONCLUSIONS:

Many older drug consumers have medication information needs that are not being met. Since a large proportion of the callers appeared to be self-motivated women, MILE may not be accessing all older consumers in need of information. This analysis also suggests that many older consumers are not aware that the pharmacist is available and capable of providing drug information.
Health Behaviors and Pharmacotherapy
Authors: Kehoe William A , Katz Roger C
Published: March 2004

OBJECTIVE:

To review factors related to health beliefs and behavior that affect treatment adherence, and to suggest behavioral strategies for improving adherence.

DATA SOURCES:

We conducted MEDLINE and PSYHLIT (January 1966–October 1997) searches of English-language literature pertaining to behavioral medicine and health behavior as they relate to treatment adherence. Additional articles from these sources and reference texts were identified.

DATA EXTRACTION:

All articles and chapters identified were considered. The most pertinent information, as judged by the authors, was selected for discussion.

DATA SYNTHESIS:

Health care is moving into an era of disease management, and practitioners will be called upon to help patients change health-related behaviors and to improve adherence to treatment. Fundamental to this new paradigm of practice is an understanding of behavior, its relationship to health, and methods by which it can be altered. Current concepts of health behavior have been heavily influenced by social learning theory, self-efficacy theory, and a biopsychosocial view of health and disease. The intent of this review is to provide clinicians with an overview of factors that affect health-related behaviors, as well as suggestions for helping patients to improve them. As illustrations, behavioral interventions used in patients with asthma are presented.

CONCLUSIONS:

Adherence to treatment recommendations depends on a complex interplay of many psychological variables. An understanding of these factors, and how behavioral techniques may be used, will help healthcare providers to assist patients in improving adherence.
Medication Bezoars: A Literature Review and Report of a Case
Authors: Taylor James R , Streetman Daniel S , Castle Sharon S
Published: March 2004

OBJECTIVE:

To describe a case of a medication bezoar and to review the clinical presentation, diagnosis, risk factors, pathogenesis, complications, and treatment of medication bezoars.

DATA SOURCES AND STUDY SELECTION:

A MEDLINE search (January 1966–December 1997) of the English-language literature pertaining to bezoars was performed. These articles were scanned, and literature specifically discussing medication bezoars was selected. Additionally, the reference sections of pertinent review and case reports were scanned for additional relevant literature.

DATA SYNTHESIS:

Bezoars are concretions of foreign material within the body. In the case of medication bezoars, these concretions occur within the digestive tract and are composed of medications and/or medication vehicles. Rarely, however, is bezoar formation solely due to a medication. In nearly all reported cases the patient had one or more significant risk factors that contributed to bezoar formation. The exact method by which medication bezoars form is dependent on the particular type or combination of medications involved. Bezoar formation may be associated with significant complications for the patient due to the presence of the bezoar and because of the effects of the medication within the bezoar. Treatment of medication bezoars depends largely on the location and the cause of the bezoar.

CONCLUSIONS:

Medication bezoars are a rare but potentially serious complication of medication use in certain patients. These patients often present with signs and symptoms consistent with an obstruction of the gastrointestinal tract and represent an even greater diagnostic challenge due to the rarity of this complication. These patients also face significant complications from both the bezoar and the medication within the bezoar. To date, treatment of medication bezoars involves mainly physical manipulation of the bezoar through lavage, endoscopic removal, or, in most cases, surgical removal.
Evaluating the Delivery of Nebulized and Metered-Dose Inhalers in an in vitro Infant Ventilator Lung Model
Authors: Avent Minyon L , Gal Peter , Ransom J Laurence , Brown Yvonne L , Hansen Charles J , Ricketts William A , Soza Felicia
Published: March 2004

OBJECTIVE:

To evaluate drug delivery to the lungs of nebulized and metered-dose inhalers (MDIs) in an in vitro infant lung model.

METHODS:

An in vitro lung model was modified to study drug delivery. A 1000 mL intravenous bag filled with 500 mL deionized water was attached to a 3.5 mm (12 cm length) endotracheal tube. An inline Marquest Whisper Jet infant circuit nebulizer system delivered 2.5 mg/3 mL albuterol sulfate inhalation solution (Ventolin nebules) at a flow rate of 5 L/min. An Aerochamber (Monaghan) was placed at the endotracheal tube for the delivery of the MDIs. Albuterol MDI (Ventolin) 10 inhalations and beclomethasone MDI (Beclovent) 20 inhalations were delivered. A Servo 900C (Siemens-Elma) was used at the following ventilator settings: positive inspiratory pressure 30 cm H2O), intermittent mandatory ventilation 40 breaths/min, positive end expiratory pressure 4 cm H2O, inspiratory time 0.4 sec. Each formulation was run at least 10 times and assayed in duplicate by HPLC. An unpaired Student's t-test was used to analyze the statistical significance of the data.

RESULTS:

There was a significantly greater percentage of drug delivery with MDI albuterol (1.96 ± 0.50) as compared with nebulized albuterol (1.26 ± 0.37) (p = 0.002) or beclomethasone diproprionate (0.51 ± 0.24) (p = 0.001).

CONCLUSIONS:

Albuterol MDI provides a more efficient delivery of drug to the lung as compared with nebulized albuterol and MDI beclomethasone diproprionate.
Drug and Environmental Factors Associated with Adverse Pregnancy Outcomes Part III: Folic Acid: Pharmacology, Therapeutic Recommendations, and Economics
Authors: Lewis Dale P , Van Dyke Don C , Stumbo Phyllis J , Berg Mary J
Published: March 2004

OBJECTIVE:

To review folic acid's mechanism of action, adverse effects, therapeutic recommendations, compliance, and cost.

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, homocysteine, and methylenetetrahydrofolate reductase.

STUDY SELECTION:

Animal and human studies examining the effects of folate were reviewed.

DATA EXTRACTION:

Data collected included mechanism of action, safety issues, dosing recommendations, compliance with recommendations, and economics.

DATA SYNTHESIS:

Folic acid decreases neural tube defect risk through an effect on methionine–homocysteine metabolism. In addition, increased folate intake may reduce cardiovascular morbidity and mortality. Since toxicity is minimal, everyone can potentially benefit from increased folate consumption. To help achieve this, the Food and Drug Administration has mandated that cereal grain be fortified with 140 μg of folic acid per 100 g of grain, which will add approximately 0.1 mg of folate to the average diet. Studies recommend supplementing with 0.2 mg to promote optimal homocysteine concentrations and for preventing neural tube defects.

CONCLUSIONS:

Despite fortification, most women will still receive less folate than the 0.4 mg/d recommended by the Public Health Service. All population groups would benefit from increased folate intake. Current studies indicate 200 μg/d may be the minimum effective amount of fortification needed for normalizing homocysteine concentrations and preventing a significant number of neural tube defects; thus, a higher level of food fortification may be warranted.
Pleurodesis with Iodized Talc for Malignant Effusions Using Pigtail Catheters
Authors: Thompson Robert L , Yau Jonathan C , Donnelly Ronald F , Gowan Debra J , Matzinger Frederick RK
Published: March 2004

OBJECTIVE:

To assess the efficacy of using an iodized talc slurry as a sclerosing agent instilled into the pleural space via a 12-French pigtail catheter for controlling malignant pleural effusions.

DESIGN:

A prospective study in which patients were followed until their death.

SETTING:

A university-affiliated tertiary-care teaching hospital.

PATIENTS:

Medical oncology patients admitted with symptomatic malignant pleural effusions were considered for iodized talc pleurodesis.

MAIN OUTCOME MEASURES:

The control of pleural effusion. Treatment failure was defined as any reaccumulation of fluid in the pleural space.

RESULTS:

Fifteen patients were treated for a total of 17 instillations. The median follow-up on all patients until death was 6 months (range 1–20). The most frequent adverse effect in the study group was pleuritic chest pain (60%). The probability of control of effusion, as determined by the method of Kaplan–Meier, was 81% (SEM 9.7%). The cost of preparing 5 g of iodized talc was $4.32 (US).

CONCLUSIONS:

Iodized talc slurry instilled through a small-bore pigtail catheter is a safe, economical, and effective treatment for malignant pleural effusion.
Factors Associated with Preventability, Predictability, and Severity of Adverse Drug Reactions
Authors: Gholami Kheirollah , Shalviri Gloria
Published: March 2004

OBJECTIVE:

To determine the rate of adverse drug reactions (ADRs) in hospitalized patients in an Iranian hospital and to assess factors associated with preventability, predictability, and severity of ADRs.

DESIGN AND PARTICIPANTS:

A prospective, randomized study was conducted on 370 patients in a hospital at the Tehran Medical Sciences University, from March to December 1996. Patients who experienced at least one ADR (n = 62) were entered into the database. Preventability, predictability, and severity of reactions were determined, based on the available algorithms developed by other investigators.

SETTING:

A 1200-bed tertiary care university teaching hospital in Tehran, Iran.

RESULTS:

Approximately 16.8% (n = 62) of the 370 patients who were included in this study had at least one ADR. One hundred two ADRs were reported during this study. Approximately 58.8% of the ADRs (60 reactions) were identified as preventable reactions and 96.1% as predictable reactions. The severity of 9.8% of the ADRs was identified as mild, 86.3% as moderate, 1% as severe, and 2.9% as lethal. The length of hospitalization increased with the severity of the ADRs. Preventable ADRs were more severe than those that were nonpreventable. In addition, the incidence of preventable ADRs increased with the patients' age and caused longer hospitalization than did nonpreventable ones. The most predictable ADRs were hematologic.

CONCLUSIONS:

This study noted that the rate of ADRs in Iran is probably as high as the rate in other parts of the world. These results indicate a need for a strong national ADR program that detects and reports adverse drug events in Iran.
Successful Desensitization to Dapsone for Pneumocystis Carinii Prophylaxis in an HIV-Positive Patient
Authors: Cook Donna E , Kossey Joyce L
Published: March 2004

OBJECTIVE:

To report a case of successful desensitization to dapsone for Pneumocystis carinii pneumonia (PCP) prophylaxis in a patient unable to tolerate trimethoprim/sulfamethoxazole (TMP/SMX) desensitization or dapsone at standard doses.

CASE SUMMARY:

A 37-year-old HIV-positive African-American man was treated for pneumonia with TMP/SMX and then continued on the drug for PCP prophylaxis. After experiencing a pruritic maculopapular rash with TMP/SMX, both at standard doses and after attempting a desensitization regimen to the drug, he was started on dapsone for PCP prophylaxis. He experienced a rash and fever after taking dapsone at standard PCP prophylactic doses. At this time, an 18-day oral dapsone rechallenge by dose escalation was attempted, and it was well tolerated.

CONCLUSIONS:

This case suggests that utilization of a dapsone desensitization regimen may permit a viable treatment option in patients previously thought to be intolerant to the agent. More regimens of this type should be attempted and the results published, using both dapsone and TMP/SMX, so that standard desensitization treatment guidelines may eventually be adopted.
Concomitant Rash and Blood Dyscrasias in Geriatric Psychiatry Patients Treated with Carbamazepine
Authors: Cates Marshall , Powers Richard
Published: March 2004

BACKGROUND:

Rashes and blood dyscrasias are disconcerting adverse effects associated with carbamazepine therapy. Rashes are quite common, as are mild blood dyscrasias, such as mild leukopenias. Fortunately, severe rashes and blood dyscrasias are rare. There are few reports on the relationship between carbamazepine-induced rashes and blood dyscrasias, including a prospective study in which rash appeared concomitantly with leukopenia and/or thrombocytopenia in 10 patients, two case reports in which simultaneous rash and agranulocytosis occurred, and two case reports in which rashes served as harbingers of fatal aplastic anemia.

CASE REPORTS:

We report two cases of concomitant rashes and blood dyscrasias in geriatric psychiatry patients receiving carbamazepine therapy for bipolar disorder. One patient was found to have a severe leukopenia within several days after rash onset. The other patient was discovered to have a severe leukopenia and thrombocytopenia within about a month after rash onset.

DISCUSSION:

Current hematologic monitoring guidelines for carbamazepine rely heavily on the recognition of signs and symptoms of blood dyscrasias by clinicians and patients. We believe that our cases support the suggestion that patients who develop rashes receive more vigilant monitoring of the complete blood count, should carbamazepine therapy be continued. Given the currently available case reports and the fact that the incidence of drug-induced blood dyscrasias increases with advanced age, this recommendation may be particularly relevant for geriatric patients.

CONCLUSIONS:

Further study is required to establish whether carbamazepine-induced concomitant rashes and blood dyscrasias are valid associations insofar as monitoring is concerned.
Vancomycin-Induced Acute Interstitial Nephritis
Authors: Wai Amy O , Lo Agnes MS , Abdo Ayman , Marra Fawziah
Published: March 2004

OBJECTIVE:

To report a case of acute interstitial nephritis (AIN) related to administration of vancomycin for the treatment of Staphylococcus aureus sternal wound infection, osteomyelitis, and infective endocarditis.

CASE SUMMARY:

Reports in the literature regarding vancomycin-induced AIN are scarce. We describe the fifth known case of AIN, in a 64-year-old white man who developed fever, maculopapular rash, acute renal failure, eosinophilia, and eosinophiluria after approximately 1 month of vancomycin treatment. The results of the renal biopsy were consistent with an allergic drug reaction. Four months after his initial episode of AIN, the patient was rechallenged with vancomycin for the treatment of S. aureus septic arthritis. One day after initiation of vancomycin, serum eosinophils started to rise, his urine tested positive for eosinophils, but his serum creatinine remained stable.

CONCLUSIONS:

Our case report and others from the literature suggest vancomycin causes allergic AIN. Clinicians should be aware of this adverse effect in an era of increasing use of vancomycin for treatment of resistant gram-positive organisms.
Iritis Associated with Intravenous Cidofovir
Authors: Tseng Alice L , Mortimer Clive B , Salit Irving E
Published: March 2004

OBJECTIVE:

To report two patients with AIDS and cytomegalovirus retinitis who developed iritis after receiving intravenous cidofovir. Both experienced recurrent symptoms upon rechallenge.

CASE SUMMARIES:

Two HIV-positive patients with cytomegalovirus retinitis infections previously controlled with intravenous ganciclovir or foscarnet were treated with intravenous cidofovir. Symptoms of iritis developed after the second or third dose of cidofovir. One patient experienced symptoms unilaterally, while the other patient had bilateral symptoms. In both patients, the iritis resolved with topical ophthalmic therapy, but recurred following subsequent infusions of cidofovir. Therapy with cidofovir was discontinued, and no further recurrences of iritis were noted. One patient had post-inflammatory fixed dilated pupils.

CONCLUSIONS:

Iritis can uncommonly occur in patients receiving intravenous cidofovir and oral probenecid. With prompt drug discontinuation and administration of topical corticosteroids and/or mydriatic agents, symptoms are usually reversible.
Trovafloxacin: A New Fluoroquinolone
Authors: Alghasham Abdullah A , Nahata Milap C
Published: March 2004

OBJECTIVE:

To review the pharmacology, antimicrobial activity, pharmacokinetics, clinical efficacy, and safety of trovafloxacin.

DATA SOURCES:

A MEDLINE search (January 1966–April 1998) was conducted for relevant literature using the terms CP-99,219, CP-116,519, trovafloxacin, and alatrofloxacin. Abstracts published by the American Society of Microbiology during 1995–1997 meetings were also reviewed.

STUDY SELECTION AND DATA EXTRACTION:

All in vitro, animal, and human studies were reviewed for the antimicrobial activity, pharmacokinetics, efficacy, and safety of trovafloxacin.

DATA SYNTHESIS:

Trovafloxacin is a new fluoroquinolone with enhanced activity against gram-positive and anaerobic microorganisms. The oral bioavailability under fasting conditions is approximately 88%. The elimination half-life of trovafloxacin is approximately 10 hours. Less than 10% of trovafloxacin is eliminated unchanged in the urine. Trovafloxacin is effective in the treatment of community-acquired pneumonia and nosocomial pneumonia with cure rates of >90% and 77%, respectively. Trovafloxacin is comparable with ceftriaxone in the treatment of meningococcal meningitis in children; each produces a cure rate of ∼90%. In treatment of uncomplicated urinary tract infection, both ciprofloxacin and trovafloxacin achieve an eradication rate of ≥93%. Trovafloxacin is similar to ofloxacin in the treatment of urogenital Chlamydia trachomatis and acute exacerbations of chronic bronchitis, with clinical success in 97% of patients with each drug. The common adverse effects of trovafloxacin include dizziness, headache, and gastrointestinal intolerance.

CONCLUSIONS:

The advantages of once-daily dosing and enhanced activity of trovafloxacin against gram-positive and anaerobic organisms may expand its use over available fluoroquinolones. Further studies are needed to define its role in the treatment of various infectious diseases.
Relative Bioavailability of Atovaquone Suspension When Administered with an Enteral Nutrition Supplement
Authors: Freeman Collin D , Klutman Neil E , Lamp Kenneth C , Dall Lawrence H , Strayer Andrew H
Published: March 2004

OBJECTIVE:

To compare the relative bioavailability of a single atovaquone 750 mg suspension oral dose when administered in the fasting state, after a normal breakfast, and after an enteral nutrition supplement.

DESIGN:

Ten healthy volunteers received a single dose of atovaquone suspension 750 mg/5 mL while fasting. At 2-week intervals, the subjects were then randomized in a crossover design to receive the atovaquone dose within 1 hour of consuming a normal breakfast (fat content 21 g) and 16 oz. of Sustacal Plus (fat content 28 g). Blood samples were collected at seven time points after each atovaquone dose. HPLC was used to determine the atovaquone concentrations in plasma.

RESULTS:

Administering atovaquone suspension with either a normal breakfast or an enteral nutrition supplement, such as Sustacal Plus, significantly increased the oral relative bioavailability. The mean AUC0–24 after the fasting dose was 43.4 μg · h/mL. The mean AUC0–24 values with breakfast (103.8 μg · h/mL) and Sustacal Plus (118.8 μg · h/mL) were significantly greater compared with fasting (p < 0.0001).

CONCLUSIONS:

This study has shown that the new atovaquone oral suspension also has significantly greater bioavailability when administered after food or a nutrition supplement that has a moderate fat content. Patients who require atovaquone therapy can use Sustacal Plus without risk of reduced absorption.
Domperidone: A Peripherally Acting Dopamine2-Receptor Antagonist
Authors: Barone Joseph A
Published: March 2004

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and safety of domperidone in the treatment of gastrointestinal motility disorders and emesis.

DATA SOURCES:

MEDLINE and Excerpta Medica online databases were searched to identify published reports.

STUDY SELECTION:

Domperidone has been marketed worldwide outside the US since 1978, and extensive clinical data for this drug are available. This review focuses on the clinical experience from controlled studies of domperidone in the treatment of motility disorders, particularly diabetic gastroparesis. Also, case reports are used in summarizing safety. The control comparator groups included placebo or other prokinetic drugs (metoclopramide and cisapride). Controlled clinical trials of domperidone's efficacy and safety as an antiemetic are also briefly examined. Although a variety of domperidone dosage forms have been marketed, data generated from trials using the 10-mg tablet are highlighted because this is the only dosage form available in Canada and is under investigation in the US.

DATA EXTRACTION:

Because symptoms do not correlate with objective measures of gastrointestinal motility and they are the primary reason that patients with motility disorders seek treatment, the primary outcome extracted from the clinical studies was symptomatic response to treatment. Safety and efficacy between domperidone and placebo, metoclopramide, or cisapride were compared.

DATA SYNTHESIS:

Domperidone, a peripheral dopamine2-receptor antagonist, regulates the motility of gastric and small intestinal smooth muscle and has been shown to have some effects on the motor function of the esophagus. It also has antiemetic activity as a result of blockade of dopamine receptors in the chemoreceptor trigger zone. In controlled clinical trials, domperidone provided better relief of symptoms (anorexia, nausea, vomiting, abdominal pain, early satiety, bloating, distension) than placebo in patients with symptoms of diabetic gastropathy; symptomatic improvement was similar with domperidone and metoclopramide or cisapride. Domperidone also provided short-term relief of symptoms in patients with dyspepsia or gastroesophageal reflux, prevented nausea and vomiting associated with emetogenic chemotherapy, and prevented the gastrointestinal and emetic adverse effects of antiparkinsonian drugs. Because very little domperidone crosses the blood–brain barrier, reports of central nervous system adverse effects, such as dystonic reactions, are rare.

CONCLUSIONS:

Domperidone is a unique gastrokinetic and antiemetic drug. Because of its favorable safety profile, domperidone appears to be an attractive alternative to metoclopramide. In the management of diabetic gastropathy, domperidone's antiemetic activity distinguishes it from cisapride.
Respiratory Failure following Oral Administration of Metoclopramide
Authors: MacLaren Robert , Shields Catherine A
Published: March 2004

OBJECTIVE:

To report a case of respiratory failure, possibly due to anaphylaxis or asthma exacerbation, following the administration of metoclopramide.

CASE SUMMARY:

A 32-year-old white woman with a history of severe asthma and short-bowel syndrome was admitted for Hickman catheter line sepsis. Two doses of oral metoclopramide 10 mg in solution were administered for nausea and vomiting. Transient dyspnea followed the first dose of metoclopramide, but respiratory failure requiring intubation followed the second dose.

DISCUSSION:

Respiratory failure has been reported with metoclopramide-induced movement disorders. Three other cases of respiratory failure from anaphylaxis or asthma exacerbation following metoclopramide administration have been reported. Respiratory failure in our patient may be due to anaphylaxis or bronchoconstriction from metoclopramide-induced cholinergic activity of the vagus nerve, possibly through inhibition of acetylcholinesterase.

CONCLUSIONS:

The use of metoclopramide in patients with pulmonary dysfunction may warrant caution.