bluuebunny/crossref_metadata_2025_split huggingface dataset:
The AIDS Drug Assistance Programs and Coverage of HIV-Related Medications
Authors: Smith Scott R , Buchanan Robert J 
Published: June 2003

BACKGROUND: AIDS drug assistance programs (ADAPs) have been implemented in each state to facilitate access to medications for low-income, uninsured, and underinsured people with HIV disease. Policies for each ADAP differ, and these differences influence the access people with HIV have to medications. OBJECTIVE: To compare the coverage of medications and sources of program funding for the state ADAPs. DESIGN: A self-administered mailed survey, sent to administrators of the 50 state ADAPs and the District of Columbia ADAP in December 1998. RESULTS: Forty-nine of the 51 ADAPs (96%) responded to the survey. Title II of the Ryan White Comprehensive AIDS Resources Emergency Act provided a large majority of the funding for the ADAPs, with a number of states also using state funds and/or Title I funds for their programs. The formularies of all ADAPs were nearly identical with respect to coverage of antiretrovirals, but differed in the number and types of other medications included. Some states limited access to medications through waiting lists, enrollment caps, and other policies. Sixteen ADAPs reported that the coverage of protease inhibitors resulted in an appropriation of state government funds to their ADAP, while eight states reported an ADAP budget shortfall. In general, ADAPs in poorer and more rural states included a fewer number of medications on their formularies. CONCLUSIONS: Access to antiretrovirals and other medications is available through state ADAPs, but may be limited in some states due to waiting lists, controls on the enrollment of new beneficiaries, and policies on the number and types of medications beneficiaries may receive.
Aggrenox: A Fixed-Dose Combination of Aspirin and Dipyridamole
Authors: Lenz Thomas L , Hilleman Daniel E 
Published: June 2003

OBJECTIVE: To describe the pharmacology, pharmacokinetics, efficacy, and safety of a fixed-dose combination of aspirin and extended-release (ER) dipyridamole indicated for the secondary prevention of stroke. DATA SOURCES: Published articles and abstracts were identified from a MEDLINE search (1966–December 1999) using the search terms dipyridamole, aspirin, antiplatelet, antiaggregation, and stroke prevention. Pertinent articles written in English were considered for review. Additional articles were identified from the references of retrieved literature. STUDY SELECTION AND DATA EXTRACTION: Studies including a combination of aspirin/dipyridamole in human subjects were evaluated. Emphasis was placed on randomized, controlled trials. DATA SYNTHESIS: Aspirin is a platelet inhibitor that works by inhibiting platelet cyclooxygenase, which reduces the production of thromboxane A2. Dipyridamole is a platelet inhibitor that is thought to work in part by inhibiting platelet cyclic-3',5'-adenosine monophosphate and cyclic-3',5'-guanosine monophosphate phosphodiesterase. The active metabolite of aspirin, salicylic acid, is highly bound to plasma protein and has a plasma half-life of two to three hours. Dipyridamole is also highly bound to plasma proteins, and the ER formulation has a plasma half-life of 13 hours. The first European Stroke Prevention Study (ESPS-1) found the combination of aspirin/dipyridamole to be superior to placebo in the prevention of stroke and transient ischemic attack (TIA). The ESPS-1, however, did not include an aspirin-only treatment arm. Therefore, it was unclear whether the combination of aspirin/dipyridamole was superior to aspirin alone. As a result, a second trial was conducted that included treatment arms of aspirin alone, ER dipyridamole alone, combination therapy, and placebo. The combination of aspirin 25 mg plus ER dipyridamole 200 mg twice daily was shown in the ESPS-2 to be significantly better than either agent given individually in preventing stroke and TIAs (p < 0.001). CONCLUSIONS: The American College of Chest Physicians (ACCP) recommends aspirin 50–325 mg/d to be the initial antiplatelet of choice for the prevention of atherothrombotic cerebral ischemic events. However, with the favorable results of the ESPS-2, it may be appropriate to substitute aspirin/ER dipyridamole for aspirin alone as the drug of choice. This combination appears to have a favorable adverse effect profile. The relative effectiveness of aspirin/ER dipyridamole compared with clopidogrel and ticlopidine has yet to be determined. If alternative antiplatelet therapy is needed, the ACCP recommends clopidogrel rather than ticlopidine because of its lower incidence of adverse effects. The ACCP further states that the combination of aspirin plus dipyridamole may be more effective than clopidogrel; these agents have a similarly favorable adverse effect profile.
Pneumococcal Resistance: The Treatment Challenge
Authors: Amsden Guy W , Amankwa Kwadwo 
Published: June 2003

OBJECTIVE: To review in vitro and in vivo information dealing with pneumococcal antibiotic resistance and provide a review of the incidence, mechanisms, and controversies surrounding this growing problem. The review is also intended to provide clinicians with relevant recommendations on treatment and prevention of this organism. DATA SOURCES AND SELECTION: Primary and review articles were identified by MEDLINE search (1966–August 2000) and through secondary resources such as conference proceedings. All of the articles identified from the data sources were evaluated, and all information deemed relevant was included in this review. DATA SYNTHESIS: The growing incidence and reporting of pneumococcal isolates that are resistant to one or more classes of antibiotics have become a troubling trend that has resulted in significant shifts in treatment. Although clinicians have shifted to a new generation or class of antibiotics when faced with a resistance trend, data with resistant pneumococci show that this may not be necessary. By incorporating the pharmacokinetic and pharmacodynamic data of antimicrobials into the decision-making process, many of the drugs that we have become hesitant to use due to this resistance may still be appropriate if used correctly. CONCLUSIONS: Appropriate dosing of antimicrobials, combined with optimal use of pneumococcal vaccines, will not only prolong the longevity of some agents, but also hopefully slow resistance development.
Drug Interaction between St. John's Wort and Cyclosporine
Authors: Barone Gary W , Gurley Bill J , Ketel Beverley L , Lightfoot Meredith L , Abul-Ezz Sameh R 
Published: June 2003

OBJECTIVE: To report a probable drug interaction between the herbal dietary supplement St. John's wort and cyclosporine. CASE REPORT: A 29-year-old white woman who received a cadaveric kidney and pancreas transplant, with stable organ function and stable cyclosporine concentrations began self-medicating with St. John's wort. After taking St. John's wort supplements for four to eight weeks, her cyclosporine concentrations became subtherapeutic; this was associated with organ rejection. Four weeks after stopping St. John's wort, her cyclosporine concentrations again became therapeutic. Subsequent to this rejection episode, she has developed chronic rejection and now has returned to dialysis. DISCUSSION: St. John's wort is suspected to be a significant inducer of CYP3A4 isoenzyme activity and of P-glycoprotein (P-gp) expression, both of which are important in the metabolism and absorption of cyclosporine. Cyclosporine exhibits a relatively small therapeutic window and is sensitive to medications that can modulate the CYP3A4 isoenzyme and P-gp in both the liver and small intestines. CONCLUSIONS: Patients taking St. John's wort concomitant with other prescription medications whose absorption and metabolism are mediated by the CYP3A4 isoenzyme and P-gp require close monitoring. Patient medication histories should include inquiries into the use of herbal dietary supplements.
Accidental Over-Anticoagulation: Substitution Error by a Foreign Pharmacy
Authors: Suwanvecho Suthida , Baker J Robert 
Published: June 2003

OBJECTIVE: To describe an episode of inadvertent and excessive anticoagulation caused by mistaken substitution of medication by a pharmacy outside the US. CASE SUMMARY: A 57-year-old white woman was found to have profound prolongation of her prothrombin time (56.9 sec) and international normalized ratio (22.18), with other coagulation parameters relatively normal. She had no prior history of bleeding diatheses and was not taking any prescribed anticoagulants. Her coagulopathy rapidly corrected with the administration of fresh frozen plasma and vitamin K. After her medications were visually inspected, it was discovered that she had purchased her prescription medications from a pharmacy in Mexico and that she inadvertently had been taking a preparation of warfarin (proprietary name in Mexico, “Romesa”) instead of the prescribed ramipril for her hypertension (proprietary name in Mexico, “Ramace”). After removal of the incorrect medication, she experienced no further prolongation of her coagulation parameters. DISCUSSION: Medication errors contribute significantly to adverse events for patients. The frequency of different types of medication errors is reviewed, and problems specific to the use of warfarin are detailed. Circumstances that might lead to a patient seeking prescription medication outside of the US are also discussed. CONCLUSIONS: The acquisition of prescription medications from pharmacies outside of the US can have adverse consequences, especially if the foreign name of the medication is different from its American name, while sounding similar to other medications that also might be dispensed in foreign pharmacies.
Topiramate Titration and Tolerability
Authors: Biton Victor , Edwards Keith R , Montouris Georgia D , Sackellares J Chris , Harden Cynthia L , Kamin Marc ,   Topiramate TPS-TR Study Group
Published: June 2003

OBJECTIVE: To evaluate the tolerability and efficacy of two titration rates for topiramate initiated as adjunctive therapy in adults with partial-onset seizures, with or without secondary generalization, in a multicenter, double-blind trial. METHODS: After a two-week baseline phase, 188 patients were randomized to either a 50/50 titration schedule (initial dosage 50 mg/d increased in 50-mg/d increments at weekly intervals; n = 95) or to a 100/200 titration schedule (initial dosage 100 mg/d increased by 100–200 mg/d at weekly intervals; n = 93). The maximum dosage of 400 mg/d was therefore achieved in eight weeks or three weeks, respectively. RESULTS: Compared with the 100/200 titration rate, the 50/50 titration rate significantly reduced the cumulative incidence of treatment-emergent adverse events (TEAEs) leading to changes in topiramate therapy (i.e., dosage reductions, interruptions or discontinuations of therapy) (p = 0.048) and significantly reduced treatment interruptions or withdrawals due to TEAEs (p = 0.040). Mild or moderate effects involving the central nervous system were the most frequent adverse events. At the final visit, therapeutic responses were comparable in the 50/50 and 100/200 titration groups: median percent seizure reduction was 42% vs. 33%, proportion of patients with ges; 50% seizure reduction was 42% vs. 38%, and proportion of patients with no seizures during double-blind treatment was 14% vs. 10%, respectively. Seizure frequency was substantially reduced from baseline during topiramate titration. At day 22, with the 50/50 titration group receiving 150 mg/d and the 100/200 titration group receiving 400 mg/d, the median percent seizure reduction was 51% and 54%, respectively. CONCLUSIONS: Gradual initiation of topiramate therapy can significantly enhance patient tolerability without delaying therapeutic response.
Fluorouracil and the New Oral Fluorinated Pyrimidines
Authors: Kuhn John G 
Published: June 2003

OBJECTIVE: To briefly review the biotransformation and bioavailability of fluorouracil (5-FU); discuss the effects of dihydropyrimidine dehydrogenase (DpD) on the efficacy and toxicity profiles of 5-FU; and review a new class of drugs known collectively as the oral fluorinated pyrimidines, which inhibit or circumvent DpD activity and, when administered with 5-FU, alter its pharmacokinetic and pharmacodynamic properties. DATA SOURCES: A MEDLINE literature search was conducted (1966–March 1999), using the search terms fluoropyrimidines, fluorouracil, 5-FU, fluorinated pyrimidines, capecitabine, eniluracil, uraciltegafur, uracilftorafur, UFT, S1, BMS-247616, and BOF-A2. Reference lists, bibliographies of pertinent articles, and abstracts from the American Society of Clinical Oncology and the San Antonio Breast Cancer Symposium annual meetings were also identified and reviewed. Both preclinical and clinical literature were reviewed and analyzed. DATA SYNTHESIS: The new oral fluorinated pyrimidines appear to produce antitumor activity equivalent or superior to that of intravenously administered 5-FU by achieving higher intratumoral 5-FU concentrations or sustained 5-FU exposure. These agents are generally associated with manageable and non-life—threatening toxicities. The oral route of administration facilitates ease of administration and may reduce total healthcare costs associated with 5-FU—sensitive tumors. More studies are needed to assess the therapeutic and economic benefits of the oral fluorinated pyrimidines. CONCLUSIONS: The bioavailability, efficacy, and toxicity of 5-FU depend on its catabolic rate—limiting enzyme, DpD. The new oral fluorinated pyrimidines inhibit or circumvent DpD activity and, when combined with 5-FU, increase 5-FU's bioavailability and cytotoxic effects and decrease its toxicities. Results of Phase I and II studies in patients with a variety of malignancies suggest positive outcomes, including greater efficacy, less drug-related toxicity, lower costs related to drug administration, and greater patient convenience.
Spironolactone in the Treatment of Congestive Heart Failure
Authors: Lloyd Stanley J , Mauro Vincent F 
Published: June 2003

OBJECTIVE: To evaluate evidence supporting the use of spironolactone in managing congestive heart failure. DATA SOURCES: Literature accessed through MEDLINE (January 1966–December 1999) and cross-referencing of selected articles. Search terms included spironolactone and heart failure. DATA SYNTHESIS: Heart failure is a leading cause of morbidity and mortality. Through aldosterone antagonism, spironolactone may be an effective pharmacotherapeutic addition to patients not responding to standard drug therapy for heart failure. RESULTS: Clinical trials have demonstrated that, in patients with heart failure, spironolactone improves laboratory indices, quality of life, and morbidity. Recently, spironolactone has been demonstrated to improve the survival of patients with New York Heart Association (NYHA) III or IV heart failure. CONCLUSIONS: Spironolactone use should be considered in patients with NYHA Class III or IV heart failure.
Stability of Filgrastim and Epoetin Alfa in a System Designed for Enteral Administration in Neonates
Authors: Calhoun Darlene A , Juul Sandra E , McBryde Eric V , Veerman Mark W , Christensen Robert D 
Published: June 2003

OBJECTIVE: To determine the stability of recombinant granulocyte colony—stimulating factor (rG-CSF, filgrastim) and recombinant erythropoietin (rEpo, epoetin alfa) in a solution designed for enteral administration in the neonatal intensive care unit. DESIGN: Filgrastim and epoetin alfa were added to a solution with NaCl 0.9%, sodium acetate, potassium chloride, and human albumin in concentrations designed to mimic human amniotic fluid. Additionally, the solution was dripped through polyvinyl chloride feeding tubes to simulate feedings, and aliquots were collected before, during, and after priming of the tube. Other aliquots were either frozen immediately, stored at room temperature, or refrigerated for 0, 6, 12, 18, and 24 hours. MAIN OUTCOME MEASURES: Filgrastim and epoetin alfa concentrations in the various aliquots were compared with the concentrations in the original solution. RESULTS: Filgrastim and epoetin alfa concentrations were stable for at least 24 hours when refrigerated and for at least three weeks when frozen. At room temperature, filgrastim was stable for 18 hours and epoetin alfa for 24 hours. Filgrastim concentrations did not vary significantly before, during, or after priming of the feeding tube, whereas epoetin alfa concentrations decreased significantly unless the feeding tube was primed with 10 mL of solution. CONCLUSIONS: Filgrastim and epoetin alfa were stable in our amniotic fluid—like solution. In this respect, our solution is suitable for enteral administration to patients in the neonatal intensive care unit.
Use of Enoxaparin in a Preterm Infant
Authors: Dunaway Kimberly K , Gal Peter , Ransom J Laurence 
Published: June 2003

OBJECTIVE: To describe the use of enoxaparin to treat suspected thrombosis in a preterm neonate. CASE DESCRIPTION: A 29-week-gestation white infant with a family history of protein S deficiency lost color and blood flow to the right hand several hours after removal of the umbilical artery catheter. Although normal color returned to all except the distal first, second, and third fingers after warming, Doppler flow showed a radial artery defect, indicating a lack of blood flow. Enoxaparin 1 mg/kg intravenously every eight hours was then started. Heparin concentrations measured via anti-Xa assay drawn four and eight hours after a dose were 0.78 and 0.39 units/mL, respectively. Pharmacokinetic parameters calculated from these concentrations using a one-compartment model were elimination half-life four hours, volume of distribution 0.13 L/kg, and clearance 0.022 L/kg/h. No adverse effects were noted. Blood flow eventually returned, leaving only the third fingertip chronically injured. DISCUSSION: Differences between the neonatal and adult hemostatic systems contribute to an increased risk of thromboembolic events and an altered sensitivity to heparin anticoagulation in the neonate. Although heparin is currently the anticoagulant of choice, it may produce several adverse effects, such as hemorrhage and thrombocytopenia, which may be avoided by use of low-molecular-weight heparins (LMWHs). However, despite the efficacy and improved safety profile of LMWHs in adults, data regarding their use in children and neonates are scarce. This case demonstrates that enoxaparin can be used safely and effectively in a preterm infant through appropriate monitoring of heparin concentrations to adjust dosages. A larger volume of distribution of enoxaparin was noted in this neonate than in adults. CONCLUSIONS: Enoxaparin 1 mg/kg intravenously every eight hours was used safely in this preterm infant with suspected thrombosis, suggesting that more than one dosing regimen may be appropriate in this population.
Cost-Effectiveness Results from the US Carvedilol Heart Failure Trials Program
Authors: Vera-Llonch Montserrat , Menzin Joseph , Richner Randel E , Oster Gerry 
Published: June 2003

OBJECTIVE: To evaluate the cost-effectiveness of carvedilol, a β-blocker that is approved for use in the US for the treatment of heart failure, based on data from Phase III clinical trials. METHODS: We conducted an economic evaluation alongside the US Carvedilol Heart Failure Trials Program, which consisted of four concurrent, randomized, double-blind, placebo-controlled clinical trials; the mean duration of follow-up across these four trials was 6.5 months (the program was terminated prematurely based on a finding of a 65% mortality benefit). Using data from these trials, we examined the cost-effectiveness of carvedilol in terms of the estimated cost per death averted among patients randomized to such therapy versus those receiving placebo. Attention was focused on the cost of carvedilol therapy plus the cost of cardiovascular-related inpatient care. Costs of care were estimated by combining information on healthcare utilization from the clinical trials with secondary sources of cost data. RESULTS: Patients randomized to receive carvedilol had lower mean ± SD estimated costs of cardiovascular-related inpatient care over 6.5 months compared with those receiving placebo ($1912 ± $7595 vs. $4463 ± $20 565, respectively). As mortality also was lower among carvedilol patients, the estimated cost per death averted was negative. The probability that carvedilol would both increase survival and decrease costs of cardiovascular-related care over a 6.5-month period was estimated to be 0.98. CONCLUSIONS: Data from the US Carvedilol Heart Failure Trials Program indicate that carvedilol reduces mortality in patients with heart failure; our study suggests that it also may be cost-saving over a period of approximately six months.
Prasterone (DHEA) and Mania
Authors: Dean Charles E 
Published: June 2003

OBJECTIVE: To inform clinicians and investigators of the potential for severe mania in conjunction with the use of prasterone (DHEA; dehydroepiandrosterone). CASE SUMMARY: A 31-year-old Hispanic man was admitted on a 72-hour observation period from a neighboring hospital after threatening to kill himself, family members, and a friend. A loaded rifle was found under his bed. The family confirmed that he had begun using DHEA several weeks prior to his mood and behavioral changes. He denied any past violence, but had once been given an unsubstantiated diagnosis of bipolar disorder. He used alcohol episodically, and had difficulties controlling his anger while intoxicated. Although he improved with valproate, his threats of homicide led to involuntary commitment. DISCUSSION: Several studies and case reports strongly suggest that anabolic steroids can induce significant psychiatric difficulties, including mania, impaired cognition, and overt psychosis. Although the Food and Drug Administration noted in 1985 that the efficacy and safety of DHEA were never confirmed, the agent continues to be sold over the counter. Several groups have used DHEA in the treatment of AIDS, memory loss, and depression, but reported no serious adverse events; however, recent studies indicate that severe psychiatric symptoms can develop in a subset of users. Although uncertain, potential risk factors include high doses of DHEA; history of mood disorder; concurrent use of alcohol, street drugs, or antidepressants; and cytochrome P450 polymorphisms. CONCLUSIONS: The use of DHEA in those under age 35 years may be especially risky, as endogenous DHEA concentrations peak at age 20–30 years. Those using or investigating DHEA should be cognizant of the potential for severe psychiatric complications.