Epoetin in the 'untransfusable' anaemic patient: a retrospective case series and systematic analysis of literature case reports.

BACKGROUND: Erythropoiesis stimulating agents [erythropoietin (EPO)] have been recommended to treat anaemic patients who cannot receive or refuse blood tranfusion ('untransfusable' patients). OBJECTIVE: The objective of the study was to quantify the association of EPO use with haemoglobin (Hgb) recovery in anaemic untransfusable hospitalised patients. METHODS/MATERIALS: EPO treated anaemic untransfusable patients were identified through the combination of a retrospective case review and a systematic review of the medical literature. Literature reports of untransfusable patients not treated with any EPO were used as a comparator group. Hgb concentrations before and following EPO use were abstracted and used to determine the rate of Hgb recovery for each case. Multilevel mixed effects modelling was used to determine the association of Hgb recovery with EPO use. RESULTS: A total of 76 EPO treated cases (19 cases from the retrospective hospital case review and 57 from the literature), and 33 non-EPO treated comparator patients from the literature were included in the study. Hgb increased similarly over time in all groups at an overall mean standard error (SE) rate of 0·13 (0·01) g dL(-1) day(-1) . The Hgb recovery rate was higher in patients with lower baseline Hgb, regardless of EPO use. No association was found between the rate of Hgb recovery and EPO use, dose or therapy duration. CONCLUSIONS: In anaemic, 'untransfusable' hospitalised patients, EPO use was not associated with increased Hgb recovery at anytime within 28 days.

Medication-prescribing errors in a teaching hospital. A 9-year experience.

BACKGROUND: Improved understanding of medication prescribing errors should be useful in the design of error prevention strategies. OBJECTIVE: To report analysis of a 9-year experience with a systematic program of detecting, recording, and evaluating medication-prescribing errors in a teaching hospital. METHODS: All medication-prescribing errors with potential for adverse patient outcome detected and averted by staff pharmacists from January 1, 1987, through December 31, 1995, were systematically recorded and analyzed. Errors were evaluated by type of error, medication class involved, prescribing service, potential severity, time of day, and month. Data were analyzed to determine changes in medication-prescribing error frequency and characteristics occurring during the 9-year study period. RESULTS: A total of 11,186 confirmed medication-prescribing errors with potential for adverse patient consequences were detected and averted during the study period. The annual number of errors detected increased from 522 in the index year 1987 to 2115 in 1995. The rate of errors occurring per order written, per admission, and per patient-day, all increased significantly during the study duration (P < .001). Increased error rates were correlated with the number of admissions (P < .001). Antimicrobials, cardiovascular agents, gastrointestinal agents, and narcotics were the most common medication classes involved in errors. The most common type of errors were dosing errors, prescribing medications to which the patient was allergic, and prescribing inappropriate dosage forms. CONCLUSIONS: The results of this study suggest there may exist a progressively increasing risk of adverse drug events for hospitalized patients. The increased rate of errors is possibly associated with increases in the intensity of medical care and use of drug therapy. Limited changes in the characteristics of prescribing errors occurred, as similar type errors were found to be repeated with increasing frequency. New errors were encountered as new drug therapies were introduced. Health care practitioners and health care systems must incorporate adequate error reduction, prevention, and detection mechanisms into the routine provision of care.

Lindane (Kwell)-induced aplastic anemia.

Numerous toxic exposures have been implicated in causing aplastic anemia. Thirteen cases of aplastic anemia and 5 cases of other blood dyscrasias, eg, red blood cell aplasia and thrombocytopenia, associated with lindane, have been reported in the literature. However, aplastic anemia secondary to the scabicidal product (lindane [Kwell]) has not been documented, to our knowledge. We present the case of a 21-year-old man with a diagnosis of aplastic anemia, known prolonged exposure to lindane, and documented elevated serum lindane levels. His clinical course is described as well as various defects are explored for the aplasia.

Fluorescein and fluorescein glucuronide pharmacokinetics after intravenous injection.

The permeability of the blood-retinal and blood-aqueous barriers to fluorescein (F) and the rate of aqueous flow can be estimated by measurements of F in the vitreous, aqueous, and plasma after systemic administration. F is commonly measured by fluorescence, but fluorescein glucuronide (FG), a metabolite of F, also fluoresces. To assess the influence of FG on the quantitation of F by fluorescence, we studied the pharmacokinetics of F and FG for 38 hr in the plasma of five normal subjects given 14 mg/kg of sodium fluorescein intravenously. The plasma and the plasma ultrafiltrate were measured by fluorescence and by high performance liquid chromatography. In our fluorophotometer, FG was 0.124 times as fluorescent as F. F was rapidly converted to FG, and within 10 min the concentration of unbound FG exceeded that of unbound F. The terminal half-lives of F and FG in the plasma ultrafiltrate were 23.5 and 264 min, respectively, so that FG contributed almost all of the plasma fluorescence after 4-5 hr. Because FG was less bound in the plasma than F, the ratio of the fluorescence of the plasma ultrafiltrate to that of the plasma increased with time. The greatest proportion of the total F available to penetrate into the ocular compartments occurred shortly after injection. We concluded that FG is an important contributor to the fluorescence of the plasma ultrafiltrate after intravenous injection and that accurate quantitation of physiologic parameters calculated from the plasma F requires taking this factor into account.

Relationship between patient variables and lithium dosage requirements.

The relationships between several patient variables and lithium dosage requirements were determined in 71 inpatients receiving a slow-release lithium product. Age, weight, ideal body weight, sex, body surface area, creatinine clearance, presence of depression, concurrent use of tricyclic antidepressants, and acuteness of symptoms were significantly related to dosage requirements. The contribution of each factor to dosage requirements was further defined using multiple regression analysis and used to assess a published patient variable-based lithium dosing technique. Addition to that model of information concerning presence of depression, acuteness of symptoms, and creatinine clearance minimally improved predictability. The published model is recommended as an alternative to empiric methods.

Errors in the use of medication dosage equations.

BACKGROUND: Calculation errors in prescribing are a well-recognized problem; however, no systematic studies of actual errors involving calculation or other errors in the use of drug dosage equations are available. OBJECTIVE: To characterize the nature and potential adverse consequences of actual prescribing errors involving dosage equations. DESIGN: Analysis of the characteristics of 200 consecutive prescribing errors with potentially adverse outcomes involving dosage equations. SETTING: Tertiary care teaching hospital. MEASUREMENTS: Potential adverse outcomes, prescribing service, medication class, and the process point at which the error was made. RESULTS: Errors most commonly involved children (69.5%) and antibiotics (53.5%). Forty-two percent of errors were considered to put the patient at risk for a serious or severe preventable adverse outcome. Errors in decimal point placement, mathematical calculation, or expression of dosage regimen accounted for 59.5% of dosage errors. The dosage equation was wrong in 29.5% of dosage errors. CONCLUSIONS: The use of equations to determine medication dosages presents considerable risk to patients for errant dosing and subsequent adverse events or therapeutic failure. Errors may occur in any component of a dosage equation. Health care organizations should implement procedures to reduce the risk for errors resulting from the use of dosage equations.

Comparison of programs for preventing drug-nutrient interactions in hospitalized patients.

Three programs with different levels of pharmacist intervention designed to prevent drug-nutrient interactions (DNIs) were studied. Six drugs were selected for the study on the basis of their potential for involvement in significant DNIs and the hospital's drug-use profile. During a two-week control phase, the existing pharmacy system, in which no patient-specific information on DNIs is provided, was assessed. During the next four weeks, patients were randomly assigned to intervention 1, placement of a brightly colored label in the medication drawer and on the cover of the nursing medication card flip-chart, or to intervention 2, placement of the labels plus a five-minute structured patient-counseling session. Occurrence of DNIs and nurses' and patients' knowledge of DNIs were assessed. A DNI was defined as potentially altered drug absorption due to inappropriate timing or administration of a drug in relation to food. The occurrence of DNIs decreased significantly under the label system (from 24% to 19%) and under the combined label-counseling system (to 16%). However, the frequency of DNIs did not differ significantly between the two intervention groups. Patients' and nurses' knowledge of DNIs improved as a result of the interventions. The frequency of DNIs decreased when labels were used to alert nurses to proper medication timing.

Antiretroviral medication errors for patients with HIV infection.

Errors in prescribing antiretroviral agents for patients with HIV infection may lead to treatment failure, drug resistance, or drug toxicity. Several published reports describe such errors, which appear to be related to a lack of knowledge, inexperience, complexities of the antiretroviral regimens, and sound-alike and look-alike names. Clinicians caring for patients with HIV infection should be aware of the potential for prescribing errors and develop strategies to prevent them.

Standardized dosing tables to reduce errors involving high-dose methylprednisolone for acute spinal cord injury.

High-dose methylprednisolone administered after spinal cord injury improves neurologic recovery. Repeated errors in the prescribing and administration of the recommended regimen occurred in a regional trauma center. Standardized dosage tables for high-dose methylprednisolone were developed for prescribers, nurses, and pharmacists. Verification of ordered doses by pharmacists is critical in assuring appropriate use of this regimen. All institutions are urged to develop standard procedures for ordering, preparing, and administering high-dose methylprednisolone for acute spinal cord injury.

Comparison of ophthalmic beta-blocking agents.

Glaucoma is described, and the chemistry, pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage and administration of betaxolol and levobunolol in comparison with timolol are reviewed. Betaxolol and levobunolol are two beta-adrenergic blocking agents being marketed as ophthalmic solutions for treatment of primary open-angle glaucoma (POAG) and ocular hypertension (OHT). Betaxolol is a relatively cardioselective beta-adrenergic blocker, while levobunolol is a nonselective beta-adrenergic blocking agent. Double-blind comparative trials have suggested that betaxolol has an equal to slightly lower efficacy and levobunolol has equal efficacy in reducing intraocular pressure (IOP) compared with timolol, the first ophthalmic beta blocker. A mean reduction in intraocular pressure of 15-35% occurs with both betaxolol and levobunolol and is reported to be maintained with prolonged use. Betaxolol is associated with a higher (25%) incidence of local ocular adverse reactions than timolol. However, betaxolol produces less systemic beta 2- and possibly beta 1-adrenergic receptor blockade than either timolol or levobunolol. Betaxolol may be relatively safer to use in patients with reactive airway disease than either timolol or levobunolol. Levobunolol causes a similar to greater incidence of local ocular adverse reactions and similar systemic beta blockade compared with timolol. Levobunolol may possibly be longer acting than timolol, allowing more patients to be controlled by once-daily dosing. Betaxolol and levobunolol appear to be similar to timolol in controlling IOP in patients with POAG and OHT; additional experience with these agents is needed to assess the advantages and disadvantages of each agent.

DUE (drug usage evaluation) of ticarcillin and clavulanate potassium: determining appropriate and cost-effective therapeutic options.

The initial 46 patients who were prescribed the combination drug ticarcillin disodium and clavulanate potassium in a 640-bed teaching hospital were evaluated to determine the potential usefulness of the drug in the institution. The review revealed frequent use of the drug for inappropriate indications and in situations for which less expensive antimicrobials were appropriate. The results demonstrate that an increase in costs can occur when an agent that is being considered for formulary addition--because of its cost-saving potential--is not used as expected. In order to optimally utilize the clinical or cost advantages of newer antimicrobials, a program of prescriber education, drug use controls or guidelines, and a concurrent monitoring program may be required and should be implemented at the time of initial drug use within an institution.

Antimicrobial drug delivery to the eye.

A major obstacle in the treatment of ocular infections is the difficulty in obtaining adequate antimicrobial drug concentration at the site of infection. This article reviews the pharmacokinetic principles of ophthalmic drug delivery as it pertains to antimicrobial therapy. The administration of antimicrobials by topical application, subconjunctival injection, intravitreal injection, vitreous replacement fluid, and systemic administration are addressed. Representative data on the intraocular penetration of antimicrobials as well as recommended doses of drugs for ocular infections are presented.

Preventing medication prescribing errors.

Medication errors may arise in the manufacture, preparation, distribution, and administration of drugs. Physician prescribing errors are of particular importance as such errors have been associated with significant adverse patient outcomes. The pharmacist plays an important role in preventing such errors from reaching the patient. The purpose of this article is to define and illustrate the various error types and the mental attitudes that cause individuals to prescribe errant orders. Through better understanding of the cause of prescribing errors, pharmacists may be able to improve the error prevention services they provide. Based on the error types discussed and their causes, recommendations are proposed to decrease the frequency of such errors and thereby improve the quality of patient care.

Survey of antibiotic control policies in university-affiliated teaching institutions.

OBJECTIVE: To determine the type and extent of antibiotic control policies currently in use in a group of university-affiliated teaching institutions. DESIGN: A survey of antibiotic control policies and procedures (e.g., antibiotic order sheets, formulary restrictions, automatic stop orders for specific indications) was developed. SETTING: The University Hospital Consortium (UHC), a nonprofit group of academic health centers located in 33 states throughout the US. PARTICIPANTS: The survey was mailed to 60 UHC members. RESULTS: The survey was returned by 48 (80%) institutions. Most hospitals use either restrictions (81%) and/or official recommendations (56%) to manage antibiotic use. Antibiotics were restricted most commonly by service or unit (69%), indication (69%), or to the infectious disease service (60%). Antibiotic order sheets are used in 21 (44%) of the hospitals, of which 14 require completion by the prescriber. Monitoring of compliance with established restrictions is primarily the responsibility of the pharmacist processing the order (84%) and/or a clinical pharmacist (53%). When an order does not comply with restrictions or compliance cannot be determined, the prescriber is contacted prior to dispensing in 77% and 83% of the cases, respectively. In cases of noncompliance in which the prescriber refuses to alter an order to meet restrictions, 40% of hospitals refuse to dispense the drug and 35% dispense the drug but refer the case to another authority (infectious disease service or pharmacy and therapeutics committee). CONCLUSIONS: Considering the widespread use of antibiotic control programs, further investigation of the success of such programs in optimizing drug therapy, improving patient outcome, and cutailing the antibiotic budget within and among specific institutions is warranted.

Factors related to errors in medication prescribing.

OBJECTIVE: To quantify the type and frequency of identifiable factors associated with medication prescribing errors. DESIGN AND SETTING: Systematic evaluation of every third prescribing error detected and averted by pharmacists in a 631-bed tertiary care teaching hospital between July 1, 1994, and June 30, 1995. Each error was concurrently evaluated for the potential to result in adverse patient consequences. Each error was retrospectively evaluated by a physician and 2 pharmacists and a factor likely related to the error was identified. PARTICIPANTS: All physicians prescribing medications during the study period and all staff pharmacists involved in the routine review of medication orders. MAIN OUTCOME MEASURES: Frequency of association of factors likely related to medication errors in general and specific to medication classes and prescribing services (needed for medical, pediatric, obstetric-gynecologic, surgical, or emergency department patients); and potential consequences of errors for negative patient outcomes. RESULTS: A total of 2103 errors thought to have potential clinical importance were detected during the 1-year study period. The overall rate of errors was 3.99 errors per 1000 medication orders, and the error rate varied among medication classes and prescribing services. A total of 696 errors met study criteria (ie, errors with the potential for adverse patient effects) and were evaluated for a likely related factor. The most common specific factors associated with errors were decline in renal or hepatic function requiring alteration of drug therapy (97 errors, 13.9%), patient history of allergy to the same medication class (84 errors, 12.1%), using the wrong drug name, dosage form, or abbreviation (total of 79 errors, 11.4%, for both brand name and generic name orders), incorrect dosage calculations (77 errors, 11.1%), and atypical or unusual and critical dosage frequency considerations (75 errors, 10.8%). The most common groups of factors associated with errors were those related to knowledge and the application of knowledge regarding drug therapy (209 errors, 30%); knowledge and use of knowledge regarding patient factors that affect drug therapy (203 errors, 29.2%); use of calculations, decimal points, or unit and rate expression factors (122 errors, 17.5%); and nomenclature factors (incorrect drug name, dosage form, or abbreviation) (93 errors, 13.4%). CONCLUSIONS: Several easily identified factors are associated with a large proportion of medication prescribing errors. By improving the focus of organizational, technological, and risk management educational and training efforts using the factors commonly associated with prescribing errors, risk to patients from adverse drug events should be reduced.

Accuracy of penicillin allergy reporting.

The consistency of penicillin allergy documentation in the patient chart, pharmacy profile, and medication administration record was assessed, along with the correctness of the self-reported patient history of penicillin allergy. One hundred fifty adult inpatients with a reported penicillin allergy were interviewed about their allergy. Questions included length of time since the allergic reaction, symptoms of the reaction, and whether rechallenge was ever attempted. Patients were classified into categories of (1) more severe allergy, (2) less severe allergy, or (3) intolerance on the basis of results of the interview. The patient pharmacy profile, chart, and medication administration record were reviewed to determine whether the allergy label was present. Patients who received antimicrobials during their hospitalization were evaluated. Of 117 patients, 82.9% were classified as allergic and 17.1% as intolerant. The allergy was documented in 98.7% of patient charts and 96.7% of medication administration records. The symptoms of the allergic reaction were described in the chart for only 34% of patients. Agents substituted for penicillin were potentially more toxic in 70.4% of cases, equally effective in all cases, and more costly in 55.5% of cases. Most, but not all, patients labeled as penicillin allergic had a history consistent with an allergy to the drug. Pharmacists can help ensure accurate allergy documentation by evaluating patients and educating both patients and health care professionals.