We conducted a retrospective analysis to identify characteristics of preventable adverse drug reactions (ADRs). We reviewed reports on 612 ADRs occurring in hospitalized patients over 4 years, identified by the hospital's spontaneous ADR reporting program, and classified the events as potentially preventable or not preventable. Characteristics related to ADR preventability in the univariate analysis were the patient's clinical service, organ system involved in the ADR, class of drug causing the ADR, relationship to dosage, type of ADR, and probability that the reaction was due to the drug. Among these, relationship to dosage (p<0.001) and type of ADR (p<0.001) appeared to be most strongly related to preventability. In a multivariate analysis, preventable ADRs were associated with dosing (OR 3.82, 95% CI 2.42-6.03) and previous allergy to the drug (OR 3.46, 95% CI 1.01-11.88). An ADR that was classified as an allergic (OR 0.50, 95% CI 0.27-0.94) or idiosyncratic reaction (OR 0.44, 95% CI 0.28-0.71) was unlikely to be considered preventable. Preventable ADRs in hospitalized patients are likely to be dosage related or to occur among patients allergic to the specific agent.

We attempted to determine health and economic outcomes from the perspective of an integrated health system of administering enoxaparin 30 mg twice/day versus heparin 5000 U twice/day for prophylaxis against venous thrombosis after major trauma. A decision-analytic model was developed from best literature evidence, institutional data, and expert opinion. We assumed that 40% of proximal deep vein thromboses (DVTs) and 5% of distal DVTs are diagnosed and confirmed with initial or repeat duplex scanning; 50% of undiagnosed proximal DVTs result in pulmonary embolism; 2% and 1% of undiagnosed proximal DVTs will lead to readmission for DVT and pulmonary embolism, respectively, and pulmonary embolism-related mortality rates range from 8-30%. Length of hospital stay data and 1996 institutional drug use and acquisition cost data were used to estimate the cost of enoxaparin and heparin therapy. Diagnosis and treatment costs for DVT and pulmonary embolism were derived from institutional charge data using cost:charge ratios. A second analysis of patients with lower extremity fractures was completed. One-way and multiway sensitivity analyses were performed. For 1000 mixed trauma patients receiving enoxaparin versus heparin, our model showed that 62.2 (95% CI -113 to -12) DVTs or pulmonary emboli would be avoided, resulting in 67.6 (8 to 130) life-years saved at a net cost increase of $104,764 (-$329,300 to $159,600). Enoxaparin versus heparin resulted in a cost of $1684 (-$3600 to $9800) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $2303 (-$8100 to $19,000). For 1000 patients with lower extremity fractures, enoxaparin versus heparin resulted in a cost of $751 (-$4200 to $3300) for each DVT or pulmonary embolus avoided and a discounted cost/life-year saved of $1017 (-$10,200 to $6300). Although enoxaparin increases overall health care costs, it is associated with a cost/additional life-year saved of only $2300, which is generally lower than the commonly used hurdle rate of $30,000/life-year saved. The cost-effectiveness ratio is more favorable in patients with lower extremity fractures than in the general mixed trauma population.

We performed a literature search for all clinical studies reporting outcomes in patients with the acquired immunodeficiency syndrome (AIDS) receiving granulocyte-macrophage colony-stimulating factor (GM-CSF) for any indication. Safety outcomes included human immunodeficiency virus replication, immune status, and frequency of opportunistic infections and neoplasms. Data were synthesized qualitatively. We identified 22 studies (274 patients): 12 addressed AIDS neutropenia, 8 AIDS cancer therapy, and 2 opportunistic infections. Viral burden was assessed by serum p24Ag in 15 studies. Nine reported no change in levels, three net decreases, and three net increases. All studies showing net increases involved patients receiving GM-CSF without a concurrent antiretroviral. The CD4 counts were unchanged in 5 studies, increased in 3, and not reported in 14. The incidence of neoplasms or new opportunistic infections was low. The literature suggests no increased risk of viral replication or clinical deterioration in patients with AIDS who take GM-CSF concurrently with zidovudine.

Pharmacists at the 1995 American College of Clinical Pharmacy Pediatric Practice and Research Network meeting volunteered to act as coordinators at their sites and survey pediatric and neonatal nurses, pharmacists, and physicians regarding dependency in neonatal and pediatric patients after therapeutic administration of narcotics. Thirteen (60%) of 21 coordinators returned 244 surveys. Primary symptoms of withdrawal reported by clinicians were agitation (100%), irritability (100%), inconsolability (100%), crying (99%), tremors (98%), high heart rate (98%), fidgets (98%), high blood pressure (97%), less sleep (96%), and sweating (94%). Most clinicians considered narcotic withdrawal to be a problem (74%) that should be treated (87%). A dependency scale is being developed and will include symptoms reported by more than 75% of respondents.

We hypothesized that a pharmacist-provided comprehensive education program in conjunction with care provided by a pulmonologist would lead to improved economic, clinical, and humanistic outcomes in adults with asthma, compared with similar patients receiving care from a pulmonologist alone. The experimental group reported receiving more information about asthma self-management (p=0.001), were more likely to monitor peak flow readings (p=0.004), and had increased satisfaction with care, and perceived higher quality of care. Both groups had less lost productivity, fewer emergency department visits, fewer hospitalizations, and fewer physician visits, as well as improvement in symptoms scores within 45 days. Both groups improved in all functional status domains except the mental component score of the SF-12. Our results show a positive impact on outcomes in adults with asthma who received pharmaceutical care.

To review the clinical efficacy and role of amiodarone in the management of supraventricular and ventricular arrhythmias and its effects on mortality. Review of relevant studies and reports. Amiodarone exerts significant effects on atrial tissue. In most studies it was completely or partly effective in preventing recurrences of atrial fibrillation or flutter in up to 80% of patients. Amiodarone may be superior to class Ia agents for maintaining normal sinus rhythm. Large randomized trials indicate that it is a potent suppressor of ventricular arrhythmia and reduces arrhythmic death after myocardial infarction. In patients with cardiomyopathy, it suppresses asymptomatic arrhythmias and increases left ventricular ejection fraction. Meta-analysis of relevant studies indicated that amiodarone reduces the risk of arrhythmic and sudden death by 29% in high-risk patients with recent myocardial infarction or congestive heart failure. This translates into an overall 13% reduction in total mortality. Because of its effectiveness against a broad range of arrhythmias, amiodarone is a valuable addition to the antiarrhythmic pharmacopeia.

The discovery of antipsychotic agents in the 1950s revolutionized the treatment of schizophrenia. A large body of evidence supports the dopamine D2 receptor antagonist's efficacy in the treatment of psychotic symptoms. However, the advent of newer agents seems to point to a more complex interaction of neurotransmission in the pathophysiology of schizophrenia. In fact, a defining characteristic of atypical agents is a higher ratio of serotonin (5HT2) receptor blockade to D2 receptor blockade. Clozapine was the first atypical agent to be introduced; it was followed by risperidone, olanzapine, and now quetiapine, which is a dibenzothiazepine derivative structurally related to clozapine and olanzapine.

Involvement of the cytochrome P450 (CYP) 3A subfamily in the metabolism of vincristine is well established. However, information is limited regarding vincristine's drug interaction profile. All the substrates and inhibitors of CYP3A4 such as the azole antifungals (itraconazole, ketoconazole), cyclosporine, isoniazid, and nifedipine have very high propensity to interfere with vincristine metabolism. The proposed mechanism is most likely attributed to either inhibition of 3A4 enzymes or blockade of P-glycoprotein pumps. These interactions are clinically significant and can lead to severe vincristine toxicity if not detected. Although case reports discussed here exclusively involve vincristine, it is important to assume that all vinca alkaloids interact in the same manner until proved otherwise, because they share similar metabolism pathways.

To review the historical development of amiodarone and the changing perceptions of the drug, and discuss its electrophysiologic, pharmacologic, and pharmacokinetic properties. Review of relevant literature. In the 1970s and 1980s a plethora of new antiarrhythmic agents, including amiodarone, was introduced. Amiodarone is predominately a class III antiarrhythmic, but also possesses class I, II, and IV effects. By 1977 it was described as the ideal antiarrhythmic agent. However, clinicians underestimated potential difficulties caused by misunderstanding its variable absorption, slow initial response at nonloading dosages, and extended half-life. Elevated dosages also produced frequent adverse effects. Thus, early enthusiasm for the drug's efficacy was gradually replaced by a focus on its toxicity. The 1990s witnessed reacceptance of the agent as more logical initial regimens and lower maintenance dosages decreased adverse effects, and amiodarone emerged as one of the few drugs effective in suppressing and preventing arrhythmias that does not increase mortality. Remaining challenges include delineation of an optimal oral regimen, identification of markers useful in clinical monitoring, and elucidation of the relationship between dose-tissue concentration and response and dose-toxicity associations. Amiodarone is an increasingly valuable component of today's antiarrhythmic therapy.

Chronic pain is commonly encountered in elderly patients. About 20-50% of community-dwelling elderly experience it, and 45-80% of nursing home residents may be affected. Selection of pharmacologic therapy for the management of chronic pain must take into consideration the increased potential for adverse effects in this population. Major classes of drugs used to treat chronic pain (nonsteroidal antiinflammatory drugs, opioids, antidepressants) have adverse effects that occur more frequently in elderly than in younger patients. Given the often prolonged duration of therapy, optimal management requires minimizing the risk of adverse reactions.