Case presentations of medication management for patients at risk for drug-associated acute kidney injury identified with a CDS system and a novel biomarker.

PURPOSE: Traditional methods used to evaluate changes in kidney function to identify acute kidney injury (AKI) have significant limitations. Damage biomarkers can identify patients at risk for AKI prior to changes in kidney function. While clinical trials have shown that biomarker-guided treatment can improve outcomes, whether these biomarkers can influence providers' choice of treatment strategy for risk prediction, surveillance, or diagnostic evaluation in clinical practice is uncertain. SUMMARY: This case series describes 4 patients at an academic medical center whose care was informed by kidney biomarker utilization in conjunction with a clinical decision support system (CDSS). Though each patient's clinical presentation was unique, kidney biomarkers were successfully employed as clinical tools in evaluating the risks and benefits of nephrotoxic medications. CONCLUSION: This case series demonstrates 4 scenarios in which a kidney injury biomarker used in conjunction with CDSS and consideration of the patients' clinical presentation informed treatment strategies with the intent to prevent AKI.

Interventions, Barriers, and Proposed Solutions Associated With the Implementation of a Protocol That Uses Clinical Decision Support and a Stress Biomarker Test to Identify ICU Patients at High-Risk for Drug Associated Acute Kidney Injury.

BACKGROUND: Damage biomarkers are helpful in early identification of patients who are at risk of developing acute kidney injury (AKI). Investigations are ongoing to identify the optimal role of stress/damage biomarkers in clinical practice regarding AKI risk prediction, surveillance, diagnosis, and prognosis. OBJECTIVE: To determine the impact of utilizing a clinical decision support system (CDSS) to guide stress biomarker testing in intensive care unit (ICU) patients at risk for drug-induced acute kidney injury (D-AKI). METHODS: A protocol was designed utilizing a clinical decision support system (CDSS) alert to identify patients that were ordered 3 or more potentially nephrotoxic medications, suggesting risk for progressing to AKI from nephrotoxic burden. Once alerted to these high-risk patients, the pharmacist determined if action was needed by ordering a stress biomarker test, tissue inhibitor of metalloproteinase-2-insulin-like growth factor-binding protein 7 (TIMP-2•IGFBP7). If the biomarker test result was elevated, the pharmacist provided nephrotoxin stewardship recommendations to the team. Pharmacists recorded the response to the clinical decision support alert, ordering, and interpreting the TIMP-2•IGFBP7, and information regarding clinical interventions. An alert in conjunction with TIMP-2•IGFBP7 as a strategy for AKI risk prediction and stimulant for patient care management was assessed. In addition, barriers and solutions to protocol implementation were evaluated. RESULTS: There were 394 total activities recorded by pharmacists for 345 unique patients. Ninety-three (93/394; 23.6%) actionable alerts resulted in a TIMP-2•IGFBP7 test being ordered. Thirty-one TIMP-2•IGFBP7 results were >0.3 (31/81; 38.3%), suggesting a high-risk of progression to AKI, which prompted 191 pharmacist/team interventions. On average, there were 1.64 interventions per patient in the low-risk patients, 3.43 in high-risk patients, and 3.75 in the highest-risk patients. CONCLUSION AND RELEVANCE: Stress biomarkers can be used in conjunction with CDSS alerts to affect therapeutic decisions in ICU patients at high-risk for D-AKI.

Transforming the Medication Regimen Review Process Using Telemedicine to Prevent Adverse Events.

BACKGROUND/OBJECTIVES: Federally-mandated consultant pharmacist-conducted retrospective medication regimen reviews (MRRs) are designed to improve medication safety in nursing homes (NH). However, MRRs are potentially ineffective. A new model of care that improves access to and efficiency of consultant pharmacists is needed. The objective of this study was to determine the impact of pharmacist-led telemedicine services on reducing high-risk medication adverse drug events (ADEs) for NH residents using medication reconciliation and prospective MRR on admission plus ongoing clinical decision support alerts throughout the residents' stay. DESIGN: Quality improvement study using a stepped-wedge design comparing the novel service to usual care in a one-year evaluation from November 2016 to October 2017. SETTING: Four NHs (two urban, two suburban) in Southwestern Pennsylvania. PARTICIPANTS: All residents in the four NHs were screened. There were 2,127 residents admitted having 652 alerts in the active period. INTERVENTION: Upon admission, pharmacists conducted medication reconciliation and prospective MRR for residents and also used telemedicine for communication with cognitively-intact residents. Post-admission, pharmacists received clinical decision support alerts to conduct targeted concurrent MRRs and telemedicine. MEASUREMENT: Main outcome was incidence of high-risk medication, alert-specific ADEs. Secondary outcomes included all-cause hospitalization, 30-day readmission rates, and consultant pharmacists' recommendations. RESULTS: Consultant pharmacists provided 769 recommendations. The intervention group had a 92% lower incidence of alert-specific ADEs than usual care (9 vs 31; 0.14 vs 0.61/1,000-resident-days; adjusted incident rate ratio (AIRR) = 0.08 (95% confidence interval (CI) = 0.01-0.40]; P = .002). All-cause hospitalization was similar between groups (149 vs 138; 2.33 vs 2.70/1,000-resident-days; AIRR = 1.06 (95% CI = 0.72-1.58); P = .75), as were 30-day readmissions (110 vs 102; 1.72 vs 2.00/1,000-resident-days; AIRR = 1.21 (95% CI = 0.76-1.93); P = .42). CONCLUSIONS: This is the first evaluation of the impact of pharmacist-led patient-centered telemedicine services to manage high-risk medications during transitional care and throughout the resident's NH stay, supporting a new model of patient care.

Use of Telemedicine to Enhance Pharmacist Services in the Nursing Facility.

OBJECTIVE: To conduct a systematic literature review to determine what telemedicine services are provided by pharmacists and the impact of these services in the nursing facility setting. DATA SOURCES: MEDLINE®, Scopus®, and Embase® databases. STUDY SELECTION: The terms "telemedicine" or "telehealth" were combined by "and" with the terms "pharmacist" or "pharmacy" to identify pharmacists' use of telemedicine. Also, "telepharmacy" was added as a search term. The initial search yielded 322 results. These abstracts were reviewed by two individuals independently, for selection of articles that discussed telemedicine and involvement of a pharmacist, either as the primary user of the service or as part of an interprofessional health care team. Those abstracts discussing the pharmacist service for purpose of dispensing or product preparation were excluded. DATA EXTRACTION: A description of pharmacists' services provided and the impact on resident care. DATA SYNTHESIS: Only three manuscripts met inclusion criteria. One was a narrative proposition of the benefits of using telemedicine by senior care pharmacists. Two published original research studies indirectly assessed the pharmacists' use of telemedicine in the nursing facility through an anticoagulation program and an osteoporosis management service. Both services demonstrated improvement in patient care. CONCLUSION: There is a general paucity of practice-related research to demonstrate potential benefits of pharmacists' services incorporating telemedicine. Telemedicine may be a resource-efficient approach to enhance pharmacist services in the nursing facility and improve resident care.

Physician Perceptions of Consultant Pharmacist Services Associated with an Intervention for Adverse Drug Events in the Nursing Facility.

OBJECTIVE: To assess the importance and performance of consultant pharmacist services delivered before and after an intervention to detect and manage adverse drug events among nursing facility residents. DESIGN: Before and after intervention survey of physicians participating in a randomized, controlled trial. SETTING: Four nonprofit, academically affiliated nursing facilities. PARTICIPANTS: Attending physicians providing nursing facility care who were randomized to intervention or control groups. INTERVENTIONS: Within the intervention arm, consultant pharmacists provided academic detailing in which trained health care professionals visit practicing physicians in their offices and present the most up-to-date clinical information. Physicians responded to alerts from a medication monitoring system, adjudicated system alerts for adverse drug events (ADEs), and provided structured recommendations about ADE management. MAIN OUTCOME MEASURES: We compared physicians' assessments of the importance and performance of consultant pharmacist services before and after the trial intervention in the intervention and control groups. RESULTS: In the intervention group, ratings of importance increased for all 24 survey questions, and 5 of the changes were statistically significant (P < 0.05). In the control group, ratings of importance increased for 16 questions, and none of the changes were statistically significant. In the intervention group, ratings of performance increased for all 24 questions, and 20 of the changes were statistically significant. In the control group, ratings of performance increased for 16 questions, and none of the changes was statistically significant. CONCLUSION: A multifaceted, consultant pharmacist-led intervention comprising academic detailing, computerized decision support, and structured communication framework can improve physicians' assessment of importance and performance of consultant pharmacist services. ABBREVIATIONS: ADE = Adverse drug event, M = Statistically significant mean, RCT = Randomized controlled trial, SBAR = Situation, Background, Discussion, Recommendation, SD = Standard deviation.

Off-Label Use of Agents for Management of Serious or Life-threatening Angiotensin Converting Enzyme Inhibitor-Induced Angioedema.

OBJECTIVE: To evaluate the place in therapy of fresh frozen plasma (FFP), C1 esterase concentrate (C1-INH), ecallantide, and icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (ACEI-IA). DATA SOURCES: A literature search was performed using PubMed (1946 through August 2015) and Embase (<1966 through August 2015). References from identified articles were reviewed. STUDY SELECTION AND DATA EXTRACTION: Consensus papers, practice guidelines, case reports/series, clinical trials, and meeting abstracts published in English and involving humans were included. DATA SYNTHESIS: No medications are currently Food and Drug Administration-approved for managing ACEI-IA. Emerging evidence suggests that FFP and medications approved for management of acute attacks of hereditary angioedema, another bradykinin-mediated event, may be effective for use in ACEI-IA. Positive efficacy results were reported with FFP and C1-INH while mixed results have been seen with ecallantide. Off-label icatibant has the most evidence supporting its use in ACEI-IA with rapid symptom resolution (10 minutes to 6 hours) and avoidance of intubation and tracheotomy in several cases. These agents were well-tolerated in ACEI-IA. CONCLUSION: ACEI-IA is typically a self-limiting event. First-line therapies include ACEI discontinuation, observation, and supportive medications (eg, corticosteroids, antihistamines, and epinephrine). Symptom progression can be life-threatening and may require interventions such as tracheotomy and intubation. Off-label use of FFP and medications approved for hereditary angioedema have resulted in rapid resolution of symptoms and avoidance of intubation. Among these agents, icatibant has the most supporting evidence and has been incorporated into practice guidelines and algorithms as a second-line agent for serious life-threatening ACE-IA.

Using a Clinical Surveillance System to Detect Drug-Associated Hypoglycemia in Nursing Home Residents.

OBJECTIVES: To determine whether a clinical surveillance system could be used to detect drug-associated hypoglycemia events and determine their incidence in nursing home (NH) residents. DESIGN: Retrospective cohort. SETTING: Four NHs in western Pennsylvania. PARTICIPANTS: Any resident of the four NHs who had a computer-generated alert detecting potential drug-associated hypoglycemia over a 6-month period were included. MEASUREMENTS: Descriptive statistics were used to summarize all variables, including the frequency and distribution of alert type according to glucose threshold. Analyses were conducted according to numbers of alerts and residents. The medications associated with the drug-associated hypoglycemia alerts were identified, and frequency of their inclusion in alerts was calculated. Additional calculations included time to drug-associated hypoglycemic event alert from date of admission and frequency of events associated with postacute, short-stay (≤35 days) admissions. RESULTS: Seven hundred seventy-two alerts involving 141 residents were detected. Ninety (63.8%) residents had a glucose level of 55 mg/dL or less, and 42 (29.8%) had a glucose level of 40 mg/dL or less. Insulin orders were associated with 762 (98.7%) alerts. Overall incidence of drug-associated hypoglycemia events was 9.5 per 1,000 resident-days. CONCLUSION: Hypoglycemia can be detected using a clinical surveillance system. This evaluation found a high incidence of drug-associated hypoglycemia in a general NH population. Future studies are needed to determine the potential benefits of use of a surveillance system in real-time detection and management of hypoglycemia in NHs.

Determining the incidence of drug-associated acute kidney injury in nursing home residents.

OBJECTIVE: Although acute kidney injury (AKI) is well studied in the acute care setting, investigation of AKI in the nursing home (NH) setting is virtually nonexistent. The goal of this study was to determine the incidence of drug-associated AKI using the RIFLE (Risk, Injury, Failure, Loss of kidney function, or End-Stage kidney disease) criteria in NH residents. DESIGN/SETTING/PARTICIPANTS/MEASUREMENTS: We conducted a retrospective study between February 9, 2012, and February 8, 2013, for all residents at 4 UPMC NHs located in southwest Pennsylvania. The TheraDoc™ Clinical Surveillance Software System, which monitors laboratory and medication data and fires alerts when patients have a sufficient increase in serum creatinine, was used for automated case detection. An increase in serum creatinine in the presence of an active medication order identified to potentially cause AKI triggered an alert, and drug-associated AKI was staged according to the RIFLE criteria. Data were analyzed by frequency and distribution of alert type by risk, injury, and failure. RESULTS: Of the 249 residents who had a drug-associated AKI alert fire, 170 (68.3%) were women, and the mean age was 74.2 years. Using the total number of alerts (n = 668), the rate of drug-associated AKI was 0.41 events per 100 resident-days. Based on the RIFLE criteria, there were 191, 70, and 44 residents who were classified as AKI risk, injury, and failure, respectively. The most common medication classes included in the AKI alerts were diuretics, angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers (ACEIs/ARBs), and antibiotics. CONCLUSION: Drug-associated AKI was a common cause of potential adverse drug events. The vast majority of cases were related to the use of diuretics, ACEIs/ARBs, and antibiotics. Future studies are needed to better understand patient, provider, and facility risk factors, as well as strategies to enhance the detection and management of drug-associated AKI in the NH.

Evaluating the impact of computer-generated rounding reports on physician workflow in the nursing home: a feasibility time-motion study.

OBJECTIVES: To determine the feasibility and impact of a computer-generated rounding report on physician rounding time and perceived barriers to providing clinical care in the nursing home (NH) setting. SETTING: Three NHs located in Pittsburgh, PA. PARTICIPANTS: Ten attending NH physicians. MEASUREMENTS: Time-motion method to record the time taken to gather data (pre-rounding), to evaluate patients (rounding), and document their findings/develop an assessment and plan (post-rounding). Additionally, surveys were used to determine the physicians' perception of barriers to providing optimal clinical care, as well as physician satisfaction before and after the use of a computer-generated rounding report. RESULTS: Ten physicians were observed during half-day sessions both before and 4 weeks after they were introduced to a computer-generated rounding report. A total of 69 distinct patients were evaluated during the 20 physician observation sessions. Each physician evaluated, on average, four patients before implementation and three patients after implementation. The observations showed a significant increase (P = .03) in the pre-rounding time, and no significant difference in the rounding (P = .09) or post-rounding times (P = .29). Physicians reported that information was more accessible (P = .03) following the implementation of the computer-generated rounding report. Most (80%) physicians stated that they would prefer to use the computer-generated rounding report rather than the paper-based process. CONCLUSIONS: The present study provides preliminary data suggesting that the use of a computer-generated rounding report can decrease some perceived barriers to providing optimal care in the NH. Although the rounding report did not improve rounding time efficiency, most NH physicians would prefer to use the computer-generated report rather than the current paper-based process. Improving the accuracy and harmonization of medication information with the electronic medication administration record and rounding reports, as well as improving facility network speeds might improve the effectiveness of this technology.

Use of an abnormal laboratory value-drug combination alert to detect drug-induced thrombocytopenia in critically Ill patients.

PURPOSE: The aim of this study was to assess the performance of a commercially available clinical decision support system (CDSS) drug-laboratory result alert in detecting drug-induced thrombocytopenia in critically ill patients. MATERIALS AND METHODS: Adult patients admitted to the medical and cardiac intensive care unit during an 8-week period and identified by 1 of 3 signals in the CDSS, TheraDoc, were eligible. Alerts were generated when the patient had a low platelet count and was ordered a potentially causal drug. Patients were evaluated in real time for the occurrence of an adverse drug reaction using 3 causality instruments. Positive predictive values were calculated for the alert. RESULTS: Sixty-four patients with a mean age of 54 years met the inclusion criteria, generating 350 alerts. Positive predictive values were 0.36, 0.83, and 0.40 for signals 1, 2, and 3, respectively. Overall, there were 137 adverse drug reactions identified in the 350 alerts, with heparin, vancomycin, and famotidine as the 3 most common potential causes. CONCLUSIONS: A commercial CDSS drug-laboratory alert is effective at identifying drug-induced thrombocytopenia in the intensive care unit and may improve patient safety. Compared with previous studies, the combination alert performs better than alerts based exclusively on laboratory values and should be considered to reduce alert fatigue.

Telaprevir: an oral protease inhibitor for hepatitis C virus infection.

PURPOSE: The pharmacology, pharmacokinetics, pharmacodynamics, clinical efficacy, safety, drug interactions, viral drug resistance, dosage and administration, and place in therapy of telaprevir are reviewed. SUMMARY: Telaprevir is an oral NS3/4A protease inhibitor that was recently approved by the Food and Drug Administration for the treatment of chronic hepatitis C virus (HCV) genotype 1 infection in adult patients with compensated liver disease, including cirrhosis. In Phase II clinical trials, triple therapy (telaprevir with peginterferon alfa and ribavirin) demonstrated 20-39% higher rates of sustained virological response (SVR) versus standard therapy (peginterferon alfa and ribavirin) in patients with chronic HCV genotype 1. Higher SVR rates were observed in treatment-naive patients or patients who did not respond to prior therapy (did not achieve SVR). Phase III studies also found improved SVR rates in patients treated with triple therapy. Telaprevir is recommended in combination with peginterferon alfa-2a and ribavirin for treatment-naive patients and patients who did not previously respond to peginterferon alfa-2a and ribavirin therapy. Telaprevir is a substrate and inhibitor of cytochrome P-450 (CYP) isoenzyme 3A4 and P-glycoprotein. Drugs that induce or inhibit CYP3A4 may affect concentrations of telaprevir, resulting in reduced efficacy or increased concentrations of telaprevir (and an increased risk for adverse reactions). The most common adverse events reported with telaprevir monotherapy versus placebo were diarrhea, nausea, fatigue, and dry skin. CONCLUSION: Telaprevir, an HCV NS3/4A protease inhibitor, has been shown to be effective in increasing SVR rates when used with peginterferon alfa and ribavirin in patients with chronic HCV genotype 1 infection, regardless of treatment history.

Coagulation factor VIIa (recombinant) in nonhemophilic patients requiring neurosurgery.

PURPOSE: The clinical outcomes, safety, and use of resources associated with the administration of factor VIIa (recombinant) to nonhemophilic patients requiring neurosurgery were evaluated. METHODS: An interdisciplinary group created guidelines for the pharmacy and therapeutics committee for the unlabeled use of factor VIIa (recombinant). Nonhemophilic patients were eligible to receive the agent without approval from the hematology-coagulation service if they had an intracranial hemorrhage (ICH), were undergoing an emergency neurosurgical procedure, and had coagulopathy. A standard single dose of 40 microg/kg was recommended for these patients. Data were prospectively collected between March 2004 and March 2006 for all neurological surgery patients receiving factor VIIa (recombinant). RESULTS: A total of 92 nonhemophilic patients received single doses of factor VIIa (recombinant) under the guidelines during the two-year study period. The majority of patients had a baseline International Normalized Ratio (INR) of >2, underwent emergency neurosurgical procedures, and had an intracranial hemorrhage. All guideline criteria for indication and approval were followed for 48 patients. Eighty-seven patients received concomitant treatment for reversal of anticoagulation. A significant correction in the baseline INR after administration of factor VIIa (recombinant) was noted (p < 0.0001). Five patients experienced adverse events. Implementation of the guidelines decreased the annual cost of factor VIIa (recombinant) by 46%. CONCLUSION: A protocol calling for administration of factor VIIa (recombinant) 40 microg/kg in nonhemophilic patients with coagulopathy and ICH led to a rapid and significant decrease in the INR, allowing for emergency surgical intervention. Few adverse events were detected in these patients, and none were deemed to be directly related to factor VIIa (recombinant).

Formulary decisions for pre-1938 medications.

PURPOSE: A process is described for formulary revisions consistent with the Food and Drug Administration (FDA)'s current initiative to ensure that all drugs marketed in the United States have been approved for safety and efficacy. SUMMARY: A list of pre-1938 drugs (i.e., formulations marketed before the Federal Food, Drug, and Cosmetic Act established safety requirements) was compiled from USP DI Volume III and International Journal of Pharmaceutical Compounding lists. Products on the resulting list were reviewed for current marketing and FDA approval status and for availability. The project team recommended formulary addition or retention if a product had been used and been purchased more than once at the hospital in the past year, if no formulary alternative was available, or if the product had been approved by FDA. Nonformulary status was recommended if none of these criteria applied or the product was no longer available. Of 88 pre-1938 formulations of 59 drugs, only 3 had been approved by FDA before 1962 (when evidence of efficacy was first required) and 14 thereafter. Of the 88 formulations, 47 were on the hospital's formulary. The team recommended that 37 formulations be retained on or added to the formulary and that 51 be maintained or designated as nonformulary. The hospital's pharmacy and therapeutics (P&T) committee accepted the recommendations, provided that the 30 nonapproved formulations recommended for formulary status be reviewed as FDA continues its effort to have manufacturers either apply for approval of their products or remove them from the market. The recommendations were also accepted by the health system's P&T committee. CONCLUSION: A systematic approach to reviewing pre-1938 medications for the purpose of formulary revision was successful in addressing safety concerns about these older drug formulations.

Evaluation of conflicting literature and application to formulary decisions.

PURPOSE: Guidelines were developed for grading the quality, quantity, and consistency of drug literature in support of formulary recommendations. METHODS: Four developmental steps were taken to create a comprehensive literature evaluation system. The first step identified the attributes of a body of literature that were most reflective of its applicability to patient care. The next step defined each domain (quality, quantity, consistency), as determined by the Agency of Healthcare Research and Quality (AHRQ), in terms of the specific qualities to be assessed; a value was assigned to those qualities. Also, a literature search was conducted to identify strategies for evaluating bodies of literature employed in published assessment tools. Following the analysis of previously published systems, which were evaluated with respect to their inclusion of the AHRQ-identified domains, the next step was the development of specific domains and definitions to get a composite grade (with "better" evidence earning more points) for formulary recommendations. The final step was the creation of a system that aggregated the final score for the recommendation. The recommendation was categorized according to quality, quantity, and consistency of supporting evidence, and the total number of points was calculated and the recommendation given letter and numerical grades. RESULTS: The guidelines that were developed allow the user to accurately, consistently, and easily determine the strength of recommendations for a body of literature that may be conflicting. The addition of criteria for quantity and consistency to previously-published grading systems has made the guidelines more objective. CONCLUSION: A system that accounts for the quality, quantity, and consistency of drug literature was developed to assist in making formulary decisions.

Advanced practice internship: experiential learning in a drug use and disease state management program.

OBJECTIVE: Establish a 3-year hospital internship within a drug use and disease state management program that would provide doctor of pharmacy students with experiential learning while still completing their classroom studies. DESIGN: As paid interns, students engaged in group and individual activities that assessed clinical practice guidelines. Patient monitoring and clinical intervention techniques were learned through prospective evaluation of drug therapy. Students designed evidence-based treatment guidelines and participated in all phases of development, including multidisciplinary approval, implementation, and evaluation stages. ASSESSMENT: Student competency was continually monitored through direct observation by a preceptor and written examinations. Patient case studies, group discussions, and poster presentations allowed assessment of student growth in knowledge and communication skills. CONCLUSION: The comprehensive structure of this internship provides a broad perspective for understanding the role of the hospital pharmacist in providing pharmaceutical care. Close supervision maximizes student learning potential and fosters a mentoring relationship for both personal and professional growth.

Challenge and rechallenge: drotrecogin alfa (activated)-induced prolongation of activated partial thromboplastin time in a patient with severe sepsis.

An 81-year-old woman with ischemic bowel underwent laparotomy with small-bowel resection and developed septic shock. She required broadspectrum antibiotics, norepinephrine, and mechanical ventilation. The patient received drotrecogin alfa (activated) 24 microg/kg/hour for a total of 67.5 hours. Coagulation parameters were monitored during her therapy. Significant increases in activated partial thromboplastin time (aPTT) during infusion led to two temporary discontinuations of the drug. Coagulation parameters decreased when the drug was held and increased with each rechallenge. The patient survived the episode and was discharged on postoperative day 27. Medical records of 26 other patients who received drotrecogin alfa (activated) at our institution from November 2001-August 2003 were reviewed retrospectively for coagulation parameters and bleeding rate. Of the 26 patients, nine (35%) were treatment compliant (>90% of the 96-hr course). Coagulopathy and bleeding resulted in early discontinuation in four (15%) and six (23%) patients, respectively. An increase in aPTT from baseline to during infusion of drotrecogin alfa (activated) was noted in 14 patients with complete data (p=0.56). A decrease in median platelet count from baseline to during infusion was noted in the six patients who bled during therapy (p=0.01). Two of these patients had platelet counts less than 30x10(3)/mm3 during administration. Drotrecogin alfa (activated) should be considered an anticoagulant. In postmarketing reports, clinically significant bleeding occurred more frequently than was noted in a large, randomized, multicenter trial. Patients receiving drotrecogin alfa (activated) should be closely monitored for prolongation of coagulation parameters. Temporary discontinuation of the drug should be considered when international normalized ratio is greater than 3.0, platelet count is less than 15x10(3)/mm3, and aPTT is greater than 100 seconds.

A clinical and pharmacoeconomic justification for intravenous acetylcysteine: a US perspective.

Paracetamol (acetaminophen) poisoning remains the most common exposure reported to US poison information centres and the leading cause of poisoning-related fatalities, despite the availability of an effective antidote, acetylcysteine. Oral acetylcysteine solution has been approved for the management of acetaminophen poisoning in the US for four decades. Until the recent approval of intravenous acetylcysteine in the US, it was necessary to compound the oral solution for intravenous administration. The effectiveness and tolerability of oral and intravenous acetylcysteine for the prevention of hepatotoxicity induced by paracetamol poisoning are well established in the literature. Intravenous acetylcysteine may be preferred over oral administration based on improved tolerability, ease of administration and the shortened course of therapy (20 hours intravenous vs 72 hours oral). The two intravenous acetylcysteine regimens documented in the literature, 48 hours and 20 hours, have similar efficacy when started within 8-10 hours of ingestion. Although there are no legal concerns with continuing the routine compounding of the oral solution to an intravenous product, new standards for pharmacy compounding of sterile preparations set forth by the US Pharmacopoeia highlight that the risk of compounding products for intravenous use must be assessed carefully. Changing the route of administration of a sterile oral solution to an intravenous preparation, when a commercial sterile and pyrogen-free product is available, may not be advisable. The best cost-containment strategies must be used for introduction of the more costly sterile, pyrogen-free intravenous acetylcysteine formulation by hospitals and healthcare systems. The intravenous acetylcysteine product is more cost effective when given for 20 hours than other treatment protocols based on the costs of acetylcysteine and hospitalisation. If used per protocol, the 20-hour intravenous acetylcysteine regimen may decrease hospital length of stay, thereby, offsetting the increased drug cost. Data conflict on the efficacy and administration of intravenous acetylcysteine for off-label uses, such as radiographic contrast media-induced nephropathy prevention and reperfusion in orthotopic liver transplantation. The costs for the intravenous formulation for these indications is significantly higher than use of the oral formulation for oral administration in radiographic contrast media-induced nephropathy prevention and compounded for intravenous use in orthotopic liver transplantation. The oral solution should be retained by healthcare systems for oral and inhalation applications, such as respiratory conditions, oral administration for radiographic contrast media nephropathy prevention, or the use of the 72-hour oral protocol to treat paracetamol poisoning, when the intravenous preparation cannot be used.

Meeting the modified drug information requirements of ASHP-accredited pharmacy practice residency programs.

The current standards for meeting drug information (DI) requirements in American Society of Health-System Pharmacists (ASHP)-accredited pharmacy practice residency (PPR) programs and the impact of changes in ASHP standards for the DI requirements were studied. In September 2002 a nine-question survey was e-mailed to the directors of all ASHP-accredited PPR programs listed with an available e-mail address on ASHP's residency directory Web page as of August 2002. The program directors were asked to provide information on the demographics of their practice settings, the current methods of completing the DI requirements of their programs, whether the DI requirements had changed between the 2001-02 and 2002-03 residency years, and whether any changes in the DI requirements were anticipated. A total of 178 (49%) of 365 PPR programs responded. Of the respondents, 87% were located in a hospital setting, 33% were affiliated with a school of pharmacy, and 40% had a formal onsite DI center. Half of the respondents fulfilled DI requirements through a longitudinal rotation, 20% through a block rotation, and 27% through both. Eighty-two percent of the respondents were familiar with the revised ASHP DI requirements, and 26% had modified their DI requirements between the 2001-02 and 2002-03 residency years. Seventeen percent anticipated changing their DI requirements in the future. Influences for modifications to the programs' DI requirements were mainly ASHP revisions and feedback from preceptors and residents. A national survey suggested that DI requirements in PPR programs are primarily achieved through a longitudinal rotation design.