bluuebunny/crossref_metadata_2025 huggingface dataset:
Gabapentin for Treatment of Behavioral and Psychological Symptoms of Dementia
Authors: Miller Lisa J
Published: June 2003

OBJECTIVE:

To report the use of gabapentin in the treatment of behavioral and psychological symptoms of dementia (BPSD) and to review the available literature relating to the use of gabapentin in this population.

CASE SUMMARY:

A 62-year-old white man was admitted to the hospital due to a worsening state of confusion, anxiety, depressed mood, insomnia, and verbal and physical aggressiveness toward his wife. He had a past medical history significant for vascular dementia. He had been intolerant of or had failed to respond to numerous antidepressants, benzodiazepines, and neuroleptics. The addition of gabapentin to the patient's medication regimen resulted in reduced agitation, sexual inappropriateness, and lability. He was discharged to his home on a dose of gabapentin 300 mg three × daily.

DATA SOURCES:

A MEDLINE search (1966–August 2000) was performed to identify case reports and clinical trials discussing the efficacy of gabapentin in the treatment of BPSD.

DISCUSSION:

Gabapentin, like other anticonvulsants, has been used with success in several psychiatric illnesses. Available literature indicates that the drug may have some efficacy in the treatment of BPSD. It has a favorable adverse effect profile in the elderly, which makes it an attractive alternative to standard therapies, including benzodiazepines and neuroleptics. Optimal dosing remains unclear.

CONCLUSIONS:

This case suggests that gabapentin is a reasonable alternative therapy for patients whose behavioral symptoms do not respond to conventional agents.
Prevention and Treatment of Veno-Occlusive Disease
Authors: Pegram Anita A , Kennedy LeAnne D
Published: June 2003

OBJECTIVE:

T o review the current options for prevention and treatment of veno-occlusive disease in bone marrow transplant patients.

DATA SOURCES:

Articles were selected from a MEDLINE search (1966–October 1999) using the key terms veno-occlusive disease and bone marrow transplantation. In addition, references of all articles were examined for articles not found in the computer-based search.

DATA EXTRACTION:

All clinical trials, case—control studies, and case reports were evaluated.

RESULTS:

Heparin, low-molecular-weight heparin, prostaglandin E1, ursodiol, and glutamine have been studied for prevention of veno-occlusive disease. Heparin has been studied most extensively; however, no preventive regimen has a defined role in therapy. For treatment, tissue plasminogen activator has been evaluated most thoroughly, yet its safety and efficacy have not been clearly established in patients with veno-occlusive disease. Other possible treatment options include antithrombin-III, defibrotide, glutamine plus vitamin E, and surgery.

CONCLUSIONS:

Based on the available data, the most promising agents are ursodiol for prevention and defibrotide or glutamine plus vitamin E for treatment of veno-occlusive disease. Further clinical trials are needed to establish the appropriate preventive and treatment options available for bone marrow transplant patients suffering from veno-occlusive disease. To date, such decisions depend largely on poorly designed trials, case reports, and clinical experience.
Levofloxacin Failure in a Patient with Pneumococcal Pneumonia
Authors: Empey Philip E , Jennings Heath R , Thornton Alice C , Rapp Robert P , Evans Martin E
Published: June 2003

OBJECTIVE:

To report a case of levofloxacin failure in a patient with a penicillin-sensitive Streptococcus pneumoniae pneumonia.

CASE SUMMARY:

A previously healthy, immunocompetent, 53-year-old white man presented with penicillin-sensitive S. pneumoniae pneumonia. The patient was empirically placed on levofloxacin monotherapy, which was continued due to a local penicillin shortage. When the patient failed to improve, further susceptibility testing was ordered. The organism was found to have a penicillin minimum inhibitory concentration (MIC) of 0.023 μg/mL and a levofloxacin MIC of 6 μg/mL. Effective antimicrobial therapy was delayed, as clinicians did not anticipate fluoroquinolone resistance.

DISCUSSION:

Newer fluoroquinolones such as levofloxacin have good activity against most S. pneumoniae isolates and are used for the treatment of pneumonia. Although resistance to these agents is rare, it has been reported. Current guidelines from the National Committee for Clinical Laboratory Standards do not recommend initial fluoroquinolone susceptibility testing.

CONCLUSIONS:

As fluoroquinolone resistance may not be identified by susceptibility patterns to other antibiotics, early fluoroquinolone susceptibility testing and increased awareness of resistance may aid clinicians in their treatment of pneumococcal disease.
Evaluation of a New Integrated Discharge Prescription Form
Authors: Paquette-Lamontagne Nicolas , McLean William M , Besse Lysanne , Cusson Jean
Published: June 2003

OBJECTIVE:

To determine whether a new discharge prescription form which integrates admission medications, in-hospital changes, and discharge medications could enhance the accuracy of information in patient profiles in community pharmacies after hospital discharge.

DESIGN:

Nonrandomized, prospective, multi-site study.

SETTINGS:

Internal medicine wards of the three teaching hospitals (1200 beds) of the Centre Hospitalier de l'Université de Montréal.

SUBJECTS:

Patients admitted to the internal medicine wards between January 4 and 31, 1999, at St.-Luc and Notre-Dame Hospitals formed the control group and received a usual discharge form (UD). Those admitted between February 1 and 28, 1999, received the new discharge prescription form (DPF) capturing the list of admission medications and revisions during hospitalization; they served as the experimental group.

METHODS:

Patient profiles were reviewed to calculate conformity rates of community pharmacy patient profiles after discharge and the rate of overall conformity for each group in the study. Each drug in the patient profile was assessed according to six criteria. Healthcare providers' satisfaction with the DPF was assessed via a written questionnaire.

RESULTS:

Eighty-nine patients and 669 discharge medications were studied. The patient profiles had a higher conformity rate in the DPF group than in the UD group (82% vs. 40%; p < 0.001); improvement could be attributed to higher conformity rates, particularly for two criteria (medications stopped in hospital and dose changes in hospital).

CONCLUSIONS:

Integration of admission medications, in-hospital changes, and discharge medications on a single form increases the conformity rates of community pharmacy patient profiles after hospitalization. This tool is well accepted by both pharmacists and physicians and may lead to a major decrease in drug-related problems.
Antidepressant Prescribing to Hispanic and Non-Hispanic White Patients in Primary Care
Authors: Sleath Betsy L , Rubin Richard H , Huston Sally A
Published: June 2003

OBJECTIVE:

To examine whether there was a difference in the prescribing of selective serotonin-reuptake inhibitors (SSRIs) and non-SSRI antidepressants to Hispanic and non-Hispanic white patients in primary care.

METHODS:

Twenty-seven family practice and internal medicine resident physicians and 407 of their Hispanic and non-Hispanic white patients who were fluent in English or Spanish participated in the study. The medical records of all patients were reviewed and information about patient diagnoses and antidepressant prescriptions was abstracted. Logistic regression was used to examine whether Hispanic ethnicity influenced physician prescribing of SSRI and non-SSRI antidepressants while controlling for other patient characteristics and diagnoses. For patients with a diagnosis of depression, logistic regression was used to examine whether Hispanic ethnicity influenced whether patients received antidepressant treatment while controlling for other patient characteristics.

RESULTS:

Twenty-seven percent of patients received a prescription for one or more antidepressants. Hispanic and non-Hispanic white patients were equally likely to be prescribed SSRI and non-SSRI antidepressant medications. Having a diagnosis of depression and having a diagnosis of chronic pain was significantly correlated with the prescribing of a non-SSRI antidepressant (p < 0.001; p < 0.01, respectively). Having a diagnosis of depression was significantly correlated with the prescribing of an SSRI antidepressant (p < 0.001). Hispanic and non-Hispanic white patients with a diagnosis of depression were equally likely to be prescribed antidepressant treatment. Patients with a diagnosis of depression in the general medicine clinic were significantly less likely to receive antidepressant therapy than patients in the family practice clinic.

CONCLUSIONS:

Hispanic ethnicity did not influence antidepressant prescribing. Future research in other settings is needed to further determine whether Hispanic ethnicity influences antidepressant prescribing.
Role of Therapeutic Drug Monitoring for Protease Inhibitors
Authors: John Leela , Marra Fawziah , Ensom Mary HH
Published: June 2003

OBJECTIVE:

To review the role of therapeutic drug monitoring (TDM) for protease inhibitors in the treatment of HIV infection.

DATA SOURCES:

Primary articles were identified using MEDLINE (1966–October 2000), EMBASE (1987–October 2000), AIDSLINE (1980–October 2000), Current Contents, PubMed, and Medscape. Further articles were identified from bibliographic review of primary articles and review papers. Abstracts presented at the World AIDS Conference, Interscience Conference on Antimicrobial Agents and Chemotherapy, and Conference on Retroviruses and Opportunistic Infections were also identified from 1997 to 2000.

STUDY SELECTION AND DATA EXTRACTION:

All English-language, prospective clinical trials, as well as selected retrospective studies and case series, pertaining to therapeutic drug monitoring of protease inhibitors were included.

DATA SYNTHESIS:

A number of clinical studies have found a good relationship between concentration and pharmacologic response and/or toxicity as well as wide interpatient variability in the pharmacokinetics of protease inhibitors. There also is some preliminary evidence of the usefulness of plasma drug concentrations to guide dosage adjustments of protease inhibitors in patients with liver dysfunction. Furthermore, there is preliminary evidence of a relationship between drug concentrations and resistance.

CONCLUSIONS:

A number of clinical studies support the usefulness of TDM of protease inhibitors. However, before TDM can be of the most value, further evaluation requires simplified and standardized assays to be performed routinely by clinical laboratories; determination of the appropriate target concentration and therapeutic range, as well as the best predictor of pharmacologic response; and refined interpretation of plasma drug concentrations. Randomized, controlled clinical trials of patient outcomes are needed to assess the clinical utility of TDM for protease inhibitors.
Relief of Fibromyalgia Symptoms following Discontinuation of Dietary Excitotoxins
Authors: Smith Jerry D , Terpening Chris M , Schmidt Siegfried OF , Gums John G
Published: June 2003

BACKGROUND:

Fibromyalgia is a common rheumatologic disorder that is often difficult to treat effectively.

CASE SUMMARY:

Four patients diagnosed with fibromyalgia syndrome for two to 17 years are described. All had undergone multiple treatment modalities with limited success. All had complete, or nearly complete, resolution of their symptoms within months after eliminating monosodium glutamate (MSG) or MSG plus aspartame from their diet. All patients were women with multiple comorbidities prior to elimination of MSG. All have had recurrence of symptoms whenever MSG is ingested.

DISCUSSION:

Excitotoxins are molecules, such as MSG and aspartate, that act as excitatory neurotransmitters, and can lead to neurotoxicity when used in excess. We propose that these four patients may represent a subset of fibromyalgia syndrome that is induced or exacerbated by excitotoxins or, alternatively, may comprise an excitotoxin syndrome that is similar to fibromyalgia. We suggest that identification of similar patients and research with larger numbers of patients must be performed before definitive conclusions can be made.

CONCLUSIONS:

The elimination of MSG and other excitotoxins from the diets of patients with fibromyalgia offers a benign treatment option that has the potential for dramatic results in a subset of patients.
Calcium-Channel Antagonists and Nitrates in Coronary Artery Bypass Patients Receiving Radial Artery Grafts
Authors: Kalus James S , Lober Cheryl A
Published: June 2003

OBJECTIVE:

To review the literature assessing the role of vasodilators for the prevention of vasospasm leading to graft failure in patients receiving the radial artery (RA) as a conduit in coronary artery bypass grafting (CABG).

DATA SOURCES:

A MEDLINE search (January 1966–May 2000) was performed using calcium-channel antagonists, nitrates, radial artery, and coronary artery bypass as key words. English-language articles were identified, and the references of these articles were used to further identify pertinent articles.

DATA SYNTHESIS:

RAs can be used as conduits in CABG. It has been suggested that failure of these grafts may be due to vasospasm, leading to occlusion observed angiographically. Calcium-channel antagonists and nitrates have been proposed as a means of preventing vasospasm and subsequent graft failure.

CONCLUSIONS:

Currently published data on the use of calcium-channel antagonist or nitrate therapy as prophylaxis against vasospasm in patients receiving RA grafts are inconclusive. Systematic evaluations of currently available pharmacologic agents are needed to guide clinical practice in this area.
Colesevelam Hydrochloride: A Novel Bile Acid-Binding Resin
Authors: Aldridge Martha A , Ito Matthew K
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, efficacy, and adverse effects of colesevelam hydrochloride, a bile acid—binding resin.

METHODS:

MEDLINE searches (1966–June 2000) and manufacturer prescribing literature were employed to find articles on colesevelam. Additional studies and abstracts were identified from the bibliographies of reviewed literature.

STUDY SELECTION AND DATA EXTRACTION:

All articles identified from data sources were evaluated, and all information deemed relevant was included in this review. Priority was given to randomized, double-blind, placebo-controlled studies.

FINDINGS:

Colesevelam HCl is a nonabsorbed hydrogel with bile acid sequestrant properties. Monotherapy using colesevelam in once-daily or two divided daily doses of 1.5–4.5 g has produced significant reductions in total cholesterol and low-density lipoprotein (LDL) cholesterol. Mean LDL cholesterol decreases to 20% have been noted when the patient is on 3.75–4.5 g/d. Increases in high-density lipoprotein (HDL) cholesterol have been observed (up to 9%), whereas triglycerides (TG) have increased significantly to 25% in some studies. In unpublished studies, combined use of colesevelam plus hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor have produced greater reductions in LDL cholesterol than either the statin or colesevelam administered alone. The efficacy of colesevelam monotherapy is slightly less than or similar to cholestyramine or colestipol in decreasing LDL cholesterol, although colesevelam is more potent on a gram-to-gram basis. Adverse effects have been minimal with colesevelam in published studies; this suggests an advantage over cholestyramine or colestipol therapy. Colesevelam appears to be more cost-effective than the packet dosage form of the brand formulation of the older bile acid resins. Care in selection of an appropriate agent should be exercised when considering the issues of adverse effects and palatability.

CONCLUSIONS:

Colesevelam alone or combined with an HMG-CoA reductase inhibitor is effective in the reduction of total and LDL cholesterol. Since colesevelam is formulated as a tablet, problems with palatability such as with the powder formulation of the bile acid—binding resins are likely to be eliminated.
Transient Hypoparathyroidism Due to Amphotericin B—Induced Hypomagnesemia in a Patient with β–Thalassemia
Authors: Marcus Nufar , Garty Ben Zion
Published: June 2003

OBJECTIVE:

To report a case of transient hypoparathyroidism that developed in a β-thalassemic patient due to amphotericin B—induced hypomagnesemia.

CASE SUMMARY:

A 21-year-old man with β-thalassemia was treated with amphotericin B for Candida albicans intravenous line sepsis. After five days of treatment (cumulative dose 160 mg), he developed hypomagnesemia, which caused hypoparathyroidism and hypocalcemia; all three abnormalities resolved after the drug was withdrawn.

DISCUSSION:

Patients with β-thalassemia may develop endocrinologic abnormalities due to excessive iron deposition. Some may have subclinical hypoparathyroidism that clinically emerges after even a mild homeostasis disturbance. Amphotericin B is associated with variable adverse effects including renal tubular insult, which may induce hypomagnesemia following relatively short treatment. The resolution of hypomagnesemia, hypocalcemia, and hypoparathyroidism in our patient after discontinuation of amphotericin B treatment suggests that the endocrine dysfunction was due to a drug-related adverse effect and not to parathyroid dysfunction caused by iron deposition.

CONCLUSIONS:

This case demonstrates a known but rarely reported adverse effect of amphotericin B, namely hypomagnesemia, that may occur even at a low cumulative dose. It also emphasizes that patients with an underlying disease, such as thalassemia, may be more susceptible to hypoparathyroidism and hypocalcemia during treatment with amphotericin B.
Adherence to ATS Guidelines for Hospitalized Patients with Community-Acquired Pneumonia
Authors: Malone Daniel C , Shaban Hanan M
Published: June 2003

OBJECTIVE:

To compare outcomes of care and antibiotic utilization for community-acquired pneumonia (CAP) throughout a group of not-for-profit hospitals.

METHODS:

A retrospective chart review of patients from community hospitals with a diagnosis of pneumonia at discharge admitted from December 1997 to May 1998. Data were collected based on American Thoracic Society (ATS) criteria.

RESULTS:

Medical records of 330 patients were reviewed; mortality was 7%. Using ATS guidelines, 51 (15.5%) patients were not treated with recommended antimicrobial therapy. Of these patients, 14 had nonsevere cases of CAP and 37 cases were severe. Factors found to be associated with in-hospital mortality included nonadherence to ATS guidelines (OR 4.46; 95% CI 1.38 to 14.43), decreased urine output (OR 7.72; 95% CI 1.70 to 35.04), and increasing age (OR 1.06; 95% CI 1.01 to 1.12). Significant predictors of length of stay (LOS) included age, nonadherence to ATS criteria, suspected aspiration, discharge status, low pulse oximetry on admission, decreased urine output, use of vasopressor medications, and interstitial lung disease. More than 80% of patients had at least one culture performed, but only 27.5% of these cultures were positive. The most commonly prescribed antibiotic was cefuroxime injection, representing 25% of the antibiotic orders.

CONCLUSIONS:

Patients with CAP treated inconsistently with ATS guidelines had a 4.46-fold higher risk of inpatient mortality and had significantly longer LOS.
Antiepileptic Hypersensitivity Syndrome in Children
Authors: Bessmertny Olga , Hatton Randy C , Gonzalez-Peralta Regino P
Published: June 2003

OBJECTIVE:

To assess clinical features and outcomes of childhood antiepileptic hypersensitivity syndrome (AHS). AHS is an idiosyncratic reaction to aromatic anticonvulsants that can result in severe multiorgan dysfunction and death.

METHODS:

Children with suspected AHS (fever, rash, lymphadenopathy, liver dysfunction) were identified by an in-house computerized adverse drug event reporting system. The medical charts of children with suspected AHS were reviewed. A MEDLINE search (from 1966 to October 1999) was performed using the term antiepileptic hypersensitivity syndrome.

RESULTS:

Fourteen of 36 children who experienced a rash, urticaria, pruritus, fever, or hepatotoxicity associated with aromatic anticonvulsants met the criteria for AHS (mean age 10.4 ± 6.5 y; males to females 8:6, white to African-American to biracial 10:3:1). Eight patients were receiving phenytoin, six carbamazepine, and four phenobarbital alone or in combination. The mean time from exposure to development of symptoms was 23.0 ± 14.8 days. In addition to rash and fever (present in all patients by definition), other common features of AHS were lymphocytosis (71.4%), elevated erythrocyte sedimentation rate (64.3%), elevated aminotransferases (64.3%), lymphadenopathy (57.1%), eosinophilia (42.8%), coagulopathy (42.8%), leukocytosis (35.7%), leukopenia (35.7%), hyperbilirubinemia (35.7%), and nephritis (7.1%). All children recovered except one, who died from complications of liver failure. Clinical outcome was similar between children who received systemic steroid therapy (n = 5) and those who did not. Antiepileptics producing AHS were discontinued in all patients.

CONCLUSIONS:

AHS can be fatal in children if not promptly recognized. Fever, rash, and hepatotoxicity should serve as presumptive evidence for AHS, which requires immediate discontinuation of an offending anticonvulsant.
Prophylaxis for Paclitaxel Hypersensitivity Reactions
Authors: Kintzel Polly E
Published: June 2003

OBJECTIVE:

To evaluate clinical literature supporting the prophylactic use of single-dose intravenous dexamethasone to prevent hypersensitivity reactions (HSRs) to paclitaxel infusion.

DATA SOURCES:

Clinical literature accessed through MEDLINE (from 1986 to 2000).

DATA SYNTHESIS:

Prophylaxis for paclitaxel-related HSRs generally includes repeated dexamethasone doses beginning 12 hours before paclitaxel, and administration of diphenhydramine plus a histamine2-receptor antagonist 30 minutes before infusion of paclitaxel. Single-dose intravenous dexamethasone administered with ancillary medications 30 minutes before infusion of paclitaxel has been used to prevent regimen-related HSRs.

CONCLUSIONS:

Single-dose intravenous dexamethasone can be used in combination with appropriate ancillary medications to prevent paclitaxel-related HSRs.
Pulmonary Fibrosis Induced by Cyclophosphamide
Authors: Segura Angel , Yuste Ana , Cercos Ana , López-Tendero Pedro , Gironés Regina , Pérez-Fidalgo José A , Herranz Constantino
Published: June 2003

OBJECTIVE:

To report a case of pulmonary fibrosis resulting from use of cyclophosphamide as chemotherapy to treat a patient with breast cancer.

CASE SUMMARY:

We describe the case of a 52-year-old woman with breast cancer who developed pulmonary fibrosis after four cycles of chemotherapy that included cyclophosphamide. Pulmonary function tests revealed the presence of a severe ventilatory restriction. The open lung biopsy revealed pulmonary fibrosis with vascular sclerosis and signs of pulmonary hypertension.

DISCUSSION:

Cyclophosphamide is an alkylating agent that has been associated with interstitial pneumonia and pulmonary fibrosis. The frequency of these unwanted effects is '1%. The clinical picture consists of the progressive appearance of dyspnea and a nonproductive cough that progresses to severe pulmonary insufficiency. The risk factors described for these complications have been the use of chemotherapy regimens that include other drugs with known pulmonary toxicities, the cumulative total dose, the addition of radiotherapy, and the use of high doses of cyclophosphamide.

CONCLUSIONS:

Even though the frequency of pulmonary fibrosis in patients treated with cyclophosphamide-based chemotherapy regimens is low, the presence of dyspnea and an interstitial pattern in a patient makes it necessary to consider that possible drug toxicity. The open lung biopsy is the most accurate diagnostic technique for these cases. The discontinuation of cyclophosphamide and treatment with corticosteroids is usually followed by clinical recovery in approximately 50% of patients and, in some cases, reversal of the lung injury.
Lack of Tacrolimus-Induced Cardiomyopathy
Authors: Coley Kim C , Verrico Margaret M , McNamara Dennis M , Park Sang C , Cressman Michael D , Branch Robert A
Published: June 2003

BACKGROUND:

Hypertrophic cardiomyopathy (HCM) has been reported in pediatric transplant patients receiving tacrolimus. It is unclear whether tacrolimus is associated with HCM in adult transplant recipients.

OBJECTIVE:

To determine the prevalence of HCM in noncardiac adult transplant patients receiving tacrolimus.

METHODS:

A retrospective analysis of nonheart transplant recipients who received tacrolimus at our institution from January 1982 to April 1996 was conducted. Patients with left-ventricular hypertrophy (LVH) defined as a posterior or septal wall thickness ≥1.3 cm by echocardiography (ECHO) were independently evaluated.

RESULTS:

There were 3609 patients who met entry criteria including 2257 liver, 1333 kidney, and 19 other organ transplants. Of the 502 patients who had undergone ECHOs after transplantation, 171 had LVH. The etiology of LVH was categorized as valvular disease (36%), hypertensive disease (29%), ischemic heart disease (17%), or multifactorial (15%). There were six patients in whom, after detailed chart review, no underlying cause of LVH was evident. Five of these patients had HCM, representing an overall prevalence of 0.1% in the entire group of tacrolimus-treated patients, and 1% in patients referred for ECHO.

CONCLUSIONS:

The prevalence of HCM in our tacrolimus-treated adult transplant population is similar to that reported in general population studies. These data suggest that tacrolimus is not a risk factor for HCM in adult transplant recipients.
Failure of Tolterodine to Treat Clozapine-Induced Nocturnal Enuresis
Authors: English Brett A , Still Daniel J , Harper John , Saklad Steven R
Published: June 2003

OBJECTIVE:

To report the use and subsequent failure of the bladder-selective agent tolterodine, to treat clozapine-induced nocturnal enuresis in an adolescent patient with psychotic illness.

CASE SUMMARY:

A 16-year-old Hispanic girl was admitted to the state psychiatric hospital with a diagnosis of bipolar disorder with psychotic features. Clozapine therapy was initiated, and after three months of treatment the patient began experiencing episodes of nocturnal enuresis. The bladder-selective agent tolterodine was tried and subsequently failed to resolve the enuresis episodes. Desmopressin was initiated, which resulted in amelioration of symptoms.

DISCUSSION:

This is the first published report of using tolterodine to treat clozapine-induced nocturnal enuresis. Several methods to decrease clozapine-induced urinary incontinence have been used and typically include the addition of agents with high anticholinergic properties. Tolterodine is a bladder-selective anticholinergic agent indicated for the treatment of urinary urge incontinence and may be employed as a treatment for antipsychotic-induced incontinence.

CONCLUSIONS:

Nocturnal enuresis is an adverse effect that infrequently occurs with use of clozapine therapy. Although tolterodine was ineffective in our patient to treat clozapine-induced nocturnal enuresis, further trials are required to appropriately evaluate the effectiveness of tolterodine to treat this adverse drug reaction.
Trimethoprim/Sulfamethoxazole—Induced Toxic Epidermal Necrolysis
Authors: See Sharon , Mumford James M
Published: June 2003

OBJECTIVE:

To report a case of toxic epidermal necrolysis (TEN) associated with trimethoprim/sulfamethoxazole (TMP/SMX).

CASE SUMMARY:

A 34-year-old Asian woman developed a severe, desquamating mucocutaneous reaction (TEN) after six days of taking TMP/SMX to treat a presumed urinary tract infection (UTI).

DISCUSSION:

TMP/SMX is often recommended as first-line therapy for UTIs, sinusitis, bronchitis, and as prophylaxis and treatment for Pneumocystis carinii pneumonia. TEN is a rare, but severe condition associated with sulfonamide use. This article describes a typical case and offers an opportunity for review of this potentially serious reaction.

CONCLUSIONS:

Sulfonamides are often implicated in the majority of drug-induced cases of TEN. This case report illustrates the typical presentation of sulfonamide-induced TEN with a prodrome, characteristic rash, mucous membrane lesions, and systemic involvement. Practitioners should be aware of this rare adverse effect and closely observe patients for cutaneous manifestations or complaints. Any suspected drug should be discontinued if clinical evaluation leads to the suspicion of Stevens—Johnson syndrome or TEN.
Management of Childhood Acute Respiratory Infections at Private Pharmacies in Vietnam
Authors: Chuc Nguyen TK , Larsson Mattias , Falkenberg Torkel , Do Nguyen T , Binh Nguyen T , Tomson Goran B
Published: June 2003

OBJECTIVE:

To investigate the knowledge and practice among private pharmacy staff in Hanoi regarding case management of mild acute respiratory infection (ARI) in children.

METHODS:

Sixty private pharmacies in Hanoi were randomly selected. Knowledge was assessed through interviews with pharmacy staff using a questionnaire; practice was assessed through the Simulated Client Method.

RESULTS:

In the questionnaire, 20% of the pharmacy staff stated that they would dispense antibiotics. In practice, 83% of the pharmacies dispensed antibiotics. Only 36% of the cases were handled according to guidelines. In the questionnaire, 81% of interviewees stated that antibiotics are not effective in short therapeutic courses. In practice, 48% of the antibiotics were dispensed in courses less than five days. Traditional herbal medicines were dispensed in 41% of the encounters. In the questionnaire, 53% of the pharmacy staff stated that they would ask the patient about difficulty of breathing. In practice, questions related to difficulty of breathing were asked in less than 10% of the encounters.

CONCLUSIONS:

Dispensing of antibiotics for mild ARI was common practice among private pharmacies, and there was a significant difference between knowledge and practice. Interventions are needed to improve pharmacy practice in Hanoi.
Statin—Fibrate Combination Therapy
Authors: Shek Allen , Ferrill Mary J
Published: June 2003

BACKGROUND:

Precautionary warnings for severe myopathy and rhabdomyolysis from the coadministration of statins and fibrates have been well publicized. However, a recent cerivastatin labeling change made the combined use with fibric acid derivatives a contraindication. Practical recommendations for clinicians who care for patients with refractory mixed hyperlipidemia are needed.

OBJECTIVE:

To provide recommendations for clinicians in the treatment of refractory mixed hyperlipidemia.

DATA SOURCES:

A comprehensive MEDLINE (1966–July 2000) and bibliographic search was performed.

DATA SYNTHESIS:

Thirty-six published clinical trials and 29 case reports involving combination therapy with hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors and fibric acid derivatives regarding the occurrence of rhabdomyolysis or myopathy were reviewed. The literature review demonstrated that combination therapy with a statin and fibrate increases the risk of muscle damage, with an incidence of 0.12%. Risk factors that predispose patients to myopathy caused by combination statin—fibrate therapy include increased age, female gender, renal or liver disease, diabetes, hypothyroidism, debilitated status, surgery, trauma, excessive alcohol intake, and heavy exercise.

CONCLUSIONS:

Combination therapy with a statin and fibrate offers significant therapeutic advantage for the treatment of severe or refractory mixed hyperlipidemia. Although such a combination does increase the risk of myopathy, with an incidence of approximately 0.12%, this small risk of myopathy rarely outweighs the established morbidity and mortality benefits of achieving lipid goals. Nevertheless, a higher incidence of myopathy has been reported with statin monotherapy. When monotherapy with a statin fails to control mixed hyperlipidemia, combination therapy may be considered. Niacin may be added before a fibrate is considered, as it appears to have less risk of myopathy. Statin—fibrate combination therapy must be undertaken cautiously and only after careful risk—benefit analysis. Patient counseling on the risks and warning signs of myopathy is extremely important.
Systemic Hemostatic Medications for Reducing Surgical Blood Loss
Authors: Erstad Brian L
Published: June 2003

OBJECTIVE:

To review randomized trials involving the use of systemic hemostatic medications for reducing surgical blood loss.

DATA SOURCES:

Articles were obtained through searches of MEDLINE (1966–September 2000). The bibliographies of retrieved publications were reviewed for additional references.

STUDY SELECTION:

All randomized studies and pharmacoeconomic evaluations that involved medications used for systemic hemostasis in the perioperative period were included.

DATA EXTRACTION:

Randomized studies involving conjugated estrogens, aminocaproic acid, tranexamic acid, desmopressin, and aprotinin for systemic hemostasis were extracted. Studies of proton-pump inhibitors for upper gastrointestinal bleeding and octreotide for variceal bleeding were excluded, as were trials involving the use of any hemostatic agent for cardiovascular surgery. The primary outcome under review was a reduction in bleeding as defined by reduced transfusion requirements.

DATA SYNTHESIS:

There is limited efficacy and toxicity information concerning the use of conjugated estrogens for reducing surgery-related bleeding. Similarly, there are a limited number of randomized studies involving aminocaproic acid and tranexamic acid, and with the exception of tranexamic acid for reducing transfusion requirements with knee surgery, the study results are either conflicting or negative. For desmopressin, evidence from a substantial number of randomized trials documents its lack of efficacy. Aprotinin has reduced bleeding and transfusion requirements in a number of randomized studies involving patients undergoing orthopedic surgery, but cost-effectiveness studies are needed to better define its therapeutic role. Trials of aprotinin during hepatic surgery have yielded conflicting results.

CONCLUSIONS:

Most hemostatic medications used for reducing surgery-related bleeding have limited or contradictory evidence of efficacy.
Verteporfin for Age-Related Macular Degeneration
Authors: Messmer Karen J , Abel Steven R
Published: June 2003

OBJECTIVE:

To review the pharmacology, pharmacokinetics, clinical efficacy, adverse effects, drug—drug interactions, and the therapeutic issues concerning the use of verteporfin in patients with age-related macular degeneration (AMD).

DATA SOURCES:

Published articles and abstracts in English were identified by MEDLINE (1990–August 2000) searches using the search terms verteporfin, treatment of age-related macular degeneration, and photodynamic therapy (PDT). Additional references were identified from the bibliographies of the retrieved articles. Data were also obtained from approved product labeling.

DATA EXTRACTION:

The literature was assessed for adequate description of patients, methodology, and outcomes.

DATA SYNTHESIS:

Verteporfin is a synthetic benzoporphyrin derivative and a cytotoxic photosensitizing agent, which is one component of PDT. PDT involves administration of verteporfin for injection and nonthermal red light at a wavelength of 689 nm. It is metabolized, to a small extent, to its diacid metabolite by liver and plasma esterases. Information concerning drug interactions is limited. In clinical trials, verteporfin was effective in patients with wet AMD as demonstrated in standard visual acuity scores. Adverse events were related to injection site reactions and visual disturbances.

CONCLUSIONS:

Verteporfin is a welcome alternative to laser photocoagulation, which can result in damage to the retina and lead to visual loss. Although long-term trials have not been performed in humans, results from monkeys indicate possible improvement in vision following PDT with verteporfin.
Warfarin Pharmacodynamics Unaffected by Cilomilast
Authors: Kelly John , Murdoch Robert D , Clark David J , Webber Dawn M , Fuder Hermann
Published: June 2003

OBJECTIVE:

To demonstrate a lack of effect of steady-state concentrations of cilomilast, a new oral phosphodiesterase 4 inhibitor for the treatment of chronic obstructive pulmonary disease, on warfarin-induced anticoagulation.

METHODS:

This 28–day, randomized, double-blind, placebo-controlled, parallel-group study involved 36 healthy men. All volunteers received warfarin once daily on days 1 through 24 of the study. After a standard 5–mg loading dose on days 1 and 2, the warfarin dose was titrated between days 3 and 10 to achieve a stable prothrombin time, expressed as international normalized ratio (INR). Volunteers received either cilomilast 15 mg twice daily or placebo on days 18 through 24. The primary end point was the INR on day 24.

RESULTS:

On day 24, the mean ± SEM INR in subjects receiving concurrent warfarin and cilomilast was 1.35 ± 0.05, compared with 1.38 ± 0.07 in those receiving concurrent warfarin and placebo. The point estimate (90% CI) for the difference in day 24 INR values between cilomilast and placebo (adjusted for baseline) was 0.02 (90% CI −0.13 to 0.17), which translates to an INR ratio of 1.02 (90% CI 0.91 to 0.13). The 90% confidence interval for the ratio of mean INR (cilomilast:placebo) on day 24 was completely contained within the 25% equivalence range, indicating a lack of interaction between warfarin and cilomilast. The adverse event profiles of warfarin/placebo and warfarin/cilomilast were similar and favorable.

CONCLUSIONS:

The pharmacodynamics of warfarin are unaffected by coadministration of cilomilast at steady-state concentrations in healthy volunteers.
Fenoldopam in the Prevention of Contrast Media—Induced Acute Renal Failure
Authors: Chu Valery L , Cheng Judy WM
Published: June 2003

OBJECTIVE:

To examine the role of fenoldopam in prevention of contrast media—induced acute renal failure (ARF).

DATA SOURCES:

A literature search of MEDLINE (from 1966 to October 2000) was performed using the following title search terms: fenoldopam, contrast, and renal failure.

STUDY SELECTION:

English-language human studies, abstracts, and pertinent animal data were reviewed.

DATA SYNTHESIS:

Small trials using animals with artificially induced ARF receiving fenoldopam demonstrated improvement in renal function. Preliminary trials in healthy humans have also demonstrated similar results using doses not affecting systemic blood pressure.

CONCLUSIONS:

Fenoldopam may have a role in the management of ARF induced by contrast dye. However, due to the lack of a large-scale study, it cannot be routinely recommended.
Fibrinolytic Therapy in Intraventricular Hemorrhage
Authors: Andrews Carlota O , Engelhard Herbert H
Published: June 2003

OBJECTIVE:

To review the literature concerning intraventricular administration of fibrinolytic agents to treat patients with intraventricular hemorrhage (IVH).

DATA SOURCES:

An extensive literature search (MEDLINE, EMBASE, Conference Proceedings) was conducted to identify articles in English published between 1966 and May 2000 pertaining to the pathophysiology of IVH and its treatment by intraventricular administration of recombinant tissue plasminogen activator (alteplase) or urokinase (u-PA). The bibliographies of selected identified articles were also screened for publications not found in the computerized search.

STUDY SELECTION:

All pertinent publications were reviewed and considered. Those describing the intraventricular administration of fibrinolytic agents to patients with IVH were included.

DATA SYNTHESIS:

IVH has a poor prognosis, partly due to the mass effect of blood clots on the ventricular walls. The cerebrospinal fluid has a limited fibrinolytic system. Therefore, clots may remain in the ventricles for months after a hemorrhage. The management of IVH is primarily directed at controlling intracranial pressure through an external ventricular drain, but this catheter often becomes occluded by coagulated blood. To overcome this problem, and to dissolve the residual blood clot, investigators have administered alteplase or u-PA directly into the ventricles of patients with IVH. Complications of this therapy include infection and possible rebleeding. Clinical studies of fibrinolytic therapy for IVH have found a 30–35% reduction in mortality with treatment, but to date, have not clearly documented improved neurologic outcome of the survivors.

CONCLUSIONS:

Fibrinolytic therapy with alteplase or u-PA may be life-saving in severe cases of IVH. Yet many technical issues remain to be resolved, such as the optimal dose, frequency, method, timing, and duration of administration of the agent. Additional randomized, double-blind, placebo-controlled studies need to be performed so that the true value of this therapy can be assessed.
Compound Cardiac Toxicity of Oral Erythromycin and Verapamil
Authors: Goldschmidt Neta , Azaz-Livshits Tanya , Gotsman Israel , Nir-Paz Ran , Ben-Yehuda Arie , Muszkat Mordechai
Published: June 2003

OBJECTIVE:

To report a case of complete atrioventricular (AV) block and QTc prolongation following coadministration of high-dose verapamil and erythromycin.

CASE SUMMARY:

A 79-year-old white woman was admitted to the hospital due to extreme fatigue and dizziness. On admission, heart rate was 40 beats/min and blood pressure was 80/40 mm Hg. An electrocardiogram showed complete atrioventricular (AV) block, escape rhythm of 50 beats/min, and QTc prolongation 583 msec. This event was attributed to concomitant treatment with verapamil 480 mg/d and erythromycin 2000 mg/d, which was prescribed one week before admission.

DISCUSSION:

This is the first case published describing complete AV block and prolongation of QTc following coadministration of erythromycin and verapamil. CYP3A4 is the main isoenzyme responsible for metabolism of erythromycin and verapamil. Both drugs are potent inhibitors of CYP3A4 and of P-glycoprotein; this may be the basis for the pharmacokinetic interaction between erythromycin and verapamil. In addition to being a woman, our patient had other risk factors for QT prolongation: slow baseline heart rate (probably induced by verapamil), left-ventricular hypertrophy, and possibly ischemic heart disease.

CONCLUSIONS:

This life-threatening arrhythmia was probably the result of a pharmacokinetic and/or pharmacodynamic interaction of high-dose verapamil and erythromycin.
Treatment of Bulimia Nervosa with Ondansetron
Authors: Fung Stacey M , Ferrill Mary J
Published: June 2003

OBJECTIVE:

To evaluate ondansetron as a treatment for bulimia nervosa.

DATA SOURCE:

Literature was accessed through MEDLINE (1966–November 2000). Key terms included ondansetron, bulimia nervosa, binge eating, and eating disorders.

DATA SYNTHESIS:

Treatment of bulimia nervosa includes cognitive behavioral therapy and antidepressants. Fluoxetine is approved by the Food and Drug Administration for binge eating and vomiting behaviors in moderate to severe bulimia nervosa. An evaluation of ondansetron for bulimia nervosa was conducted.

CONCLUSIONS:

Ondansetron for bulimia nervosa was reported to be effective in three small trials by one group of investigators, and may be an option after failure of traditional therapies. Further studies will define the role of serotonin (5-HT3) receptor antagonists in the management of bulimia nervosa.
Hepatotoxicity after Short-Term Trazodone Therapy
Authors: Rettman Kristina S , McClintock Claudia
Published: June 2003

OBJECTIVE:

To report a case of severe hepatotoxicity from a four-day course of trazodone in a patient being treated according to protocol in a detoxification center.

CASE SUMMARY:

A 46-year-old HIV-positive man with a past medical history of intravenous drug abuse and hepatitis C, who was well controlled with HIV medications, was admitted for cocaine withdrawal. The patient was started on a standard protocol at the detoxification center with methadone 50 mg/d, clonidine 0.1 mg twice daily for four days, and trazodone 200 mg/d for four days. Laboratory results showed acute hepatitis and cholestasis five days following admission. Trazodone and clonidine were discontinued at that time. His methadone and HIV regimens remained unchanged. Liver function test results were greatly improved 10 days after trazodone and clonidine discontinuation.

DISCUSSION:

This is the first case report of trazodone-induced liver damage after only a few days of therapy. Previous reports describe hepatitis developing after weeks to months of trazodone therapy. All comorbidities thought to affect the described laboratory abnormalities were ruled out as a cause by a hepatologist. The observation of the sudden rise and fall of liver enzymes is characteristic of a drug reaction in the absence of trauma and severe shock.

CONCLUSIONS:

Due to the temporal relationship of the introduction and withdrawal of trazodone in the medication regimen and the elevations in liver enzymes, we conclude that this patient experienced acute hepatitis induced by trazodone 200 mg/d therapy for four days. The findings of this case warrant caution and closer monitoring in a patient with multiple risk factors for liver damage.
Amiodarone in the New AHA Guidelines for Ventricular Tachyarrhythmias
Authors: Caron Michael F , Kluger Jeffrey , White C Michael
Published: June 2003

OBJECTIVE:

To delineate amiodarone's role in the new American Heart Association guidelines for ventricular tachyarrhythmias, review the literature that supports the use of amiodarone in ventricular tachyarrhythmias, describe the pharmaceutical properties of amiodarone and elucidate their clinical implications, and discuss the dosing, preparation, and administration of amiodarone.

DATA SOURCES:

A search of MEDLINE (1966–October 2000) database and EMBASE Drugs and Pharmacology database (1980–October 2000) was performed. References from published articles and tertiary references were used to gather additional data.

DATA EXTRACTION:

All articles were screened, and pertinent studies were identified and evaluated.

DATA SYNTHESIS:

Recent trials have demonstrated amiodarone's usefulness in the setting of ventricular tachyarrhythmias. Based on these investigations and contrary to past guidelines, amiodarone is included in the 2000 advanced cardiovascular life support guidelines as a possible agent for hemodynamically stable monomorphic ventricular tachycardia (VT), non-QT prolonged polymorphic VT, and ventricular fibrillation (VF)/pulseless VT. Although not specifically evaluated in the setting of hemodynamically stable monomorphic VT and non-QT prolonged polymorphic VT, investigations by the Intravenous Amiodarone Multicenter Trial Group and other clinical trials make amiodarone an acceptable choice for these arrhythmia categories. The results of the ARREST (Resuscitation of Refractory Sustained Ventricular Tachyarrhythmias) trial prove amiodarone to be the antiarrhythmic of choice for VF/pulseless VT.

CONCLUSIONS:

Amiodarone is classified as a IIb therapeutic intervention for all three arrhythmia categories, which makes it an acceptable, safe, and useful agent with fair to good evidence to support its use. In addition, amiodarone requires careful preparation and delivery to achieve safe and effective outcomes.