bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Cyclooxygenase-2 Inhibitors: Safety and Effectiveness
Authors: Kaplan-Machlis Barbara , Klostermeyer Barbara Storyk 
Published: March 2004

OBJECTIVE: To review the development of cyclooxygenase-2 (COX-2) inhibitors and discuss specific agents that are currently under investigation or have been marketed. DATA SOURCES: Primary literature on selective COX inhibitors was identified from a comprehensive MEDLINE, English-literature search from January 1966 through September 1998, with additional studies selected by review of the references. Abstracts from recent meetings and package insert literature from approved agents were also used as source material. Indexing terms included COX-2 inhibitors, meloxicam, celecoxib, rofecoxib, flosulide, SC-58635, and MK-966. STUDY SELECTION: Human clinical, pharmacokinetic, and dose-ranging trials performed in Europe and the US and randomized comparative trials were reviewed. DATA SYNTHESIS: With the discovery of at least two COX isoforms, a better understanding of the mechanism of action and gastrointestinal toxicity of nonsteroidal antiinflammatory drugs (NSAIDs) has been realized. While COX-1 is involved in physiologic maintenance, COX-2 seems to be involved in inflammation, mitogenesis, and specialized signal transductions. Selective COX-2 inhibitors may allow maximum antiinflammatory activity while improving the safety profile associated with NSAID therapy. Celecoxib and rofecoxib have been approved by the Food and Drug Administration for the treatment of osteo- and rheumatoid arthritis; meloxicam is undergoing Phase III clinical trials. Preliminary data indicate that the selective COX-2 inhibitors provide analgesic and antiinflammatory efficacy comparable with older NSAIDs, with fewer adverse gastrointestinal effects. CONCLUSIONS: Specific COX-2 inhibitors offer promising benefits over older NSAIDs with regard to gastrointestinal safety while maintaining analgesic and antiinflammatory efficacy. Further study is required to determine long-term efficacy and safety in clinical use.
Factors Influencing the Incidence of Lamotrigine-Related Skin Rash
Authors: Wong Ian CK , Mawer George E , Sander Josemir WAS 
Published: March 2004

OBJECTIVE: To determine the incidences of serious and nonserious lamotrigine-related rash, determine the risk factors for lamotrigine-related rash, and evaluate the impact on the incidence of rash of the manufacturer's recommendation to reduce the starting dose of lamotrigine. METHODS: This was a retrospective case record survey at five tertiary referral epilepsy centers in the UK. The risk factors for lamotrigine-related rash were identified by logistic regression. The independent factors tested were gender, age, epilepsy type, concurrent medication, and starting dose of lamotrigine. The incidences of rash before and after the recommendation of reduction in starting dose were compared by •2 analysis. RESULTS: A total of 1050 patients were included. The incidences of serious and nonserious rash were 1.1% (95% CI 0.5% to 1.8%) and 7% (95% CI 5.5% to 8.6%), respectively. Females were at higher risk of developing rash than were males, with a relative risk of 1.8 (95% CI 1.2 to 2.8). The starting dose of lamotrigine was reduced in response to the manufacturer's recommendation, and there was a significant reduction (p = 0.045) in the incidence of serious rash, from 1.5% (12/805) to 0% (0/245). However, there was no reduction in the overall incidence of lamotrigine-related rash, with 63/805 (8%) before and 23/245 (9%) after the recommendation. CONCLUSIONS: Failure to detect a reduction in the incidence of lamotrigine-related rash since the new (reduced) recommended starting dose of lamotrigine may arise from failure to reduce the starting dose below a critical threshold level, incomplete compliance with current recommendations, or insufficient sample size. The results of this and other studies show that the starting dose of lamotrigine is a significant factor affecting the incidence of rash; furthermore, this study also shows that significant reduction in the incidence of serious rash can be achieved by reducing the starting dose. Therefore, clinicians should not deviate from the recommendations.
Health-Related Quality of Life in Primary Care Patients with Gastroesophageal Reflux Disease
Authors: Kaplan-Machlis Barbara , Spiegler Gerard E , Revicki Dennis A 
Published: March 2004

OBJECTIVE: To describe the clinical characteristics and health-related quality of life of family medicine patients with clinically diagnosed gastroesophageal reflux disease (GERD). METHODS: The study involved the baseline assessment of 268 patients enrolled in a randomized clinical trial comparing treatments for GERD. The study was conducted in a five-center, university-based family practice in southeastern West Virginia. Patients with a clinical diagnosis of GERD and who had not received treatment in the past 30 days were eligible; pregnant and lactating women and patients with severe renal or hepatic insufficiency were excluded. RESULTS: Two hundred sixty-eight patients were included in the analysis. Mean ± SD age was 44.9 ± 14.1 years; 61.2% were women and 91.4% were white. Mean ± SD body mass index was 30.3 ± 6 kg/m2, and >15.3% of patients had no insurance. One hundred seventy-four (64.9%) patients were enrolled from nonurban primary care clinics. One hundred sixty-four patients (61.2%) were prescribed at least one medication prior to study enrollment (mean ± SD 2.88 ± 1.71; range 1–9). When adjusted for age, gender, comorbidity status, and rural status, severity of GERD was associated with decreased health-related quality of life. GERD patients without comorbidity demonstrated decrements in health-related quality of life when compared with the US general population. When compared with another GERD population, the study patients reported fairly consistent GERD symptomatology and health-related quality of life. CONCLUSIONS: GERD symptom severity was associated with impaired health-related quality of life in a predominantly rural primary care population.
Tolterodine Use for Symptoms of Overactive Bladder
Authors: Ruscin J Mark , Morgenstern Nora E 
Published: March 2004

OBJECTIVE: To describe the pharmacology, pharmacokinetics, clinical efficacy, and safety of tolterodine for the treatment of overactive bladder. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (January 1980–October 1998) using the terms tolterodine, PNU-200583E, urge incontinence, overactive bladder, detrusor instability, detrusor overactivity, and antimuscarinic. Pertinent articles written in English were considered for review. Additional articles were identified from the bibliographies of retrieved articles. Data from the Food and Drug Administration– approved product labeling and the manufacturer were also used in the absence of published data. STUDY SELECTION AND DATA EXTRACTION: Clinical studies of tolterodine involving human subjects were evaluated. DATA SYNTHESIS: Tolterodine is a competitive muscarinic receptor antagonist with relative functional selectivity for bladder muscarinic receptors. It is metabolized in the liver by CYP2D6 to an active metabolite (DD 01), which is partially responsible for its pharmacologic activity. Those who are genetically devoid of CYP2D6 will have higher concentrations of the parent compound and virtually undetectable concentrations of DD 01; however, the clinical efficacy does not appear to be altered. In dosages of 2 mg twice daily, tolterodine has shown consistent reductions in the number of micturitions per 24 hours and less consistently decreased incontinence episodes in patients with detrusor overactivity. The functional selectivity of tolterodine for bladder muscarinic receptors results in fewer systemic adverse effects, such as dry mouth, than occur with comparable nonselective antimuscarinic agents. CONCLUSIONS: Clinical studies have shown that the effectiveness of tolterodine for symptoms of overactive bladder is similar to that of oxybutynin. The adverse effect profiles of tolterodine and oxybutynin are similar; however, comparative clinical trials have shown significantly fewer patients taking tolterodine require dosage reductions or discontinue therapy due to antimuscarinic adverse effects such as dry mouth. Although more costly than oxybutynin, tolterodine represents a modest improvement over oxybutynin with respect to adverse effect profile, which may allow more patients with incontinence to tolerate therapeutic doses. Further research is necessary to determine whether tolterodine has clinical advantages over similar agents in patients with other muscarinic adverse effects, such as constipation or cognitive impairment.
Successful Use of Clopidogrel for Cerebrovascular Accident in a Patient with Suspected Ticlopidine-Induced Hepatotoxicity
Authors: Zeolla Mario M , Carson John J 
Published: March 2004

OBJECTIVE: To report a case of successful clopidogrel use in a patient who developed suspected ticlopidine-induced hepatotoxicity during therapy for a cerebrovascular accident. CASE REPORT: A 79-year-old white woman with a history of hypertension, type 2 diabetes, Alzheimer disease, and coronary artery disease started receiving ticlopidine 250 mg twice daily three days after hospital admission for a cerebrovascular accident. Medications prior to admission included quinapril, furosemide, insulin, atorvastatin, conjugated estrogen, medroxyprogesterone, donepezil, and vitamin E. The estrogen, medroxyprogesterone, and donepezil were discontinued on admission. Laboratory tests on admission revealed that total bilirubin, alkaline phosphatase, and aspartate aminotransferase (AST) were within normal limits. On day 39 of hospitalization, laboratory tests showed marked increases in alkaline phosphatase, AST, alanine aminotransferase, γ-glutamyl-transferase, and 5' nucleotidase. Physical examination revealed no signs of jaundice or hepatomegaly, and laboratory tests for viral hepatitis were negative. A presumptive diagnosis of ticlopidine-induced hepatotoxicity was made and ticlopidine was discontinued. The following day, clopidogrel 75 mg/d was initiated. Liver function tests returned to baseline over the following four months with ongoing clopidogrel therapy. DISCUSSION: Ticlopidine-induced hepatotoxicity is well documented in the literature. In the present case, clopidogrel, a structurally similar thienopyridine, was substituted for ticlopidine following the development of presumptive ticlopidine-induced hepatotoxicity. Serum liver enzyme concentrations returned to baseline with continued clopidogrel therapy, suggesting that clopidogrel is a suitable alternative in patients who develop ticlopidine-induced hepatotoxicity. CONCLUSIONS: Clopidogrel may be a suitable alternative for patients who develop ticlopidine-induced hepatotoxicity.
Economic Evaluation of Risperidone in an Outpatient Population
Authors: Hammond Constance M , Pierson Jerome F , Grande Thomas P , Munetz Mark R , Wilson Daniel R , Pathak Dev S 
Published: March 2004

OBJECTIVE: To study the impact of risperidone use on the cost of services provided to severely mentally disabled outpatients and on hospital avoidance, and to analyze patterns in the use of concomitant medications as a surrogate marker of changes in adverse effects or patient well-being. METHODS: The patients were 31 clients of community mental health centers who had received risperidone for at least three months and for whom there were at least three months of available data on medication use and costs prior to risperidone treatment. The actual average monthly costs of community mental health services obtained from a county mental health board were compared with service costs prior to use of risperidone, using the patients as their own controls, and compared with a control group. RESULTS: Compared with the pre-risperidone period, the average cost per month of providing mental health services increased by 73.7% during the risperidone treatment period. Compared with the pre-risperidone period, the average total cost of treatment (including medications) increased by 113.3% during the risperidone treatment period. The average total cost of medication increased by 422.8% during the risperidone treatment period compared with the pre-risperidone treatment period. CONCLUSIONS: From the perspective of the community mental health board, risperidone treatment did not reduce the cost of services provided to these clients, but substantially and significantly increased total costs, including medication.
Treatment of Wegener's Granulomatosis with Immune Globulin: CNS Involvement in an Adolescent Female
Authors: Taylor Charles T , Buring Shauna M , Taylor Kelly H 
Published: March 2004

OBJECTIVE: To describe the use of intravenous immune globulin (IVIG) to treat Wegener's granulomatosis (WG) in an adolescent female with an abnormal magnetic resonance imaging (MRI) scan and electroencephalogram (EEG), as well as central nervous system involvement manifesting as generalized seizures. CASE SUMMARY: A 15-year-old white girl diagnosed with WG and receiving prednisone and cyclophosphamide was admitted with new-onset tonic–clonic seizures. The patient received phenobarbital and phenytoin to control seizures and was receiving cyclophosphamide and corticosteroids for WG. She developed cyclophosphamide-induced cystitis and was started on a four-day therapeutic course of IVIG following the discontinuation of cyclophosphamide. After 16 days of hospitalization, repeat EEG and MRI were within normal limits, and laboratory and clinical improvement was evident in at least nine of the affected organ systems including pulmonary, hematologic, renal, ocular, cutaneous, musculoskeletal, central nervous system, gastrointestinal, and genitourinary. The patient was discharged with clinical involvement of WG documented in two organ systems, hematologic and renal. DISCUSSION: WG is a form of vasculitis believed to develop due to an autoimmune disorder. The diagnosis is based on radiographic and histopathologic findings, as well as the presence of elevated antineutrophil cytoplasmic antibodies and a suggestive clinical presentation. The presentation is widely variable and is most commonly associated with upper-airway involvement such as sinusitis, cough, pulmonary infiltrates, and cavitary nodules. Renal involvement signifies generalized disease. Conventional treatment for WG includes cyclophosphamide and prednisone. Little information is available describing therapeutic alternatives. Cytotoxicity related to immunosuppressant regimens limits continuous treatment and may necessitate the use of alternative agents. CONCLUSIONS: This case describes the use of IVIG in an adolescent patient presenting with WG as a generalized, active disease with neurologic complications. IVIG may be useful in generalized, active WG complicated by intolerance to cyclophosphamide and seizures, but further study is necessary to define its role.
The Impact of Pharmaceutical Services in Community and Ambulatory Care Settings: Evidence and Recommendations for Future Research
Authors: Singhal Puneet K , Raisch Dennis W , Gupchup Gireesh V 
Published: March 2004

OBJECTIVE: TO review and evaluate research on pharmaceutical services in community and ambulatory care pharmacy settings, specifically study designs and patient outcome measures, and to provide recommendations to improve future research on pharmaceutical services in community and ambulatory care pharmacy settings. DATA SOURCE: English-language articles were identified by searching MEDLINE (1966-December 1998) and International Pharmaceutical Abstracts (1970-December 1998), using a combination of search terms: pharmacist services, pharmacist interventions, community pharmacy, ambulatory care, primary care, and patient outcomes. Relevant studies were selected based on article abstracts. DATA EXTRACTION: From each relevant study, we extracted the study objectives, sample size, study period, study design, major tasks performed by pharmacists, and economic, clinical, and humanistic outcomes (ECHO). Results were tabulated separately for research on community pharmacy and ambulatory care pharmacy settings. RESULTS: We identified 95 relevant studies. Of these, 21 studies were conducted in community pharmacy settings and 74 in ambulatory care settings. Ten community pharmacy studies used prospective, single group, pretest/posttest, or posttest only designs; seven used prospective two or more group comparison designs; and four used randomized, controlled designs. Nine studies on community pharmacies measured clinical outcomes, two measured humanistic outcomes, and five measured economic outcomes. Four studies measured both clinical and humanistic outcomes and one measured humanistic and economic outcomes. No study measured all three ECHO variables. Twenty-three studies in ambulatory care settings used prospective or retrospective, single group, pretest/posttest or posttest only designs; 21 used prospective or retrospective two-or-more group comparison designs; and 30 used randomized, controlled designs. Thirty-six measured clinical outcomes, five measured humanistic outcomes, and 15 measured economic outcomes. Fifteen studies measured clinical and economic outcomes and three measured clinical and humanistic outcomes. CONCLUSIONS: Only 21 of 95 selected studies were conducted in community pharmacy settings and measured the impact of pharmaceutical services on patient outcomes. Few studies employed adequate research designs to control threats to internal and external validity. In order to obtain a comprehensive and accurate picture of the impact of pharmaceutical services on patient outcomes, an attempt must be made to measure all three ECHO variables while employing adequate research design.
Rifapentine: Its Role in the Treatment of Tuberculosis
Authors: Temple Mary E , Nahata Milap C 
Published: March 2004

OBJECTIVE: To review the pharmacokinetics, efficacy, adverse effects, and cost of the newest antitubercular drug, rifapentine. DATA SOURCES: A MEDLINE search using key terms such as rifapentine, rifampin, isoniazid, Mycobacterium tuberculosis, and pyrazinamide was conducted for the time period 1966–November 1998. STUDY SELECTION: Animal data were used for basic information and human studies were selected for inclusion if they were randomized, controlled studies assessing efficacy, or if they were single- or multiple-dose studies assessing the pharmacokinetics of rifapentine. Background articles on the pathophysiology of tuberculosis and cost of care and noncontrolled studies assessing drug interactions were also included. DATA SYNTHESIS: Compared with an oral solution, the relative bioavailability of rifapentine is 70% following oral administration of tablets. Food increased bioavailability by 55%. Rifapentine accumulated significantly in human macrophages and its elimination half-life was longer than that of rifampin. Comparative studies of rifapentine and rifampin in humans during intensive- and continuation-phase treatment of tuberculosis suggest that at currently accepted doses, rifapentine was slightly less effective than rifampin. The most significant drug interaction with rifapentine involves indinavir: the maximum concentration and AUC of indinavir are reduced by 55% and 70%, respectively, when rifapentine is coadministered with indinavir. Adverse events of rifapentine may occur less frequently at the currently recommended 600-mg dose as compared with rifampin; however, the difference was not statistically significant. If only drug costs were evaluated during the six-month treatment of tuberculosis, rifapentine is more expensive than rifampin. CONCLUSIONS: Rifapentine can be administered twice weekly during the intensive phase of tuberculosis treatment and then once weekly during the continuation phase of treatment. This may improve patient adherence over some other treatments and possibly reduce costs of treatment by preventing development of resistant tubercular strains due to nonadherence. Rifapentine is well tolerated, with most patients experiencing adverse effects at a similar rate as rifampin. Rifapentine induces cytochrome P450 somewhat less than rifampin, although few drug interaction studies have been done with rifapentine. Its efficacy at the currently approved dosage of 600 mg may be slightly lower than that of rifampin. Studies are needed to determine if equal or greater efficacy can be achieved with higher doses of rifapentine. Rifampin is less expensive than rifapentine. Further pharmacoeconomic studies are needed to evaluate costs of relapse and failure in patients receiving these agents.
Role of Lamivudine in the Treatment of Chronic Hepatitis B Virus Infection
Authors: Hagmeyer Kathleen O , Pan Yu-Yuan 
Published: March 2004

OBJECTIVE:To examine the evidence regarding the therapeutic effectiveness of lamivudine in the treatment of chronic hepatitis B virus (HBV) infection in immunocompetent patients.DATA SOURCES:Using chronic hepatitis B and lamivudine as MeSH headings, MEDLINE was searched from 1966 to September 1998 for all published randomized controlled trials evaluating lamivudine in chronic HBV infection. Relevant articles from selected bibliographies were also retrieved.STUDY SELECTION:Only randomized, single- and double-blind trials in human HBV carriers published in the English language were included.DATA SYNTHESIS:Evidence from the controlled trials suggests that lamivudine has a therapeutic effect in suppressing HBV replication in immunocompetent patients. Lamivudine 100 mg/d appears to suppress HBV replication in as many as 97% of patients within two weeks after the initiation of therapy and is capable of suppressing histologic damages. However, viral suppression is effective only during the therapy; on discontinuation of lamivudine therapy, most patients return to the pretreatment condition. Viral resistance to lamivudine has been observed. Most patients with chronic HBV infection appear to tolerate 100 mg/d of lamivudine therapy.CONCLUSIONS:Evidence has shown that oral lamivudine 100 mg/d will produce rapid and significant suppression of viral replication in immunocompetent patients with chronic HBV infections. Treatment periods up to one year have been effective and well tolerated. The suppression of viral replication may not be sustained after cessation of lamivudine therapy, and very few patients have complete elimination of HBV during therapy. Therefore, long treatment periods may be necessary. Efficacy and tolerability of treatment beyond one year need to be investigated. Resistance to lamivudine has been reported in patients receiving therapy. A combination anti-HBV regimen using lamivudine and other agents with different mechanisms of action should be investigated to maximize the elimination of the viral infection while minimizing or preventing damage to the liver cells and tissues and the development of viral resistance.