bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of Number of Medications on Cardiovascular Therapy Adherence
Authors: Shalansky Stephen J , Levy Adrian R
Published: June 2003

OBJECTIVE:

Increasing regimen complexity is generally assumed to result in lower medication adherence, but there is conflicting evidence. This study determined the relationship between the number of medications dispensed and adherence with chronic cardiovascular regimens.

METHODS:

A survey was administered to 367 patients who had taken an angiotensin-converting enzyme inhibitor or lipid-lowering medication for at least 3 consecutive months. Information was collected on nonprescription drug use, demographics, adverse effects, and use of adherence aids. Prescription drug use data over the previous 12 months were obtained for each subject from the British Columbia prescription claims database. Adherence for each prescription medication was calculated based on prescription fill dates and number of days supplied. Univariate and multivariate analyses were used to identify predictors of nonadherence (>80%) with cardiovascular medications.

RESULTS:

Forty-five subjects (12%) were categorized as nonadherent. Nonadherent subjects took fewer regularly scheduled prescription medications per day (4.1 ± 2.7 vs. 5.9 ± 3.4; p = 0.001), fewer pills per day (5.3 ± 3.6 vs. 9.2 ± 7.1; p < 0.001), and had fewer administration × per day (1.8 ± 0.7 vs. 2.4 ± 0.9; p = 0.001). A multivariate logistic regression model adjusting for age, gender, reported adverse effects, reported nonprescription drug use, and use of adherence aids identified fewer regularly scheduled prescription drugs as an independent predictor of nonadherence with chronic cardiovascular medications (OR = 0.85 per medication, 95% CI 0.74 to 0.94; p = 0.01).

CONCLUSIONS:

Contrary to popular belief, taking fewer medications was associated with lower adherence with chronic cardiovascular regimens.
Clonidine-Induced Hypertension in a Patient with a Spinal Lesion
Authors: Backo Angel L , Clause Steven L , Triller Darren M , Gibbs Karen A
Published: June 2003

OBJECTIVE:

To report a case of possible clonidine-induced hypertension (by Naranjo score) in a patient with a C4 spinal lesion.

BACKGROUND:

Clonidine is a medication long used to treat hypertension, and it is still used in the treatment of refractory hypertension. Although effective, clonidine use is hindered by adverse effects and its dual mechanism of action.

CASE SUMMARY:

A 39-year-old white, quadriplegic man with poorly controlled pain displayed many characteristics consistent with autonomic dysfunction (e.g., C4 spinal lesion, orthostatic hypotension, hypertension). The patient was routinely receiving transdermal clonidine and also received transdermal nitroglycerin paste as needed for control of acute hypertensive episodes. On the recommendation of the home healthcare pharmacists, clonidine was discontinued. Since that time, the patient's blood pressure and the use of emergent antihypertensive treatment have decreased significantly (maximum systolic and diastolic BP by ∼50 and 25 mm Hg, respectively).

CONCLUSIONS:

Many of the characteristics of autonomic dysfunction, such as refractory hypertension, can seem selective for the use of clonidine and, because of its reliance on central α2-activity for its hypotensive effects, clonidine may induce hypertension in patients with autonomic dysfunction. Clonidine should be used with great caution when autonomic dysfunction is suspected.
Treatment of Azole-Resistant Oropharyngeal Candidiasis with Topical Amphotericin B
Authors: Grim Shellee A , Smith Kelly M , Romanelli Frank , Ofotokun Ighovwerha
Published: June 2003

OBJECTIVE:

To report a case of successful treatment of azole-refractory oropharyngeal candidiasis with topical amphotericin B.

CASE SUMMARY:

A 30-year-old white woman presented with recurrent oral thrush. The patient had been exposed to azole antifungals for >20 years, and in vitro susceptibility tests revealed class resistance. The patient started taking amphotericin B 100 mg oral suspension swish-and-spit 4 × daily. After 4 weeks of topical amphotericin B treatment, the patient reported significant symptomatic improvement. The oral candidiasis worsened following a course of oral antibiotics, but improved once the antibiotic was discontinued and after receiving amphotericin B swish-and-swallow for 4 additional weeks.

DISCUSSION:

Current Infectious Diseases Society of America guidelines include topical amphotericin B as a potentially effective option for the treatment of oropharyngeal candidiasis. There is limited evidence to support this recommendation. Besides lack of data, an appropriate dosing regimen and consistent means of product formulation need to be determined.

CONCLUSIONS:

This report demonstrates the potential role for topical amphotericin B in the treatment of azole-refractory oral candidiasis. Double-blind, randomized, controlled trials are needed to define dosing, efficacy, administration, and long-term safety of oral amphotericin B.
Interferon Therapy for Acute Hepatitis C during Pregnancy
Authors: Özaslan Ersan , Yılmaz Rahmi , Simsek Halis , Tatar Gonca
Published: June 2003

OBJECTIVE:

Due to their antiproliferative activity, the probable effects of interferons on a fetus are a concern. We report on a pregnant patient who developed acute hepatitis C during pregnancy and was treated with a short course of interferon alfa therapy with a successful outcome.

CASE SUMMARY:

A 26-year-old woman was diagnosed with acute hepatitis C at the 16th week of pregnancy. She received a total dose of 72 million units of interferon alfa-2b during a 2 1/2 month period. Although the therapy was discontinued due to adverse effects, a complete biochemical and virologic response was obtained. Premature labor occurred and healthy, but growth-restricted, twin infants were born transvaginally. At 18 months of age, they had normal development, with a negative hepatitis C serology.

DISCUSSION:

The rate of transmission of hepatitis C virus from mother to infant is within the range of 1–5%. Although acute hepatitis C during pregnancy is a very rare occurrence, the mother is at a great risk for chronic infection. There is scarce literature about the probable effects of interferon use during pregnancy due to a lack of controlled studies in this special population. A total of 8 infants, including ours, exposed to interferon alfa and/or ribavirin during pregnancy showed no congenital anomalies or malformations.

CONCLUSIONS:

Patients with chronic hepatitis whose therapy can be delayed should not be treated with interferon due to a lack of controlled studies. However, women exposed to interferon inadvertently during pregnancy may be encouraged to continue pregnancy. In patients with acute hepatitis C during pregnancy, the use of interferon therapy should be considered with close monitoring.
Citalopram-Associated SIADH
Authors: Barclay Teresa S , Lee Audrey J
Published: June 2003

OBJECTIVE:

To report a case of the syndrome of inappropriate secretion of antidiuretic hormone (SIADH) associated with use of citalopram in an elderly male patient and to review the English-language literature for any previous reports of SIADH or hyponatremia caused by citalopram.

CASE SUMMARY:

An 87-year-old Filipino man was admitted to the hospital reporting malaise, confusion, dizziness, and falls approximately 3 weeks following an increase in his citalopram dosage from 10 to 20 mg/d. On physical examination, the patient was euvolemic and had no evidence of malignancy, cardiac, renal, or hepatic disease. Pertinent laboratory test results revealed hyponatremia, serum hypoosmolality, urine hyperosmolality, and elevated urine sodium concentration, leading to a diagnosis of SIADH. Citalopram was discontinued and fluid restrictions were instituted. The patient was discharged after his serum sodium increased from 122 to 128 mEq/L and he reported increased strength and decreased confusion. Five days after discharge, the patient denied experiencing any new falls, weakness, confusion, or lethargy. His serum sodium measured that day was 131 mEq/L; 2 months later, it was 135 mEq/L.

DISCUSSION:

We report the seventh case of citalopram-induced hyponatremia published in the English language and the second in a man. Review of the cases demonstrated that the onset of citalopram-induced hyponatremia or SIADH ranged from 6 to 20 days. Potential risk factors for SIADH due to citalopram included advanced age, female gender, concomitant use of medications known to cause SIADH or hyponatremia, and, possibly, higher citalopram doses.

CONCLUSIONS:

Elderly patients receiving citalopram should be monitored for signs and symptoms of SIADH, especially in the first few weeks of therapy, in the presence of risk factors, and during dose escalation.
Interaction of Colony-Stimulating Factors and Fluorodeoxyglucose F18 Positron Emission Tomography
Authors: Mayer Dmitri , Bednarczyk Edward M
Published: June 2003

OBJECTIVE:

To evaluate reports of altered diagnostic images with fluorodeoxyglucose F18 (FDG) positron emission tomography (PET) after treatment with colony-stimulating factors (CSFs).

DATA SOURCES:

Literature was identified by a MEDLINE search (1966–December 2001). Key search terms included granulocyte colony-stimulating factor, granulocyte—macrophage colony-stimulating factor, macrophage colony-stimulating factor, fluorodeoxyglucose, and emission-computed tomography. English language literature was reviewed.

DATA SYNTHESIS:

Reports have suggested altered FDG PET images following CSF treatment. Studies that assessed the effect of CSF administration on FDG PET imaging of the bone and bone marrow were reviewed.

CONCLUSIONS:

Administration of CSFs may interfere with accurate FDG PET imaging. Separating FDG PET imaging from CSF therapy by ≥5 days may diminish this interference.
Levofloxacin and Warfarin Interaction
Authors: Jones Cade B , Fugate Susan E
Published: June 2003

OBJECTIVE:

To report 4 cases of hypoprothrombotic response resulting from addition of levofloxacin therapy to chronic warfarin therapy and to review related literature to support or refute a warfarin—levofloxacin interaction.

CASE SUMMARY:

Four patients, 34–81 years old, were prescribed levofloxacin concomitantly with stable warfarin therapy. Three patients had a target international normalized ratio (INR) range of 2.0–3.0 and experienced an increase in INR to 3.5, 8.12, and 11.5 on days 11, 5, and 4 of a 10-day course of levofloxacin, respectively. The fourth patient experienced minor bleeding, with a slightly elevated INR on the second day of levofloxacin therapy that required up to a 19% warfarin dose reduction during levofloxacin treatment.

DISCUSSION:

An initial premarketing clinical trial concluded that levofloxacin had no effect on warfarin's pharmacokinetics and pharmacodynamic response. Two case reports have since documented an increase in INR in patients taking long-term warfarin on completion of levofloxacin therapy. Our case reports provide further evidence of a significant increase in INR observed during concomitant levofloxacin therapy. The proposed mechanism of this interaction is displacement of warfarin from protein binding sites, reduction in gut flora producing vitamin K, and decreased warfarin metabolism.

CONCLUSIONS:

Prolonged prothrombin response in patients undergoing chronic warfarin therapy has been well documented with many antibiotics, including fluoroquinolones. Recognition of newer antibiotics' effects on warfarin therapy is important to guide safe use and monitoring of anticoagulation therapy. Our case studies demonstrate significant elevations in INR values during and up to 1 day after levofloxacin therapy in patients undergoing stable warfarin therapy.
Citalopram in Children and Adolescents with Depression or Anxiety
Authors: Baumgartner Jennifer L , Emslie Graham J , Crismon M Lynn
Published: June 2003

OBJECTIVE:

To investigate the efficacy and tolerability of citalopram in children and adolescents.

METHOD:

Retrospective chart review of 17 outpatients treated with citalopram at a tertiary care center. Subjects were diagnosed with a depressive or anxiety disorder with or without comorbidities and may have received concurrent medications. The primary outcome measure was the Clinical Global Impression Improvement Scale (CGI-I). Secondary outcome measures were the Children's Depression Rating Scale—Revised (CDRS-R), Inventory of Depressive Symptomatology, and Screen for Child Anxiety-Related Emotional Disorders (SCARED). Adverse effects were assessed via chart documentation.

RESULTS:

Patients were treated with a mean citalopram dose of 22.4 ± 7.3 mg for 12 weeks. Thirteen patients (76%) had CGI-I scores ≤2: 8 of 12 patients with depression and 5 of 5 patients with an anxiety disorder. The mean time to response was 7.6 ± 3.6 weeks. Additionally, 6 of 8 patients had ≥50% reduction from baseline CDRS-R score, with 3 patients (38%) meeting criteria for remission. Three of 4 patients had a >50% reduction for baseline SCARED-parent score. Overall, adverse effects appeared minor and transient. One patient discontinued citalopram due to intolerable adverse effects, and 1 patient required dose reduction.

CONCLUSIONS:

Citalopram appears to be effective and well tolerated in this group of children and adolescents with depressive or anxiety disorders and a high degree of comorbidity. Controlled studies in this patient population are indicated.
Pain and Distress from Bone Marrow Aspirations and Lumbar Punctures
Authors: Holdsworth Mark T , Raisch Dennis W , Winter Stuart S , Frost Jami D , Moro Michele A , Doran Nivine H , Phillips Joyce , Pankey Jan M , Mathew Prasad
Published: June 2003

OBJECTIVE

To compare the efficacy of 3 different pharmacologic regimens to relieve pain and distress in children with cancer undergoing bone marrow aspirations (BMAs) and lumbar punctures (LPs).

DESIGN

Retrospective cohort study with crossovers for some patients.

PATIENTS AND METHODS

The pain and distress ratings of patients undergoing BMAs (n = 73) and LPs (n = 105) were examined in a comparison of 3 different interventions: (1) a topical eutectic mixture of lidocaine and prilocaine (EMLA cream), (2) oral midazolam and EMLA cream, or (3) propofol/fentanyl general anesthesia. The choice of the intervention depended on patient/parent request. A validated faces pain scale was completed by the child or parent following each BMA or LP. The faces pain scale includes ratings of the severity of pain (from 0 = none to 5 = severe) and ratings of how frightened (from 0 = not scared to 5 = scared) the child was prior to each procedure. Comparisons of the pain and distress ratings were made among all patients for their first procedure and also within individual patients who had received >1 of the 3 interventions. Independent comparisons between the first treatments received by each patient were analyzed using Kruskal–Wallis tests. Comparisons of different crossover treatments received by individual patients were analyzed using Wilcoxon tests.

RESULTS

For all first procedures, mean ± SD pain and distress ratings during LPs were significantly lower when propofol/fentanyl was used (n = 43; 0.4 ± 1.0 and 1.4 ± 1.7) versus either EMLA (n = 29; 2.4 ± 1.7 and 2.9 ± 1.9) or midazolam/EMLA (n = 33; 2.4 ± 1.8 and 2.7 ± 1.8), respectively. Pain and distress ratings during BMAs were also significantly lower with propofol/fentanyl (n = 29; 0.5 ± 1.0 and 1.2 ± 1.7) versus EMLA (n = 21; 3.5 ± 1.6 and 3.3 ± 1.8) or midazolam/EMLA (n = 23; 3.3 ± 1.5 and 3.0 ± 1.9), respectively. When data were analyzed within each patient, these differences were also present.

CONCLUSIONS

Children receiving propofol/fentanyl general anesthesia experienced significantly less procedure-related pain and distress than did those receiving either EMLA or oral midazolam/EMLA.
Treatment of Tick-Borne Diseases
Authors: Donovan Brian J , Weber David J , Rublein John C , Raasch Ralph H
Published: June 2003

OBJECTIVE:

To review the data regarding the pharmacotherapy of Lyme disease, Rocky Mountain spotted fever (RMSF), and the human ehrlichioses.

DATA SOURCES:

English-language literature was identified via MEDLINE (1966–January 2002) using the keywords Lyme disease, Rocky Mountain spotted fever, and ehrlichiosis. Textbooks and other pertinent resources were also reviewed.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified through the data sources above were evaluated and reviewed if pertinent to the objective.

DATA SYNTHESIS:

Tick-borne diseases are the most common vector-transmitted diseases in North America. Each disease causes significant morbidity and, in the case of RMSF, mortality if patients go untreated. If the disease syndromes are recognized early and treatment is initiated, complications are greatly reduced. Doxycycline is active against each of the causative organisms, simplifying empiric treatment.

CONCLUSIONS:

Effective pharmacotherapy exists to treat each of these diseases, assuming diagnosis is made quickly. The β-lactam and tetracycline antibiotics appear to be the most effective therapy for Lyme disease. The tetracyclines, but not the β-lactams, are effective for RMSF and the human ehrlichioses. Since Borrelia burgdorferi and the human granulocytic ehrlichiosis agent are becoming more common coinfecting pathogens, tetracycline or doxycycline should be considered the drugs of choice for patients from endemic areas where exposure to both pathogens may have occurred. Doxycycline is the preferred agent because of decreased frequency of administration and adverse effects.
Steroid-Induced Myopathy in the ICU
Authors: Polsonetti Bryan W , Joy Saju D , Laos Luis F
Published: June 2003

OBJECTIVE:

To report a case of steroid-induced myopathy resulting from prolonged administration of corticosteroids in an asthmatic patient in a medical intensive care unit.

CASE SUMMARY:

A 30-year-old white man presented with status asthmaticus requiring intubation for respiratory failure. His hospital course was complicated by the need for reintubation and the development of “quadriplegia.” Electromyography does not identify neuropathy. After rapid tapering of systemic steroids, the patient quickly regained muscle strength, was extubated, and was transferred to a rehabilitation facility for prolonged physical therapy.

DISCUSSION:

Steroid-induced myopathy is a rare occurrence in the intensive care setting. Cases of myopathy that have been reported have been associated with prolonged and combined use of corticosteroids with neuromuscular blocking agents or aminoglycosides. Corticosteroids are thought to produce deleterious effects through 1 or all of 3 main pathways: altered electrical excitability of muscle fibers, loss of thick filaments, and/or inhibition of protein synthesis. All of these pathways are believed to increase the rate of muscle catabolism and result in loss of muscle movement.

CONCLUSIONS:

Steroid-induced myopathy is a complication of high-dose steroid use. Unfortunately, in this patient, initial treatment of status asthmaticus required intravenous steroids in high doses to adequately treat the presenting illness. Clinicians should be aware of neuromuscular findings and act aggressively to appropriately eliminate systemic steroids from the treatment regimen.
Myopathy Due to Statin/Fibrate Use in the Netherlands
Authors: Mantel-Teeuwisse Aukje K , Klungel Olaf H , Herings Ron MC , van Puijenbroek Eugène P , Porsius Arijan J , de Boer Anthonius
Published: June 2003

OBJECTIVE:

To estimate the number of expected cases of myopathy based on the prevalence of lipid-lowering drug use, and to compare this number with the observed number of cases of myopathy due to lipid-lowering drug use in the Netherlands.

METHODS:

Prevalence of lipid-lowering drug use in 1998 was estimated by using data from the PHARMO record linkage system comprising pharmacy records linked to hospital admission data. The expected number of cases of myopathy was calculated by multiplying the total number of person-years of lipid-lowering drug use by the excess incidence rates of myopathy due to those drugs as reported in the literature. The observed number of cases was obtained from PHARMO and the Dutch Pharmacovigilance Foundation Lareb.

RESULTS:

Based on the estimated prevalence of lipid-lowering drug use in the Netherlands in 1998 (n = 520 800), we expected 60 cases of idiopathic myopathy due to hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) or fibric acid derivatives (fibrates). This low number was confirmed by data from PHARMO (n = 11; none of these were related to current use of lipid-lowering drugs) and Lareb (n = 43).

CONCLUSIONS:

The expected number of statin- or fibrate-related idiopathic myopathy is low and observed numbers are even lower in the Netherlands. This should, therefore, not compromise continued use of lipid-lowering drugs.
Readability of Printed Patient Information for Epileptic Patients
Authors: Foster David R , Rhoney Denise H
Published: June 2003

BACKGROUND:

Written information can be a valuable tool in patient education. Studies evaluating written information for various disease states have frequently demonstrated that the majority of literature is written at a readability level that exceeds that of the average patient, and it has been recommended that written communications for adult patients should be provided at a fifth-grade level or lower.

OBJECTIVE:

To assess the readability of printed patient information available to patients with epilepsy.

METHODS:

Samples of written patient information (n = 101) were obtained from various sources. The information was classified based on source, content, and intended audience, and readability was assessed using the Flesch Reading Ease Score (FRES) and Flesch—Kincaid Grade Level (FKGL) score.

RESULTS:

The mean FRES and FKGL score for all samples were 50.2 and 9.4, respectively. Significant differences were observed in both the FRES and FKGL score of material obtained from different sources; however, no differences were observed when material was analyzed according to content. The mean FRES and FKGL score for materials intended for adults were 49.6 and 9.5, respectively. In comparison, mean FRES and FKGL scores for materials intended for children/adolescents were 78.9 and 5.3, respectively.

CONCLUSIONS:

The majority of information tested was written at a level that exceeds the reading ability of many patients. The information intended for children is actually written at the appropriate level for an adult. Efforts should be taken to develop written teaching tools that target low-level readers, especially for a disease state that affects many children.
Acute Pancreatitis Associated with Angiotensin II Receptor Antagonists
Authors: Fisher Alexander A , Bassett Mark L
Published: June 2003

OBJECTIVE:

To report a case of acute pancreatitis in a patient receiving a combination formulation of irbesartan and hydrochlorothiazide (HCTZ).

CASE SUMMARY:

A 33-year-old white woman developed acute pancreatitis 10 days after starting irbesartan 300 mg and hydrochlorothiazide 12.5 mg for treatment of hypertension. Her symptoms disappeared and serum concentrations of lipase and amylase returned to normal 2 days after irbesartan/HCTZ was discontinued. A search of MEDLINE (1990–September 2002) and the Australian Adverse Drug Reaction Advisory Committee database revealed 1 additional case of pancreatitis associated with irbesartan/HCTZ and 3 cases of pancreatitis associated with losartan.

DISCUSSION:

An objective causality assessment indicates that it is probable that pancreatitis was caused by the angiotensin II receptor antagonist irbesartan (and the same is probably true for losartan). It is less likely that the hydrochlorothiazide in irbesartan/HCTZ caused pancreatitis in our patient since the dose was lower than that usually associated with thiazide-induced pancreatitis. Angiotensin II receptors are thought to be important in regulation of pancreatic secretion and microcirculation, but the mechanism of pancreatitis induced by angiotensin II receptor antagonists remains unclear.

CONCLUSIONS:

Clinicians should be aware that irbesartan/HCTZ or losartan may cause acute pancreatitis. If abdominal pain develops, the medication should be discontinued and the patient investigated for acute pancreatitis.
Aspirin Dose for Prevention of Cardiovascular Disease in Diabetics
Authors: Nowak Sandra N , Jaber Linda A
Published: June 2003

OBJECTIVE

To determine whether a specific dose of aspirin can be recommended for prevention of cardiovascular disease in patients with diabetes.

DATA SOURCE

Biomedical literature was accessed through MEDLINE (1990–February 2002). Key terms included diabetes, cardiovascular protection, and aspirin.

DATA SYNTHESIS

Pharmacologic and clinical studies focusing on the dose–response relationship of aspirin therapy were reviewed. Evidence supports the benefit of low-dose aspirin therapy in reducing vascular events in secondary and primary prevention trials in various patient populations; however, some studies suggest larger doses of aspirin may be needed in certain patients.

CONCLUSIONS

Review of the evidence does not support a particular dose of aspirin for cardiovascular protection in diabetic patients. Clinical guidelines recommend aspirin therapy in the range of 81–325 mg/d. However, due to an increased prevalence of cardiovascular morbidity and disturbances in coagulation in diabetic patients, the dose of aspirin for prevention of cardiovascular disease in these individuals may be different from that in other populations and requires further evaluation.
Amlodipine versus Angiotensin-Receptor Blockers for Nonhypertension Indications
Authors: Kalus James S , White C Michael
Published: June 2003

OBJECTIVE:

To review the efficacy and safety data of amlodipine and the angiotensin-receptor blockers (ARBs), focusing on heart failure, angina, percutaneous coronary intervention (PCI), and renal protection.

DATA SOURCE:

A MEDLINE search (1966–December 2001) was completed using amlodipine, angiotensin-receptor antagonist, losartan, valsartan, candesartan, and telmisartan as key words. English-language articles were identified and included.

STUDY SELECTION AND DATA EXTRACTION:

All identified articles were evaluated. Articles representative of the subject matter of our review were included.

DATA SYNTHESIS:

Amlodipine and the ARBs lower blood pressure to a similar extent. Amlodipine is an effective antianginal agent, whereas ARBs are not. However, amlodipine is not effective in the treatment of heart failure; ARBs may be useful in this setting. ARBs are also effective in preserving renal function and may provide some protection from restenosis in patients who have had a PCI. The ARBs may also be useful in preventing both diabetic and nondiabetic nephropathy.

CONCLUSIONS:

Concomitant disease states should be considered when choosing between an ARB and amlodipine for the management of hypertension.
Acute Cholestatic Hepatitis Associated with Celecoxib
Authors: Grieco Antonio , Miele Luca , Giorgi Andrea , Civello Ignazio M , Gasbarrini Giovanni
Published: June 2003

OBJECTIVE:

To report a case of acute cholestatic hepatitis associated with the selective cyclooxygenase-2 inhibitor celecoxib.

CASE SUMMARY:

A 41-year-old white man was hospitalized for jaundice after 2 doses of celecoxib 200 mg for pain associated with right-knee trauma. Laboratory workup showed hyperbilirubinemia, mildly elevated serum transaminase concentrations, and cholestasis. Abdominal imaging showed no dilation of the biliary tree. Histology showed cholestasis, with bile plugs in dilated bile canaliculi and a mild portal infiltrate that are highly suggestive of drug-induced cholestasis.

DISCUSSION:

This is the fourth report in the English-language literature describing cholestatic hepatitis temporally related to celecoxib use, the second supported by histologic findings typical of drug-induced cholestasis, and the first in a patient who denied use of alcoholic beverages and was taking no other drugs or herbal products at the time of the reaction. The Naranjo probability scale indicated that celecoxib was a probable cause of acute cholestatic hepatitis in this patient.

CONCLUSIONS:

Cholestatic hepatitis is a well-recognized adverse effect of several drugs. Although celecoxib is considered to have a very low potential for hepatic toxicity, well-documented reports of adverse reactions can contribute significantly to the definition of more accurate safety profiles for new drugs introduced into clinical practice.
International Survey of Self-Reported Medicine Use Among Adolescents
Authors: Hansen Ebba H , Holstein Bjørn E , Due Pernille , Currie Candace E
Published: June 2003

OBJECTIVE:

To examine gender, age, and country variations in adolescents' self-reported medicine use.

DESIGN:

Cross-sectional school surveys of representative samples of 11- to 15-year-old girls and boys were used. The 1997-1998 Health Behaviour in School-aged Children study was referenced. A standardized questionnaire was completed during school hours.

SETTING:

Canada, US, Greenland, Israel, and 24 European countries.

PARTICIPANTS:

123 227 participants equally distributed by gender and by 3 age groups (mean 11.7, 13.6, 15.6 y).

MAIN OUTCOME MEASURES:

Self-reported medicine use for headache, stomachache, difficulties in getting to sleep, and nervousness during the past month.

RESULTS:

The magnitude of the adolescents' medicine use for headache, stomachache, difficulties in getting to sleep, and nervousness varied substantially across countries. In each of the 28 countries, more girls than boys used medicine for pain. Use of medicine for headache increased by age; use of medicine for stomachache increased by age among girls, but decreased among boys; and use of medicine for difficulties in getting to sleep and nervousness decreased from the age of 11 to 15 years. There was an increase in the crude girl versus boy ratios for medicine use by age for all 4 symptoms. Multivariate logistic regression analyses, adjusting for age group and country, revealed the following odds ratios (95% CI) for girls' versus boys' medicine use: headache 1.56 (1.53 to 1.60), stomachache 2.16 (2.10 to 2.22), difficulties in getting to sleep 0.96 (0.91 to 1.00), and nervousness 1.04 (0.99 to 1.08).

CONCLUSIONS:

Substantial proportions of adolescents used medicine for common health problems. The prevalence of use differed between type of symptom for which the medicine was used, between countries, and between gender and age groups. We suggest that young people's medicine use should be addressed in public health policy.
Fluvoxamine Interaction with Warfarin
Authors: Limke Kristi K , Shelton Angela R , Elliott Ellie S
Published: June 2003

OBJECTIVE:

To report a case of an elevated international normalized ratio (INR) in a patient receiving fluvoxamine and warfarin.

CASE SUMMARY:

A 79-year-old white woman was admitted for suicidal thoughts. Her medical history included depression, chronic obstructive pulmonary disorder, asthma, hypertension, atrial fibrillation with pacemaker placement, and breast cancer with lumpectomy and subsequent left mastectomy. Her medication list prior to admission was extensive, including warfarin 5 mg on Sunday, Monday, Wednesday, and Friday; warfarin 2.5 mg on Tuesday, Thursday, and Saturday, and citalopram 10 mg/d. Citalopram was changed to fluvoxamine during her hospital stay. This resulted in an elevated INR that persisted for approximately 7 days.

DISCUSSION:

The metabolism of warfarin involves several cytochrome P450 isoenzymes, including CYP1A2, CYP2C9, CYP2C19, and CYP3A4. Fluvoxamine has the potential to inhibit CYP1A2, CYP2C9, CYP2C19, and CYP3A4 to a significant degree. It also has 11 inactive metabolites that may contribute to enzyme inhibition. Fluvoxamine has an extensive elimination half-life of 17–22 hours after a single dose, which increases with multiple dosing by 30–50%. It can take approximately 10 days to reach a steady-state concentration. In the elderly, the half-life is increased by 50%.

CONCLUSIONS:

The coadministration of warfarin and fluvoxamine can result in an increase in the anticoagulant effect of warfarin. This anticoagulant effect can be seen for several days after the discontinuation of fluvoxamine. Our case emphasizes the need to closely monitor potential drug interactions in the elderly, especially those concerning fluvoxamine and warfarin.
Caspofungin Acetate for Treatment of Invasive Fungal Infections
Authors: Pacetti Staci A , Gelone Steven P
Published: June 2003

OBJECTIVE

To briefly discuss the changing epidemiology of fungal infections and review currently available agents; provide a review of caspofungin; and discuss its pharmacology, pharmacokinetics, dosing guidelines, safety and efficacy, and role in the treatment of invasive fungal infections as it relates to current antifungal therapy.

DATA SOURCES

A MEDLINE (1966 to August 2002) database search using key words caspofungin, echino candins, fungal infections, and invasive aspergillosis, was completed to identify relevant articles including reviews, recent studies, treatment guidelines, and data from Merck and Company.

STUDY SELECTION

In vitro studies and all clinical trials were evaluated to summarize the clinical efficacy and safety of caspofungin.

DATA SYNTHESIS

The incidence of fungal infections is increasing as the population at risk expands. Cost, resistance, and morbidity and mortality are key issues. Adding to the antifungal armamentarium is necessary to address these therapeutic dilemmas. Caspofungin is the first member of a new class of antifungal agents, the echinocandins, to be approved for clinical use. Caspofungin is classified as a glucan synthase inhibitor and represents a class of agents with a novel mechanism of action. Unlike currently available agents (polyenes, pyrimidines, azoles) that exert their effect on the fungal cell membrane, the echinocandins are the first agents to inhibit fungal cell wall synthesis. Caspofungin exhibits activity against Aspergillus spp. and Candida spp., including non-albicans species. Data from clinical trials demonstrate that caspofungin is effective in patients with invasive aspergillosis as well as candida esophagitis. Its Food and Drug Administration–approved indication is limited to invasive aspergillosis refractory to or intolerant of current therapy.

CONCLUSIONS

Caspofungin has activity against Aspergillus spp. as well as a variety of Candida spp. Clinical data support its usefulness in the treatment of invasive aspergillosis and select candida infections. As additional clinical data become available, it seems likely that the therapeutic role of caspofungin will expand. THIS ARTICLE IS APPROVED FOR CONTINUING EDUCATION CREDIT ACPE UNIVERSAL PROGRAM NUMBER: 407-000-03-001-H01
Therapeutic Controversies; Lack of Therapeutic Interchangeability of HMG-CoA Reductase Inhibitors
Authors: Chong Pang H
Published: June 2003

OBJECTIVE:

To review relevant literature and provide an opinion on the class effect of hydroxymethylglutaryl coenzyme A reductase inhibitors (statins).

DATA SOURCES:

Primary and review articles were identified by MEDLINE search (1990–July 2002).

STUDY SELECTION AND DATA EXTRACTION:

Editorials, studies, and review articles related to the class effect or therapeutic interchangeability of statins were reviewed. Also included was information that is relevant to this topic.

DATA SYNTHESIS:

Although statins share common main actions, they may have clinically important differences in terms of efficacy and safety. At fixed or allowable dosages, rosuvastatin, atorvastatin, and simvastatin produced greater low-density lipoprotein cholesterol—lowering effects compared with other statins. Some statins have shown reduction in either cardiovascular and/or total mortality. Statins also differ in their structure, pharmacokinetics, potency, and rate of metabolism, any or all of which may have clinical significance. Although inconclusive, subtle differences in nonlipid effects of some statins may have contributed to positive benefits observed in clinical studies. As a result of drug-related deaths, cerivastatin was withdrawn voluntarily from the market, which may raise the question whether there is therapeutic interchangeability (due to class effect) among statins.

CONCLUSIONS:

Despite the competition for market share and strategies attempting to identify differences in therapeutic value, few head-to-head comparisons between statins have been performed. The limited, available data suggest that statins are not therapeutically interchangeable.
Chronic Metoclopramide Therapy for Diabetic Gastroparesis
Authors: Lata Paul F , Pigarelli Denise L Walbrandt
Published: June 2003

OBJECTIVE

To review the safety and efficacy of chronic metoclopramide for diabetic gastroparesis.

DATA SOURCES

Medical literature was accessed through MEDLINE (1965 to October 2002) and PubMed (1965 to October 2002). Key search terms included metoclopramide; diabetic gastroparesis; and dyskinesia, drug induced.

DATA SYNTHESIS

Metoclopramide is often used for diabetic gastroparesis, despite the risk of tardive dyskinesia. Published information is limited regarding long-term efficacy and toxicity of metoclopramide. The literature was assessed concerning these topics.

CONCLUSIONS

Limited data do not provide sufficient evidence to conclude whether metoclopramide is efficacious for chronic use. Routine monitoring may mitigate the risk associated with metoclopramide therapy.
Concurrent Administration of Interferon Alfa-2b and Beta-1a
Authors: Tanvetyanon Tawee , Stadtmauer Edward A , Kerson Lawrence A
Published: June 2003

OBJECTIVE

To describe the concurrent use of interferon (IFN) alfa and beta in a patient with multiple sclerosis (MS) and chronic myeloid leukemia (CML).

CASE SUMMARY

A 60-year-old white man developed CML while receiving IFN beta-1a treatment for MS. The patient was started on IFN alfa-2b 1 million units 3 times weekly with IFN beta-1a 30 μg weekly. The dosage of IFN alfa was increased to 3 million units/d 1 month later. He achieved complete hematologic remission in 3 months. The observed adverse effects were mild and included fatigue, somnolence, weight loss, and difficulty with memory. At 19 months after treatment, the patient remained in hematologic remission and his expanded disability status scale score remained unchanged.

DISCUSSION

Concomitant treatment with interferon alfa and beta by a gradual increase in the dosage of IFN alfa was well tolerated. Although imatinib mesylate may be a preferred treatment for patients with CML and MS at this time, our experience with safe concurrent use of IFN alfa and beta may benefit other patients who require this combined treatment.

CONCLUSIONS

Concurrent administration of interferon alfa-2b and beta-1a was well tolerated by our patient with CML and MS.
Goiter in a Newborn Exposed to Lithium in Utero
Authors: Frassetto Florence , Martel Florence Tourneur , Barjhoux Claude-Elisabeth , Villier Céline , Le Bot Brigitte , Vincent Françoise
Published: June 2003

OBJECTIVE:

To report a case of neonatal goiter and biological hypothyroidism in a newborn exposed to lithium in utero resulting from therapy given to the mother before and during her pregnancy.

CASE SUMMARY:

A male neonate, born at 37 weeks' gestation, presented with a goiter without other signs of hypothyroidism. His serum thyroid-stimulating hormone concentration was high and unbound tetrathyroxine concentration was low, indicating that chronic exposure to lithium was present. Oral thyroxine treatment was initiated when the infant was 3 days old and continued for 11 weeks. Treatment was effective in reducing the goiter and hormone concentrations, and allowing normal growth and psychomotor development during the following 3.5 months. Other drugs taken by the mother during pregnancy are not known to induce thyroid abnormalities.

DISCUSSION:

Lithium is used for prophylaxis and treatment of bipolar disorder. Goiter and hypothyroidism in adults have been described in patients treated with lithium; thyroid disorders are reversible if lithium is discontinued. Few cases of goiter and hypothyroidism have been reported in newborns exposed to lithium in utero. In our patient, congenital hypothyroidism required longer thyroxine treatment than lithium-induced thyroid disorders. The delay before improvement seems to be similar to that observed in adults. The Naranjo probability scale indicated that lithium was the probable cause of hypothyroidism resulting from in utero exposure.

CONCLUSIONS:

Lithium is a well-known goitrogenic agent. Thus, if lithium treatment needs to be continued during pregnancy in women with bipolar disorder, adequate screening for morphology by ultrasonography and systematic hormonal biological control in newborns are recommended.
Combined Budesonide/Formoterol Turbuhaler Treatment of Asthma
Authors: Remington Tami L , Heaberlin Andrea M , DiGiovine Bruno
Published: June 2003

OBJECTIVE:

To provide product information; review and analyze the clinical literature studying combination therapy, budesonide, and formoterol in asthmatics; and to define the role for this therapy in asthma treatment.

DATA SOURCES:

A MEDLINE search (1990–September 2001) was conducted to identify the primary literature. Bibliographies were reviewed for further relevant citations.

STUDY SELECTION/DATA EXTRACTION:

All randomized, blinded, controlled studies at least 3 months in duration exploring the efficacy of the combination of budesonide and formoterol (in 1 or separate formulations) compared with other treatments were selected to be included in the review of clinical studies.

DATA SYNTHESIS:

The combination of budesonide and formoterol was more effective than increasing the dose of budesonide in patients with moderate or severe persistent asthma and in patients with mild asthma not previously controlled with inhaled corticosteroids. Milder corticosteroid-naïve asthmatics did not derive benefit compared with inhaled corticosteroids alone.

CONCLUSIONS:

Combination therapy in 1 device is a preferred treatment option in patients with moderate to severe persistent asthma and in those with milder asthma not controlled with inhaled corticosteroids. Advantages of this product include rapid onset of action, long duration of action, and a wide dosing range to assist with titration. Further research is required to evaluate this therapy in asthmatic children <5 years old and in patients with oral corticosteroid—dependent asthma. Investigations into the effect of this combination product on other disease outcomes, such as quality of life and productivity, will further define the role for this drug therapy.
Economic Impact of Ramipril on Hospitalization of High-Risk Cardiovascular Patients
Authors: Carroll Cathryn A , Coen Michael M , Piepho Robert W
Published: June 2003

OBJECTIVE:

To estimate differences in direct costs attributable to avoided hospitalizations and procedures during the years of the HOPE (Heart Outcomes Prevention Evaluation) study after the cost of treatment with ramipril or alternative angiotensin-converting enzyme inhibitor therapy was taken into account.

METHODS:

A decision analytical model was developed to estimate the economic impact of reductions in hospitalizations and/or procedures both at annual increments and over the first 4 years of the HOPE study. The analysis compared the number of cardiovascular events per endpoint per year in the intervention and placebo group with hospitalization and procedural costs. Cost data were derived from the literature and inflated to the appropriate index year using the consumer price index.

RESULTS:

For approximately 9000 patients studied, the gross estimated savings in direct costs for 297 events avoided were more than $5 million over 4 years. After the cost of treatment was deducted for both groups, the net estimated savings were $871 000 over 4 years.

CONCLUSIONS:

The results demonstrate that the use of ramipril provides cost-effective treatment for high-risk cardiovascular patients with an ejection fraction >40%.
Economic Impact of Pharmacists' Interventions with Nonsteroidal Antiinflammatory Drugs
Authors: Guignard Adrienne P , Couray-Targe Sandrine , Colin Cyrille , Chamba Geneviève
Published: June 2003

Objective:

To estimate the economic impact of community pharmacists' interventions following the detection of problems related to nonsteroidal antiinflammatory drugs (NSAIDs), whether in a prescription or self-medication format. The evaluation focused on the gastroduodenal adverse events that could be avoided and the subsequent savings of healthcare resources spent on treating these adverse effects.

Methods:

A previous study conducted during a 12-week period in 924 French community pharmacies provided the number of interventions for drug-related problems concerning NSAIDs. A simulation model was constructed to compare 2 strategies: a systematic pharmacist's intervention and the absence of intervention. The base-case patient was assumed to have been taking an NSAID for 3 months. The model's inputs were extracted from medical literature and from an institutional medical database.

Results:

In this study, 608 interventions were the results of NSAID-related problems. All of these interventions reduced the risk of gastrointestinal adverse events and avoided a total cost of €37 300.

Conclusions:

This model indicates that the dispensing of NSAIDs by pharmacists and related pharmaceutical care activities have a positive impact by reducing the number of gastrointestinal complications. The model quantifies the costs thus avoided. It also underlines the necessity of effective collaboration between the prescriber and the pharmacist if optimal patient management is to be achieved.
Venous Thromboembolism Prevention with LMWHs in Medical and Orthopedic Surgery Patients
Authors: Deitelzweig Steven B , Vanscoy Gordon J , Niccolai Cynthia S , Rihn Thomas L
Published: June 2003

OBJECTIVE:

To discuss the role of low-molecular-weight heparins (LMWHs) in the prevention of venous thromboembolism (VTE) in medical and orthopedic surgery patients. VTE prophylaxis trials in these practice settings establishing the current use of LMWHs marketed in the US are included. An overview is also provided of VTE incidence, risk factors, and prophylaxis consensus guidelines.

DATA SOURCES AND STUDY SELECTION:

Clinical trials, review articles, and meta-analyses for Food and Drug Administration–approved LMWHs were identified from a MEDLINE search (1980–March 2002). Search terms included dalteparin, enoxaparin, internal medicine, low-molecular-weight heparin, orthopedic surgery, risk factors, tinzaparin, and venous thromboembolism.

DATA SYNTHESIS:

Consensus guidelines are useful as an initial guide to appropriate VTE prophylaxis; however, a review of the primary literature is needed to identify optimal agents, regimens, or interventions. LMWHs have demonstrated sound efficacy in VTE prevention; however, the quantity and quality of literature are not always comparable for the available agents.

CONCLUSIONS:

Enoxaparin has demonstrated efficacy and safety in VTE prevention in medical patients, whereas information is limited or lacking for dalteparin and tinzaparin. Total hip replacement (THR) trials have been conducted with all US-marketed LMWHs and have demonstrated the efficacy and safety of each agent. Trials specifically establishing the efficacy of an LMWH in total knee replacement surgery (TKR) have been published for enoxaparin. One combination THR and TKR trial has been published for tinzaparin. These trial outcomes have positioned the LMWHs as key alternatives to adjusted-dose warfarin for VTE prophylaxis in orthopedic surgery. Inherent differences between LMWHs prevent the extrapolation of clinical outcomes from 1 trial to another.