Contribution of Renal Impairment to Potentially Preventable Medication-Related Hospital Admissions (May).

Ann Pharmacother. 2012 May 8;

Authors: Leendertse AJ, van Dijk EA, Agm De Smet P, Egberts TC, Mla van den Bemt P

Abstract
BACKGROUND:Medication errors and renal impairment contribute to severe adverse drug events, which may lead to hospital admission.OBJECTIVE:To determine whether medication errors and renal impairment contribute to hospital admission and examine these errors for strategies to prevent admissions.METHODS:The 714 medicationn-related hospital admissions reported in the prospective multicenter study HARM (Hospital Admissions Related to Medication) were analyzed. The patients were divided into 3 groups based on the availability of creatinine levels: group A, the home-monitored group (n = 227); group B, the hospital-monitored group (n = 420); and group C, the unmonitored group (n = 67).RESULTS:After assessment, 70 admissions (10%) were considered to be related to a medication error and renal impairment (A, 29; B, 41; C, none). In these 70 patients, 85 errors occurred in group A, 66 errors in group B, and none in group C. Dosing errors were identified in 46 patients (A, 14; B, 32), a drug-drug interaction in 22 patients (A, 13; B, 9), and a drug-disease interaction in 17 patients (A, 10; B, 7).CONCLUSIONS:Renal impairment and medication errors may lead to medication-related hospital admissions. Monitoring renal function and adjusting pharmacotherapy according to renal function might help to prevent hospital admissions. This can be a strategy for research on how to decrease the number of medication-related hospital admissions.

PMID: 22570433 [PubMed - as supplied by publisher]

Risk of Venous Thromboembolism in Patients with Chronic Liver Disease and the Utility of Venous Thromboembolism Prophylaxis (June).

Ann Pharmacother. 2012 May 8;

Authors: Pincus KJ, Tata AL, Watson K

Abstract
OBJECTIVE:To review the current literature on the risk of venous thromboembolism (VTE) in patients with chronic liver disease (CLD).DATA SOURCES:Literature was accessed through MEDLINE/PubMed (1996-December 2011) using the search terms liver disease, cirrhosis, venous thromboembolism, deep vein thrombosis, and pulmonary embolism.STUDY SELECTION AND DATA EXTRACTION:Relevant observational and population-based studies were included to present BACKGROUND: Liver disease affects the synthesis of procoagulants and anticoagulants, resulting in hemostatic alterations and abnormal laboratory values. Retrospective studies characterized the VTE incidence to be 0.5-6.3%. Population-based studies reported VTE relative risks of 1.74-2.10 in patients with CLD compared with population controls and VTE odds ratios of 0.9-1.39 for hospitalized patients with CLD compared with controls without liver disease. There is a paucity of data on the use of pharmacologic prophylaxis in patients with CLD.CONCLUSIONS:Patients with CLD should be assessed for VTE risk and given VTE prophylaxis when the benefits outweigh the risks. Diagnoses of CLD or elevated international normalized ratio do not confer protection against development of VTE and do not justify withholding pharmacologic prophylaxis based on this diagnosis.

PMID: 22570429 [PubMed - as supplied by publisher]

Daptomycin Experience in Critical Care Patients: Results from a Registry (April).

Ann Pharmacother. 2012 Mar 27;

Authors: Brown JE, Fominaya C, Christensen KJ, McConnell SA, Lamp KC

Abstract
BACKGROUND:Vancomycin is often the drug of choice in critically ill patients with gram-positive infections, although circumstances often prevent its use. In these situations, clinicians are frequently left with limited data regarding alternative agents.OBJECTIVE:To describe patients with reported sepsis receiving daptomycin in a critical care unit.METHODS:This multicenter, noncomparative, noninterventional study identified patients in critical care units, using the Cubicin Outcomes Registry and Experience (CORE) 2005-2009 registry. A descriptive account of patient characteristics, infectious etiology, outcomes at the end of daptomycin therapy, and 30-day mortality is reported. Nonevaluable patients were excluded from the efficacy analysis but included in the safety analysis.RESULTS:We identified 128 patients, 98 (77%) of whom were evaluable for efficacy. Patient characteristics for the efficacy population were 55 (56%) males,30 (31%) aged 66 years or older, 38 (39%) had creatinine clearance less than 30 mL/min, and 27 (28%) were on dialysis. Common underlying diseases included acute or chronic renal failure 44 (45%), hypertension 40 (41%), and diabetes 27 (28%). Seventy-two (73%) patients were bacteremic. The most common pathogens found were methicillin-resistant Staphylococcus aureus (32%), vancomycin-resistant Enterococcus faecium (21%), and coagulase-negative staphylococci (20%). Prior to daptomycin, antibiotics were used in 84 (86%) patients, most commonly vancomycin (65/84; 77%). The median (range) initial daptomycin dose was 6 mg/kg (3-10) and duration of 10 days (1-58). Overall success rate was 70% (31% cured; 39% improved). Twelve adverse events possibly related to daptomycin were reported in 9 of 128 (7%) patients in the safety population; 4 of these in 4 (3%) patients were serious. The mortality rate within 30 days of completing daptomycin was 42 of 128 (33%) patients.CONCLUSIONS:These data provide preliminary results on the use of daptomycin in critically ill patients with complicated conditions. Controlled studies are needed to best evaluate daptomycin use in these patients.

PMID: 22454446 [PubMed - as supplied by publisher]

Roflumilast: A Novel Treatment for Chronic Obstructive Pulmonary Disease (April).

Ann Pharmacother. 2012 Mar 20;

Authors: Reid DJ, Pham NT

Abstract
OBJECTIVE:To evaluate the efficacy and safety of roflumilast, approved by the Food and Drug Administration in February 2011 as a treatment to reduce the risk of chronic obstructive pulmonary disease (COPD) exacerbations in patients with severe COPD associated with chronic bronchitis and a history of exacerbations.DATA SOURCES:Literature was retrieved through MEDLINE (1977-December 2011), using the terms roflumilast and COPD. In addition, US government Web sites, including clinicaltrials.gov and fda.gov, were reviewed for pertinent information. Lastly, reference citations from publications identified were reviewed.STUDY SELECTION AND DATA EXTRACTION:All articles published in English identified from the DATA SOURCES: Limited treatment options are available for patients with moderate-to-severe COPD and repeated exacerbations. In 6 published Phase 3 trials to date, roflumilast 500 ?g daily exhibited modest improvements in lung function, measured by pre- and postbronchodilator forced expiratory volume in 1 second, and reduced rates of moderate and severe exacerbations. Roflumilast was generally well tolerated, with diarrhea, nausea, and headache the most common adverse events seen in clinical trials, although it has also been associated with an increased risk of neuropsychiatric abnormalities and dose-limiting weight loss. The greatest benefit seen with roflumilast was among patients with moderate-to-severe COPD associated with chronic bronchitis along with a recent history of exacerbations. The benefits were demonstrated with monotherapy and in combination with long-acting ?(2)-agonists or anticholinergic agents.CONCLUSIONS:Despite its only modest benefits in improving lung function and reducing exacerbation rates, roflumilast serves as a safe and effective option in the treatment of COPD.

PMID: 22433610 [PubMed - as supplied by publisher]

Clinical Outcomes with Ertapenem as a First-Line Treatment Option of Infections Caused by Extended-Spectrum ?-Lactamase Producing Gram-Negative Bacteria (March).

Ann Pharmacother. 2012 Mar 6;

Authors: Fong JJ, Rosé L, Radigan EA

Abstract
BACKGROUND:Infections caused by extended-spectrum ?-lactamase (ESBL)-producing gram-negative organisms are a growing concern in hospitalized patients. Traditionally, these infections can be effectively treated by the carbapenem class of drugs. In 2005, our institution initiated a protocol for use of ertapenem, a carbapenem, as the first-line treatment option for these infections. It is unknown whether ertapenem is associated with similar clinical response and microbiologic cure rates as those achieved with group 2 carbapenems (imipenem, meropenem, doripenem).OBJECTIVE:To describe clinical response and microbiologic cure rates associated with ertapenem as first-line treatment of infections caused by ESBL-producing organismsMETHODS:This case series included patients who received ertapenem for more than 48 hours to treat a documented infection with a positive culture for an ESBL-producing organism. Efficacy was determined by the clinical response and microbiologic cure rates achieved with ertapenem.RESULTS:Seventy-three patients received ertapenem for a mean (SD) of 10.7 (5.9) days. The most common (59%) infection site was urine. The most common causative organisms were ESBL-producing Klebsiella pneumoniae (47%) and Escherichia coli (48%). Clinical response was observed in 78% of patients. Microbiologic cure was achieved in 92% of the evaluable population (n = 50).There were no significant differences in clinical or microbiologic cure rates across important subgroups.CONCLUSIONS:Patients treated with ertapenem achieved favorable clinical response and microbiologic cure rates. Our data suggest that ertapenem can be used as an alternative to group 2 carbapenems for the treatment of infections caused by ESBL-producing gram-negative organisms.

PMID: 22395250 [PubMed - as supplied by publisher]

Pegloticase: A Novel Agent for Treatment-Refractory Gout (March).

Ann Pharmacother. 2012 Mar 6;

Authors: Shannon JA, Cole SW

Abstract
OBJECTIVE:To evaluate efficacy and safety of pegloticase, approved by the Food and Drug Administration in September 2010 for treatment of patients with chronic treatment-refractory gout.DATA SOURCES:Literature searches were conducted using PubMed (1948-January 2012), TOXLINE, International Pharmaceutical Abstracts (1970-January 2012), and Google Scholar using the terms pegloticase, puricase, PEG-uricase, gout, uricase, and Krystexxa. Results were limited to English-language publications. References from selected articles were reviewed to identify additional citations.STUDY SELECTION AND DATA EXTRACTION:Studies evaluating the pharmacology, pharmacokinetics, safety, and efficacy of pegloticase for the treatment of chronic treatment-refractory gout were included.DATA SYNTHESIS:Pegloticase represents a novel intravenous treatment option for patients who have chronic gout refractory to other available treatments. Pegloticase is a recombinant uricase and achieves therapeutic effects by catalyzing oxidation of uric acid to allantoin, resulting in decreased uric acid concentrations. Results of published trials demonstrate the ability of pegloticaseto maintain uric acid concentrations below 7 mg/dL in patients with chronic gout. Data supporting reduction of gout flares are limited. Pegloticase is well tolerated but associated with gout flares and infusion reactions. Other adverse events include nausea, dizziness, and back pain. During Phase 3 trials, 2 patients in the pegloticase biweekly group and 1 in the monthly group experienced heart failure exacerbation; another patient in the monthly group experienced a nonfatal myocardial infarction. Providers should exercise caution before administering pegloticase to patients with cardiovascular disease. The cost burden and safety profile may limit its use in practice, in addition to limited data available to support decreases in patient-centered outcomes (eg, gouty attacks).CONCLUSIONS:Pegloticase is an effective option for patients with symptomatic gout for whom current uric acid-lowering therapies are ineffective or contraindicated.

PMID: 22395256 [PubMed - as supplied by publisher]

Effect of Medication Reconciliation on Medication Costs After Hospital Discharge in Relation to Hospital Pharmacy Labor Costs (March).

Ann Pharmacother. 2012 Mar 6;

Authors: Karapinar-Çarkit F, Borgsteede SD, Zoer J, Egberts TC, van den Bemt PM, van Tulder M

Abstract
BACKGROUND:Medication reconciliation aims to correct discrepancies in medication use between health care settings and to check the quality of pharmacotherapy to improve effectiveness and safety. In addition, medication reconciliation might also reduce costs.OBJECTIVE:To evaluate the effect of medication reconciliation on medication costs after hospital discharge in relation to hospital pharmacy labor costs.METHODS:A prospective observational study was performed. Patients discharged from the pulmonology department were included. A pharmacy team assessed medication errors prevented by medication reconciliation. Interventions were classified into 3 categories: correcting hospital formulary-induced medication changes (eg, reinstating less costly generic drugs used before admission), optimizing pharmacotherapy (eg, discontinuing unnecessary laxative), and eliminating discrepancies (eg, restarting omitted preadmission medication). Because eliminating discrepancies does not represent real costs to society (before hospitalization, the patient was also using the medication), these medication costs were not included in the cost calculation. Medication costs at 1 month and 6 months after hospital discharge and the associated labor costs were assessed using descriptive statistics and scenario analyses. For the 6-month extrapolation, only medication intended for chronic use was included.RESULTS:Two hundred sixty-two patients were included. Correcting hospital formulary changes saved €1.63/patient (exchange rate: EUR 1 = USD 1.343) in medication costs at 1 month after discharge and €9.79 at 6 months. Optimizing pharmacotherapy saved €20.13/patient in medication costs at 1 month and €86.86 at 6 months. The associated labor costs for performing medication reconciliation were €41.04/patient. Medication cost savings from correcting hospital formulary-induced changes and optimizing of pharmacotherapy (€96.65/patient) outweighed the labor costs at 6 months extrapolation by €55.62/patient (sensitivity analysis €37.25-71.10).CONCLUSIONS:Preventing medication errors through medication reconciliationresults in higher benefits than the costs related to the net time investment.

PMID: 22395255 [PubMed - as supplied by publisher]

Fidaxomicin for the Treatment of Clostridium difficile Infections (February).

Ann Pharmacother. 2012 Feb 7;

Authors: Whitman CB, Czosnowski QA

Abstract
OBJECTIVE:To evaluate the pharmacology, microbiology, safety, and efficacy of fidaxomicin for treatment of Clostridium difficile infections (CDI).DATA SOURCES:Literature was identified through Ovid MEDLINE (1948-December 2011) and International Pharmaceutical Abstracts (1970-December 2011) using the search terms fidaxomicin, OPT-80, PAR-101, OP-118, difimicin, tiacumicin, lipiarmycin, Clostridium difficile, Clostridium difficile infection, Clostridium difficile-associated diarrhea, and cost. Drug monographs were retrieved from manufacturers' Web pages, and the Red Book component of Micromedex wasused for cost information.STUDY SELECTION AND DATA EXTRACTION:All pertinent Phase 1, 2, and 3 studies published in English were included.DATA SYNTHESIS:Fidaxomicin is a macrocyclic compound bactericidal against C. difficile and inhibits toxin and spore production. It has poor oral absorption with high fecal concentrations. Available Phase 2 and 3 data with fidaxomicin 200 mgorally every 12 hours demonstrate similar effectiveness in treating CDI compared to oral vancomycin. Fidaxomicin was shown to have less frequency of recurrent infections. Adverse effects are uncommon and occur at similar rates as with oral vancomycin. The most frequently reported adverse effects are gastrointestinal, hematologic, and electrolyte disorders. Available data are lacking in several areas, including the efficacy and safety of fidaxomicin compared to established regimens for mild-to-moderate,life-threatening, and recurrent CDIs. The cost of a 10-day course of fidaxomicin is significantly more than that of metronidazole and vancomycin for treatment of mild-to-moderate CDI.CONCLUSIONS:Fidaxomicin appears to be an effective and safe alternative to oral vancomycin for treatment of mild-to-moderate and severe CDI. Data on its use compared to guideline-recommended therapies for mild-to-moderate and life-threatening CDI are needed. Further data assessing the cost-effectiveness of fidaxomicin are needed. Currently, it cannot be recommended over vancomycinfor treatment of CDI. However, it may be considered for treatment of recurrent infections.

PMID: 22318930 [PubMed - as supplied by publisher]

Evaluating Outcomes Associated with Alternative Dosing Strategies for Piperacillin/Tazobactam: A Qualitative Systematic Review (February).

Ann Pharmacother. 2012 Jan 24;

Authors: Mah GT, Mabasa VH, Chow I, Ensom MH

Abstract
OBJECTIVE:To perform a qualitative systematic review of the evidence comparing traditional strategies against prolonged intermittent or continuous infusion strategies for piperacillin/tazobactam, based on clinical and pharmacodynamic outcomes.DATA SOURCES:MEDLINE (1950-September 2011), EMBASE (1980-September 2011), and International Pharmaceutical Abstracts (1970-September 2011) were searched, using the terms piperacillin, tazobactam, pharmacokinetics, pharmacodynamics, dosing, and infusion. Reference lists from relevant publications were also reviewed.STUDY SELECTION AND DATA EXTRACTION:Articles evaluating the administration of piperacillin/tazobactam to adults and comparing at least 2 dosing regimens (1 of which included the traditional, manufacturer-recommended 30-minute infusion; the other, a prolonged or continuous infusion strategy) were included. Prespecified clinical outcomes of interest included mortality, clinical cures, and adverse events. The pharmacodynamic endpoint of interest was percent time of unbound drug concentration remaining above the minimum inhibitory concentration.DATA SYNTHESIS:Twelve studies were included in this review, 7 of which assessed clinical outcomes and 5 that assessed pharmacodynamic endpoints using Monte Carlo simulations. Prolonged or continuous infusions of piperacillin/tazobactam consistently achieved higher pharmacodynamic endpoints than did traditional infusions. The association of prolonged or continuous infusions with improved clinical outcomes, however, is unclear. Two retrospective studies found improved mortality rates with prolonged infusions (1 in a subgroup of patients with higher APACHE II [Acute Physiology and Chronic Health Evaluation II] scores), while another retrospective study found improved clinical cure rates with continuous infusions in patients with ventilator-associated pneumonia. These clinical benefits have not been substantiated in prospective randomized trials. No study has provided evidence of reduced adverse effects with prolonged or continuous infusions.CONCLUSIONS:The limited evidence available does not firmly support widespread adoption of administering piperacillin/tazobactam as prolonged intermittent or continuous infusions to improve clinical outcomes despite the achievement of higher pharmacodynamic targets in simulated studies. Retrospective studies indicate that critical care patients are the subgroup most likely to benefit from these dosing strategies. Well-designed prospective clinical trials are required to confirm potential benefits observed in retrospective studies.

PMID: 22274145 [PubMed - as supplied by publisher]

Ketamine in Adult Emergency Medicine: Controversies and Recent Advances (December).

Ann Pharmacother. 2011 Dec 6;

Authors: Sih K, Campbell SG, Tallon JM, Magee K, Zed PJ

Abstract
OBJECTIVE:To review the evidence for the use of ketamine in adult emergency medicine for procedural sedation and analgesia (PSA) and rapid sequence intubation (RSI), as well as to focus on the issues of recovery agitation, combination with propofol for PSA, and the use of ketamine as an induction agent in patients with acute head injury in need of definitive airway management.DATA SOURCES:PubMed (1949-July 2011), EMBASE (1980-July 2011), Google Scholar (to July 2011), International Pharmaceutical Abstracts (1964-July 2011), and Cochrane databases were searched independently. A manual search of references was also performed.STUDY SELECTION:English-language, full reports of experimental and observational studies evaluating ketamine in adults undergoing PSA and RSI in the emergency department (ED) were included if they reported efficacy or safety outcomes.DATA EXTRACTION:Two reviewers independently assessed each article for inclusion, data extraction, and study limitations.DATA SYNTHESIS:Six studies that used ketamine for PSA were included. The majority reported adequate sedation with high patient satisfaction and lack of pain and procedural recall. There is no evidence to support the superiority of a combination of ketamine and propofol compared to propofol alone for PSA in adults. Recovery agitation is common but can be minimized with premedicationwith midazolam (number needed to treat 6). Two studies were identified that evaluated the role of ketamine for induction during RSI in the ED. Although ketamine is not a first-line agent for RSI, it is an alternative and may be used as an induction agent in patients requiring endotracheal intubation.CONCLUSIONS:Ketamine is an effective agent in adults undergoing PSA and RSI in the ED. The best available evidence provides sufficient confidence to consider use of this agent in the ED.

PMID: 22147144 [PubMed - as supplied by publisher]

Takotsubo Cardiomyopathy as a Complication of Electroconvulsive Therapy (December).

Ann Pharmacother. 2011 Nov 24;

Authors: Sharp RP, Welch EB

Abstract
OBJECTIVE:To examine the evidence regarding takotsubo cardiomyopathy as a complication of electroconvulsive therapy (ECT).DATA SOURCES:Searches in MEDLINE, EMBASE, and International Pharmaceutical Abstracts (1966-August 2011) were conducted.STUDY SELECTION AND DATA EXTRACTION:Published studies and case reports that mentioned takotsubo cardiomyopathy following ECT were reviewed.DATA SYNTHESIS:Twelve case reports were available for review. There were 7 documented cases of takotsubo cardiomyopathy, 4 cases of myocardial stunning, and 1 case of cardiogenic shock following ECT. Although takotsubo cardiomyopathy was not mentioned in 5 of the cases, some clinical characteristics were consistent with this diagnosis. Left ventricular ejection fraction and the electrocardiogram returned to normal within a few days in the majority of the cases. All cases were in women, the majority of whom were postmenopausal (average age 64 years). Takotsubo cardiomyopathy developed after a single course of ECT in 6 of the cases, while the syndrome developed after more than 1 course in the other 6 cases. ECT was successfully readministered without syndrome recurrence in 4 of the cases, but only after 3 of the 4 patients received a ?-adrenergic receptor blocking agent prior to each subsequent therapy session. The ?-adrenergic blocking agents used were esmolol in 1 case and labetolol in the other 2.CONCLUSIONS:Takotsubo cardiomyopathy is a serious but transient potential complication of electroconvulsive therapy. Limited evidence indicates that ?-adrenergic receptor blocking agents may help prevent its reoccurrence in patients needing further electroconvulsive treatment. Health care providers in psychiatry should be aware of this potential complication of electroconvulsive therapy, especially in postmenopausal women. However, many questions remain regarding this issue.

PMID: 22116995 [PubMed - as supplied by publisher]

Beers Criteria as a Proxy for Inappropriate Prescribing of Other Medications Among Older Adults (November).

Ann Pharmacother. 2011 Oct 4;

Authors: Lund BC, Steinman MA, Chrischilles EA, Kaboli PJ

Abstract
BACKGROUND:The Beers criteria are a compilation of medications deemed potentially inappropriate for older adults, widely used as a prescribing quality indicator.OBJECTIVE:To determine whether Beers criteria serve as a proxy measure for other forms of inappropriate prescribing, as measured by comprehensive implicit review.METHODS:Data for patients 65 years and older were obtained from the Veterans Affairs Enhanced Pharmacy Outpatient Clinic (EPOC) and the Iowa Medicaid Pharmaceutical Case Management (PCM) studies. Comprehensive measurement of prescribing quality was conducted using expert clinician review of medical records according to the Medication Appropriateness Index (MAI). MAI scores attributable to non-Beers medications were contrasted between patients who did and did not receive a Beers criteria medication.RESULTS:Beers criteria medications accounted for 12.9% (EPOC) and 14.0% (PCM) of total MAI scores. Importantly, non-Beers MAI scores were significantly higher in patients receiving a Beers criteria medication in both studies (EPOC: 15.1 vs 12.4, p = 0.02; PCM:11.1 vs 8.7, p = 0.04), after adjusting for important confounding factors.CONCLUSIONS:Beers criteria utility extended beyond direct measurement of a limited set of inappropriate prescribing practices by serving as a clinically meaningful proxy for other inappropriate practices. Using prescribing quality indicators to guide interventions should thus identify patients for comprehensive medication review, rather than identifying specific medication targets for discontinuation. Future research should explore both the quality measurement and the intervention targeting applications of the Beers criteria, particularly when integrated with other indicators.

PMID: 21972251 [PubMed - as supplied by publisher]

Clinical outcomes of a collaborative, home-based postdischarge warfarin management service.

Ann Pharmacother. 2011 Mar;45(3):325-34

Authors: Stafford L, Peterson GM, Bereznicki LR, Jackson SL, van Tienen EC, Angley MT, Bajorek BV, McLachlan AJ, Mullan JR, Misan GM, Gaetani L

Abstract
BACKGROUND: Warfarin remains a high-risk drug for adverse events, especially following discharge from the hospital. New approaches are needed to minimize the potential for adverse outcomes during this period.
OBJECTIVE: To evaluate the clinical outcomes of a collaborative, home-based postdischarge warfarin management service adapted from the Australian Home Medicines Review (HMR) program.
METHODS: In a prospective, nonrandomized controlled cohort study, patients discharged from the hospital and newly initiated on or continuing warfarin therapy received either usual care (UC) or a postdischarge service (PDS) of 2 or 3 home visits by a trained, HMR-accredited pharmacist in their first 8 to 10 days postdischarge. The PDS involved point-of-care international normalized ratio (INR) monitoring, warfarin education, and an HMR, in collaboration with the patient's general practitioner and community pharmacist. The primary outcome measure was the combined incidence of major and minor hemorrhagic events in the 90 days postdischarge. Secondary outcome measures included the incidences of thrombotic events, combined hemorrhagic and thombotic events, unplanned and warfarin-related hospital readmissions, death, INR control, and persistence with therapy at 8 and 90 days postdischarge.
RESULTS: The PDS (n=129) was associated with statistically significantly decreased rates of combined major and minor hemorrhagic events to day 90 (5.3% vs 14.7%; p=0.03) and day 8 (0.9% vs 7.2%; p=0.01) compared with UC (n=139). The rate of combined hemorrhagic and thrombotic events to day 90 also decreased (6.4% vs 19.0%; p=0.008) and persistence with warfarin therapy improved (95.4% vs 83.6%; p=0.004). No significant differences in readmission and death rates or INR control were demonstrated.
CONCLUSIONS: This study demonstrated the ability of appropriately trained accredited pharmacists working within the Australian HMR framework to reduce adverse events and improve persistence in patients taking warfarin following hospital discharge. Widespread implementation of such a service has the potential to enhance medication safety along the continuum of care.

PMID: 21386021 [PubMed - indexed for MEDLINE]

Incidence of Hospitalized Rhabdomyolysis with Statin and Fibrate Use in an Insured US Population (October).

Ann Pharmacother. 2011 Sep 13;

Authors: Amend KL, Landon J, Thyagarajan V, Niemcryk S, McAfee A

Abstract
BACKGROUND:The incidence of hospitalized rhabdomyolysis is not well characterized among patients taking statin-fibrate combination therapies.OBJECTIVE:To estimate and compare the rates of hospitalized rhabdomyolysis during periods of exposure to different statins and fibrates.METHODS:We retrospectively identified a cohort of patients who initiated a statin or fibrate between January 1, 1998, and December 31, 2007, using a database of a large US health insurer. Patients were followed for the occurrence of hospitalized rhabdomyolysis, determined by clinical review of medical records. Exposure status during the study period was determined by electronic records of statin and fibrate dispensing. Incidence rates (IRs) and incidence rate ratios (IRRs) for various combinations of fibrate and statin exposure were modeled, using Poisson regression.RESULTS:There were 1,116,805 patients who initiated statin and/or fibrate therapy, with 2.4 million person-years of observation. Seventy cases of hospitalized rhabdomyolysis were confirmed. Adjusted analyses showed a persistent increased risk of rhabdomyolysis with combination therapy, while statin and fibrate therapy alone showed similar, nonsignificant increases in risk. The adjusted IRR for a statin and fenofibrate was 3.26 (95% CI 1.21 to 8.80), while the adjusted IRR for a statinand gemfibrozil was 11.93 (95% CI 3.96 to 35.93) versus statin therapy alone. The individual IRs for statin monotherapy ranged from 0.00 to 3.34 per 100,000 person-years. The number needed to harm was lower for combination statin-gemfibrozil therapy (2753) compared with that for statin therapy alone (454,545).CONCLUSIONS:The incidence of hospitalized rhabdomyolysis is rare, but higher in patients with concomitant statin-fibrate treatment than in patients on statin therapy alone. The rate found in this study is consistent with the known profile of the statin-fibrate treatment option for mixed dyslipidemia.

PMID: 21917557 [PubMed - as supplied by publisher]

Evaluation of the Accuracy of a Pharmacokinetic Dosing Program in Predicting Serum Vancomycin Concentrations in Critically Ill Patients (October).

Ann Pharmacother. 2011 Sep 6;

Authors: Aubron C, Corallo CE, O Nunn M, Dooley MJ, Cheng AC

Abstract
BACKGROUND:Optimization of the timing of appropriate antibiotics is crucial to improve the management of patients in severe sepsis and septic shock. Vancomycin is commonly used empirically in cases of nosocomial infections in critically ill patients. Therefore, early optimization of vancomycin pharmacokinetics is likely to improve outcomes.OBJECTIVE:To evaluate a pharmacokinetic program to predict serum vancomycin concentrations in accordance with administered dose, weight, height, and creatinine clearance in a critically ill population.METHODS:We conducted a prospective observational single-center study in a 45-bed intensive care unit (ICU). All patients hospitalized in the ICU requiring intravenous treatment with vancomycin for a suspected infection were enrolled. The modalities of vancomycin therapy and the monitoring of serum concentrations were left to the discretion of the treating clinician. We compared the measured serum vancomycin concentrations with those predicted by the MM-USCPACK program and analyzed the factors influencing the prediction.RESULTS:Fifty-four intravenous vancomycin courses were administered in 48 critically ill patients over the 3-month study. The precision was considered acceptable, based on a relative precision equal to 8.9% (interquartile range 3.5-18.9%) and the relative bias for all predictions was equal to -1.3%. Overall, 77.3% of predictions were within 20% of observed concentrations; factors correlating with a poorer prediction were a change in renal function, obesity, and the magnitude of organ dysfunction on initiation of vancomycin (expressed by a Systemic Organ Failure Assessment score >11).CONCLUSIONS:The MM-USCPACK program is a useful and reliable tool for prediction of serum vancomycin concentrations in patients hospitalized in ICU and likely reflects the close monitoring of renal function in this setting. For some patients (more severely ill, obese, or significant change in renal function during vancomycin therapy), predictions were less precise.

PMID: 21896920 [PubMed - as supplied by publisher]