bluuebunny/crossref_metadata_2025 huggingface dataset:
Nelfinavir Mesylate: A Protease Inhibitor
Authors: Pai Vinita B , Nahata Milap C
Published: March 2004

OBJECTIVE:

To review the clinical pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage guidelines of nelfinavir mesylate.

DATA SOURCE:

A MEDLINE search restricted to English-language literature from January 1966 to February 1998 and an extensive review of journals was conducted to prepare this article. MeSH headings included protease inhibitors, nelfinavir mesylate, and AG1343. Abstracts presented at meetings and data submitted to the Food and Drug Administration (FDA) were also reviewed.

DATA EXTRACTION:

The data on efficacy, pharmacokinetics, adverse effects, and drug interactions were obtained from in vitro studies, as well as open-label and controlled trials.

DATA SYNTHESIS:

Nelfinavir inhibits HIV protease enzyme resulting in formation of immature and noninfectious virions. In combination with nucleoside reverse transcriptase inhibitors, nelfinavir is effective in reducing the viral load below the quantifiable limit (<500 copies/mL) and increasing the mean CD4+ cell count. This antiviral effect is sustained at least over 21 months. The bioavailability of nelfinavir ranges from 20% to 80%, and it increases when nelfinavir is administered with food. Following multiple dosing of nelfinavir 750 mg three times daily, maximum concentration at steady-state was 3–4 μg/mL and minimum concentration was 1–3 μg/mL. The elimination half-life for nelfinavir ranges from three to five hours. Nelfinavir is primarily metabolized in the liver by the cytochrome P450 isoenzymes and excreted in the feces. Current dosing recommendations are 750 mg three times daily for adults and adolescents and 20–30 mg/kg/dose three times daily for children aged 2–13 years. Studies of twice-daily regimens in adults are being conducted and are promising. Use of nelfinavir as salvage therapy is also being studied. Some of the commonly reported adverse events of nelfinavir are diarrhea, nausea, vomiting, and abdominal pain.

CONCLUSIONS:

Despite the limited published data, the FDA has approved nelfinavir in combination therapy for the treatment of HIV infection. The choice of antiretroviral (ARV) regimens should be made based on the risk of disease progression as indicated by HIV RNA concentrations and CD4+ cell counts, patients' previous ARV experiences and responses, concomitant drug therapy, compliance history, underlying disease states, and adverse reaction history.
Ibutilide: An Antiarrhythmic Agent for the Treatment of Atrial Fibrillation or Flutter
Authors: Howard Patricia A
Published: March 2004

OBJECTIVE:

To discuss the clinical pharmacology of the antiarrhythmic drug ibutilide in patients with atrial fibrillation (AF) or atrial flutter (AFl).

DATA SOURCES:

A MEDLINE search (January 1983–December 1997) was used to identify pertinent English-language articles on ibutilide. Key search terms included ibutilide, AF, AFl, cardioversion, and sinus rhythm. The MEDLINE search was supplemented by references included in the bibliographies of comprehensive review articles and studies.

STUDY SELECTION:

Studies and review articles describing the chemistry, pharmacology, and pharmacokinetics of ibutilide were selected. All abstracts and published clinical trials evaluating the efficacy and safety were reviewed.

DATA EXTRACTION:

Pertinent information on the pharmacology and mechanism of action of ibutilide was summarized. Data were extracted from the clinical trials describing trial design, patient population, interventions, methods of evaluation, outcomes, and statistical significance.

DATA SYNTHESIS:

Ibutilide is a Vaughan–Williams class III antiarrhythmic agent approved for intravenous use for the rapid termination of recent-onset AF or AFl. The drug is extensively metabolized by the liver, has a volume of distribution of 11–15 L/kg, is 40% protein bound, and has an elimination half-life of 6 hours (range 2–12). Data from two placebo-controlled trials demonstrated the efficacy of ibutilide for converting AF or AFl of short duration (≤90 d) to normal sinus rhythm. A third placebo-controlled trial demonstrated efficacy in patients who developed AF or AFl following cardiac surgery. Comparative trials with procainamide and sotalol have shown at least similar and perhaps superior efficacy with ibutilide. There are no comparative trials with other antiarrhythmic drugs or with direct current cardioversion (DCC). In 586 clinical trial patients receiving ibutilide, the most significant adverse effect was the development of torsade de pointes in 25 patients (4.3%) including 10 cases (1.7%) in which the rhythm was sustained. All cases of torsade de pointes were terminated electrically and none resulted in death or severe morbidity. No prospective cost-effectiveness studies are available; however, results from two decision models suggest that ibutilide may have advantages over other drugs and first-line electrical cardioversion.

CONCLUSIONS:

Ibutilide appears to be an effective alternative method for rapid conversion of recent-onset AF or AFl. The drug may be particularly useful in patients who have undergone recent cardiac surgery or those who are not ideal candidates for DCC. Although studies suggest that the risk of proarrhythmia and in particular torsade de pointes is relatively low, caution is advised until additional experience is gained in clinical practice.
Torsade De Pointes Induced by Cisapride/Clarithromycin Interaction
Authors: Piquette Rosemary K
Published: March 2004

OBJECTIVE:

To highlight a case of torsade de pointes ventricular arrhythmia induced by the concomitant use of cisapride and clarithromycin.

CASE SUMMARY:

A 77-year-old white woman was admitted to the hospital with a diagnosis of pneumonia and exacerbation of congestive heart failure. In addition to her usual medications, which included cisapride, the patient was prescribed trimethoprim/sulfamethoxazole and clarithromycin for pneumonia. Within 48 hours, the patient had documented episodes of symptomatic torsade de pointes arrhythmia, which eventually responded to therapy. Both cisapride and clarithromycin were discontinued, and the patient did not have any recurring episodes during a 32-month follow-up.

DISCUSSION:

Cisapride has been implicated in causing adverse cardiac events, including torsade de pointes arrhythmia. In most cases, the patients had preexisting risk factors for torsade de pointes and/or were receiving other medications known to inhibit the hepatic CYP3A4 enzyme system and the metabolism of cisapride. There is evidence that clarithromycin, a relatively new macrolide antibiotic, also inhibits the isoenzyme CYP3A4. The resulting accumulation of cisapride caused by concomitant clarithromycin therapy was believed to have been the cause of the torsade de pointes arrhythmia in this patient.

CONCLUSIONS:

Concomitant use of cisapride and clarithromycin may cause torsade de pointes arrhythmia.
Pill-Induced Esophagitis Caused by Oral Rifampin
Authors: Smith Steve J , Lee Audrey J , Maddix Daniel S , Chow Albert W
Published: March 2004

OBJECTIVE:

To report a case of pill-induced esophagitis caused by oral rifampin.

DATA SOURCES:

English-language references identified via a MEDLINE search from January 1966 to May 1998 and a bibliographic review of pertinent articles.

DATA SYNTHESIS:

A large number of oral medications have been reported to cause pill-induced esophagitis. This case represents the second report attributed to rifampin. A 70-year-old white man receiving vancomycin, gentamicin, and oral rifampin for treatment of Staphylococcus epidermidis prosthetic valve endocarditis reported dysphagia immediately after swallowing a rifampin capsule on the fourth day of therapy. The following day, fiberoptic laryngoscopy and esophagoscopy demonstrated a red capsule partially embedded in the neopharynx. A day later, upper esophageal obstruction consistent with edema related to pill-induced esophagitis was identified by barium swallow. Following the procedure, the patient was placed on total parenteral nutrition and took nothing by mouth. Sixteen days after first reporting dysphagia, he was placed on a full liquid diet. Several factors may have increased the patient's risk for pill-induced esophagitis, including age, bedridden state, gastroesophageal reflux disease, simultaneous administration of several medications, and neopharyngeal stricture.

CONCLUSIONS:

Oral rifampin may cause esophagitis. Healthcare providers should be alert to the possibility of pill-induced esophagitis in susceptible patients. Patients with predisposing factors for the development of pill-induced esophagitis should be educated about proper swallowing of oral medications.
INR Elevation Associated with Diarrhea in a Patient Receiving Warfarin
Authors: Smith Joseph K , Aljazairi Abdulrazaq , Fuller Stephen H
Published: March 2004

OBJECTIVE:

To report a case of international normalized ratio (INR) prolongation in a patient receiving warfarin who experienced several episodes of diarrhea.

CASE SUMMARY:

A 56-year-old white woman, previously controlled on warfarin therapy (INR 2.5–3.5) after aortic valve replacement, experienced six episodes of INR elevation, each associated with an acute bout of diarrhea lasting from one to four days. The patient had not received additional warfarin or new medications (including nonprescription medications and herbal remedies) prior to the episodes. The patient had no obvious signs of bleeding (except bruising on 1 episode) or signs of infection determined through physician evaluation of the patient and her stools. In addition, she had no diagnosis of liver disease or acute or chronic malabsorption. The patient did report that her dietary intake decreased to 25–50% of normal during these episodes of diarrhea, which may result in decreased vitamin K ingestion.

DISCUSSION:

This is one of the first case reports documenting a trend of INR elevation specifically with episodes of diarrhea. Since most of the common reasons for acute INR elevation have been eliminated, diarrhea with decreased oral intake are the most probable causes for these observed changes in the INR. Several reports suggest that acute diarrhea results in malabsorption of vitamin K, which can predispose patients taking warfarin to INR elevations, but in many of these reports patients had other risk factors for INR elevation. Although the effect of diarrhea on vitamin K absorption and the INR is difficult to quantify, the INR elevation reported here seemed to be directly associated with the duration of each diarrheal episode.

CONCLUSIONS:

Diarrhea episodes in patients receiving warfarin can result in prolongation of the INR and possible bleeding. Patients who experience diarrhea or decreased oral intake resulting in elevated INRs should have their INRs evaluated more frequently and their warfarin doses adjusted appropriately.
Evaluation of Amlodipine Dosing for Conversion of Nifedipine Extended-Release to Amlodipine in the Treatment of Hypertension
Authors: Yamreudeewong Weeranuj , Halverson Valerie J , Lower Dennis L , Kilpatrick David M , Enlow Ann M , Montopoli George
Published: March 2004

OBJECTIVE:

To evaluate the appropriate dosing of amlodipine when converting patients from nifedipine extended-release (nifedipine ER) to amlodipine in the treatment of hypertension.

METHODS:

Patients of the Outpatient Clinic of Cheyenne Veterans Affairs Medical Center, Wyoming, receiving nifedipine ER for the management of hypertension (systolic BP or SBP >140 mm Hg and diastolic BP or DBP >90 mm Hg), participated in this study. Nifedipine ER was changed to amlodipine on entry into this study. An inclusion criterion was the BP had to be under control (SBP <140 mm Hg and DBP <90 mm Hg) before the switch. The BP in each study patient was monitored once weekly (once every 2 wk in some patients) for a total of six clinic visits or until BP was under control. Dosing titration of amlodipine was required in 16 of 27 patients after the switch. To assess the adequacy of the conversion, the statistical significance of the difference of the mean BP values before and at the end of the monitoring period was estimated by using the t-test for paired data.

RESULTS:

Twenty-seven male patients completed this study. BP in all study patients was adequately controlled after nifedipine ER was switched to amlodipine. The SBP and DBP values before and after the switch were similar (SBP: 124 ± 12 vs. 126 ± 9 mm Hg, CI of the mean difference −6.10 to 1.80; DBP: 76 ± 8 vs. 76 ± 7 mm Hg, CI of the mean difference −2.45 to 3.63). Initial amlodipine dose of 5 or 10 mg once daily was used in our study. No serious adverse effects were observed in any of the study patients after the drug switch.

CONCLUSIONS:

This study indicates the amlodipine dosage of 5 or 10 mg once daily can be used when nifedipine ER is converted to amlodipine in the treatment of hypertension. Dosage titration of amlodipine may be required to obtain adequate control of BP.
Hepatotoxicity Possibly Caused by Amphotericin B
Authors: Gill John , Sprenger Henry R , Ralph Edward D , Sharpe Michael D
Published: March 2004

OBJECTIVE:

To report a case of possible amphotericin B–induced hepatotoxicity in a patient with pulmonary blastomycosis.

A 26-year-old white man with life-threatening pulmonary blastomycosis developed elevation of his liver enzymes after the addition of amphotericin B to his initial itraconazole therapy. The hepatotoxicity resolved rapidly with discontinuation of the amphotericin B, and the blastomycosis was successfully treated with itraconazole alone.

DISCUSSION:

This case illustrates an unusual occurrence of hepatotoxicity associated with a short course of amphotericin B. Liver biopsy was compatible with drug-induced changes and showed no evidence of blastomycosis. Discontinuation of amphotericin B with no other therapeutic changes resulted in a rapid resolution of hepatotoxicity. A possible adverse drug interaction with itraconazole and amphotericin B is postulated based on the mechanism of action of each drug.

CONCLUSIONS:

Amphotericin B therapy can be associated with many adverse effects, but reports of hepatotoxicity are rare. Closer monitoring of liver enzymes in patients receiving amphotericin B, especially in combination with potentially hepatotoxic agents, including azole antifungal drugs, would be prudent.
Angiotensin-Converting Enzyme Gene Polymorphism: Is There a Link to Nephropathy in Patients with Type 1 Diabetes?
Authors: Martin Julie K , Hayney Mary S
Published: March 2004

OBJECTIVE:

To evaluate the association between the angiotensin-converting enzyme (ACE) gene polymorphism and diabetic nephropathy in patients with type 1 diabetes.

DATA SOURCES:

Citations were selected using the MEDLINE database. Only those citations involving human subjects and available in English were selected. Key search words included angiotensin-converting enzyme (ACE), polymorphism, nephropathy, and type 1 diabetes.

STUDY SELECTION:

Selection criteria consisted of all MEDLINE-referenced clinical trials, review articles, and editorial comments assessing the potential link between the ACE gene polymorphism and diabetic nephropathy in insulin-dependent diabetes mellitus published between January 1990 and February 1998.

DATA SYNTHESIS:

Because diabetic nephropathy is a serious complication of type 1 diabetes, focus has been placed on the early identification of and intervention with patients genetically susceptible to this complication. Because the ACE gene polymorphism has an effect on plasma ACE concentration variations among individuals, it has been investigated as a potential genetic marker for diabetic nephropathy. The best studies to date are reviewed in order to assess the utility of the ACE polymorphisms as a genetic marker of diabetic nephropathy in patients with type 1 diabetes, and to determine what implications this holds for drug treatment.

CONCLUSIONS:

Although the ACE gene polymorphism's potential link to diabetic nephropathy in patients with type 1 diabetes has been debated, the most definitive studies show that an association exists. Large epidemiologic studies must now be conducted to determine the implications this polymorphism holds for the best treatment strategies in the care of these patients.
Treatment of Malignant Melanoma
Authors: García Esther Durán , Santolaya Rosario , Requena Teresa
Published: March 2004

OBJECTIVE:

To review the current treatments for cutaneous melanoma and discuss treatment approaches for each patient population.

DATA SOURCES:

MEDLINE and IOWA database search from January 1990 to December 1998.

DATA EXTRACTION:

Clinical trials and review articles were selected and classified to answer questions considered of clinical relevance.

RESULTS:

Patients with stage I, II, and III melanoma should undergo excision after biopsy. In patients with stage IV melanoma, surgical excision of metastatic melanoma is not considered curative but can provide palliation and improve quality of life. Therapeutic lymph node dissection should be performed in patients with melanoma in stages III and IV once pathologic confirmation is obtained. Patients at high risk for recurrence or metastasis may also be considered for elective node dissection. Adjuvant therapy after surgery excision is not a standard of care in patients with stage I and IIa melanoma. In patients with stage IIb and III melanoma, the best results have been obtained with high doses of interferon alfa-2b, although toxicity is of concern. Isolated limb perfusion with melphalan adjuvant to surgery has demonstrated clinically significant benefit in patients with locally recurrent melanoma and in-transit metastases. Studies comparing efficacy and quality of life with this technique or with high doses of interferon alfa-2b are needed. The technique cannot be recommended for high-risk primary melanoma of an extremity with no clinical evidence of metastatic disease.

CONCLUSIONS:

To date, dacarbazine still appears to be the treatment of first choice in metastatic melanoma, outside of a clinical trial. The combination of chemotherapy with interferon alfa-2b or interferon alfa-2a enhances toxicity without a significant survival advantage. Aldesleukin may be an alternative in selected patients when other treatments have failed, but the higher toxicity and cost must be considered.
Glutamine Supplementation in Catabolic Patients
Authors: Sacks Gordon S
Published: March 2004

OBJECTIVE:

To evaluate the safety and efficacy of parenteral and enteral glutamine supplementation in patients who are catabolic.

DATA SOURCES:

English-language clinical trials and review articles identified by MEDLINE searches (January 1970–December 1997) and from bibliographies of selected articles were considered for possible inclusion. Key words used in the search strategy were glutamine, critical illness, stress, catabolism, injury, enteral nutrition, and parenteral nutrition.

STUDY SELECTION AND DATA EXTRACTION:

Inclusion was restricted to pertinent studies that evaluated the safety of glutamine supplementation, as well as effects of glutamine on amino acid metabolism, immune function, and patient outcome. Data from 18 clinical trials and multiple review articles were compiled into a review format.

DATA SYNTHESIS:

Glutamine is an important metabolic fuel for intestinal enterocytes, lymphocytes and macrophages, and metabolic precursors such as purines and pyrimidines. Although originally considered a nonessential amino acid, experimental work suggests that glutamine is essential for maintaining intestinal function, immune response, and amino acid homeostasis during periods of severe stress. In the past decade, clinical trials conducted in metabolically stressed patients indicate that glutamine improves nitrogen balance, increases cellular proliferation, decreases the incidence of infection, and shortens hospital stay in some catabolic patients.

CONCLUSIONS:

Glutamine has been studied extensively over the past decade for its role during critical illness. Clinical trials conducted in humans demonstrate glutamine to be well tolerated without adverse consequences, even during times of stress. Although glutamine has shown promise in select groups of catabolic patients, additional studies are needed to define which patient populations derive the greatest benefit from supplemental glutamine and the mechanisms by which these effects are exerted.
Bupropion Mimics a Transient Ischemic Attack
Authors: Humma Larisa M , Swims Melanie P
Published: March 2004

OBJECTIVE:

To report the development of symptoms suggesting transient ischemic attacks during bupropion treatment for smoking cessation.

CASE SUMMARY:

A 67-year-old white man experienced paresthesia, dizziness, tinnitus, confusion, and gait impairment shortly after starting bupropion as an aid to smoking cessation. Bupropion was discontinued on hospital admission, and testing for vertebral basilar artery disease was negative. His symptoms resolved, and he remained asymptomatic until restarting bupropion two days after hospital discharge.

DISCUSSION:

Although separate case reports have reported sensory disturbances, tinnitus, and balance impairment associated with bupropion use, the combination of symptoms occurring in this patient has not been previously published.

CONCLUSIONS:

The temporal relationship between bupropion exposure and symptomatology suggests that bupropion caused symptoms mimicking transient ischemic attacks in this patient.
Cholinesterase Inhibitors: A Therapeutic Strategy for Alzheimer Disease
Authors: Krall Wanda J , Sramek John J , Cutler Neal R
Published: March 2004

OBJECTIVE:

To provide a review of acetylcholinesterase inhibitors (AChEIs) tested as therapeutic agents for Alzheimer disease (AD).

DATA SOURCES:

MEDLINE searches (January 1986–July 1998) identified pertinent literature. Selected references from these articles, as well as abstracts from recent meetings and package insert literature from approved compounds, were also used as source material.

DATA EXTRACTION:

AChEIs were reviewed with regard to chemical structure, mechanism of inhibition, substrate specificity, pharmacokinetics/pharmacodynamics, safety/tolerability, and efficacy.

DATA SYNTHESIS:

Cholinergic deficits, leading to cognitive impairment, are a significant aspect of neurodegeneration in AD. AChEIs reduce the degradation of acetylcholine, thus enhancing cholinergic transmission. In addition to the two agents approved by the Food and Drug Administration, tacrine and donepezil, six other compounds of diverse chemical structure and mechanism of inhibition including physostigmine, metrifonate, rivastigmine, and galantamine are under investigation as potential therapy for AD. These compounds are structurally diverse, possess unique patterns of specificities for the various forms of cholinesterase enzymes, use distinct mechanisms of enzyme inhibition, present unique adverse event profiles, and offer relatively similar mean gains in cognitive abilities to patients with AD in controlled clinical trials.

CONCLUSIONS:

Relative to placebo, new AChEIs in development provide modest improvements in cognition for patients with mild to moderate AD, with improved tolerability profiles and more convenient dosing relative to tacrine. The availability of a wide array of AChEIs soon to be accessible to patients with AD will provide additional options to those who cannot tolerate or do not respond to drugs currently used for AD.
Etidronate and Alendronate in the Treatment of Postmenopausal Osteoporosis
Authors: Beauchesne Marie-France , Miller Penny F
Published: March 2004

OBJECTIVE:

To review the clinical trials evaluating the efficacy of etidronate and alendronate in the treatment of established postmenopausal osteoporosis.

DATA SOURCE:

A MEDLINE search was performed (from 1966 through September 1998) using the search terms bisphosphonates, etidronate, alendronate, and postmenopausal osteoporosis. English-language articles were considered for review.

STUDY SELECTION AND DATA EXTRACTION:

Prospective, randomized, double-blind, placebo-controlled clinical trials using fracture as an end point were selected to review the efficacy of etidronate and alendronate in the treatment of postmenopausal osteoporosis. Results for the outcomes of bone mineral density (BMD) and fracture are summarized.

DATA SYNTHESIS:

Etidronate and alendronate increase spinal BMD in postmenopausal women with osteoporosis. In one study, etidronate decreased the number of women sustaining new radiographic vertebral fractures over two years, but this effect was lost after three years of treatment. Alendronate reduces the number of radiographic vertebral fractures in postmenopausal women with a low bone mass. In women with preexisting fractures, alendronate decreases the number of patients with radiographic vertebral fractures, clinical (i.e., symptomatic vertebral and nonvertebral) fractures, and hip fractures. A significant reduction in the overall number of nonvertebral fractures has not been demonstrated in clinical trials evaluating either alendronate or etidronate.

CONCLUSIONS:

No studies have directly compared the efficacy of alendronate and etidronate and the results of long-term clinical trials (i.e., >5 y) have not been published. Based on the results obtained in clinical trials using fracture as an end point, alendronate appears to be the bisphosphonate of choice. Safety profiles and cost should also be considered in the choice of etidronate or alendronate for the treatment of postmenopausal osteoporosis.
Fosinopril and Hydrochlorothiazide Combination versus Individual Components: Lack of a Pharmacokinetic Interaction
Authors: Uderman Howard D , Much David R , Brennan John , Delaney Carol L , Morgenthien Elizabeth A , Weaver Jerry , Stouffer Bruce C , Chang Shu-Ying , VanHarken Donald , Liao Wei-Chi
Published: March 2004

OBJECTIVE:

To evaluate the pharmacokinetic interaction and bioequivalence of a combination formulation of the angiotensin-converting enzyme inhibitor fosinopril and the diuretic hydrochlorothiazide (HCTZ).

METHODS:

In an open-label, balanced, randomized incomplete block, three-way crossover fashion, healthy men received single doses of three of four regimens in one of two independent studies. Regimens for study A (36 subjects): (1) fosinopril 10-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 10 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 10 mg and HCTZ 12.5 mg. Study B (40 subjects) received: (1) fosinopril 20-mg tablet, (2) HCTZ 12.5-mg tablet, (3) a combination tablet of fosinopril 20 mg plus HCTZ 12.5 mg, or (4) coadministered tablets of fosinopril 20 mg and HCTZ 12.5 mg.

RESULTS:

There was no evidence of any significant effect of HCTZ on the pharmacokinetics of fosinoprilat, based on maximum concentration value, AUC, or cumulative urinary recovery over 24 hours. Fosinoprilat had no clinically important effect on the pharmacokinetics of HCTZ only slightly decreasing its AUC by 14% in study A. Coadministration was well tolerated; no new adverse events were reported with the combination tablet.

CONCLUSIONS:

Fosinopril and HCTZ in a combination tablet display pharmacokinetic profiles similar to those achieved when either drug is administered alone or when coadministered in separate tablets. When used with HCTZ, the favorable pharmacokinetic feature of fosinopril, dual and compensatory pathways of renal and hepatic elimination, is preserved.
A Critical Evaluation of the Methodology of the Literature on Medication Compliance
Authors: Nichol Michael B , Venturini Francesca , Sung Jennifer CY
Published: March 2004

OBJECTIVE:

To develop a simple evaluation tool to assess methodologic rigor of the literature on patient compliance with medications, and to apply the tool to a sample of the literature.

METHODS:

A computerized search of the MEDLINE database (January 1980–December 1996) was performed. All English-language articles on compliance with medications were identified, using the MeSH terms patient-compliance and drug-therapy. A 10% sample was then randomly selected for review. Methodologic rigor was assessed on eight standards: study design, specification of patient sample, power analysis, specification of disease, specification of therapeutic regimen, duration of follow-up, definition of compliance, and compliance measurement. The raw scores of the eight standards were then combined in three summary scores, standardized from 0 to 100: study design, disease-related features, and compliance issues.

RESULTS:

Seventy-two articles from 719 identified were reviewed. The majority of the research articles were descriptive (63.9%), and patients in these studies were selected mainly from a convenience sample (41.7%). Just nine studies were multicenter studies, and three employed power analysis. The compliance definition was replicable in 41.7% of the studies. In 22 articles neither the compliance measure nor the criteria were stated. One-quarter of the studies (18) used a nonvalidated measure of compliance. Only two studies reached a score of 6 in the compliance measure, and eight studies used two different measures of compliance simultaneously. The median values in the summary scores were: study design 8.3, disease 42.9, compliance issues 50.

CONCLUSIONS:

The quality of the compliance research was generally poor. These low scores reflect very important shortcomings in the methodology. Such oversights make it difficult for the reader to critically assess the validity of the conclusions.
High-Dose Methotrexate–Doxycycline Interaction
Authors: Tortajada-Ituren Juan José , Ordovás-Baines Juan Pablo , Llopis-Salvia Pilar , Jiménez-Torres N Victor
Published: March 2004

OBJECTIVE:

To report a case in which an interaction occurred between doxycycline and high-dose methotrexate (HD-MTX) and discuss its clinical, quality of life, and economic repercussions.

CASE SUMMARY:

A 17-year-old girl diagnosed with high-degree osteosarcoma in her left femur was admitted to our hospital to receive her eleventh postoperative cycle of HD-MTX, according to the clinical protocol approved at our hospital. Simultaneously, due to a palpebral abscess in her left eye, the patient received systemic treatment with doxycycline 100 mg every 12 hours. As in previous cycles, pharmacokinetic monitoring of methotrexate (MTX) plasma concentrations was performed to improve leucovorin calcium rescue. The biological half-life 12 and 24 hours after infusion showed that the patient was at high risk of intoxication. She then developed hematologic as well as gastrointestinal toxicity and remained hospitalized for 11 days. The patient was readmitted 48 hours after hospital discharge because of a febrile episode that required an additional hospital stay of 12 days, and the twelfth cycle of HD-MTX had to be postponed 18 days because of the results of the previous cycle.

DISCUSSION:

Significant differences (p < 0.05) were observed in the eleventh HD-MTX cycle for plasma concentrations and pharmacokinetic parameters compared with the previous 10 cycles. The interaction resulted in clinical, quality of life, and economic repercussions.

CONCLUSIONS:

The potential interaction between MTX and doxycycline may cause pharmacokinetic changes, and its clinical repercussions on the quality of life of the patient and associated costs should be considered.
Estrogen for Dementia-Related Aggression in Elderly Men
Authors: Shelton Penny S , Brooks Valerie G
Published: March 2004

OBJECTIVE:

To report the use of conjugated estrogens for aggression in two elderly men with dementia and to review the available literature relating to estrogen use for aggression in the elderly.

CASE SUMMARIES:

Case 1. A 78-year-old white man had probable Alzheimer dementia and aggression (verbal and physical) that was nonresponsive to antipsychotic, antidepressant, and mood stabilizer therapy. However, conjugated estrogens 1.875 mg/d reduced his physical aggression, as evidenced by a 75% decline in aggressive episodes, per 24-hour nursing reports and progress notes. Case 2. A 78-year-old African-American man with vascular dementia, physical aggression, and sexual inappropriateness was unsuccessfully managed with several antipsychotic and benzodiazepine trials. He did, however, exhibit a decline in physical and sexual aggression by 80%, as well as a 55% reduction in sexual comments, after daily treatment with conjugated estrogens 0.625 mg. Estrogen was well tolerated by both patients.

DATA SOURCES:

MEDLINE (January 1966–May 1998) and PsychLit (January 1974–May 1998) database searches were performed to identify case reports, letters, or clinical trials discussing estrogen use in aggressive elderly patients.

CONCLUSIONS:

As with previous reports, these cases suggest that conjugated estrogens may be used to reduce physical and sexual aggression associated with dementia in elderly men. Additional study is needed to determine the exact role of this alternative pharmacologic intervention.
Clinical and Financial Impact of Intravenous Erythromycin Therapy in Hospitalized Patients
Authors: Classen David C , Burke John P , Pestotnik Stanley L , Lloyd James F
Published: March 2004

OBJECTIVE:

To determine the economic consequences of intravenous erythromycin use in hospital patients in a variety of clinical circumstances.

DESIGN:

Retrospective cohort study of patients with specified primary diagnosis-related group discharge diagnoses treated from January 1, 1990, to December 31, 1994, who received erythromycin, and a matched cohort group from the same period who did not receive erythromycin.

SETTING:

LDS Hospital, Salt Lake City, UT, a 520-bed teaching hospital.

PATIENTS:

A long-term archive of clinical and financial data from a computerized hospital information system was searched for patients meeting a strict case definition. This archive contained information on erythromycin exposure as well as concurrent drug therapy and adverse drug events that had been prospectively evaluated during hospitalization throughout the study and cohort periods. Detailed costs were available for each patient.

MAIN OUTCOME MEASURE:

Attributable differences in lengths of stay and total costs determined using linear regression modeling.

RESULTS:

For 797 erythromycin patients and 2771 cohort patients, we found an attributable increased length of stay of 2.14 days and an increased cost of hospitalization of $6061 for erythromycin case patients. Case patients also had a significantly increased risk of adverse drug events. Linear regression modeling showed that erythromycin use was significantly related to increased length of stay and cost of hospitalization.

CONCLUSIONS:

Intravenous erythromycin use has been associated with significant increases in hospital length of stay and total hospital cost.
Famotidine in the Management of Schizophrenia
Authors: Martinez Maribeth C
Published: March 2004

OBJECTIVE:

To evaluate the use and potential benefit of famotidine in the management of schizophrenia.

DATA SOURCES:

Clinical literature accessed through MEDLINE (February 1998–October 1998). Key search terms included famotidine, schizophrenia, and histamine.

DATA SYNTHESIS:

Schizophrenia is a complicated disorder associated with high morbidity if left unmanaged. Histamine2 (H2)-antagonists may be an alternative to conventional treatments. An evaluation of studies focusing on famotidine in the management of schizophrenic symptoms was conducted.

CONCLUSIONS:

Famotidine can improve schizophrenic symptoms that were otherwise refractory to typical antipsychotic agents. Further studies should be conducted to determine if other H2-antagonists are also effective.
Estimating Risk Factors for Patients with Potential Drug-Related Problems Using Electronic Pharmacy Data
Authors: Isaksen Sune Faurschou , Jonassen Jacob , Malone Daniel C , Billups Sarah J , Carter Barry L , Sintek Charles D
Published: March 2004

OBJECTIVE:

To validate a computer-based program to identify patients at high risk for drug-related problems.

DESIGN:

Computerized analysis of pharmacy dispensing records and manual review of medical records.

SETTING:

Ambulatory clinics at a Veterans Affairs Medical Center.

PATIENTS:

246 randomly selected patients who were receiving at least one outpatient medication in the previous 24 months.

MAIN OUTCOME MEASURES:

Presence of six previously established criteria regarding medication use. These criteria are five or more medications, ≥12 doses per day, four or more changes to the medication regimen, three or more chronic diseases, history of noncompliance, and presence of a drug requiring therapeutic drug monitoring (TDM).

RESULTS:

Spearman rho rank order correlation coefficients ranged from 0.63 to 0.91 for criteria pertaining to the number of medications, daily doses, changes in the medication regimen, and number of chronic diseases (all significant, p = 0.0001). The computer program underestimated the number of chronic diseases and overestimated the number of daily doses. The level of agreement between the computer program and chart review for patient noncompliance was low (Kappa = 0.38), with the computer more likely to indicate a patient was noncompliant. A high level of agreement was seen between the computer program and chart review for the presence of a drug requiring TDM (Kappa = 0.83). For all six criteria, the computer program had a sensitivity of 65.7% and specificity of 88.2%.

CONCLUSIONS:

When compared with medical records, the use of this program to evaluate electronic pharmacy data can be efficient to screen large numbers of patients who may be at high risk for drug-related problems. This method may be useful for clinical pharmacists in providing pharmaceutical services to patients who are most likely to benefit.
Donepezil Overdose: A Tenfold Dosing Error
Authors: Shepherd Greene , Klein-Schwartz Wendy , Edwards Robin
Published: March 2004

OBJECTIVE:

To report toxicity resulting from donepezil administration following a tenfold dosing error.

CASE SUMMARY:

A 79-year-old white nursing home patient with a history of Alzheimer disease and hypertension was inadvertently given 50 mg of donepezil instead of her usual 5-mg dose. She presented to the emergency department with nausea, vomiting, and persistent bradycardia (HR in the 40s). Routine laboratory studies were all within normal limits. Basilar rales were noted five hours after arrival. She was treated with atropine 0.2 mg as needed for bradycardia (HR <50 beats/min); a total of 3.0 mg was administered over 18 hours. Each bolus kept her HR >60 beats/min for one-half to two hours. No further vomiting or evidence of pulmonary edema occurred after her initial episodes. She returned to baseline by day 2 (HR in the 70s) and was returned to the nursing home.

DISCUSSION:

Donepezil is a centrally acting, reversible cholinesterase inhibitor that is used in the treatment of Alzheimer disease. Donepezil is highly specific for neural acetylcholinesterases, preferentially binding acetylcholinesterase by greater than three orders of magnitude over butyrylcholinesterases. This specificity minimizes peripheral adverse effects at therapeutic doses. Our patient mainly experienced bradycardia and had minimal secretory effects compared with what is usually seen with nonspecific cholinesterase inhibition. Medication errors like the one that produced this overdose are a common but preventable cause of morbidity in healthcare facilities.

CONCLUSIONS:

A tenfold dosing error caused donepezil toxicity. The main effect of this overdose was bradycardia, which responded to atropine therapy.
Lyme Disease Prevention and Vaccine Prophylaxis
Authors: Hayney Mary S , Grunske Mike M , Boh Larry E
Published: March 2004

OBJECTIVE:

To provide a comprehensive review of the epidemiology, diagnosis, and prevention of Lyme disease with a focus on the Lyme disease vaccine.

DATA SOURCE:

A computerized search of MEDLINE (January 1996–December 1998) was used to identify articles regarding Lyme disease, Borrelia burgdorferi, epidemiology, prevention, and vaccine.

DATA SYNTHESIS:

Lyme disease is a condition caused by infection with B. burgdorferi. The organism is carried by certain species of Ixodes ticks and is the most common tick-borne disease in the US. In patients with clinical manifestations of Lyme disease, various pharmacotherapeutic approaches have proven effective in treatment of the clinical features. Prevention strategies exist; however, their application is sometimes difficult. A vaccine for the prevention of Lyme disease is available, and another is being considered for approval. The recombinant outer surface protein A (OspA) vaccines to prevent Lyme disease are immunogenic and have an acceptable adverse effect profile. These vaccines are highly efficacious for the prevention of Lyme disease.

CONCLUSIONS:

Lyme disease is the most common tick-borne disease in the US. The infection, caused by B. burgdorferi, results in dermatologic, neurologic, cardiovascular, and musculoskeletal manifestations. Until recently, tick bite prevention strategies were the only means of decreasing the risk of acquiring the infection. The OspA vaccines are efficacious for the prevention of infection. Although universal immunization with these vaccines is unlikely, the availability of effective vaccines represents an important tool for the prevention of Lyme disease in endemic regions of the US.
Ototoxicity Associated with Vinblastine
Authors: Moss Patrick E , Hickman Scot , Harrison Bruce R
Published: March 2004

OBJECTIVE:

To describe a patient with ototoxicity associated with vinblastine chemotherapy.

CASE SUMMARY:

A 29-year-old white man with recurrent Hodgkin's disease received doxorubicin, bleomycin, vinblastine, and dacarbazine (ABVD) chemotherapy once every two weeks for 12 cycles. He reported tinnitus after each treatment, with an onset of about six hours and a duration of seven to 10 days. This interfered with reading, watching television, and general concentration. Symptoms returned to baseline prior to the beginning of each subsequent cycle. Audiograms performed before and after several cycles showed mild sensorineural hearing loss in the high-decibel range, but no loss of speech recognition.

DISCUSSION:

No reported cases of ototoxicity or tinnitus from ABVD were found. All concomitant medications were eliminated as possible causes either due to lack of temporal association with the symptoms or no reports of ototoxicity in the literature. Vincristine, a more commonly used vinca alkaloid very similar to vinblastine, was noted to have caused several cases of sensorineural hearing loss.

CONCLUSIONS:

This case suggests that vinblastine may cause ototoxicity.
Once-Daily Aminoglycosides in the Treatment of Gram-Positive Endocarditis
Authors: Tam Vincent H , Preston Sandra L , Briceland Laurie L
Published: March 2004

OBJECTIVE:

To examine the role of once-daily aminoglycosides (ODA) in the treatment of gram-positive endocarditis.

DATA SOURCES:

A MEDLINE search was conducted from January 1984 to August 1998, and a Current Contents search was performed from September 1998 to December 1998, using endocarditis or aminoglycoside as key words. In addition, relevant articles were cross-referenced to screen for additional information.

DATA EXTRACTION:

Data published in English regarding the use of aminoglycosides in endocarditis are cited. Emphasis was placed on animal and human studies, but in vitro studies and review articles are also included.

DATA SYNTHESIS:

Endocarditis and the pharmacology of aminoglycosides are briefly reviewed. ODA is an alternative to conventional dosing in the treatment of endocarditis. Extensive work in endocarditis has been done recently in animals and humans to add to our understanding. Limited clinical data exist to support the theoretical advantages of increased efficacy, reduced toxicity, and potential cost savings versus traditional synergistic aminoglycoside dosing. Optimal monitoring of ODA remains undefined.

CONCLUSIONS:

Routine use of ODA for the treatment of endocarditis is not yet advocated. Promising supporting evidence and speculation of success of ODA in gram-positive endocarditis justify well-designed trials to further define its role in therapy.
Sibutramine: A Serotonin–Norepinephrine Reuptake-Inhibitor for the Treatment of Obesity
Authors: Luque Carla A , Rey Jose A
Published: March 2004

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy data, adverse effects, and drug interactions of sibutramine as a treatment for obesity.

DATA SOURCES:

English-language clinical studies, abstracts, and review articles were identified using MEDLINE, EMBASE, and a manual search from January 1980 through December 1998. References were also obtained from the reference section of published articles.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified were evaluated for possible inclusion in this review. Evaluative and comparative data from prospective, open-label, double-blind, and controlled studies were reviewed.

DATA SYNTHESIS:

Sibutramine is a serotonin–norepinephrine reuptake-inhibitor effective in the treatment of obesity. It does not act as a releasing agent of these neurotransmitters. Sibutramine undergoes extensive metabolism in the liver via CYP3A4, forming two pharmacologically active metabolites. This agent has demonstrated efficacy superior to placebo in reducing weight when used as part of an integrated regimen involving behavior modification, physical activity, and a reduced-calorie intake. The most frequently reported adverse effects include dry mouth, anorexia, headache, insomnia, and constipation. Sibutramine has also been shown to substantially increase blood pressure and heart rate in some patients.

CONCLUSIONS:

Based on anorectic efficacy data, sibutramine, a serotonin–norepinephrine reuptake-inhibitor, is a viable therapeutic option for the treatment of obesity. Recommended candidates for this medication are patients with a body mass index (BMI) ≥30 kg/m2 without concomitant risk factors or patients with a BMI ≥27 kg/m2 with concomitant risk factors. Sibutramine should be used with caution in patients with a history of hypertension and should not be used in those with uncontrolled hypertension and concomitant cardiovascular disease. Further studies need to be conducted in order to identify long-term outcomes beyond one year.
Concomitant Digoxin Toxicity and Warfarin Interaction in a Patient Receiving Clarithromycin
Authors: Gooderham Melinda J , Bolli Peter , Fernandez Peter G
Published: March 2004

OBJECTIVE:

To report a case of a clarithromycin-associated warfarin interaction and digoxin toxicity in a patient.

CASE SUMMARY:

A 72-year-old white woman with chronic atrial fibrillation receiving long-standing therapy with digoxin 0.25 mg/d and warfarin 22.5 mg/wk was prescribed clarithromycin 500 mg three times daily for eradication of Helicobacter pylori. The patient presented to the emergency department with gastrointestinal symptoms, weakness, dizziness, and visual changes 12 days after initiation of clarithromycin. Laboratory results revealed a serum digoxin concentration of 4.6 ng/mL (normal 1.0–2.6) and an international normalized ratio of 7.3 (2.0–3.0). Digoxin, warfarin, and clarithromycin were discontinued and the patient was admitted to the hospital for treatment to resolve the symptoms and to return laboratory values to a safe range. Reduced dosages of digoxin (0.125 mg/d) and warfarin (17.5 mg/wk) were restarted on day 7 of hospitalization. The patient was discharged on day 11 in good condition.

DISCUSSION:

Several reports of clarithromycin-induced drug interactions with digoxin and with warfarin have been published. Previously, case reports of macrolide-associated interactions mainly involved erythromycin, but more recently have implicated clarithromycin. The interaction between clarithromycin and warfarin is thought to occur from an inhibition of the cytochrome P450 drug metabolizing system. Clarithromycin is thought to cause digoxin toxicity by an alteration of the digoxin-metabolizing gut flora, thereby causing an increase in the digoxin concentration in susceptible individuals. Drug interactions can occur by different mechanisms in the same patient.

CONCLUSIONS:

Potential drug interactions can occur between commonly prescribed medications. It is important to monitor patients for symptoms and alterations in laboratory values to prevent not only serious complications, but also unnecessary hospitalizations.