bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cilostazol: Treatment of Intermittent Claudication
Authors: Reilly Muredach P , Mohler Emile R 
Published: June 2003

OBJECTIVE: To review the pharmacology and clinical utility of cilostazol, an antiplatelet and vasodilator agent approved for the management of intermittent claudication. DATA SOURCES: Primary literature on cilostazol was identified from a comprehensive MEDLINE literature search (1980–February 2000). Selected meeting abstracts and manufacturer literature were also used as source material. Indexing terms included cilostazol, intermittent claudication, platelet inhibitors, and restenosis. STUDY SELECTION: Human clinical, pharmacokinetic and randomized comparative trials performed in the US and Asia were reviewed. Selected in vitro, ex vivo, and animal studies were evaluated when human data were not available. DATA SYNTHESIS: Intermittent claudication, defined as reproducible discomfort of a muscle group induced by exercise and relieved by rest, is the most common clinical manifestation of peripheral arterial disease (PAD). Cilostazol, a specific inhibitor of cyclic adenosine monophosphate phosphodiesterase in platelets and vascular smooth-muscle cells, is a potent antiplatelet agent and vasodilator that reduces vascular proliferation and has lipid-lowering effects in vivo. Recent multicenter, randomized, placebo-controlled trials have led to approval of cilostazol by the Food and Drug Administration for relief of intermittent claudication in patients with stable PAD. Cilostazol doubled walking distances and improved quality of life compared with placebo in these studies. One trial found that cilostazol was more effective than pentoxifylline, the only alternative pharmacologic therapy for claudication. Although frequent (∼50%) minor adverse effects, including headache, diarrhea, and palpitations, may occur in clinical practice, cilostazol has not been associated with major adverse events or increased mortality. Small, nonblind studies suggest that cilostazol may prove useful in preventing thrombosis and restenosis following percutaneous coronary interventions, although these remain unlabeled uses. CONCLUSIONS: The unique combination of antiplatelet, vasodilatory, and antiproliferative effects of cilostazol appear to make it an attractive agent for use in patients with PAD. Clinical trials demonstrating a significant improvement in walking distances with cilostazol therapy suggest that it will be an important tool in improving symptoms and quality of life in patients with intermittent claudication.
Computerized System for Outcomes-Based Antiemetic Therapy in Children
Authors: Holdsworth Mark T , Adams Val R , Raisch Dennis W , Wood Jim G , Winter Stuart S 
Published: June 2003

OBJECTIVE: To introduce a computerized data collection system used for an outcomes-based approach to antiemetic therapy in children, and to present data collected with this system in support of a new antiemetic dosing regimen. METHODS: A validated nausea/vomiting survey was used to collect data on nausea severity (NSEV), vomiting severity (VSEV), daily activity interference (DAI), and the number of vomiting episodes. NSEV, VSEV, and DAI were rated as 0 = none to 3 = severe. All children and/or their parents were surveyed following the completion of each highly emetogenic chemotherapy regimen. This survey was computerized and transferred to a handheld data entry unit. Time and motion studies were performed to compare the time required to collect nausea/vomiting data and transfer the data to a computerized database with the handheld system versus traditional paper (manual) surveys. The handheld technology was used to collect survey data for children receiving a new antiemetic regimen (daily ondansetron and dexamethasone [OD]), which was then compared with data obtained with a previously employed regimen (thrice-daily ondansetron and daily methylprednisolone [OM]). Statistical analysis and a cost-effectiveness analysis (CEA) were performed to compare the two antiemetic regimens. RESULTS: The mean time required for total data entry with the manual system was 5.2 minutes per survey versus 2.4 minutes with the handheld technology (p = 0.0026). A total of 376 nausea/vomiting surveys in 78 children receiving the OM antiemetic regimen were compared with 153 surveys in 38 children treated with the OD regimen. The mean survey scores were as follows: NSEV (1.2 vs. 0.8), VSEV (1.0 vs. 0.7), DAI (1.0 vs. 0.7), and number of vomiting episodes (4.3 vs. 2.1) for OM and OD, respectively; all were significantly lower with the OD regimen (p < 0.05). The percentage of patients with complete control of nausea and vomiting (19.2% vs. 39.2%) and good control (55.6% vs. 65.4%) were significantly greater with the OD regimen (p < 0.05). The CEA revealed that the OD resulted in a reduction of approximately $31 per patient for good protection and a $258 reduction for complete protection from nausea and vomiting. CONCLUSIONS: A computerized outcomes-based system aided by handheld technology allowed for more prompt and efficient collection of nausea/vomiting data. The OD antiemetic regimen was shown to be a more cost-effective alternative for children receiving severely emetogenic chemotherapy.
Role of Antimicrobial Therapy in Acute Exacerbations of Chronic Obstructive Pulmonary Disease
Authors: Russo René L , D'Aprile Michelle 
Published: June 2003

OBJECTIVE: To define the role of antimicrobial therapy in the treatment of acute bronchitic exacerbations of chronic obstructive pulmonary disease (COPD) through review of placebo-controlled clinical trials. Specifically, to determine the benefit of antimicrobial therapy on patient outcome. DATA SOURCES: Placebo-controlled clinical trials identified by MEDLINE search (1957–December 1999). STUDY SELECTION AND DATA EXTRACTION: All placebo-controlled clinical trials that included COPD patients with no evidence of pneumonia or underlying asthma were included in the evaluation. DATA SYNTHESIS: The role of antimicrobial agents in the treatment of acute exacerbations of COPD is controversial. Patients with COPD are often chronically colonized with bacteria, and many exacerbations are due to nonbacterial causes. Four placebo-controlled clinical trials and a meta-analysis have demonstrated significant improvements in outcome for patients treated with an antibiotic versus placebo. In contrast, six studies failed to demonstrate statistical differences, possibly due to the small sample size and the subjectivity of outcome measures. Overall, the data suggest that the benefit of antimicrobial therapy in acute exacerbations of COPD may be related to exacerbation severity. CONCLUSIONS: Antimicrobial agents may have a beneficial effect in the treatment of acute exacerbations of COPD in certain patients. Pending further research in this area, we recommend antimicrobial therapy only for COPD patients with acute bronchitic exacerbations characterized by increased dyspnea, sputum volume, and purulence.
Orlistat — A Novel Weight Loss Therapy
Authors: Lucas Kristy H , Kaplan-Machlis Barbara 
Published: June 2003

OBJECTIVE: To review the pharmacology, pharmacokinetics, clinical safety and efficacy, drug interactions, and therapeutic issues related to the use of orlistat for treatment of obesity. DATA SOURCES: English-language articles were identified from MEDLINE (1966–July 2000), Roche Laboratories, organizational guidelines, National Institutes of Health and Food and Drug Administration Web sites, and Doctor's Guide online. Key words included obesity, orlistat, and lipase inhibitors. References were also identified from reference sections of published articles. STUDY SELECTION AND DATA EXTRACTION: Prospective, randomized, double-blind, placebo-controlled, human trials were selected for review and discussion. DATA SYNTHESIS: Orlistat is the first agent in the lipase inhibitor class of antiobesity drugs. Orlistat is minimally absorbed and has been shown to reduce body weight by inhibiting absorption (by ∼30%) of ingested dietary fat. Safety and efficacy have been established in one- and two-year double-blind, placebo-controlled trials; adverse effects were primarily, and almost exclusively, gastrointestinal. Due to its ability to block fat absorption, orlistat also has the capability to inhibit absorption of fat-soluble vitamins. Therefore, a daily multiple vitamin is recommended while taking orlistat. CONCLUSIONS: By inhibiting fat absorption, orlistat offers a new treatment modality for weight loss and maintenance. Preliminary data from clinical trials suggest that orlistat may be beneficial in patients with comorbid conditions related to obesity, such as diabetes and hyperlipidemia. However, further studies during postmarketing surveillance are needed to fully establish orlistat's long-term benefits and safety. Orlistat should be considered a useful adjunctive therapy for weight loss and maintenance in obese patients (i.e., body mass index ≥30 kg/m2 or ≥27 kg/m2 if other risk factors are present) committed to lifestyle changes including diet, exercise, and behavioral modification.
Vitamin C in the Prevention of Nitrate Tolerance
Authors: Daniel Tamara A , Nawarskas James J 
Published: June 2003

OBJECTIVE: To evaluate the efficacy of vitamin C in preventing the development of nitrate tolerance. DATA SOURCES: A MEDLINE search (from 1966 to July 2000) was conducted to identify relevant articles, with additional references obtained from the bibliographies of these articles. DATA SYNTHESIS: One possible mechanism of nitrate tolerance involves superoxide-induced deactivation of nitric oxide, providing the rationale for the use of antioxidants. Most published research concerning deactivation of nitric oxide has involved vitamin C; a summary of this information is presented here. CONCLUSIONS: Preliminary studies seem to support the role of vitamin C in attenuating the development of nitrate tolerance. Considering these findings, larger, long-term trials are necessary to further establish the role of vitamin C in this situation.
Characteristics of Tranquilizer Use among Australian Vietnam War Veterans
Authors: Alderman Christopher P , Gilbert Andrew L , Condon John T 
Published: June 2003

OBJECTIVE: To examine characteristics of tranquilizer use in a cohort of Australian Vietnam War veterans. DESIGN: Prospective analysis of medication use and assessment of social and clinical variables, including tranquilizer dependence. PATIENTS: Fifty-one Australian Vietnam War veterans were recruited from the department of psychiatry of an Australian teaching hospital. All subjects were men, with a mean ± SD age of 52.2 ± 3.3 years. MAIN OUTCOME MEASURES: A structured interview was used to obtain details of medical and psychiatric history, medication use, substance use, forensic history, and health service utilization data. Anxiety was assessed using the Hamilton Anxiety Rating Scale (Ham-A). A validated tranquilizer dependence rating scale was administered for each patient. RESULTS: Commonly used tranquilizers included diazepam (n = 19 patients) and zopiclone (26). Most patients (44) reported the use of one or more drugs for the purpose of nighttime sedation, while exclusive daytime use of tranquilizers for anxiolytic effect was uncommon. The median time spent in the hospital during the preceding year was 21.0 ± 56.8 days. Symptoms of anxiety were prevalent, with a mean Ham-A score of 35.5 ± 7.8. Screening criteria suggestive of tranquilizer dependence were met in 34 subjects. Health service utilization was correlated with tranquilizer intake and overall medication use. Tranquilizer dependence was independently associated with cigarette smoking (p = 0.039; odds ratio = 5.13, 95% CI 1.08 to 24.33). CONCLUSIONS: This study provides insight into the nature of tranquilizer use in an Australian population of Vietnam War veterans. The extensive use of these drugs suggests that further research and possibly intervention in this area is needed.
Leukotriene Receptor Antagonists in the Treatment of Allergic Rhinitis
Authors: Maynard Michelle L , Ernst Michael E 
Published: June 2003

OBJECTIVE: To review the literature examining the clinical use of leukotriene receptor antagonists in the treatment of allergic rhinitis. DATA SOURCES: Biomedical literature accessed through MEDLINE (1990–November 2000) and Current Contents (week 35 of 1999 to week 48 of 2000). Key terms included leukotriene antagonists, montelukast, zafirlukast, and rhinitis (allergic). DATA SYNTHESIS: Preliminary evidence on the clinical use of either montelukast or zafirlukast as monotherapy is equivocal, with one study noting benefit and another noting lack of benefit in symptom amelioration. A third study suggests that these agents may have a role in further modifying allergic rhinitis symptoms when used in combination with standard treatments. CONCLUSIONS: Future large-scale studies should assess the efficacy of these agents in the treatment of allergic rhinitis, in particular, to identify subsets of patients likely to derive the most benefit. Available data suggest it is reasonable and safe to add these agents to standard therapy if symptomatology remains unresolved.
Desensitization Protocols for Vancomycin Hypersensitivity
Authors: Wazny Lori D , Daghigh Behnam 
Published: June 2003

OBJECTIVE: To discuss the pathophysiology of vancomycin-induced immediate hypersensitivity reactions, review the process of vancomycin desensitization, and provide specific directions for ordering and preparing rapid and slow desensitization protocols. DATA SOURCES: A MEDLINE search (1966–February 2001) of English-language literature pertaining to vancomycin desensitization and hypersensitivity reactions was performed. Tertiary sources were also used. DATA EXTRACTION: Published clinical studies and case reports. DATA SYNTHESIS: The pathophysiology of vancomycin-induced hypersensitivity reactions is discussed along with the procedure of vancomycin desensitization. Desensitization should be considered in Red Man syndrome (RMS) that does not respond to the usual treatment measures, and in vancomycin-induced anaphylaxis. Rapid desensitization is preferred as it is effective in the majority of patients and enables therapeutic dosing of vancomycin within 24 hours. In patients who fail rapid desensitization, a slow desensitization protocol may be tried. CONCLUSIONS: Vancomycin-induced immediate hypersensitivity reactions include RMS and anaphylaxis. Vancomycin desensitization should be considered for severe RMS reactions not responding to usual measures and in anaphylactic reactions to vancomycin, when substitution of another antibiotic is not feasible.
The Debate regarding Continuous Use of Oral Contraceptives
Authors: Clarke Amanda K , Miller Sarah J 
Published: June 2003

OBJECTIVE: To determine whether oral contraceptives (OCs) can be used safely in a continuous manner to prevent monthly withdrawal bleeding. DATA SOURCES: Search of MEDLINE (1966–2000), International Pharmaceutical Abstracts (1970–2000), and the Internet. DATA SYNTHESIS: Several prospective studies have assessed the efficacy of continuous cycle OCs in preventing monthly withdrawal bleeding. Monophasic OCs are useful for this purpose. In studies using traditional OC regimens as a control, patients receiving continuously administered OCs experienced more breakthrough bleeding and spotting. Continuous use of OCs decreased headache and other menstruation-associated symptoms. No long-term trials have assessed the impact of continuous use of OCs on risk of cancer, thromboembolic disease, or fertility, concerns raised by opponents of the method. CONCLUSIONS: From the data available, continuous use of OCs is an effective method for delaying withdrawal bleeding. Long-term safety data are not available.
Photopatch Testing in Seven Cases of Photosensitive Drug Eruptions
Authors: Lee Ai-Young , Joo Hyun-Joong , Chey Won-Young , Kim Young-Gull 
Published: June 2003

OBJECTIVE: The most important goal in the management of photosensitive drug eruptions, as in other types of drug eruptions, is identification of the causative drugs to prevent reexposure to them. CASE SUMMARIES: Seven patients whose lesions were mainly distributed on sun-exposed areas underwent laboratory tests, phototests, and photopatch tests with suspected drugs. Phototests were done with ultraviolet A (UVA), UVB, and visible light. Drugs used in the photopatch tests were usually prepared as 10% concentrations in petroleum base, which did not produce reactions in 10 control subjects, followed by irradiation of suberythema doses of UVA. Systemic provocation by oral administration of small doses of causative drugs with irradiation of suberythema doses of UVA was performed to confirm the results of skin tests in four patients. Two patients were not rechallenged with the causative drugs. None of the patients had systemic lupus erythematosus, porphyria, or pellagra. All showed positive reactions to photopatch testing. Systemic provocation confirmed the results of photopatch tests in four patients. The two patients who were not rechallenged had no recurrence of lesions. One patient ingested only one drug at the time of eruptions, and provocation or avoidance was not attempted. A photoallergic mechanism was considered in five cases. CONCLUSIONS: Although there is no information about the appropriate concentrations or vehicles for suspected drugs, photopatch testing could be reliable for identification of causes of photosensitive drug eruptions. Besides piroxicam (a well-known photosensitizer) and carbamazepine, isoniazid and triflusal were identified as the causes of the reactions.
Fatal Fetal Outcome with the Combined Use of Valsartan and Atenolol
Authors: Briggs Gerald G , Nageotte Michael P 
Published: June 2003

OBJECTIVE: To report a case of anhydramnios, pulmonary hypoplasia, very small placenta, and fetal death in a pregnancy complicated by chronic hypertension and diabetes mellitus that had been treated through the first 24 weeks of gestation with valsartan and atenolol. CASE SUMMARY: A 40-year-old Hispanic woman with well-controlled chronic hypertension and diet-controlled type 2 diabetes mellitus was treated with valsartan and atenolol until pregnancy was diagnosed at 24 weeks' gestation. An ultrasound examination revealed normal fetal growth and anatomy but anhydramnios (amniotic fluid index 0). Valsartan was discontinued, and amniotic fluid volume normalized within two weeks. Intrauterine fetal death was documented at 33 weeks' gestation. Labor was induced, with the delivery of a stillborn female fetus with small, hypoplastic lungs (weight 41% of expected) and an extremely small, 148-g placenta (weight 48% of the 10th percentile for gestational age). DISCUSSION: The use of valsartan, a selective angiotensin II receptor antagonist (ARA), in human pregnancy has not been reported, but this class of agents would be expected to cause fetal toxicity similar to that observed with angiotensin-converting enzyme inhibitors. This toxicity includes reduced perfusion of the fetal kidneys, resulting in anuria, oligohydramnios, and subsequent pulmonary hypoplasia. The small hypoplastic lungs and very small placenta were probably a consequence of valsartan and atenolol combination therapy. CONCLUSIONS: Resolution of anhydramnios after discontinuing valsartan is evidence for ARA-induced fetal toxicity. The pulmonary hypoplasia observed in the stillborn infant was a direct result of the severe oligohydramnios. The cause of fetal death nine weeks later is uncertain, but because the woman's chronic hypertension and diabetes were well controlled, we believe the primary cause was chronic placental insufficiency resulting from the previous combination of valsartan and atenolol.
Fluvoxamine Augmentation Increases Serum Mirtazapine Concentrations Three- to Fourfold
Authors: Anttila Sami AK , Rasanen Ilpo , Leinonen Esa VJ 
Published: June 2003

OBJECTIVE: To report two cases of interaction between fluvoxamine and mirtazapine. CASE SUMMARY: A 17-year-old boy was treated with mirtazapine 30 mg/d. The addition of fluvoxamine 100 mg/d to the regimen caused a threefold increase in the mirtazapine concentration. This interaction was associated with increased anxiety. A second patient, a 43-year-old woman, was treated with mirtazapine 15 mg/d. There was a fourfold increase in her mirtazapine concentration and simultaneous mood improvements after augmentation with fluvoxamine 50 mg/d. DISCUSSION: This is the first report of any interaction between fluvoxamine and mirtazapine. Mirtazapine is mainly metabolized by cytochrome P450 isoenzymes CYP1A2, CYP2D6, and CYP3A4. Fluvoxamine and cimetidine inhibit the same isoenzymes, but fluvoxamine is probably the only agent that causes a clinically significant interaction. CONCLUSIONS: Adding fluvoxamine to treatment with mirtazapine may cause a significant increase in mirtazapine concentration. This interaction may necessitate adjustment of the mirtazapine dosage.
Symptomatic Hyperbilirubinemia with Indinavir/Ritonavir—Containing Regimen
Authors: Rayner Craig R , Esch Lori D , Wynn Heather E , Eales Richard 
Published: June 2003

OBJECTIVE: To report a case of symptomatic hyperbilirubinemia resulting from the addition of ritonavir to an indinavir-containing antiretroviral regimen. CASE SUMMARY: A 27-year-old white woman developed symptomatic hyperbilirubinemia and anemia while receiving an indinavir/ritonavir—containing antiretroviral (ARV) regimen that required disruption of therapy. Extensive laboratory examinations were performed including determination of indinavir and ritonavir concentrations. The findings were attributed to two independent processes, an unconjugated hyperbilirubinemia due to indinavir and anemia due to zidovudine. DISCUSSION: Indinavir-induced hyperbilirubinemia is generally regarded as an adverse event with no clinical relevance that does not cause significant liver toxicity and does not necessitate discontinuing indinavir. It manifests primarily as an increase in unconjugated bilirubin and is reported to be dose related. We believe that the severe hyperbilirubinemia in this patient was a result of high indinavir concentrations that occurred due to metabolic inhibition caused by ritonavir. The anemia in this case was consistent with erythrocyte maturation arrest due to zidovudine rather than hemolysis. CONCLUSIONS: Combination ARV therapy is the current standard of care for treating patients infected with HIV. It is important for providers to consider that, despite much improved pharmacokinetic profiles associated with pharmacokinetically enhanced protease inhibitor regimens, there may be undesirable effects that may differ in frequency or severity than when drugs are used individually.
Hypertension as a Complication of Topical Testosterone Therapy
Authors: Tangredi Joseph F , Buxton Iain LO 
Published: June 2003

OBJECTIVE: To report a patient developing hypertension following the use of testosterone gel. CASE SUMMARY: A 65-year-old white man who was placed on topical testosterone therapy to increase libido developed hypertension and increased hematocrit simultaneously. After discontinuation of the testosterone, the hematocrit returned to mid-normal reference range and blood pressure returned to normal; he had been normotensive prior to topical testosterone use. DISCUSSION: The popularity of hormone replacement for women for the maintenance of appearance and lifestyle and the prevention of complications such as osteoporosis has been established over several decades, and the complications and risks and benefits of this therapy have been well described. More recently, and particularly with the availability of topical preparations of testosterone, hormone replacement for men is becoming popular with both older male patients and their physicians. We describe a case of hypertension as a complication of the application of topical testosterone and link this adverse effect to the known anabolic effects of testosterone. CONCLUSIONS: Clinicians should be cautious in prescribing topical preparations of testosterone for the proper administration by the patient and alert to the development of hypertension in this population at increased risk for cardiovascular events due to their age.