Elevation of hepatic transaminases after enoxaparin use: case report and review of unfractionated and low-molecular-weight heparin-induced hepatotoxicity.

Enoxaparin, a low-molecular-weight heparin (LMWH), is widely used for the treatment and prophylaxis of thromboembolic disorders, such as deep vein thrombosis. Low-molecular-weight heparin products have smaller and more uniform molecular weights than unfractionated heparin, allowing them to exhibit a much greater affinity for factor Xa than factor IIa. Compared with traditional unfractionated heparin, LMWHs have proved to be equally efficacious and may be safer. The distinctive characteristics of LMWHs have resulted in decreased rates of bleeding and equivalent rates of thrombocytopenia compared with unfractionated heparin. This favorable safety profile has been identified in several studies and may have led clinicians to believe that LMWHs have lower frequencies of all common side effects. A 66-year-old woman developed increased hepatic transaminases during treatment with enoxaparin for a deep vein thrombosis; they returned to normal after enoxaparin discontinuation. A causal relationship between unfractionated heparin and asymptomatic, transient increases in hepatic transaminase levels has been documented; these increased levels also appear to be an underrecognized, adverse effect of LMWH therapy.

Changing physician prescribing behavior: the community-acquired pneumonia intervention trial.

The Notes section welcomes the following types of contributions: (1) practical innovations or solutions to everyday practice problems, (2) substantial updates or elaborations on work previously published by the same authors, (3) important confirmations of research findings previously published by others, and (4) short research reports, including practice surveys, of modest scope or interest. Notes should be submitted with AJHP's manuscript checklist. The text should be concise, and the number of references, tables, and figures should be limited.

Associations between initial antimicrobial therapy and medical outcomes for hospitalized elderly patients with pneumonia.

BACKGROUND: Although medical practice guidelines exist, there have been no large-scale studies assessing the relationship between initial antimicrobial therapy and medical outcomes for patients hospitalized with pneumonia. OBJECTIVE: To determine the associations between initial antimicrobial therapy and 30-day mortality for these patients. METHODS: Hospital records for 12945 Medicare inpatients (> or = 65 years of age) with pneumonia were reviewed. Associations between initial antimicrobial regimens and 30-day mortality were assessed with Cox proportional hazards models, adjusting for baseline differences in patient characteristics, illness severity, and processes of care. Comparisons were made with patients treated with a non-pseudomonal third-generation cephalosporin alone (the reference group). RESULTS: Initial treatment with a second-generation cephalosporin plus macrolide (hazard ratio [HR], 0.71; 95% confidence interval [CI], 0.52-0.96), a non-pseudomonal third-generation cephalosporin plus macrolide (HR, 0.74; 95% CI, 0.60-0.92), or a fluoroquinolone alone (HR, 0.64; 95% CI, 0.43-0.94) was independently associated with lower 30-day mortality. Adjusted mortality among patients initially treated with these 3 regimens became significantly lower than that in the reference group beginning 2, 3, and 7 days, respectively, after hospital admission. Use of a beta-lactam/beta-lactamase inhibitor plus macrolide (HR, 1.77; 95% CI, 1.28-2.46) and an aminoglycoside plus another agent (HR, 1.21; 95% CI, 1.02-1.43) were associated with an increased 30-day mortality. CONCLUSIONS: In this study of primarily community-dwelling elderly patients hospitalized with pneumonia, 3 initial empiric antimicrobial regimens were independently associated with a lower 30-day mortality. The more widespread use of these antimicrobial regimens is likely to improve the medical outcomes for elderly patients with pneumonia.

Correlates and prevalence of benzodiazepine use in community-dwelling elderly.

OBJECTIVE: To describe the prevalence of benzodiazepine use, sociodemographic and physical health factors associated with use, dosages taken, and directions for use among individuals aged 65 years and older. DESIGN: Cross-sectional analysis of baseline data from the community-based, prospective observational Cardiovascular Health Study. PATIENTS/PARTICIPANTS: Medicare eligibility lists from four U.S. communities were used to recruit a representative sample of 5,201 community-dwelling elderly, of which 5,181 participants met all study criteria. MEASUREMENTS AND MAIN RESULTS: Among participants, 511 (9.9%) were taking at least one benzodiazepine, primarily anxiolytics (73%). Benzodiazepines were often prescribed to be taken pro re nata (PRN "as needed"), and 36.5% of prescriptions with instructions to be taken regularly were taken at a dose lower than prescribed. Reported over-the-counter (OTC) sleep aid medication use was 39.2% in benzodiazepine users and 3.3% in nonusers. In a multivariate logistic model, the significant independent correlates of benzodiazepine use were being white (odds ratio [OR] 1.9; 95% confidence interval [CI] 1.0, 3.4), female (OR 1.7; CI 1.4, 2.2), and living in Forsyth County, North Carolina, or Washington County, Maryland, compared with living in Sacramento County, California, or Allegheny County, Pennsylvania (OR 2.3; CI 1.4, 2.2); having coronary heart disease (OR 1.6; CI 1.2, 2.1), health status reported as poor or fair (OR 1.8; CI 1.4, 2.3), self-reported diagnosis of nervous or emotional disorder (OR 6.7; CI 5.1, 8.7), and reporting use of an OTC sleep aid medication (OR 18.7; CI 14.1, 24.7). CONCLUSIONS: One in 10 participants reported taking a benzodiazepine, most frequently an anxiolytic, often at a lower dose than prescribed and usually PRN. The high prevalence of OTC sleep aid medication and benzodiazepine use may place the patient at increased risk of psychomotor impairment. Physicians should assess OTC sleep aid medication use when prescribing benzodiazepines.

Variations in antimicrobial use and cost in more than 2,000 patients with community-acquired pneumonia.

PURPOSE: To assess the patterns of antimicrobial use, costs of antimicrobial therapy, and medical outcomes by institution in patients with community-acquired pneumonia. PATIENTS AND METHODS: The route, dose, and frequency of administration of all antimicrobial agents prescribed within 30 days of presentation were recorded for 927 outpatients and 1328 inpatients enrolled in the Pneumonia Patient Outcomes Research Team (PORT) multicenter, prospective cohort study. Total antimicrobial costs were estimated by summing drug costs, using average wholesale price for oral agents and institutional acquisition prices for parenteral agents, plus the costs associated with preparation and administration of parenteral therapy. Thirty-day outcome measures were mortality, subsequent hospitalization for outpatients, and hospital readmission for inpatients. RESULTS: Significant variation (P <0.05) in prescribing practices occurred for 17 of the 23 antimicrobial agents used in outpatients across 5 treatment sites, and for 18 of the 20 parenteral agents used in inpatients across 4 treatment sites. The median duration of antimicrobial therapy for treatment site ranged from 11 to 13 days for outpatients (P=0.01), and from 13 to 15 days for inpatients (P=0.49). The overall median cost of antimicrobial therapy was $12.90 for outpatients, and ranged from $10.80 to $58.90 among treatment sites (P <0.0001). The overall median cost of antimicrobial therapy was $228.70 for inpatients, and ranged from $183.70 to $315.60 among sites (P <0.0001). Mortality and hospital readmission for inpatients were not significantly different across sites after adjusting for baseline differences in patient demographic characteristics, comorbidity, and illness severity. Although subsequent hospitalization for outpatients differed by site, the rate was lowest for the site with the lowest antimicrobial costs. CONCLUSION: Variations in antimicrobial prescribing practices by treatment site exist for outpatients and inpatients with community-acquired pneumonia. Although variation in antimicrobial prescribing practices across institutions results in significant differences in antimicrobial costs, patients treated at institutions with the lowest antimicrobial costs do not demonstrate worse medical outcomes.

Debilitating reaction following the initial dose of tramadol.

OBJECTIVE: To describe a debilitating reaction following a single oral dose of tramadol. CASE SUMMARY: A 32-year-old white man with no prior medical problems, allergies, or previous medication reactions experienced ataxia, dilation of the pupils, numbness in his arms and legs, tremulousness, and dysphoria lasting approximately 4 hours following an initial tramadol dose (100 mg). The patient recovered with no sequelae. DISCUSSION: Central nervous system (CNS) stimulation during therapy with tramadol was reported in 7% of patients in clinical trials. These reactions are usually mild and transient. This report describes a debilitating CNS-mediated reaction to an initial dose of tramadol in an otherwise healthy adult. The patient was phenotyped for CYP2D6 activity, the major metabolic pathway for tramadol elimination, and was determined to be an extensive metabolizer with very high CYP2D6 activity. CONCLUSIONS: The exact mechanism of the adverse response is not known; however, based on phenotyping results, we suspect that it may be related to high concentrations of the active O-desmethyl metabolite of tramadol.

Medical outcomes and antimicrobial costs with the use of the American Thoracic Society guidelines for outpatients with community-acquired pneumonia.

CONTEXT: The American Thoracic Society (ATS) published guidelines based on expert opinion and published data--but not clinically derived or validated--for treating adult outpatients with community-acquired pneumonia. OBJECTIVE: To compare medical outcomes and antimicrobial costs for patients whose antimicrobial therapy was consistent or inconsistent with ATS guidelines. DESIGN: Multicenter, prospective cohort study. SETTING: Emergency departments, medical clinics, and practitioner offices affiliated with 3 university hospitals, 1 community teaching hospital, and 1 health maintenance organization. PARTICIPANTS: A total of 864 immunocompetent, adult outpatients with community-acquired pneumonia: 546 aged 60 years or younger with no comorbidity and 318 older than 60 years or with 1 comorbidity or more. MAIN OUTCOME MEASURES: Patients' antimicrobial therapy was classified as being consistent or inconsistent with the ATS guidelines. Mortality, subsequent hospitalization, medical complications, symptom resolution, return to work and usual activities, health-related quality of life, and antimicrobial costs were compared among those treated consistently or inconsistently with the guidelines. RESULTS: Outpatients aged 60 years or younger with no comorbidity who were prescribed therapy consistent with ATS guidelines (ie, erythromycin with some exceptions) had 3-fold lower antimicrobial costs ($5.43 vs $18.51; P<.001) and no significant differences in medical outcomes. Outpatients older than 60 years or with 1 comorbidity or more who were prescribed therapy consistent with ATS guidelines (ie, second-generation cephalosporin, sulfamethoxazole-trimethoprim, or beta-lactam and beta-lactamase inhibitor with or without a macrolide) had 10-fold higher antimicrobial costs ($73.50 vs $7.50; P<.001); despite trends toward higher mortality and subsequent hospitalization, no significant differences in medical outcomes were observed. CONCLUSION: Our findings support the use of erythromycin as recommended by the ATS guidelines for outpatients aged 60 years or younger with no comorbidity. Although the antimicrobial therapy recommended in outpatients older than 60 years or with 1 comorbidity or more is more costly, this observational study provides no evidence of improved medical outcomes in the small subgroup who received ATS guideline-recommended therapy.

Neuroleptic malignant syndrome with risperidone.

Neuroleptic malignant syndrome is thought to be a result of dopamine D2 receptor blockade in the striatum of the basal ganglia. Risperidone, a benzisoxazole derivative antipsychotic, has high serotonin 5-HT2 receptor blockade and dose-related D2 receptor blockade. The high ratio is believed to impart the low frequency of extrapyramidal symptoms with risperidone at low dosages. With this low frequency of extrapyramidal symptoms, it was thought the frequency of neuroleptic malignant syndrome might also be lowered. A 73-year-old woman developed neuroleptic malignant syndrome after monotherapy with risperidone. The syndrome reversed after discontinuing risperidone and starting treatment with dantrolene and bromocriptine. It appears that the protection from extrapyramidal side effects observed with risperidone does not ensure protection from neuroleptic malignant syndrome.

Assessing pharmacotherapy outcomes: a model for clinicians.

Health-related quality of life (HQL) has become an important therapeutic end point of pharmacologic therapy. As a result, clinicians will be increasingly called on to assess HQL outcomes associated with medication use. The review of HQL measures and the model described here should provide clinicians with the necessary framework to assess medication outcomes more globally so that they can identify and quantify medication-induced changes and guide management decisions, use resources efficiently, and improve patient satisfaction with care.