bluuebunny/crossref_metadata_2025 huggingface dataset:
Antimicrobial-Coated/Bonded and -Impregnated Intravascular Catheters
Authors: Pai Manjunath P , Pendland Susan L , Danziger Larry H
Published: June 2003

OBJECTIVE:

To review the literature regarding the prevention of catheter colonization and catheter-related bloodstream infections (CRBIs) with the use of antimicrobial-coated/bonded and -impregnated intravascular catheters.

DATA SOURCES:

Primary and review English-language literature were identified using MEDLINE (1966–September 2000) pertaining to the key terms antibiotic, antimicrobial, antiseptic, silver, and bonded, coated, impregnated catheters. In addition, textbooks and relevant reference lists were reviewed.

DATA EXTRACTION:

All articles identified through the data sources were evaluated. Information deemed relevant to the objectives of the review was included.

DATA SYNTHESIS:

Significant morbidity and mortality are associated with the development of CRBIs. Preventative measures such as modification of these catheters with antimicrobial coating/bonding have produced varying results. Trials evaluating cefazolin, teicoplanin, vancomycin, silver, and chlorhexidine—silver sulfadiazine (C-SS) used for coated/bonded intravascular catheters have not demonstrated a consistent decrease in the incidence of CRBIs. However, a meta-analysis of trials evaluating C-SS intravascular catheters demonstrated a statistically significant reduction in CRBIs. A larger reduction in CRBIs has been reported with minocycline—rifampin (M-R) versus C-SS intravascular catheters. Use of the M-R and C-SS catheters may result in a cost savings of $100 million and reduce as many as 12 000 CRBI-related deaths annually when used short term (<7 d).

CONCLUSIONS:

When used for short-term catheterization, M-R catheters appear to be superior to the currently available C-SS catheters at preventing CRBIs. Significant cost savings and reduction in mortality can be anticipated with the use of M-R catheters.
Euglycemic Clamp Study in Clozapine-Induced Diabetic Ketoacidosis
Authors: Avram Anca M , Patel Vinod , Taylor Harris C , Kirwan John P , Kalhan Satish
Published: June 2003

OBJECTIVE:

To describe the fifth case of clozapine-induced diabetic ketoacidosis (DKA) with complete resolution of abnormal glucose metabolism after discontinuation of clozapine as assessed by oral glucose tolerance testing (OGTT) and the first to be serially studied with markers of pancreatic autoimmunity; to demonstrate insulin resistance using the euglycemic clamp study and reduced pancreatic insulin reserve using intravenous glucose tolerance testing (IVGTT) in clozapine-induced diabetes mellitus and DKA, when the OGTT was normal; and to systematically review the previously described cases of clozapine-induced diabetes mellitus and DKA.

CASE SUMMARY:

A 33-year-old white man without past or family history of diabetes mellitus presented with DKA after eight months of clozapine therapy (50 mg twice daily). After treatment of DKA and discontinuation of clozapine, glucose tolerance and concurrent serum insulin concentrations reverted to normal as measured by two OGTT performed 60 and 320 days after resolution of DKA.

DISCUSSION:

Antiislet-cell antibodies, antiglutamic acid decarboxylase antibodies, and human insulin antibody were negative on two separate occasions. Euglycemic clamp study demonstrated insulin resistance manifested by a glucose disposal rate of approximately 55% of mean normal values. IVGTT demonstrated a low rate of glucose disappearance (KG = 0.95) and diminished first-phase insulin response when OGTT was normal, indicating impairment in insulin sensitivity and reduction in β cell function 323 days after discontinuance of clozapine. This adverse reaction is considered probable according to the Naranjo probability scale.

CONCLUSIONS:

The occurrence of cases of DKA and new or worsening diabetes mellitus in patients using clozapine suggests a causal relationship. We hypothesize that the mechanism by which clozapine may produce glucose intolerance may require a preexisting latent defect in insulin secretion and insulin action. With the administration of clozapine, some of these patients may develop worsening insulin resistance and may fail to mount an appropriate compensatory β cell insulin secretion for the degree of insulin resistance. As a consequence, hyperglycemia develops and its persistence results in glucose toxicity, further suppressing β cell insulin secretion. Such combined defects in insulin secretion and sensitivity are known to be synergistic, leading to the development of abnormal glucose tolerance, which can be clinically manifested as a spectrum ranging from impaired glucose tolerance through severe hyperglycemia to DKA. Patients being started on clozapine should be carefully followed for the development or worsening of diabetes mellitus, regardless of the dose of the drug.
Tenecteplase for Treatment of Acute Myocardial Infarction
Authors: Turcasso Nannette M , Nappi Jean M
Published: June 2003

OBJECTIVE:

To describe the pharmacology, pharmacokinetics, efficacy, and safety of tenecteplase in reducing mortality associated with acute myocardial infarction (AMI).

DATA SOURCES:

Published articles were identified from MEDLINE (from 1966 to December 2000) and Current Contents (all sections) searches.

STUDY SELECTION AND DATA EXTRACTION:

Dose-ranging and pivotal studies were included for analysis in the clinical trials section.

DATA SYNTHESIS:

Tenecteplase is a third-generation thrombolytic indicated for the reduction of mortality associated with AMI. Tenecteplase has a longer half-life that allows for single-dose, intravenous bolus administration. Data from clinical trials support that tenecteplase is similar to alteplase in reducing 30-day mortality rates in patients who have had an AMI. In the ASSENT-2 (Assessment of the Safety and Efficacy of a New Thrombolytic) trial, patients treated with tenecteplase required fewer blood transfusions and experienced fewer episodes of noncerebral bleeding compared with those treated with alteplase.

CONCLUSIONS:

Tenecteplase is an effective thrombolytic agent for the treatment of AMI. It can be given as a single weight-based dose; however, it appears to offer no significant advantage over other agents in terms of its efficacy or rate of intracranial hemorrhage.
Photoreaction Potential of Orally Administered Levofloxacin in Healthy Subjects
Authors: Boccumini Louis E , Fowler Cynthia L , Campbell Theresa A , Puertolas Linda F , Kaidbey Kays H
Published: June 2003

OBJECTIVE:

To evaluate the photoreaction potential of levofloxacin on exposure to solar-simulating radiation. Solar-simulating is ultraviolet (UV) light, defined as UVA in the 320–400 nm range and UVB in the 290–320 nm range.

DESIGN:

In a single-center, double-blind, randomized study, 30 adults (20 men, 10 women) received oral levofloxacin (500 mg qd x 5 d) or placebo. At baseline photoexposure prior to drug administration, each subject was exposed to UVB light at 0.75, 1.0, and 2.0 times the minimal erythema dose and to UVA light (25 J/cm2). Photoexposure was repeated on day 5, two hours following final drug administration, and response was determined using both a photoreaction rating scale and investigator assessment.

RESULTS:

Using the photoreaction rating scale, following UVB exposure on day 5, no abnormal photoreactions were observed among levofloxacin recipients. UVA exposure was associated with mild reactions in 20 of 24 levofloxacin-treated and three of six placebo-treated subjects, with no associated symptoms. By investigator assessment, all subjects had a negative reaction to UVB photoexposure, and 10 of 24 levofloxacin-treated and three of six placebo-treated subjects had a photoreaction following UVA photoexposure. Dermal reactions were mild and similar for both treatment groups. No subject experienced an immediate wheal-and-flare reaction. There were no statistically significant differences between treatment groups for any of the comparisons.

CONCLUSIONS:

Levofloxacin has a low photosensitizing potential when administered to healthy subjects.
Optimization of Inpatient Warfarin Therapy: Impact of Daily Consultation by a Pharmacist-Managed Anticoagulation Service
Authors: Dager William E , Branch Jennifer M , King Jeffrey H , White Richard H , Quan Richard S , Musallam Nabil A , Albertson Timothy E
Published: June 2003

OBJECTIVE:

To determine the effect of daily consultation by a team of hospital pharmacists on the accuracy and rapidity of optimizing warfarin therapy.

DESIGN:

Comparison of a historical control cohort with a prospective cohort matched for treatment indication.

SETTING:

A 400-bed university teaching hospital.

PATIENTS:

Sixty consecutive patients hospitalized in 1992 and starting warfarin for the first time, with anticoagulation therapy managed by physicians, were compared with 60 patients matched for warfarin indication hospitalized in 1995, but with anticoagulation therapy managed with pharmacy consultation.

RESULTS:

Pharmacist management of initial warfarin therapy resulted in a significant reduction in the length of hospitalization compared with physician dosing, from 9.5 ± 5.6 days to 6.8 ± 4.4 days (p = 0.009). The number of patients and patient-days with international normalized ratio (INR) values >3.5 were reduced by pharmacist dosing from 37 patients and 142 days to 16 patients and 29 days, respectively (p < 0.001). Similarly, the number of patients and patient-days with INR >6.0 were reduced from 20 patients and 50 days to two patients and six days, respectively (p < 0.001). There were six documented bleeding complications in 1992 compared with one in 1995 (p = 0.11). The mean INR at discharge was significantly lower in the pharmacy surveillance group, 2.6 ± 0.58, compared with the physician cohort, 3.3 ± 2.1 (p = 0.07). Readmissions after discharge due to bleeding or recurrent thrombosis were reduced from five (at 1 mo) and 10 (at 3 mo) to two and five readmissions, respectively, by pharmacist intervention (p = 0.43). The number of patients with concurrently prescribed drugs known to significantly interact with warfarin was significantly lower (6 vs. 13; p = 0.02) in the pharmacy surveillance group.

CONCLUSIONS:

Among patients starting warfarin for the first time, daily consultation by a pharmacist significantly decreased the length of hospital stay and the number of patients who received excessive anticoagulation therapy. These findings translate into improved quality of care and potentially significant cost savings.
The Effect of Intravenous Verapamil on Cerebral Hemodynamics in a Migraine Patient with Hemiplegia
Authors: Ng Tien MH , Kohli Anoop , Fagan Susan C , Mohamed Ashraf E , Geiszt Gabriella
Published: June 2003

OBJECTIVE:

To describe the use of intravenous verapamil in a migraine patient with hemiplegia to reverse the symptomatology and hemodynamics of the middle cerebral artery as determined by transcranial Doppler.

CASE SUMMARY:

A 31-year-old white woman was admitted with an acute exacerbation of migraine with hemiplegia. A transcranial Doppler showed an increased flow velocity through the middle cerebral artery consistent with a migrainous process. The patient was treated with verapamil 5 mg iv and the hemiplegia gradually resolved. A transcranial Doppler indicated that the flow velocity through the middle cerebral artery was decreased after verapamil administration, indicating reversal of the vasospasm.

DISCUSSION:

Transcranial Doppler has not been previously used to determine the effect of intravenous verapamil on the migrainous process. Intravenous verapamil reversed the altered hemodynamics of the middle cerebral artery as determined by transcranial Doppler. This finding correlated with the gradual resolution of hemiplegia. Whether both subjective and objective findings in this patient can be attributed to the reversal of the cerebral artery hemodynamics is not known.

CONCLUSIONS:

Intravenous verapamil appears to reverse the vasospasm that may be associated with a migrainous process. Whether this effect is solely responsible for clinical improvement is not known. Verapamil may be a consideration for the treatment of intractable migraine, especially when there is evidence of spasm of the major cerebral arteries.
Switching Antipsychotic Therapies
Authors: Masand Prakash S , Berry Sarah L
Published: June 2003

BACKGROUND:

Atypical antipsychotics are superior to conventional antipsychotics in improving positive and negative psychotic symptoms. Atypical antipsychotics do not exacerbate mood symptoms, and may improve mood symptoms and cognitive functioning; additionally, they have better adverse effect profiles than conventional antipsychotics.

OBJECTIVE:

To review the benefits of switching patients with schizophrenia or schizoaffective disorder from a conventional to an atypical antipsychotic, or from one atypical antipsychotic to another. In spite of the higher acquisition cost of atypical antipsychotics, overall treatment costs may decrease due to lower relapse and hospitalization rates.

DATA SOURCES:

A MEDLINE search (January 1977–January 1999) was conducted for articles written in English about efficacy, adverse effects, compliance, and pharmacoeconomics for atypical and conventional antipsychotics.

STUDY SELECTION:

Large, multicenter, double-blind, controlled studies were used for efficacy, safety, tolerability, and pharmacoeconomic data. Where appropriate, recent review articles were also used.

RESULTS:

Atypical antipsychotics are superior to conventional antipsychotics in the treatment of schizophrenia. Atypical and conventional antipsychotics have different adverse effect profiles, costs, and compliance rates.

CONCLUSIONS:

Some patients may benefit by switching from a conventional to an atypical antipsychotic, from an atypical to a conventional antipsychotic, or from one atypical antipsychotic to another. Methods of switching antipsychotic therapies include tapering and cross-over strategies.
Gender Differences in Depression and Antidepressant Pharmacokinetics and Adverse Events
Authors: Frackiewicz Edyta J , Sramek John J , Cutler Neal R
Published: June 2003

OBJECTIVE:

To review data generated by studies examining gender differences in the prevalence of depression, as well as in antidepressant pharmacokinetics, pharmacodynamics, and adverse events.

DATA SOURCES:

Published articles and abstracts were identified through MEDLINE (January 1966–April 1999) using the following search terms: antidepressant, response, gender, pharmacokinetic, pharmacodynamic, female, side effect, and adverse events. All articles that assessed gender differences in antidepressant response, pharmacokinetics, and adverse events, as well as articles that evaluated postulated mechanisms for these differences, were reviewed. Additional articles were identified from bibliographies of retrieved articles.

STUDY SELECTION AND DATAEXTRACTION:

All relevant abstracts, studies, and review articles were evaluated.

DATA SYNTHESIS:

Gender differences in the prevalence of depression have been reported and may result from the interaction of several factors. Women have been shown to have a higher incidence of depression, which may be due to artifact, social, or biologic reasons. Studies suggest that the pharmacokinetic disposition of popular antidepressants varies between men and women, and women taking antidepressants may exhibit a different adverse event profile. Only one study specifically evaluated gender differences in antidepressant treatment response.

CONCLUSIONS:

Further research elucidating gender differences in response to antidepressant treatment and on depression prevalence is needed. Some studies report that the pharmacokinetics of antidepressants may vary between men and women. Therefore, clinicians should be aware that potential differences in antidepressant pharmacokinetics may exist, and a dosage adjustment may be necessary for women to ensure a favorable drug response, compliance, and decreased incidence of adverse events.
Inappropriate Prescribing for the Elderly: Beers Criteria-Based Review
Authors: Aparasu Rajender R , Mort Jane R
Published: June 2003

OBJECTIVE:

To review currently available literature applying the Beers criteria for inappropriate medication use in the elderly to prescribing practices in various settings.

DATA SOURCE:

Key words including inappropriate, Beers, medication, prescribing, elderly, geriatric, and criteria were used to search MEDLINE records from January 1992 to June 1999.

DATA EXTRACTION:

Eight relevant studies were found that applied the Beers criteria in various healthcare settings.

DATA SYNTHESIS:

Each study was examined for methodologic issues, criteria used, prevalence, nature and extent of inappropriate medication use, and factors associated with their use. Despite the methodologic differences, the review revealed some consistent patterns across healthcare settings. This review has shown that: (1) most of the researchers modified the Beers criteria to examine inappropriate medication use in the elderly; (2) studies using patient-based prevalence showed that between nearly one in four (23.5%) and one in seven (14.0%) elderly patients received an inappropriate medication as defined by either the Beers list of 20 inappropriate medications or the Modified Beers list; (3) the majority of these patients received one inappropriate agent; and (4) long-acting benzodiazepines, dipyridamole, propoxyphene, and amitriptyline were among the most frequently prescribed inappropriate medications. Univariate analyses indicated that women, patients >80 years old, and Medicaid patients appeared to receive more inappropriate medications than others; however, multivariate analyses found that only a higher number of medications was consistently associated with inappropriate medication use.

CONCLUSIONS:

Inappropriate prescribing or use trends are noteworthy because they were observed despite methodologic differences. The findings can be instrumental in developing targeted interventions to influence future prescribing practices. More research is needed to address the national trends and healthcare impact of inappropriate drug use in the elderly.
Efficacy and Safety of Lesopitron in Outpatients with Generalized Anxiety Disorder
Authors: Fresquet Anna , Sust Mariano , Lloret Antonio , Murphy Michael F , Carter Frederick J , Campbell Giedra M , Marion-Landais Gaston
Published: June 2003

OBJECTIVE:

To compare the relative efficacy and safety of lesopitron 40–80 mg/d versus lorazepam 2–4 mg/d and placebo in a subgroup of patients with anxiety history taken from a larger study of patients with a primary diagnosis of generalized anxiety disorder (GAD).

DESIGN:

Six-week, randomized, double-blind, parallel, placebo and lorazepam-controlled, Phase II, single-center, outpatient study.

SETTING:

Outpatient clinic.

PATIENTS:

One hundred sixty-one patients with GAD were randomized in the main study; 68 with a documented history of GAD or anxiety disorder not otherwise specified were included in the subgroup.

METHODS:

After a one-week placebo lead-in, patients were randomized to receive placebo, lesopitron, or lorazepam twice daily for six weeks, followed by a one-week taper period. Efficacy was assessed using the Hamilton Rating Scale for Anxiety (HAM-A) and the Clinical Global Impressions scale. Safety was assessed through physical examinations, monitoring of vital signs, 12-lead electrocardiograms, laboratory analyses, and adverse event monitoring.

RESULTS:

An overall mean improvement in the HAM-A total score between baseline and end point for all three treatment groups was seen, with mean changes of 3.4 (95% CI 2.0 to 4.8), 6.1 (95% CI 4.1 to 8.1), and 6.1 (95% CI 4.6 to 7.6) for the placebo, lesopitron, and lorazepam groups, respectively (omnibus p = 0.044, uncorrected). Positive treatment effects were also observed in the subgroup population on several other measures and suggest that additional therapeutic trials may be warranted. Future trials could be stratified on the basis of referral status (symptomatic volunteer vs. clinical patient with preexisting illness) or previous exposure to anxiolytics, and use a fixed-dose rather than flexible-fixed-dose design.

CONCLUSIONS:

The subgroup analysis represents a comparison of treatment outcome in GAD patients presenting with a history of previous episodes of GAD or anxiety disorder not otherwise specified compared with those who were experiencing their first episode of GAD and reported no anxiety history. Although the overall study analysis was equivocal, for the approximately 40% of patients with recurrent anxiety disorder, beneficial effects for both lesopitron and lorazepam are suggested.
Toxic Epidermal Necrolysis Associated with Acetaminophen Ingestion
Authors: Halevi Ayelet , Ben-Amitai Dan , Garty Ben Zion
Published: June 2003

OBJECTIVE:

To report a case of toxic epidermal necrolysis (TEN) associated with acetaminophen ingestion.

A seven-year-old girl developed TEN after acetaminophen ingestion. The diagnosis was based on clinical evaluation and skin biopsy. A later acetaminophen challenge, undertaken by an allergist who questioned the diagnosis, resulted in a similar skin reaction.

DISCUSSION:

TEN is a severe disease with a high mortality rate. TEN may be either idiopathic or associated with several clinical conditions, such as viral infections, autoimmune disorders, malignancy, and drug hypersensitivity. Because of the rarity of its association with acetaminophen, the diagnosis in our patient was questioned by an allergist who performed an oral acetaminophen rechallenge test despite the potential risk. This caused a severe skin reaction that required rehospitalization.

CONCLUSIONS:

TEN can be caused by over-the-counter medications such as acetaminophen. Rechallenge with the causative drug carries a risk of severe complications and should be avoided.
The Role of Vasopressin in the Treatment of Vasodilation in Shock States
Authors: Rozenfeld Vitalina , Cheng Judy WM
Published: June 2003

OBJECTIVE:

To review the role of vasopressin in the treatment of vasodilatory shock.

DATA SOURCES:

A MEDLINE search on published reports (1966–April 1999) was conducted.

STUDY SELECTION:

English-language studies and case reports were selected and evaluated based on quality of review of vasopressin in the treatment of vasodilatory shock.

DATA SYNTHESIS:

In patients with end-stage vasodilatory shock, baroreceptor reflex is impaired and vasopressin stores are depleted. Persistent elevation of catecholamines may lead to down-regulation of β-adrenergic receptors and reduces smooth-muscle response to catecholamines, leading to inability of maintaining organ perfusion. Small-scale studies and case reports have demonstrated vasopressin's efficacy in maintaining blood pressure in patients with septic shock, cardiac arrest, and end-stage heart failure, refractory to other vasopressor therapies.

CONCLUSIONS:

Vasopressin may be a reasonable alternative for patients in vasodilatory shock. However, larger-scale controlled clinical trials are warranted before its routine use can be recommended.
Treatment of Uncomplicated Urinary Tract Infections: Exploring Differences in Adherence to Guidelines between Three European Countries
Authors: Veninga Catharina CM , Lundborg Cecilia Stålsby , Lagerløv Per , Hummers-Pradier Eva , Denig Petra , Haaijer-Ruskamp Flora M ,   the Drug Education Project Group
Published: June 2003

OBJECTIVE:

To evaluate adherence of general practitioners to treatment guidelines regarding urinary tract infections in three European countries and to investigate whether differences in adherence at the prescribing level within and between countries could be explained by general practitioners' knowledge and attitudes, characteristics, or national setting.

DESIGN:

Prescribing data collected in 1994–1995 were analyzed regarding use of first-choice drugs and duration of treatment, knowledge and attitudes were assessed with a questionnaire, and multiple regression analysis was used to explain differences in prescribing behavior within and between countries.

RESULTS:

Our study is based on data from 85.6% of the 584 general practitioners who were scheduled to participate in a continuing education program. The mean proportion of responses in agreement with the guidelines regarding first-choice drugs was 0.69 in Sweden, 0.78 in the Netherlands, and 0.79 in Norway; regarding duration of treatment, the mean proportion was 0.56 in Sweden, 0.67 in the Netherlands, and 0.59 in Norway. The proportion of first-choice drugs prescribed for women (18–75 y) was 0.55 in Sweden, 0.83 in the Netherlands, and 1.00 in Norway (patients >16 y). The duration of treatment was 7.6 defined daily doses per prescription in Sweden, 5.9 in the Netherlands, and 6.6 in Norway. Knowledge and attitudes explained 0–17% of the variation in prescribing. Years in practice explained 0–11%, and the general practitioners' gender had no explanatory value. The national setting explained most of the variation between countries.

CONCLUSIONS:

Differences in prescribing behavior can be explained only to a small extent by deviations from the guidelines in terms of knowledge and attitudes. Between countries, differences in regulation, marketing, and distribution of drugs seem to be of much greater importance.
Factors Affecting Prescribing of the Newer Antidepressants
Authors: Garrison Gina Daubney , Levin Gary M
Published: June 2003

OBJECTIVE:

To survey various prescriber types and specialties to determine whether differences exist in prescribing patterns for the newer antidepressants.

DESIGN, SETTING, AND PARTICIPANTS:

A survey about prescribing of the newer antidepressants was mailed to 1500 New York state licensed prescribers who were randomly selected from membership rosters. Nurse practitioners; physician assistants and physicians in family medicine, primary care, general practice, and internal medicine; and psychiatrists were included.

MAIN OUTCOME MEASURES:

Prescriber responses regarding factors involved with choosing among the newer antidepressants.

RESULTS:

A total of 508 surveys (36%) were returned, of which 398 (29%) were acceptable for analysis. In choosing among the newer antidepressants, most prescribers ranked patient diagnosis and past success as a high priority, and free drug samples and drug-representative detailing as a low priority. The majority of each prescriber type preferred fluoxetine for major depression and depression associated with fatigue; paroxetine for concomitant anxiety and depression, as well as for panic disorder; and sertraline for geriatric patients and patients with suicidal ideation. Differences existed between the prescriber groups when asked whether prescribing habits for the newer antidepressants were based on familiarity with a particular agent (p = 0.0009) and on labeled indications (p = 0.002).

CONCLUSIONS:

This is the first study to demonstrate prescribing preferences for the newer antidepressants among different prescriber groups. Additional studies are needed to determine predictors of patient response to newer antidepressants and clinical guidelines for their use.
Effect of Aging on the Incidence of Digoxin Toxicity
Authors: Miura Takanori , Kojima Ryoji , Sugiura Youji , Mizutani Masaru , Takatsu Fumimaro , Suzuki Yoshio
Published: June 2003

OBJECTIVE:

To evaluate the relationship of the therapeutic serum digoxin concentration (SDC) range (0.5–2 ng/mL, as recommended in previous clinical studies) with the incidence of digoxin toxicity during digoxin maintenance therapy.

METHODS:

Subjects included all inpatients (n = 462) and outpatients (n = 437) receiving digoxin oral maintenance therapy for heart failure and/or atrial fibrillation with tachycardia at Kosei Hospital, Anjo, Japan. SDC and blood chemistry analysis were determined, and a 24-hour Holter electrocardiographic recording was performed when the SDC was at the presumed steady-state concentration.

RESULTS:

Analysis of clinical data showed that there was an overlapping (toxic and nontoxic) range of SDCs in which the incidence of digoxin toxicity was patient-dependent (1.4–2.9 ng/mL). No patient exhibited signs or symptoms of digoxin toxicity when the SDC was <1.4 ng/mL; all patients had evidence of toxicity when the SDC was >3 ng/mL. Additionally, it was shown that the concentration range of this overlapping range tended to broaden and shift to lower concentrations with increasing age. Patients with signs of toxicity when their SDCs were in the overlapping range had normal serum creatinine, blood urea nitrogen, digoxin clearance, creatinine clearance, and potassium concentrations, except for a significantly higher mean age than patients without toxicity. The incidence of digoxin toxicity was dependent on increasing age in patients whose SDCs were within the recommended therapeutic range. Moreover, clinical evidence of digoxin toxicity in patients >71 years old was 26.5%, despite their SDCs falling between 1.4 and 2 ng/mL.

CONCLUSIONS:

Increased age is most likely associated with enhanced susceptibility to digoxin toxicity, possibly due to unknown pharmacodynamic changes. This raises the possibility that patients >71 years show clinical evidence of digoxin toxicity despite having SDCs within the recommended therapeutic range.
Bayesian Approach to Control of Amikacin Serum Concentrations in Critically Ill Patients with Sepsis
Authors: Lugo-Goytia Gustavo , Castañeda-Hernández Gilberto
Published: June 2003

OBJECTIVE:

To compare the predictive performance of a Bayesian program incorporating a population model with and without severity of illness covariates in intensive care unit (ICU) patients with sepsis.

DESIGN:

The clinical, physiologic, and pharmacokinetic data of 62 patients with sepsis admitted to a tertiary-care center were analyzed retrospectively. The patients were randomly assigned to a active group and a validation group. The model was developed using a three-step approach involving Bayesian estimation of pharmacokinetic parameters, selection of covariates by principal component analysis, and final selection of covariates by stepwise multiple linear regression. The predictive performance of this model was tested in patients from the validation group and compared with that of a general population model without covariates.

RESULTS:

Regression analysis revealed that the Acute Physiologic and Chronic Health Evaluation (APACHE II) score was the most important determinant for amikacin volume of distribution (1.5 L/kg, APACHE II; r2 = 0.77). For amikacin clearance (Clamik), creatinine clearance (Clcr), positive end-expiratory pressure (PEEP), and use of catecholamines (CAT) were the most important predictors (Clamik = 44.5 + 0.67 Clcr − 1.29 PEEP − 8.34 CAT; r2 = 0.72). The relative mean error (ΔME) and root mean-square error (ΔRMSE) (95% CI) were −0.62 (−1.2 to 0.01) and 3.78 (2.3 to 4.8) mg/L, respectively. Since the 95% CI for ΔRMSE did not include zero, it appears that the model with covariates is significantly improved in terms of precision.

CONCLUSIONS:

Our results show that, in ICU patients treated with amikacin, it is relevant to consider covariates related to pathophysiologic status and therapeutic measures. Application of a Bayesian program allows improved control of the pharmacokinetic parameters in patients who exhibit rapidly changing physiologic conditions.
Management Protocol for Abacavir-Related Hypersensitivity Reaction
Authors: Clay Patrick G , Rathbun R Chris , Slater Leonard N
Published: June 2003

OBJECTIVE:

To develop an abacavir hypersensitivity reaction management protocol for the University of Oklahoma Health Sciences Center.

DATA SYNTHESIS:

Conference abstracts, published literature, and manufacturer-provided materials were reviewed to define the syndrome and manifestations and to recommend steps to take when a patient develops abacavir-related reactions.

RESULTS:

Initial education, formalized contact and response mechanism, and intervention levels were incorporated into a protocol for clinicians.

CONCLUSIONS:

Abacavir, a newly approved agent for the treatment of HIV, has been associated with a fatal hypersensitivity reaction. Our protocol provides a mechanism to minimize progression of abacavir hypersensitivity reaction by providing a formalized management procedure
Granulocyte Colony-Stimulating Factor Use in Cancer Patients
Authors: Baker Jennifer , McCune Jeannine S , Harvey R Donald , Bonsignore Carol , Lindley Celeste M
Published: June 2003

OBJECTIVE:

To conduct a retrospective drug utilization evaluation comparing the use of granulocyte colony-stimulating factor (G-CSF) at a university medical center with the American Society of Clinical Oncology (ASCO) CSFs Practice Guidelines.

METHODS:

Patients who received G-CSF from June 1, 1996, to December 31, 1996, were identified through the pharmacy computer system and the medical records were reviewed for a randomly selected sample of 26% of the 289 patients identified. Outpatient, inpatient, and electronic medical records were reviewed for the indication, dosage, day of initiation, day of discontinuation, and absolute neutrophil count (ANC) monitoring plan for each course of G-CSF; these records were subsequently compared with the ASCO guidelines.

RESULTS:

The use of G-CSF after chemotherapy was evaluated in 51 patients who received a total of 182 courses of G-CSF. The goal of chemotherapy was curative in 61% of courses. Sixty-five percent of G-CSF courses were prescribed for primary prophylaxis. Of these, 74% followed chemotherapy in patients with an expected incidence of febrile neutropenia ≥40% or followed chemotherapy in patients with compromised marrow reserve secondary to extensive prior therapy or in patients older than 60 years. Most of the G-CSF courses (75%) were rounded to the nearest vial size. The areas of greatest departure from the ASCO guidelines included aspects of initiation and discontinuation of G-CSF courses and inadequate documentation of ANC recovery.

CONCLUSIONS:

These results demonstrate a number of specific opportunites for oncology pharmacists to improve the use of G-CSF in patients receiving chemotherapy. Recommendations were made to the pharmacy and therapeutics committee and medical oncologists to improve compliance with the ASCO guidelines.
The Pharmacokinetics of Etanercept in Healthy Volunteers
Authors: Korth-Bradley Joan M , Rubin Abbe Sue , Hanna Roberta K , Simcoe Donna K , Lebsack Mary E
Published: June 2003

OBJECTIVE:

To describe the pharmacokinetics of etanercept when administered by subcutaneous injection in single doses to healthy volunteers.

METHODS:

Twenty-six healthy volunteers between 19 and 50 years of age received single doses of etanercept 25 mg by subcutaneous injection into the abdomen. Serial serum samples were collected for 21 days. An enzyme-linked immunosorbent assay with a quantitation limit of 0.3 ng/mL was used to measure the drug concentrations.

RESULTS:

Etanercept was well tolerated by healthy volunteers. A one-compartment model was found to best describe the concentration–time data and was used to determine the pharmacokinetic parameters. Etanercept is slowly absorbed from the site of injection with a time of peak concentration (± SD) of 51 ± 14 hours; peak concentration was 1.46 ± 0.72 mg/L. The AUC was 235 ± 98 mg•h/L, apparent clearance was 132 ± 85 mL/h, apparent volume of distribution was 12 ± 6 L, and the half-life was 68 ± 19 hours.

CONCLUSIONS:

Etanercept was slowly absorbed and slowly eliminated after subcutaneous administration. Dosing at the recommended rate of 25 mg twice weekly would be expected to result in concentrations of approximately 3 mg/L. Intersubject variability for apparent clearance in healthy volunteers was 64%.
Amiloride for the Prevention of Amphotericin B–Induced Hypokalemia and Hypomagnesemia
Authors: Wazny Lori D , Brophy Donald F
Published: June 2003

OBJECTIVE:

To review the published clinical data assessing the role of amiloride in the prevention of amphotericin B (AmB)–induced electrolyte disorders.

DATA SOURCES:

A MEDLINE search (January 1966–April 1999) of English-language literature pertaining to AmB, amiloride, potassium, and magnesium was performed. Tertiary sources were also used.

DATA EXTRACTION:

In vivo and in vitro human and animal data and case reports were included due to the lack of published clinical trials.

DATA SYNTHESIS:

AmB administration can result in severe hypokalemia and hypomagnesemia requiring chronic supplementation. In one prospective, controlled study of hypokalemia with AmB administration, patients receiving concomitant amiloride had significantly greater potassium concentrations (p < 0.01) and required significantly less potassium supplementation (p < 0.001). Amiloride may also reduce the amount of magnesium supplementation required by sparing elimination through the kidneys.

CONCLUSIONS:

Amiloride may be considered for the prevention of AmB-induced hypokalemia and hypomagnesemia, especially in patients at high risk for complications resulting from these electrolyte disorders. Further studies are needed to assess concomitant use of other potassium-sparing diuretics and AmB.
Criteria for Assessing the Appropriateness of Patient Counseling in Community Pharmacies
Authors: Ward Paul R , Bissell Paul , Noyce Peter R
Published: June 2003

OBJECTIVE:

To develop valid, reliable criteria for assessing the appropriateness of the management of common ailments and nonprescription drug therapy in community pharmacies in the UK.

METHODS:

The criteria were developed by an expert panel using the nominal group technique. The validity of the criteria was tested by surveying a random sample of pharmacists who were asked to rate the importance of each criterion on a semantic differential scale from 1 (low) to 7 (high). Subsequently, the reliability of the criteria was assessed: a random sample of pharmacists were each asked to apply the criteria to four vignettes of patient counseling on two separate occasions.

RESULTS:

All assessment criteria exceeded our predefined level of face, content, and consensual validity. In reliability testing, the overall assessment of appropriateness, along with five component assessment criteria, surpassed our predefined level of reliability. Three criteria, however, did not meet our predefined standard. These criteria were rational content of advice, rational product choice, and referral to another health professional.

CONCLUSIONS:

This represents the first systematic attempt to develop an instrument of general applicability for assessing the appropriateness of patient counseling and to subject it to rigorous validity and reliability testing. We suggest that further work is required to refine the criteria that did not meet reliability standards and to understand the decision-making processes underlying the assessment of vignettes of patient counseling.
Anterior Ocular Infections: An Overview of Pathophysiology and Treatment
Authors: Thielen Traci L , Castle Sharon S , Terry Jack E
Published: June 2003

OBJECTIVE:

To provide a review of the pathophysiology and treatment of anterior ocular infections.

DATA SOURCE:

A MEDLINE search (from 1970 to October 1998) as well as a review of the tertiary literature was performed to identify pertinent literature on pathophysiology and treatment of ocular infections.

STUDY SELECTION AND DATA EXTRACTION:

All articles were considered for possible inclusion in the review. Relevant studies were selected for discussion in the article.

DATA SYNTHESIS:

Ocular infections are common and vary from self-limiting to sight-threatening. Infections occur in different eye structures; presentation and treatment vary accordingly. Infections can occur when tissues of the eye are exposed to pathogens not normally present, when the eye is damaged, allowing pathogens to overcome the natural defenses of the eye, or in immunosuppressed patients where normal flora may become opportunistic. In deciding on appropriate treatment, both the causative pathogen and the structure(s) affected must be considered. The most likely pathogen can often be determined based on clinical signs and symptoms, patient history, or, in some cases, may need to be determined microbiologically. Differences in drug absorption, penetration, and availability to the various structures of the eye affect treatment decisions. Severity of infection, efficacy and safety of medication, and cost/benefit ratios must be taken into consideration in choosing the proper pharmacologic management of various ocular infections.

CONCLUSIONS:

Treatment of ocular infections depends on knowledge of the pathophysiology and drug disposition at the site of infection. An understanding of the current concepts surrounding the management of the anterior ocular infections presented will aid in the provision of optimal patient care.
Citalopram in the Treatment of Depression
Authors: Parker Nicole G , Brown Candace S
Published: June 2003

OBJECTIVE:

To review the efficacy and safety of citalopram in the treatment of depression.

DATA SOURCES:

MEDLINE search (1966–April 2000), Current Contents search, additional references listed in articles, and unpublished data obtained from the manufacturer were used to identify data from scientific literature. Studies evaluating citalopram (i.e., abstracts, clinical trials, data on file with the manufacturer) were considered for inclusion.

STUDY SELECTION:

English-language literature was reviewed to evaluate the pharmacology, pharmacokinetics, therapeutic use, and adverse effects of citalopram.

DATA EXTRACTION:

Controlled animal and human clinical studies published in the English-language literature were reviewed and evaluated. Clinical trials selected for inclusion were limited to those in human subjects and included data from animals if human data were not available.

DATA SYNTHESIS:

Citalopram is an antidepressant belonging to the class of selective serotonin-reuptake inhibitors (SSRIs) available for the treatment of depression. Citalopram offers therapeutic efficacy similar to that of the other SSRIs and a more favorable adverse effect profile than that of the tricyclic antidepressants (TCAs). Citalopram does not cause anticholinergic or cardiovascular adverse effects associated with the TCAs. Citalopram is the most selective SSRI and, unlike other SSRIs, seems to be relatively free of interaction mediated by the cytochrome P450 system. Citalopram is also the least expensive antidepressant available to date. This review of citalopram includes data from clinical trials comparing safety, tolerability, efficacy, and pharmacoeconomics with TCAs and SSRIs.

CONCLUSIONS:

Clinical trials demonstrate that citalopram's therapeutic efficacy is significantly greater than that of placebo and is comparable with that of other antidepressants. Citalopram has a favorable adverse effect profile, and thus may be useful in treating depressed patients who cannot tolerate anticholinergic or cardiovascular adverse effects associated with TCAs. It may also be useful in patients with comorbid illnesses requiring concomitant medicines.
Recent Advances in Geriatrics: Drug-Related Problems in the Elderly
Authors: Hanlon Joseph T , Shimp Leslie A , Semla Todd P
Published: June 2003

OBJECTIVE:

To review recent articles examining drug-related problems in the elderly and comment on their potential impact on geriatric pharmacy practice.

DATA SOURCES:

Six articles published in 1997 and 1998.

DATA SYNTHESIS:

One study estimated that the cost of drug-related morbidity and mortality with the services of consultant pharmacists was $4 billion, compared with $7.6 billion without the services of consultant pharmacists. A study of ambulatory elderly patients with polypharmacy documented that 35% reported experiencing at least one adverse drug event within the previous year. Another study of ambulatory elderly found that in those with discontinued medications, adverse drug withdrawal events were uncommon. Two studies, one from Canada and one from the US, describe the development, by consensus, of explicit criteria for defining and identifying inappropriate drug use in the elderly (i.e., drugs to avoid, drugs with dose limits, drug–drug and drug–disease interactions). Finally, a modified Delphi survey of an expert panel reached consensus on 18 potential risk factors for drug-related factors in long-term care facility residents.

CONCLUSIONS:

Drug-related problems are considerable for elderly patients. Data from published studies should provide some guidance for today's practitioners as well as direction regarding future research.
Enteral Nutrition Support in Acute Pancreatitis
Authors: Erstad Brian L
Published: June 2003

OBJECTIVE:

To review the controversies surrounding the use of nutritional interventions, particularly enteral support, in patients with acute pancreatitis.

DATA SOURCES:

Articles were obtained through a MEDLINE search (1966–June 1999). Additionally, several textbooks containing information on the diagnosis and management of acute pancreatitis were reviewed. The bibliographies of retrieved publications and textbooks were reviewed for additional references.

STUDY SELECTION:

All original investigations in humans pertaining to the use of enteral nutritional support in acute pancreatitis were reviewed for inclusion. Studies that investigated parenteral nutrition in acute pancreatitis were also reviewed, with preference given to controlled comparisons with enteral regimens or no nutritional support.

DATA EXTRACTION:

The primary outcomes extracted from the literature were time to oral feeding tolerance, complications (e.g., infection) associated with nutritional support, and length of stay.

DATA SYNTHESIS:

The duration of pancreatitis and time to oral feedings is similar whether patients receive enteral (i.e., jejunal tube feedings) or parenteral nutrition. Additionally, complications, length of stay, and costs are either similar or decreased with enteral versus parenteral nutrition.

CONCLUSIONS:

Current evidence suggests that the enteral rather than parenteral route should be used to provide nutrition to patients with acute pancreatitis. Parenteral nutrition should be reserved for patients in whom nasojejunal feeding is not possible.
Use of rhDNase Therapy and Costs of Respiratory-Related Care in Patients with Cystic Fibrosis
Authors: Ollendorf Daniel A , McGarry Lisa J , Watrous Marc L , Oster Gerry
Published: June 2003

OBJECTIVE:

To assess the relationship between level of use of recombinant deoxyribonuclease I (rhDNase) therapy and costs of respiratory-related care in patients with cystic fibrosis.

DESIGN:

Retrospective, cohort study using healthcare claims data from a large New England health insurer.

PATIENTS:

All cystic fibrosis patients five years of age and older who began therapy with rhDNase in 1994 (the year it was first marketed in the US). Healthcare claims were compiled for six months prior to first receipt of rhDNase (pretreatment) and for 30 months subsequently (follow-up). Patients were stratified according to their level of rhDNase use during follow-up, based on whether it was above or below the median number of therapy days for the sample.

MAIN OUTCOME MEASURES:

Costs of rhDNase, all antibiotics, and all respiratory-related outpatient (physician, home health, hospital outpatient) and inpatient care were included. All costs were expressed on an annualized basis.

RESULTS:

Twenty-four patients with cystic fibrosis who began treatment with rhDNase in 1994 met all entry criteria; the median number of therapy days over a 30-month period was 355. Among patients with low (i.e., below the median) rhDNase use (n = 12), mean ± SD annualized costs of respiratory-related care increased by almost $17000 between pretreatment and follow-up, from $29251 ± $37919 to $46109 ± $40944. Among high-use patients (n = 12), costs decreased by approximately $2500, from $37178 ± $48476 to $34592 ± $22591. The change in both groups was accounted for primarily by a change in the number of respiratory-related hospitalizations.

CONCLUSIONS:

Prolonged use of rhDNase may reduce costs of respiratory-related care in patients with cystic fibrosis; further study is required, however, to confirm these findings.