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We examined the effects of preoperative administration of enoxaparin (ENOX), a low-molecular-weight heparin, on bleeding indices and transfusion rates in patients undergoing coronary artery bypass grafting (CABG).Patients undergoing isolated CABG between 1997 and 2002 who received preoperative ENOX or a continuous infusion of unfractionated heparin (UFH) were randomly divided into three groups: continuous UFH, ENOX last administered more than 12 hours before surgery (ENOX12), and ENOX administered less than 12 hours before surgery (ENOX12). Perioperative hemoglobin values, transfusion rates, and bleeding complications were compared.A total of 69, 58, and 34 patients comprised the UFH, ENOX12, and ENOX12 groups, respectively. Preoperative demographics and hematologic data were similar among the groups. Compared with the UFH group, the ENOX12 group had significantly lower postoperative hemoglobin values (9.6 +/- 1.3 g/dL versus 10.4 +/- 1.2 g/dL, p0.05), higher transfusion rates (73.5% versus 50.7%, p0.05), and required more total packed red cells per patient (882 +/- 809 mL versus 472 +/- 626 mL, p0.05). A nonsignificant increase was noted in the risk of returning to the operating room for bleeding in patients who had received ENOX compared with patients receiving UFH (6.5% versus 2.9%).The preoperative use of ENOX less than 12 hours before CABG is associated with lower postoperative hemoglobin values and higher rates of transfusion than continuous UFH.

BACKGROUND Effective therapy for chronic heart failure (CHF) is underutilized despite a broad consensus regarding treatment recommendations. METHODS As a quality improvement project designed to reduce preventable hospitalizations associated with CHF, we examined use of angiotensin converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), and beta-adrenergic receptor blockers (BB) in a population of patients enrolled in a managed care plan. Medicare and commercial enrollees were included. Patients with CHF were identified using claims data (International Classification of Disease 9th Clinical Modification code 428) covering January 1, 1998 through December 31, 1998. Drug utilization data were obtained from the plan's pharmacy benefits database. Data were available for 1220 patients. RESULTS The mean age (+/- SD) was 71 +/- 12 years, 53% were female, and 84% were Medicare enrollees. Prescriptions for ACEI, ARB and BB were filled by 52%, 9% and 25% of patients, respectively. Prescriptions for diuretics, digitalis preparations, and calcium channel blockers (CCB) were filled by 69%, 34%, and 32%, respectively. Therefore, almost half of patients with CHF were not receiving ACEI therapy, even though it had been proven to reduce morbidity and mortality related to CHF. Furthermore, three-quarters of patients were not receiving BB therapy, a similarly effective therapy. In contrast, CCB and digitalis have not been convincingly shown to reduce mortality in patients with CHF broadly defined. Utilization of CCB and digitalis exceeded that of BB. CONCLUSIONS Managed care organizations should develop, test, and implement network-level strategies designed to optimize the appropriate utilization of effective drug therapies for patients with CHF.

OBJECTIVE: To determine the rate of publication of abstracts presented at the 1994 American Society of Health-System Pharmacists (ASHP) Midyear Clinical Meeting and the 1994 American College of Clinical Pharmacists (ACCP) Annual Meeting. METHODS: Abstracts presented at the 1994 ASHP Midyear Clinical Meeting and the 1994 ACCP Annual Meeting were evaluated for subsequent publication as full articles in journals indexed in MEDLINE, International Pharmaceutical Abstracts, and Current Contents. RESULTS: Five hundred one abstracts presented at the 1994 ASHP Midyear Clinical Meeting were evaluated; 55 (11%) of these had been published. Two hundred fifteen abstracts presented at the 1994 ACCP Annual Meeting were evaluated; 71 (33%) of these had been published. CONCLUSIONS: The publication rates for abstracts presented at ASHP and ACCP meetings were found to be lower than many of those for other medical groups. The presentation of research abstracts at professional meetings is an integral part of the exchange of scientific information; however, many of the presented abstracts are not subsequently published as full research reports. The failure to publish the results of the studies may limit the ability of a reader to judge the validity, reliability, and generalizability of the research. This could affect the use of the findings in clinical practice and in supporting or refuting other research findings.

Each year the increasing number of new medications marketed and treatment guidelines established makes it very difficult for busy physicians to keep abreast of new developments. Thus, it is necessary for physicians to have convenient access to sources of drug information (Df). The purpose of this study was to assess physicians’ access to DI resources. Approximately 1000 physicians specializing in internal medicine, family medicine, or pediatrics were randomly selected from a listing of physicians registered with the North Carolina Medical Board. A survey questionnaire designed to identify printed and computerized medication resources to which the physician has immediate access was mailed. The survey also asked the physician to estimate how often he/she consulted other health care professionals for medication-related information. Access to formal drug information centers through affiliation with an academic institution, managed care organization, or another source was also identified. Of the 279 surveys returned, 262 of them were evaluable. The most common print references responding physicians reported having access to in daily practice were the Physicians’ Desk Reference (PDR) (99%) and various medical journals (50%). Approximately one third of the physicians reported having access to Medline, while less than 25% have access to the Internet. Of the various human DI resources, physicians reported using pharmacists most frequently, followed by physician colleagues. Physicians infrequently reported using DI centers as sources of information. Overall, surveyed physicians indicated a desire to increase their access to drug information resources in daily clinical practice.

Purpose. Working with an institutional review board (IRB) to ensure compliance and ethical conduct of research involving human subjects is discussed. Summary. The Department of Health and Human Services (DHHS) and Food and Drug Administration regulations for the conduct of human research are grounded in the principles of the Belmont Report. By establishing the requirements for the function and operation of the IRB, the criteria needed for the review and approval of research, and the requirements for obtaining and documenting informed consent, the federal regulations help ensure the safety, rights and welfare of subjects. In developing research protocols and submissions to the IRB, the investigator should include clear, detailed information that addresses the regulatory requirements for the review and approval of research. Before starting a research study, review and approval by the IRB is required unless the study is determined to be minimal risk and fits one of the defined categories. Some research projects involving observation of public behavior, collection of anonymous surveys of nonvulnerable individuals in which the information is not considered sensitive, and evaluation of standard education practices may be exempt from DHHS regulations. Informed consent is central to the protection of human subjects and is required unless the IRB allows a waiver or alteration of informed consent. Once the study is approved, the investigator must conduct the study as approved by the IRB and continue to meet the regulatory requirements related to modifications, reporting unanticipated events, and continuing review. Conclusion. IRB review is integral to ensuring regulatory compliance and ethical conduct of research involving human subjects. Working closely with the IRB or colleagues who have had experience with the IRB will help junior investigators better understand the IRB submission and review process.

The chemistry, pharmacology, pharmacokinetics, adverse effects, and dosages of the three currently available angiotensin-converting enzyme (ACE) inhibitors are reviewed. This class of agents effectively inhibits the conversion of angiotensin I to the active vasoconstrictor angiotensin II, a hormone that also promotes, via aldosterone stimulation, increased sodium and water retention. The ACE inhibitors, therefore, are capable of lowering blood pressure primarily by promoting vasodilitation and reducing intravascular fluid volume. Captopril, the first orally active, commercially available ACE inhibitor, is a sulfhydryl-containing compound. Captopril was followed by the introduction of enalapril and lisinopril, two non-sulfhydryl ACE inhibitors. The pharmacokinetic profiles of these three ACE inhibitors differ. Captopril has rapid onset with relatively short duration of action, whereas enalapril and lisinopril have slower onset and relatively long duration of action. Captopril is an active ACE inhibitor in its orally absorbable parent form. In contrast, enalapril must be deesterified in the liver to the metabolite enalaprilat in order to inhibit the converting enzyme; this accounts for its delayed onset of action. Lisinopril does not require metabolic activation to be effective; however, a slow and incomplete absorption pattern explains the delay in onset of activity. Captopril and its disulfide metabolites are primarily excreted in the urine with minor elimination in the feces. Approximately two-thirds of an administered enalapril dose is excreted in the urine as both the parent drug and the metabolite enalaprilat; the remainder of these two substances are excreted in the feces. Lisinopril does not undergo measurable metabolism and approximately one-third is excreted unchanged in the urine with the remaining parent drug being excreted in the feces. The ACE inhibitors lower systemic vascular resistance with a resultant decrease in blood pressure. Their efficacy is comparable to diuretics and beta-blockers in treating patients with mild, moderate, or severe essential and renovascular hypertension. In those patients with severe congestive heart failure (CHF) the ACE inhibitors produce a reduction in systemic vascular resistance, blood pressure, pulmonary capillary wedge pressure, and pulmonary artery pressure. These drugs may produce improvement in cardiac output and stroke volume and, with chronic administration, may promote regression of left ventricular hypertrophy. The antihypertensive effects of the ACE inhibitors are enhanced when these agents are combined with a diuretic. Captopril and enalapril have been shown to be of particular benefit as adjunctive therapy in patients with congestive heart failure, both in terms of subjective improvement of patient symptoms, and in improving overall hemodynamic status. Although only captopril and enalapril are currently approved by the Food and Drug Administration for the treatment of CHF, early data with lisinopril suggest beneficial effects comparable to those of captopril. Several unapproved, experimental uses for ACE inhibitors have recently been reported and include treatment of proteinuria, scleroderma renal crisis, idiopathic edema, Raynaud's syndrome, and hypertensive emergency. The ACE inhibitors as a group are generally effective and well tolerated in most patients, although the adverse effect profile may vary somewhat among individual agents.

Glaucoma is an important public health concern in the United States, particularly among older adults (agedor=65 years). Pharmacologic therapy for glaucoma consists mainly of topical eye drops containing beta-blockers or prostaglandin analogs.The goal of this study was to assess the associations between factors of topical medication use (self reported medication compliance, belief in benefit of medication use, usage difficulty, usage assistance, and complexity of medication regimen) and health-related quality of life (HRQOL) in a cross-sectional population of older patients with glaucoma.A self-administered, 48-question survey soliciting information on medication-taking behaviors, treatmen-trelated factors, and HRQOL was mailed to members of a Medicare health maintenance organization who were agedor=65 years and had primary open-angle glaucoma. Two mailings were conducted 4 months apart; the second was sent to members whose responses to the first mailing had not yet been received. The 12-Item Short-Form Health Survey (SF-12) and the 25-Item National Eye Institute Visual Function Questionnaire (VFQ-25) were used to assess HRQOL. Other questions addressed perceptions of eye drop use in these patients. Multiple regression techniques were used to analyze associations between medication-related factors and HRQOL in this population.The questionnaire was mailed to 589 patients; 375 responded (218 in the first mailing and 157 in the second mailing). A total of 358 responses were complete and analyzable (effective response rate, 62%). After controlling for the effects of other confounders, we found that self reported difficulty in using eye drops was strongly associated with decreased HRQOL (11.5% in VFQ-25 total score and 8.4% in SF-12 mental health score, P0.05). Other medication-related factors that were examined were not significantly associated with changes in HRQOL.Based on our findings, patients agedor=65 years with glaucoma were likely to have significant comorbidity, which affected both visual and general health and well-being perception. Additionally, a significant proportion of these patients reported difficulty with use of topical medication, which was independently associated with a significant decrease in HRQOL. Care of older patients with glaucoma should incorporate strategies to minimize the difficulty associated with medication use.

Paroxysmal supraventricular tachycardia (PSVT) is seen somewhat frequently in the emergency department but less frequently during pregnancy. Although verapamil is widely used as the drug of choice for PSVT with a narrow QRS complex in a hemodynamically stable patient, the acute IV use of verapamil during pregnancy has not been well studied. Only a limited number of case reports document its safety and efficacy in the treatment of maternal or fetal PSVT. In general, the use of medication during pregnancy requires careful assessment of both the maternal and fetal risks versus benefits and documentation of patient consent. Because it crosses the placenta, one of the major concerns with the acute use of IV verapamil centers around the drug's potential effect on fetal heart rate. The case we present describes the occurrence of PSVT on two separate occasions in a woman in the third trimester of pregnancy. In both episodes, as much as 10 mg IV verapamil was given with resulting successful conversion to normal sinus rhythm. Fetal heart monitoring during drug administration failed to show significant change in fetal heart rate.

Piroxicam is a widely used nonsteroidal antiinflammatory drug available worldwide under various trade names by several manufacturers. Only one brand of piroxicam (Feldene) is currently marketed in the U.S., and the United States Pharmacopeial Convention established an official dissolution requirement for piroxicam in 1985. The purpose of this study was to evaluate and compare the dissolution performance of several internationally available piroxicam products using the United States Pharmacopeia (USP) dissolution test for piroxicam capsules. Of 25 brands of piroxicam capsules evaluated, 72 percent of the brands failed to meet the USP requirement, several by a wide margin. Although there is no specific USP dissolution test for tablets, the test for capsules was applied to five different brands of piroxicam tablets, and 80 percent of the tablet brands tested failed to meet the USP requirement. Although comparative bioavailability studies would be required to establish any definitive relationship between dissolution test performance and bioavailability, the failure of most of these products to meet the USP requirement for dissolution indicates formulation differences that could result in altered bioavailability. The substantial differences in dissolution performance observed among the piroxicam oral dosage forms tested have implications concerning the equivalency and standards of multisource products available on the international market, and should be taken into account by health care providers worldwide.

In Reply.— We are pleased to note the interest and concerns that have been raised regarding the development of drug administration guidelines for pediatric resuscitation. Our original letter identified two potential problems with the formula published in the American Heart Association (AHA) "Standards and Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiac Care" for the preparation of isoproterenol, epinephrine, and norepinephrine infusions used in pediatric resuscitation. 1 These original concerns regarding the volume of drug needed to prepare the infusions and the number of ampules of drug needed also can be raised with the formula proposed by Dr Chen. As the volume of drug to be added to an intravenous (IV) solution increases, the empty space in the IV container may not be sufficient to hold the additional volume, thereby necessitating the time-consuming process of withdrawing enough fluid from the IV container to allow for the addition of the drug. The