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In a national sample of Medicare nursing home residents with dementia treated with bisphosphonates, 20% had bisphosphonates deprescribed. Residents with clinical characteristics representing decreased likelihood for long-term benefit were more likely to have bisphosphonates deprescribed. Future studies are needed to evaluate outcomes of deprescribing bisphosphonates in this population. To determine incidence of deprescribing bisphosphonates among nursing home (NH) residents with dementia and identify factors associated with deprescribing. 2015–2016 Medicare claims, Part D prescriptions, Minimum Data Set (MDS) 3.0, and Nursing Home Compare for non-skilled NH residents aged 65 + with dementia and prescriptions for oral bisphosphonates overlapping the first 14 days of the stay. Our primary definition for deprescribing was a 90-day gap in medication supply; we also explored the reliability of different deprescribing definitions (30-, 90-, 180-day gaps). We estimated associations of NH, provider, and resident characteristics with deprescribing bisphosphonates using competing risks regression models. Most NH residents with dementia treated with bisphosphonates (n = 5312) were ≥ 80 years old (72%), white (81%), and female (90%); about half were dependent for transfers (50%) or mobility (45%). Using a 90-day gap in supply, the 180-day cumulative incidence of deprescribing bisphosphonates was 14.8%. This increased to 32.1% using a 30-day gap and decreased to 11.7% using a 180-day gap. Factors associated with increased likelihood for bisphosphonate deprescribing were age ≥ 90 years, newly admitted (vs. prevalent stay), dependent for mobility, swallowing difficulty, > 1 hospitalization in the prior year, CCRC facility, and nurse practitioner primary provider (vs. physician). Cancer and western geographic region were associated with reduced likelihood for deprescribing. In a national sample of NH residents with dementia, bisphosphonate deprescribing was uncommon, and associated with clinical characteristics signifying poor prognosis and decreased likelihood for long-term benefit. Future studies should evaluate clinical outcomes of deprescribing bisphosphonates in this population.

Hyaluronic acid intraarticular injections are gel-like medical devices used in osteoarthritis. Patients may only experience modest improvement with these devices, which may be reclassified as medications in the United States (US). Medications may require more testing than devices, and device adverse event reporting in the US has come under scrutiny. We undertook an exploratory analysis of fatal adverse events for these injections in the US. We reviewed all adverse events reported to the US Manufacturer and User Facility Device Experience and Alternative Summary Reporting databases between 2014 and 2019 under the relevant product names and product codes. Reports assigned an outcome of “death” were retained, as were reports that were found to pertain to fatality after review. Of 3449 reports, 103 were found to pertain to 63 distinct fatalities. In 54 of these fatalities, the cause of death was stated to be unknown in narratives. We judged that eight fatalities may have had a logical nexus to device use; six of these fatalities were associated with infection. Low-quality information in reports suggests that the US should review its medical device adverse event reporting processes and providers who administer hyaluronic acid intraarticular injections should use meticulous aseptic technique.

BACKGROUND/OBJECTIVES Geriatric guidelines recommend against statin use in older adults with limited life expectancy (LLE) or advanced dementia (AD). This study examined resident and facility factors predicting statin discontinuation after nursing home (NH) admission in veterans with LLE/AD taking statins for secondary prevention. DESIGN Retrospective cohort study of Veterans Affairs (VA) bar code medication administration records, Minimum Data Set (MDS) assessments, and utilization records linked to Medicare claims. SETTING VA NHs, known as community living centers (CLCs). PARTICIPANTS Veterans aged 65 and older with coronary artery disease, stroke, or diabetes mellitus, type II, admitted in fiscal years 2009 to 2015, who met criteria for LLE/AD on their admission MDS and received statins in the week after admission (n = 13,110). MEASUREMENTS Residents were followed until statin discontinuation (ie, gap in statin use ≥14 days), death, or censoring due to discharge, day 91 of the stay, or end of the study period. Competing risk models assessed cumulative incidence and predictors of discontinuation, stratified by whether the resident had their end-of-life (EOL) status designated or used hospice at admission. RESULTS Overall cumulative incidence of statin discontinuation was 31% (95% confidence interval [CI] = 30%-32%) by day 91, and it was markedly higher in those with (52%; 95% CI = 50%-55%) vs without (25%; 95% CI = 24%-26%) EOL designation/hospice. In patients with EOL designation/hospice (n = 2,374), obesity, congestive heart failure, and admission from nonhospital settings predicted decreased likelihood of discontinuation; AD, dependency in activities of daily living, greater number of medications, and geographic region predicted increased likelihood of discontinuation. In patients without EOL designation/hospice (n = 10,736), older age and several specific markers of poor prognosis predicted greater discontinuation, whereas obesity/overweight predicted decreased discontinuation. CONCLUSION Most veterans with LLE/AD taking statins for secondary prevention do not discontinue statins following CLC admission. Designating residents as EOL status, hospice use, and individual clinical factors indicating poor prognosis may prompt deprescribing.

PurposeTo examine the reporting rates of adverse drug events (ADEs) with apixaban and empagliflozin as reports move up to the next level of spontaneous reporting.MethodsThis was a retrospective cohort study of outpatients who discontinued apixaban or empagliflozin within 3 years of Food and Drug Administration (FDA) approval. We enriched the sample using an active surveillance strategy to identify subsets of patients with International Classification of Diseases (ICD) codes possibly associated with an ADE. Stratified random samples of charts were reviewed to determine if patients discontinued the medication due to an ADE. If so, we ascertained whether these were uploaded into the Veterans Administration (VA) electronic health record reporting system (Adverse Reaction Tracking System [ARTS]), VA national Web-based system (VA Adverse Drug Event Reporting System [VA ADERS]), and FDA MedWatch.ResultsFrom the cohort of 2,973 patients who discontinued apixaban, 321 patients (10.8%) were randomly sampled for chart review (including 61 patients with relevant ICD codes). During chart review, 88 ADEs were identified, with 40/61 (65.6%) from the subset with ICD codes. Of the total of 88 ADEs, 18.2%, 10.2%, and 6.8% were reported in ARTS, VA ADERS, and MedWatch, respectively. Of the 1,555 patients who discontinued empagliflozin, 179 patients (11.5%) were randomly sampled for chart review (40 patients with relevant ICD codes). During chart review, 78 ADEs were identified, with 19/40 (47.5%) from the subset with ICD codes. Of the 78 ADEs, 28.2%, 19.2%, and 7.7% were reported in ARTS, VA ADERS, and MedWatch, respectively.ConclusionWe found substantial underreporting of apixaban and empagliflozin ADEs that became worse at each higher level of spontaneous reporting.

Purpose Many medications that were marketed prior to 1962 but lack Food and Drug Administration (FDA) approval are prescribed in the United States. Usage patterns of these “unapproved medications” are poorly elucidated, which is concerning due to potential lack of data on safety and efficacy. The purpose of this project was to characterize purchases of unapproved medications within the Veterans Health Administration (VHA) by type, frequency, and cost. Methods VHA purchasing databases were used to create a list of all products with National Drug Codes (NDCs) purchased nationwide in fiscal year 2016 (FY16). This list was compared to FDA databases to identify unapproved prescription medications. For each identified combination of active pharmaceutical ingredient (API) and route of administration (“API/route combination”), numbers of packages purchased and associated costs were added. Results VHA pharmacy purchasing records contained 3,299 unapproved products with NDCs in FY16. After excluding equipment, nutrition products, compounding ingredients, nonmedication products, and duplicate NDCs, there were 600 unique NDCs associated with 130 distinct API/route combinations. The most commonly acquired product was prescription sodium fluoride dental paste (350,775 packages). The greatest pharmaceutical expenditure was for sodium hyaluronate injection ($24.5 million). Unapproved products accounted for less than 1% of overall VHA pharmacy purchasing in FY16. Conclusion VHA purchased many unapproved prescription products in FY16 but is taking action to address use of such products in consideration of safety and efficacy data and available alternatives.

Background/objective Uncertainty regarding benefits and risks associated with acetylcholinesterase inhibitors (AChEIs) in severe dementia means providers do not know if and when to deprescribe. We sought to identify which patient-, provider-, and system-level characteristics are associated with AChEI discontinuation. Design Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS), version 3.0, Area Health Resource File, and Nursing Home Compare. Cox-proportional hazards models with time-varying covariates were used to identify patient-, provider-, and system-level factors associated with AChEI discontinuation (30-day or more gap in supply). Setting US Medicare-certified nursing homes (NHs). Participants Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). Results The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). The most commonly prescribed AChEIs were donepezil (77.8%), followed by transdermal rivastigmine (14.6%). The cumulative incidence of AChEI discontinuation was 29.7% at the end of follow-up (330 days), with mean follow-up times of 194 days for continuous users of AChEIs and 105 days for those who discontinued. Factors associated with increased likelihood of discontinuation were new admission, older age, difficulty being understood, aggressive behavior, poor appetite, weight loss, mechanically altered diet, limited prognosis designation, hospitalization in 90 days prior, and northeastern region. Factors associated with decreased likelihood of discontinuation included memantine use, use of strong anticholinergics, polypharmacy, rurality, and primary care prescriber vs geriatric specialist. Conclusion Among NH residents with severe dementia being treated with AChEIs, the cumulative incidence of AChEI discontinuation was just under 30% at 1 year of follow-up. Our findings provide insight into potential drivers of deprescribing AChEIs, identify system-level barriers to deprescribing, and help to inform covariates that are needed to address potential confounding in studies evaluating the potential risks and benefits associated with deprescribing. J Am Geriatr Soc 67:1871-1879, 2019.

Clinicians struggle with whether to prescribe osteoporosis medications for fracture prevention for older nursing home (NH) residents with dementia, given the lack of evidence in this population. To better understand real-world clinical practice, we conducted a retrospective cohort study examining patterns of fracture prevention medication use for older NH residents with dementia and high fracture risk. Data sources included 2015-16 Medicare claims, Part D prescriptions, and Minimum Data Set (MDS) assessments. Among NH residents aged 65+ with dementia and prior fracture or high fracture risk based on the MDS FRAiL (Fracture Risk Assessment in Long-term care), we assessed medications for fracture prevention using prescription data from 1 year prior through 90 days after the first MDS assessment. Multivariable logistic regression was used to evaluate factors associated with receiving treatment. Most of the sample (n = 72,639) was80 years (78%), female (82%), and white (88%); 63% had moderate/severe dementia and 60% had an osteoporosis diagnosis. Only 11.6% received fracture prevention medications. In adjusted analyses, treated residents were more likely to be female, Hispanic or other non-black minority,90 years old, and newly admitted to the NH. Other associated factors included osteoporosis diagnosis, walker or wheelchair use, bone disorders (eg, Paget disease),5 medications, steroid or proton pump inhibitor use, and regions outside of the Northeast. Resident characteristics suggestive of comorbidity burden and worsening dementia were associated with reduced likelihood of treatment. Low use of fracture prevention medications for NH residents with dementia may reflect an attempt by prescribers reconcile medication use with changing goals of care, or inappropriate underuse in patients who still have high fracture risk. Additional research is needed to help clinicians better evaluate when to use these medications in this heterogeneous and vulnerable population.

The objective of this study was to evaluate the association between fluoroquinolone (FQ) use and the occurrence of aortic aneurysm/dissection (AA/AD), acute myocardial infarction (AMI), ventricular arrhythmias (VenA), and all‐cause mortality vs other commonly used antibiotics. We conducted a self‐controlled case series analysis of patients who experienced the outcomes of AA/AD, AMI, and VenA, based on diagnosis codes from emergency department visits and hospitalizations within Veterans Health Administration, and death in FY2014‐FY2018. These Veterans also received outpatient prescriptions for FQs. Conditional Poisson regression models were used to estimate the association between FQs and each of the outcomes vs antibiotics of interest (ie amoxicillin or amoxicillin/clavulanate, azithromycin, doxycycline, cefuroxime or cephalexin, or sulfamethoxazole‐trimethoprim), adjusted for time‐varying covariates. Using a 30‐day risk period after each antibiotic prescription, adjusted incidence rate ratios (aIRRs) for FQs vs each comparator antibiotic were not statistically different for outcomes of VenA or AMI. For AA/AD, incidence was higher during FQ risk periods vs amoxicillin [aIRR 1.50 (95% CI 1.01, 2.25)] and azithromycin [aIRR 2.15 (95% CI 1.27, 3.64)] risk periods. A significantly increased risk of mortality was observed with FQs vs each antibiotic of interest. FQs were associated with an increased risk of AA/AD vs amoxicillin and azithromycin and an increased risk of all‐cause mortality vs multiple antibiotics commonly used for outpatient infections. Although the differences in event rates are small, FQ use should be limited to serious infections without appropriate alternatives.

Background Accurate monitoring of intravenous unfractionated heparin (UFH) is essential to mitigate the risk of adverse drug events associated with dosing errors. Although recent data support anti-factor Xa (anti-Xa) monitoring preferentially over activated partial thromboplastin time (aPTT) to improve time to therapeutic anticoagulation, the utility of incorporating anti-Xa monitoring with a calculation-free weight-based UFH nomogram has not been formally evaluated. Objective The primary objective of this study was to evaluate the time to therapeutic anticoagulation of a calculation-free weight-based UFH nomogram integrated with anti-Xa monitoring versus a historical control of aPTT monitoring utilizing manual dose calculations. Methods This was a retrospective analysis of patients with anti-Xa monitoring and a novel calculation-free weight-based UFH nomogram compared with a historical control with aPTT monitoring and manual calculations. Results A total of 103 patients in the aPTT cohort and 100 patients in the anti-Xa cohort were analyzed. The anti-Xa cohort achieved goal therapeutic target 3.8 hours sooner than the aPTT cohort ( P = 0.03). Patients with anti-Xa monitoring required 1 fewer adjustment per 2.5 patient-days of UFH with the venous thromboembolism nomogram ( P = 0.02). Patients in the aPTT cohort required more infusion interruptions because of supratherapeutic values ( P = 0.007) and boluses because of subtherapeutic values ( P = 0.044). There were no differences in rates of thromboembolism, major bleeding, or clinically relevant nonmajor bleeding between the cohorts. Conclusion and Relevance This study demonstrated that anti-Xa UFH monitoring integrated with a calculation-free nomogram results in faster time to therapeutic anticoagulation and fewer dose adjustments compared with aPTT monitoring with manual calculations.

INTRODUCTION We evaluated the impact of deprescribing acetylcholinesterase inhibitors (AChEIs) on aggressive behaviors and incident antipsychotic use in nursing home (NH) residents with severe dementia. METHODS We conducted a retrospective study of Medicare claims, Part D, Minimum Data Set for NH residents aged 65+ with severe dementia receiving AChEIs in 2016. Aggressive behaviors were measured using the aggressive behavior scale (ABS; n = 30,788). Incident antipsychotic prescriptions were evaluated among antipsychotic non-users (n = 25,188). Marginal structural models and inverse probability of treatment weights were used to evaluate associations of AChEI deprescribing and outcomes. RESULTS The severity of aggressive behaviors was low at baseline (mean ABS = 0.5) and was not associated with deprescribing AChEIs (0.002 increase in ABS, P = .90). Incident antipsychotic prescribing occurred in 5.1% of residents and was less likely with AChEI deprescribing (adjusted odds ratio = 0.52 [0.40-0.68], P

Objectives Continuation of aspirin for secondary prevention in persons with limited life expectancy (LLE) is controversial. We sought to determine the incidence and predictors of aspirin discontinuation in veterans with LLE and/or advanced dementia (LLE/AD) who were taking aspirin for secondary prevention at nursing home admission, stratified by whether their limited prognosis (LP) was explicitly documented at admission. Design Retrospective cohort study using linked Veterans Affairs (VA) and Medicare clinical/administrative data and Minimum Data Set resident assessments. Setting All VA nursing homes (referred to as community living centers [CLCs]) in the United States. Participants Older (≥65 y) CLC residents with LLE/AD, admitted for 7 days or longer in fiscal years 2009 to 2015, who had a history of coronary artery disease and/or stroke/transient ischemic attack, and used aspirin within the first week of CLC admission (n = 13 844). Measurements The primary dependent variable was aspirin discontinuation within the first 90 days after CLC admission, defined as 14 consecutive days of no aspirin receipt. Independent variables included an indicator for explicit documentation of LP, sociodemographics, environment of care characteristics, cardiovascular risk factors, bleeding risk factors, individual markers of poor prognosis (eg, cancer, weight loss), and facility characteristics. Fine and Gray subdistribution hazard models with death as a competing risk were used to assess predictors of discontinuation. Results Cumulative incidence of aspirin discontinuation was 27% (95% confidence interval [CI] = 26%-28%) in the full sample, 34% (95% CI = 33%-36%) in residents with explicit documentation of LP, and 24% (95% CI = 23%-25%) in residents with no such documentation. The associations of independent variables with aspirin discontinuation differed in residents with vs without explicit LP documentation at admission. Conclusion Just over one-quarter of patients discontinued aspirin, possibly reflecting the unclear role of aspirin in end of life among prescribers. Future research should compare outcomes of aspirin deprescribing in this population. J Am Geriatr Soc 68:725-735, 2020.

Objectives To examine the association between central nervous system (CNS) medication dosage burden and risk of serious falls, including hip fractures, in individuals with a history of a recent fall. Design Nested case–control study. Setting Veterans Health Administration (VHA) Community Living Centers (CLCs). Participants CLC residents aged 65 and older with a history of a fall or hip fracture in the year before a CLC admission between July 1, 2005, and June 30, 2009. Each case (n = 316) was matched to four controls (n = 1264) on age, sex, and length of stay. Measurements Outcomes were serious falls identified using International Classification of Diseases, Ninth Revision (ACD‐9) or Current Procedural Terminology (CPT) E codes, diagnosis codes, or procedure codes associated with a VHA emergency department visit or hospitalization during the CLC stay. Bar code medication administration data were used to calculate CNS standardized daily doses (SDDs) for opioid and benzodiazepine receptor agonists, some antidepressants, antiepileptics, and antipsychotics received in the 6 days before the outcome date by dividing residents' actual CNS daily doses by the minimum effective geriatric daily doses and adding the results. Multivariable conditional logistic regression models were used to evaluate the association between total CNS medication dosage burden, categorized as 0, 1 to 2, and 3 or more SDDs, and the outcome of recurrent serious falls. Results More cases (44.3%) than controls (35.8%) received 3.0 or more CNS SDDs (p = .02). Risk of serious falls was greater in residents with 3.0 or more SDDs than in those with 0 (adjusted odds ratio (aOR)=1.49, 95% confidence interval (CI)=1.03–2.14). Those with 1.0 to 2.9 SDDs had a risk similar to that of those with 0 SDDs (aOR=1.03, 95%CI=0.72–1.48). Conclusion Nursing home residents with a history of a fall or hip fracture receiving 3.0 or more CNS SDDs were more likely to have a recurrent serious fall than those taking no CNS medications. Interventions targeting this vulnerable population may help reduce serious falls. J Am Geriatr Soc 67:74–80, 2019.

Background Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSAB) cause significant mortality and often require extended antibiotic therapy. Vancomycin, the most common initial MRSAB treatment, carries significant monitoring burden and nephrotoxicity risks. We compared cost-effectiveness of vancomycin and other antibiotic regimens as MRSAB treatment. Methods We estimated cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin, dalbavancin) for Veterans Health Administration (VA) patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure and adverse drug event (ADE)-related discontinuation at 7-days. Results In base-case analyses, linezolid and daptomycin were less expensive and had fewer treatment failures than other regimens at 4 and 6-weeks. Compared to linezolid, daptomycin incremental cost-effectiveness ratios were ~$45,000 (4-weeks) and ~$61,000 (6-weeks) per composite failure avoided, respectively. In one-way sensitivity analyses, daptomycin (4-weeks) was favored over linezolid if linezolid microbiological failure or ADE-related discontinuation rates were >14.8% (base case: 14.0%) or >14.3% (base case: 14.0%), respectively, assuming a willingness to pay (WTP) threshold of $40,000/ composite treatment failure avoided. Vancomycin was favored if its microbiological failure risk was < 16.4% (base case: 27.2%). In two-way sensitivity analyses, daptomycin was favored if linezolid microbiological failure and ADE-related discontinuation rates were >19% and > 16%, respectively. Linezolid, daptomycin and vancomycin were favored in 47%, 39%, and 11% of 4-week probabilistic iterations, respectively, at $40,000 WTP. Conclusion Daptomycin or linezolid are likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed to support safety of linezolid in MRSAB patients. Disclosures Cornelius J. Clancy, MD, Astellas (Consultant, Grant/Research Support)Cidara (Consultant, Research Grant or Support)Melinta (Grant/Research Support)Merck (Consultant, Grant/Research Support)Needham Associates (Consultant)Qpex (Consultant)Scynexis (Consultant)Shionogi (Consultant)

BACKGROUND/OBJECTIVE: Reevaluation of the appropriateness of acetylcholinesterase inhibitors (AChEIs) is recommended in older adults with severe dementia, given the lack of strong evidence to support their continued effectiveness and risk for medication-induced adverse events. We sought to evaluate the impact of deprescribing AChEIs on risk of all-cause events (hospitalizations, emergency department visits, and mortality) and serious falls or fractures in older nursing home (NH) residents with severe dementia. DESIGN: Analysis of 2015 to 2016 data from Medicare claims, Part D prescriptions, Minimum Data Set (MDS) version 3.0, Area Health Resource File, and Nursing Home Compare. Marginal structural models with inverse probability of treatment weights were used to evaluate the association of deprescribing AChEIs and all-cause negative events as well as serious falls or fractures. SETTING: US Medicare certified NHs. PARTICIPANTS: Nonskilled NH residents, aged 65 years and older, with severe dementia receiving AChEIs within the first 14 days of an MDS assessment in 2016 (n = 37 106). RESULTS: The sample was primarily white (78.7%), female (75.5%), and aged 80 years or older (77.4%). Deprescribing AChEIs was associated with an increased likelihood of all-cause negative events in unadjusted models (odds ratio [OR] = 1.17; 95% confidence interval [CI] = 1.11-1.23; P < .01), but not in fully adjusted models (adjusted OR [aOR] = 1.00; 95% CI = 0.94-1.06; P = .94). By contrast, deprescribing was associated with a reduced likelihood of serious falls or fractures in unadjusted models (OR = 0.59; 95% CI = 0.52-0.66; P < .001) and remained significant in adjusted models (aOR = 0.64; 95% CI = 0.56-0.73; P < .001). CONCLUSION: Deprescribing AChEIs was not associated with a significant increase in the likelihood for all-cause negative events and was associated with a reduced likelihood of falls and fractures in older NH residents with dementia. Our findings suggest that deprescribing AChEIs is a reasonable approach to reduce the risk of serious falls or fractures without increasing the risk for all-cause events. J Am Geriatr Soc 68:699-707, 2020.

PURPOSE The results of a study to assess the effectiveness and safety of hyperglycemia management provided by clinical pharmacy specialists (CPSs) versus usual care in outpatients with diabetes from 53 Veterans Affairs (VA) medical centers are reported. METHODS An historical cohort study of outpatients with baseline glycosylated hemoglobin (HbA1c) values of >9% who were referred to a CPS for management of hyperglycemia and primary care patients who were not referred to a CPS was conducted. The primary outcomes were change in HbA1c over time and time to reach an HbA1c value of

Background The objective of this study is to describe the use of targeted therapies for the treatment of advanced renal cell carcinoma (RCC) and overall survival (OS) among patients in clinical practice in the Veterans Health Administration (VHA). Methods A retrospective cohort of 286 patients from 24 VHA Medical Centers diagnosed with advanced clear cell RCC between Fiscal Year (FY) 2010 and FY2014 was followed through September 30, 2016. Among patients who received targeted therapy, we described the medications taken, duration of therapy, and overall survival. We also assessed the effect of the first therapy received on overall survival using Cox Proportional Hazards models. Results There were 66 patients who did not receive therapy for their advanced RCC. Of the 220 treated patients, the mean (sd) number of medications received was 1.9 (1.1). The medications most commonly used first were sunitinib (61.8%), pazopanib (17.3%), and temsirolimus (10.9%). The median duration of first‐line therapy was 86 days (interquartile range [IQR] 42, 210). Median total duration of therapy was 159 days (IQR 58, 397). 62.3% of patients had ≥ 1 dose of therapy held or reduced, mainly due to an adverse drug event (ADE). Median survival from the start of treatment to death was 1.08 years (IQR 0.80, 1.31). Finally, receipt of temsirolimus vs sunitinib (HR 1.95 [95%CI 1.09,3.47]) as the first targeted therapy was independently associated with an increased hazard of death. Conclusion Our analysis of targeted therapies for advanced RCC in VHA suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and ADEs are more common., Our analysis of targeted therapies for advanced renal cell carcinoma in Veterans Health Administration suggests duration of treatment is shorter in a real‐world setting than in clinical trials, and dose reductions and adverse drug events are more common.

Aims We compared the risk of mental health episodes requiring hospitalization (primary aim) or out-patient clinic visits (secondary aim) associated with varenicline versus the nicotine patch (NP) in an era prior to psychiatric boxed warnings. Design Retrospective cohort. Setting Department of Veterans Affairs (VA), USA. Participants VA patients with or without psychiatric comorbidities and a new prescription for varenicline (15 255) were propensity score-matched (1 : 2) to new users of NP (123 054) between 1 May 2006 and 30 September 2007, resulting in 11 774 and 23 548 patients in the varenicline and NP groups, respectively. Measurements The primary outcomes were hospitalizations with a primary discharge diagnosis of a range of mental health disorders: depression, schizophrenia, bipolar disorder, suicide attempt, post-traumatic stress disorder, other psychosis and drug-induced mental disorders. Secondary outcomes were out-patient clinic visits with a primary diagnosis of the above list of mental health disorders. Findings Background characteristics of the treatment groups were similar after matching. There was no statistically significant difference in risk of hospitalization for any of the studied mental health disorders with varenicline compared with NP. Among secondary outcomes there was an increased risk of out-patient clinic visits for schizophrenia among patients who received varenicline [hazard ratio (HR) = 1.27; 95% confidence interval (CI) = 1.07, 1.51], this increase being evident only in those with a pre-existing mental health disorder. Conclusion In US VA patients studied prior to the boxed warning being implemented, use of varenicline for smoking cessation was not associated with a detectable increase compared with nicotine patches in hospitalization for any mental health outcomes. There was an increased rate of out-patient attendances with a primary diagnosis of schizophrenia amounting to five per 100 person years of treatment. This increase was found only in patients with a pre-existing mental health disorder.

Background/Objectives: Identifying patients with limited life expectancy (LLE) in nursing homes (NH) is important to aid in appropriate care planning. The Minimum Data Set (MDS) Mortality Risk Index – Revised (MMRI-R) is a validated scale using MDS v2.0 assessment items to generate scores predicting 6-month mortality in NH residents. In transitioning from MDS v2.0 to v3.0, several items were changed or removed, putting into question translatability of this measure across MDS versions. Objectives were to: 1) evaluate the predictive validity of an adapted version of the MMRI-R based on MDS v3.0 assessment items (MMRI-v3) and 2) compare the predictive validity of the MMRI-v3 to a single MDS item indicating LLE. DESIGN: Retrospective, cross-sectional study of MDS assessments. Other data sources included the VA Residential History File and VA Vital Status File. SETTING: VA NHs PARTICIPANTS: Older adult Veterans ≥ 65 years old newly admitted to VA NHs between 07/01/2012-09/30/2015 MEASUREMENTS: The dependent variable was death within six months of admission date. Independent variables included MDS items used to calculate MMRI-v3 scores (renal failure, chronic heart failure, sex, age, dehydration, cancer, unintentional weight loss, shortness of breath, activities of daily living scale, poor appetite, acute change in mental status) and the MDS item indicating LLE. RESULTS: The MMRI-v3 has good predictive ability for 6-month mortality compared to the original MMRI-R (c-statistic=0.81 vs 0.76). Scores generated by the MMRI-v3 showed greater predictive ability than the single MDS indicator for LLE (c-statistic=0.76), but using the two together resulted in further increases in predictive ability (c-statistic=0.86). CONCLUSIONS: The MMRI-v3 is a useful tool in research and clinical practice that accurately predicts 6-month mortality in Veterans residing in VA NHs. Identification of residents with LLE has great utility for studying palliative care interventions and may be helpful in guiding allocation of these services in clinical practice.

PurposeResults of a study to estimate the prevalence of look-alike/sound-alike (LASA) medication errors through analysis of Veterans Affairs (VA) administrative data are reported.MethodsVeterans with at least 2 filled prescriptions for 1 medication in 20 LASA drug pairs during the period April 2014–March 2015 and no history of use of both medications in the preceding 6 months were identified. First occurrences of potential LASA errors were identified by analyzing dispensing patterns and documented diagnoses. For 7 LASA drug pairs, potential errors were evaluated via chart review to determine if an actual error occurred.ResultsAmong LASA drug pairs with overlapping indications, the pairs associated with the highest potential-error rates, by percentage of treated patients, were tamsulosin and terazosin (3.05%), glipizide and glyburide (2.91%), extended- and sustained-release formulations of bupropion (1.53%), and metoprolol tartrate and metoprolol succinate (1.48%). Among pairs with distinct indications, the pairs associated with the highest potential-error rates were tramadol and trazodone (2.20%) and bupropion and buspirone (1.31%). For LASA drug pairs found to be associated with actual errors, the estimated error rates were as follows: lamivudine and lamotrigine, 0.003% (95% confidence interval [CI], 0–0.01%); carbamazepine and oxcarbazepine, 0.03% (95% CI, 0–0.09%); and morphine and hydromorphone, 0.02% (95% CI, 0–0.05%).ConclusionThrough the use of administrative databases, potential LASA errors that could be reviewed for an actual error via chart review were identified. While a high rate of potential LASA errors was detected, the number of actual errors identified was low.

Deprescribing, which includes stopping or reducing the dosage of medications, is designed to improve safety and prevent adverse drug reactions in older patients. To date, there has been limited work on measuring decreases in dosage intensity, or deintensification, across therapeutic classes of medications. Given the ongoing focus on central nervous system (CNS) medications and the frequency with which providers encounter hypertension and diabetes in older nursing home patients, the objective of this expert review is to describe and critique innovative composite dosage intensity measures that have been, or could be, applied to quantify deintensification within three therapeutic medication targets commonly encountered in nursing home patients: CNS agents, antihypertensive therapy, and antidiabetic therapy and the extent to which they are associated with health outcomes. Composite measures for CNS medication intensity considered dividing a patient’s daily dose by defined daily dosage (DDD), or the minimum effective adult or geriatric daily dosage. In contrast, composite measures for antihypertensives used either DDD or maximum recommended daily dosage in the denominator. We were not able to identify any composite measure of intensity for antidiabetic classes. There was a paucity of interventional studies that showed reducing the dosage intensity resulted in improved health outcomes. In conclusion, we identified several innovative composite measures of dosage intensity for CNS and antihypertensive medications, and discussed possible approaches for developing an antidiabetic regimen composite measure. It is critical for future research to compare and contrast various measures and to determine their impact on important clinical outcomes.

Prescribing of medications with anticholinergic properties in older nursing home residents is relatively common, despite an association with an increased risk for falls, delirium, and other outcomes. Few studies have investigated what factors influence different levels of prescribing of these agents. The primary objective was to identify factors associated with low- and high-level anticholinergic burden in nursing home residents. A secondary objective was to examine in detail the contribution of different medications to low versus high burden to aid in determining which drugs to target in interventions. This was a retrospective, cross-sectional analysis of a national sample of 2009–2010 Medicare Part A and B claims, Part D prescription drug events, and Minimum Data Set (MDS) v2.0 assessments. The cohort included 4730 Medicare beneficiaries aged ≥ 65 years with continuous Medicare Parts A, B, and D enrollment, admitted for non-skilled stays of ≥ 14 days between 1 January 2010 and 30 September 2010. Anticholinergic burden was defined using the Anticholinergic Cognitive Burden (ACB) scale. Medication scores were summed at the patient level and categorized as high (score ≥ 3), low (score 1–2), or none. Baseline predisposing factors (age, sex, race/ethnicity), enabling factors (prior year hospitalization, emergency department, primary care, specialist visits; region; Medicaid/low-income subsidy), and medical need factors (dementia severity, anti-dementia medication, Charlson co-morbidity index [CCI], select comorbidities) were evaluated for association with anticholinergic burden using multinomial logistic regression. Overall, 29.6% of subjects had a high anticholinergic burden and 35.2% had a low burden. High burden was most often (72%) due to one highly anticholinergic medication rather than a cumulative effect. In adjusted analyses, factors associated with increased risk of both low and high anticholinergic burden included comorbidity, antidementia medication, depression, hypertension, and prior year hospitalization. Older age was associated with decreased odds of high anticholinergic burden. Urinary incontinence and prior year specialist visit were associated with increased odds of high anticholinergic burden. Severe and nonsevere dementia were associated with decreased odds of low burden but increased odds of high burden. Almost two-thirds of nursing home patients have some degree of anticholinergic burden. Several medical need variables are significantly associated with increased risk for low and high anticholinergic burden. Interventions should be developed to optimize prescribing for residents at increased risk of receiving medications with anticholinergic properties. Future study is needed to evaluate the difference in the risk of adverse outcomes associated with various levels of anticholinergic burden.

Objectives To examine the association between CNS medication burden and serious falls in those with a recent fall history. Design Nested-case control study; cases matched to four controls by age, gender, and date. Setting US nursing homes. Participants 5,556 residents age ≥65 with a recent fall history admitted to a nursing home between 1/1-9/30/2010 and followed until discharge, death, or December 31, 2010. Measurements Outcome was serious falls as per Medicare Part A and B ICD/CPT codes. CNS burden, from Medicare Part D data, was calculated by dividing the daily dose of each CNS agent (i.e., specific antidepressants, antiepileptic, antipsychotic, benzodiazepine and opioid receptor agonists) received during the 6 days prior to the index (outcome) date by the minimum effective geriatric daily dose and summing the results across medications. Results There were 367 cases and 1,468 matched controls. Those taking 3 + CNS standardized daily doses were more likely to have a serious fall than those not taking any CNS medications (Adjusted Odds Ratio 1.83; 95% confidence interval 1.35–2.48). There was no significant difference in fall risk for residents taking >0 to

Background: Nursing home patients with dementia may be more likely to suffer adverse drug events from suboptimal prescribing. Previous studies have not used national samples, nor have they examined multiple types of suboptimal prescribing by dementia severity. Objective: To examine the prevalence of and factors associated with potentially suboptimal prescribing in older veteran nursing home patients with dementia. Methods: This is a retrospective descriptive study of 1303 veterans 65 years or older admitted between January 1, 2004, and June 30, 2005, with dementia for long stays (90+ days) to 133 Veterans Affairs Community Living Centers. Dementia severity was determined by the Cognitive Performance Scale and functional status dependences. Results: Overall, 70.2% with mild-moderate dementia (n = 1076) had underuse because they did not receive an acetylcholinesterase inhibitor (AChEI), and 27.2% had evidence of inappropriate use because of a drug-disease or drug-drug-disease interaction. Of the 227 with severe dementia, 36.1% had overuse by receiving an AChEI or lipid-lowering or other agents, and 25.1% had evidence of inappropriate use as a result of a drug-disease or drug-drug interaction. Multinomial logistic regression analyses among those with mild to moderate dementia identified that living in the South versus other regions was the single factor associated with all 3 types of suboptimal prescribing. In those with severe dementia, antipsychotic use was associated with all 3 suboptimal prescribing types. Conclusions: Potentially suboptimal prescribing was common in older veteran nursing home patients with dementia. Clinicians should develop a heightened awareness of these problems. Future studies should examine associations between potentially suboptimal prescribing and health outcomes in patients with dementia.

Some clinical guidelines advocate for the withdrawal of cholinesterase inhibitors (ChEIs) in patients with severe dementia. However, there have been no studies of the outcomes of deprescribing ChEIs specifically in patients with severe dementia, and concerns about subsequent worsening of behavioral symptoms may serve as a barrier to ChEI discontinuation. Our objective was to evaluate the impact of deprescribing ChEIs on aggressive behaviors and depression severity in older nursing home (NH) residents with severe dementia. We conducted a retrospective cohort study using Medicare claims, Part D prescriptions, Minimum Data Set (MDS) v3.0, Area Health Resource File, and Nursing Home Compare, for non-skilled NH residents aged 65+ with severe dementia receiving AChEIs with ≥2 MDS assessments in 2016 (n=30,788). The Aggressive Behavior Scale (ABS) and the Patient Health Questionnaire (PHQ-9) evaluated aggression and depression, respectively. Marginal structural models with inverse probability of treatment weights evaluated the association of deprescribing with outcomes, accounting for time-dependent confounding. The sample was primarily white (78.7%), female (76.6%), >80 years old (77.6%), and 22.8% were deprescribed ChEIs. In adjusted models, deprescribing was not associated with aggression (0.002 point increase in ABS, p=0.90) or depression (0.04 point increase in PHQ-9, p=0.50). Deprescribing ChEIs in NH residents with severe dementia did not lead to an increase in aggressive behaviors or depression severity. Our findings provide insight into the potential risks and benefits associated with deprescribing ChEIs and help inform decision-making in patients with severe dementia.

Pharmacists successfully manage patients with anemia and chronic kidney disease (CKD), but the cost effectiveness of these programs is unknown. To compare the cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent (ESA) clinics with that of usual care in patients with non-dialysis-dependent (NDD)-CKD. A Markov model was used to estimate the incremental cost effectiveness of pharmacist-managed ESA clinics compared with usual care in outpatient veterans receiving ESAs for NDD-CKD in 2009. The analysis was conducted from a US Veterans Health Administration perspective with a 5-year time horizon, and the year of valuation for cost results was 2012. The effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. In the deterministic base case analysis, costs and effectiveness per patient over 5 years were US$13,412 and 2.096 quality-adjusted life-years (QALYs) in the pharmacist-managed ESA clinics and US$16,173 and 2.093 QALYs in usual care; ESA clinics dominated usual care. In one-way sensitivity analyses, ESA clinics no longer dominated if their patients’ probability of being in the target hemoglobin range fell to 52 % (base case 71 %) or if the mean cost/patient/month of epoetin or darbepoetin in ESA clinics increased to approximately US$382 (base case US$226) or US$477 (base case US$268), respectively. When all parameters were varied simultaneously in a probabilistic sensitivity analysis, ESA clinics were favored ≥80 % of the time at willingness-to-pay thresholds of US$0–$100,000 per QALY gained. Pharmacist-managed ESA clinics were less costly and more effective than usual care in patients receiving ESAs for anemia and NDD-CKD. Results were robust to variation and support the use of pharmacist-managed ESA clinics.

UnlabelledOver the past decade, the Department of Veterans Affairs (VA) Pharmacy Benefits Management Services (PBM) has enhanced its formulary management activities and added programs to ensure that the national drug plan continues to meet the pharmacy needs of veterans and to promote safe and appropriate drug therapy in the face of rising medication expenditures. This article describes the broad range of services provided by the VA PBM that work in partnership to deliver a high-quality and sustainable pharmacy benefit for veterans. In support of formulary management, VA PBM pharmacists prepare extensive clinical guidance documents (e.g., drug monographs and criteria for use) that are used by physicians and pharmacists with operational and clinical oversight of the VA national formulary. The VA PBM has utilized various contracting techniques and continually evaluates drug utilization data to identify opportunities for potential savings. Remarkably, since before 2004, the average acquisition cost for a 1-month supply of medication has remained fairly stable at approximately $13-$15. Two new VA PBM programs are the VA Center for Medication Safety (VA MedSAFE) and the Clinical Pharmacy Practice Office (CPPO). VA MedSAFE is a comprehensive pharmacovigilance program focused on the detection, assessment, and prevention of adverse drug events, and CPPO is dedicated to improving safe and appropriate medication use by supporting and expanding clinical pharmacy practice. Moving forward, the VA PBM will consider new initiatives to stay at the forefront of providing quality care while maintaining economic viability.DisclosuresNo outside funding supported this research. This work was supported by VA Pharmacy Benefits Management Services (VA PBM), Hines, Illinois, and VA Pittsburgh Healthcare System, Pittsburgh, Pennsylvania. Glassman is co-director of the VA Center for Medication Safety, which is part of the VA PBM. He is also part of the Medical Advisory Panel for the VA PMB. All other authors are employed by the VA PBM. The views expressed in this article are those of the authors, and no official endorsement by the U.S. Department of Veteran Affairs or the U.S. government is intended or should be inferred. Study concept and design were contributed by Valentino, Cunningham, Good, Aspinall, and Sales. Calabrese and Ourth took the lead in data collection, along with Good, Cunningham, Aspinall, Sales, Burk, Moore, Neuhauser, and Golterman. Data interpretation was performed by Burk, Newhauser, and Golterman, along with Glassman, Calabrese, Moore, and Ourth. The manuscript was written by Aspinall and Sales, along with Burk, Newhauser, Golterman, Ourth, and Cunningham. Good, Glassman, and Moore revised the manuscript, along with Calabrese, Valentino, and Aspinall.

Erythropoiesis-stimulating agents (ESAs) are associated with serious adverse events, and maintaining hemoglobin levels within a narrow range can be difficult. We examined the quality of ESA prescribing and monitoring in pharmacist-managed ESA clinics versus usual care in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).Historical cohort.Outpatients receiving ESAs for NDD-CKD at 10 Veterans Affairs Medical Centers with both pharmacist-managed ESA clinics (n = 314) and physician-based care (ie, usual care; n = 91) and 6 sites with usual care only (n = 167) on January 1, 2009, were followed up for 6 months.Type/site of care (ie, pharmacist-managed ESA clinic, usual care at ESA clinic site, usual-care site).Primary outcomes were proportion of hemoglobin values in the target range of 10-12 g/dL, ESA dose, and frequency of hemoglobin monitoring. Factors associated with hemoglobin values out of target range were identified using multinomial logistic regression.More hemoglobin values were in the target range in pharmacist-managed ESA clinics (71.1% vs 56.9% for usual-care sites; P0.001). The average 30-day dose of darbepoetin was 163 μg in pharmacist-managed ESA clinic patients versus 240 μg in usual-care site patients and 258 μg in usual-care patients at ESA clinic sites. For epoetin, corresponding average 30-day doses were 44,890 versus 47,141 and 57,436 IU. Veterans in pharmacist-managed ESA clinics had more hemoglobin measurements on average (5.8 vs 3.6 in usual-care sites and 3.8 in usual care at ESA clinic sites; P = 0.007). In the multinomial model, usual care was associated with hemoglobin levels out of target range, whereas heart failure and diabetes were associated with values in range.We could not assess whether different hemoglobin targets were used by usual-care providers.Relative to usual care, pharmacist-managed clinics provided improved quality of ESA dosing and monitoring for patients with NDD-CKD.

Background. Studies of drug-related hospitalizations have focused on adverse drug reactions, but few data are available on therapeutic failures (TFs) and adverse drug withdrawal events (ADWEs) leading to hospitalization among community-dwelling older adults. Thus, we sought to describe the prevalence of unplanned hospitalizations caused by TFs and ADWEs. In addition, we evaluated factors associated with these events in a nationally representative sample of older Veterans. Methods. This study included 678 randomly selected unplanned hospitalizations of older (age ≥ 65 years) Veterans between December 1, 2003, and November 9, 2006. The main outcomes were hospitalizations caused by a TF and/or an ADWE as determined by a pair of health professionals from review of medication charts and application of the Therapeutic Failure Questionnaire and/or Naranjo ADWE algorithm, respectively. Preventability (ie, medication error) of the admission was also assessed. Results. Thirty-four TFs and eight ADWEs involving 54 drugs were associated with 40 (5.9%) Veterans' hospitalizations; of these admissions, 90.0% (36/40) were rated as potentially preventable mostly due to medication nonadherence and suboptimal prescribing. The most common TFs that occurred were heart failure exacerbations (n = 8), coronary heart disease symptoms (n = 6), tachyarrhythmias (n = 3), and chronic obstructive pulmonary disease exacerbations (n = 3). Half (4/8) of the ADWEs that occurred were cardiovascular in nature. Multivariable logistic regression modeling indicated that black Veterans (adjusted odds ratio 2.92, 95% CI 1.25-6.80) were significantly more likely to experience a TF-related admission compared with white Veterans. Conclusions. TF-related unplanned hospitalizations occur more frequently than ADWE-related admissions among older Veterans. Almost all TFs and/or ADWEs are potentially preventable.

To describe the prevalence of unplanned hospitalizations caused by adverse drug reactions (ADRs) in older veterans and to examine the association between this outcome and polypharmacy after controlling for comorbidities and other patient characteristics.Retrospective cohort.Veterans Affairs Medical Centers.Six hundred seventy-eight randomly selected unplanned hospitalizations of older (aged ≥ 65) veterans between October 1, 2003, and September 30, 2006.Naranjo ADR algorithm, ADR preventability, and polypharmacy (0-4, 5-8, and ≥9 scheduled medications).Seventy ADRs involving 113 drugs were found in 68 (10%) hospitalizations of older veterans, of which 25 (36.8%) were preventable. Extrapolating to the population of more than 2.4 million older veterans receiving care during the study period, 8,000 hospitalizations may have been unnecessary. The most common ADRs that occurred were bradycardia (n = 6; beta-blockers, digoxin), hypoglycemia (n = 6; sulfonylureas, insulin), falls (n = 6; antidepressants, angiotensin-converting enzyme inhibitors), and mental status changes (n = 6; anticonvulsants, benzodiazepines). Overall, 44.8% of veterans took nine or more outpatient medications and 35.4% took five to eight. Using multivariable logistic regression and controlling for demographic, health-status, and access-to-care variables, polypharmacy (≥9 and 5-8) was associated with greater risk of ADR-related hospitalization (adjusted odds ratio (AOR) = 3.90, 95% confidence interval (CI) = 1.43-10.61 and AOR = 2.85, 95% CI = 1.03-7.85, respectively).ADRs, determined using a validated causality algorithm, are a common cause of unplanned hospitalization in older veterans, are frequently preventable, and are associated with polypharmacy.

Background Inappropriate prescribing of primarily renally cleared medications in older patients with kidney disease can lead to adverse outcomes. Objectives To estimate the prevalence of potentially inappropriate prescribing of 21 primarily renally cleared medications based on 2 separate estimates of renal function and to identify factors associated with this form of suboptimal prescribing in older VA nursing home (NH) patients. Design Longitudinal study Participants Participants were 1304 patients, aged 65 years or older, admitted between January 1, 2004, and June 30, 2005, for 90 days or more to 1 of 133 VA NHs. Main Measures Potentially inappropriate prescribing of primarily renally cleared medications determined by estimating creatinine clearance using the Cockcroft Gault (CG) and Modification of Diet in Renal Disease (MDRD) equations and applying explicit guidelines for contraindicated medications and dosing. Key Results The median estimated creatinine clearance via CG was 67 mL/min, whereas it was 80 mL/min/1.73m 2 with the MDRD. Overall, 11.89% patients via CG and only 5.98% via MDRD had evidence of potentially inappropriate prescribing of at least 1 renally cleared medication. The most commonly involved medications were ranitidine, glyburide, gabapentin, and nitrofurantoin. Factors associated with potentially inappropriate prescribing as per the CG were age older than 85 (adjusted odds ratio [AOR] 4.24, 95% confidence interval [CI] 2.42–7.43), obesity (AOR 0.26, 95% CI 0.14–0.50) and having multiple comorbidities (AOR 1.09 for each unit increase in the Charlson comorbidity index, 95% CI 1.01–1.19). Conclusions Potentially inappropriate prescribing of renally cleared medications is common in older VA NH patients. Intervention studies to improve the prescribing of primarily renally cleared medications in nursing homes are needed.

OBJECTIVES: To describe the quality of warfarin prescribing and monitoring in Veterans Affairs (VA) nursing homes and to assess the factors associated with maintaining a therapeutic international normalized ratio (INR). DESIGN: Retrospective cohort. SETTING: Five VA nursing homes. PARTICIPANTS: All veterans who received warfarin between January 1 and June 30, 2008, at the nursing homes. MEASUREMENTS: Using medical records, the percentage of person-time spent in the target INR range, the proportion of patients with INRs in the therapeutic range on 50% or more of their person-days, and the frequency of INR monitoring were estimated. Multivariable logistic regression was used to identify factors associated with maintaining a therapeutic INR 50% or more of the time. RESULTS: Over 6 months, 160 patients received 10,380 person-days of warfarin. INRs were in the therapeutic range for 55% of the person-days, and 99% of the INR tests were repeated within 4 weeks of the previous result. On an individual level, 49% of patients had INRs in the target range for 50% or more of their person-days. Achieving this outcome was more likely in patients with prevalent warfarin use than with new use (adjusted odds ratio (AOR)=2.86, 95% confidence interval (CI)=1.06–7.72). Conversely, patients with a history of a stroke (AOR=0.38, 95% CI =0.18–0.80) were less likely to have therapeutic INRs for 50% or more of their days. CONCLUSION: Warfarin appears to be prescribed and monitored effectively in VA nursing home patients. Future studies should focus on increasing time in therapeutic range in patients with poor INR control.

Objectives To establish consensus oral dosing guidelines for primarily renally cleared medications prescribed for older adults.

Background: Studies that have assessed antibiotic appropriateness in acute respiratory tract infections (RTIs) with a likely bacterial etiology have focused only on antibiotic choice and ignored other important aspects of prescribing, such as dosing, drug-drug interactions, and duration of treatment. Objective: The aim of this study was to determine the prevalence and predictors of inappropriate antibiotic prescribing practices in outpatients with acute bacterial RTIs (community-acquired pneumonia [CAP], sinusitis, or acute exacerbations of chronic bronchitis [AECB]). Methods: This retrospective, cross-sectional study enrolled outpatients with CAP, sinusitis, or AECB who were evaluated in a Veterans Affairs emergency department over a 1-year period. Using electronic medical records, trained research assistants completed data-collection forms that included patient characteristics (eg, marital status, history of alcohol abuse), diagnosis, comorbidities, concurrent medications, and antibiotics prescribed. To assess antimicrobial appropriateness, a trained clinical pharmacist reviewed the data-collection forms and applied a Medication Appropriateness Index (MAI), which rated the appropriateness of a medication using 10 criteria: indication, effectiveness, dosage, directions, practicality (defined as capability of being used or being put into practice), drug-drug interactions, drug-disease interactions, unnecessary duplication, duration, and expensiveness (defined as the cost of the drug compared with other agents of similar efficacy and tolerability). Previous studies have found good inter- and intrarater reliabilities between a clinical pharmacist's and an internal medicine physician's MAI ratings (κ = 0.83 and 0.92, respectively). Results: One hundred fifty-three patients were included (mean age, 58 years; 92% male; and 65% white). Overall, 99 of 153 patients (65%) had inappropriate antibiotic prescribing as assessed using the MAI. Expensiveness (60 patients [39%]), impracticality (32 [21%]), and incorrect dosage (15 [10%]) were the most frequently rated problem. Penicillins, quinolones, and macrolides were the most common antibiotic classes prescribed inappropriately. A history of alcohol abuse was associated with a lower likelihood of inappropriate prescribing compared with no history of alcohol abuse (adjusted odds ratio [AOR], 0.32; 95% CI, 0.10–0.98), while patients who were married were more likely to receive inappropriately prescribed antibiotics than those who were not married (AOR, 2.64; 95% CI, 1.25–5.59). Conclusions: Inappropriate antibiotic prescribing based on the MAI criteria was common (65%) in this selected patient population with acute bacterial RTIs, and often involved problems with expensiveness (39%), impracticality (21%), and incorrect dosage (10%). Future interventions to improve antibiotic prescribing should consider aspects beyond choice of agent.

Recent publications report that gatifloxacin might be associated with a greater incidence of Clostridium difficile-associated diarrhea (C. difficile, CDAD) than are other fluoroquinolones. We performed a drug use evaluation to examine this issue after adding gatifloxacin to the formulary and changing from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone in 10 Department of Veterans Affairs (VA) medical centers in the northeastern United States.To estimate (1) the overall incidence of CDAD before and after the change from levofloxacin to gatifloxacin as the preferred oral fluoroquinolone and (2) the incidence rates for ciprofloxacin, levofloxacin, and gatifloxacin separately.Using the VA's Pharmacy Benefits Management database, the total number of days of antibiotic therapy was determined for all inpatients and outpatients of the 10 medical centers who filled at least 1 antibiotic prescription between July 1, 2003, and June 30, 2004. This time frame was chosen because it included 6 months before and 6 months after the change in the preferred oral fluoroquinolone from levofloxacin to gatifloxacin for the VA health system on January 1, 2004. For the same study period and medical centers, the electronic medical records of all inpatients and outpatients with an entry for a positive C. difficile toxin were reviewed. Positive toxins that occurred within 6 weeks of a previous positive result in the same patient were excluded. Exact Poisson tests were used to compare the incidence rates of CDAD (number of CDAD cases per 1,000 days of antibiotic treatment) for antibiotics overall, the fluoroquinolones as a group, non-fluoroquinolone antibiotics, and the individual fluoroquinolones, com-paring the 6-month time periods before (pre-change) versus after (post-change) the addition of gatifloxacin as the preferred oral fluoroquinolone.Of 505 cases of CDAD in the 12-month study period, 413 (81.7%) were associated with antibiotic use in the previous 6 weeks. Among anti-biotic users, incidence rates of CDAD were 166 per 72,114 days of antibiotic therapy in the pre-change period (2.3 cases per 1,000 days of antibiotics) versus 247 per 72,354 days in the post-change period (3.4 cases per 1,000 days of antibiotics, P0.001). Fluoroquinolones accounted for 54.8% of the CDAD cases in the pre-change period and 67.2% in the post-change period, representing a 22.6% relative increase in the percentage of CDAD cases that were associated with fluoroquinolone use. The CDAD incidence rates per 1,000 days of fluoroquinolone therapy were 3.7 in the pre-change period versus 7.0 in the post-change period (P0.001). Among fluoroqui-nolone users, gatifloxacin accounted for none of the cases of CDAD in the pre-change period when it was nonformulary and 65.1% of the cases in the post-change period, for an incidence rate of 7.6 (108 per 14,239 days). The CDAD incidence rates per 1,000 antibiotic days for patients treated with ciprofloxacin were 4.6 (24 per 5,260 days) in the pre-change period and 7.4 (40 per 5,429 days) in the post-change period, a nonsignificant trend (P = 0.079). The incidence rate of CDAD for levofloxacin increased significantly from 3.9 (75 per 19,417 days) in the pre-change period to 10.7 (44 per 4,108 days) in the post-change period (P0.001). The incidence rates of CDAD in the post-change period did not differ significantly for ciprofloxacin, levofloxacin, and gatifloxacin (P = 0.119).There was an increase in the incidence of CDAD among all antibiotic users and fluoroquinolone users, but not among users of non-fluoroquinolone antibiotics, in the period following the formulary change from levofloxacin to gatifloxacin as the preferred fluoroquinolone. However, rates of CDAD among the 3 fluoroquinolone antibiotics in the post-change period were not significantly different, and levofloxacin was the only fluoroquinolone that was associated with a significant increase in the rate of CDAD between the pre-change and post-change periods. These findings suggest that the increase in the CDAD incidence rate was probably not attributable to the addition of gatifloxacin to the formulary.

The objective of this study was to evaluate the real-world cost effectiveness of adjuvant stage III colon cancer chemotherapy regimens, given that previous analyses have been based on data from clinical trials. The study was designed using integrated decision tree and Markov model, which was developed to evaluate the cost effectiveness of 5-fluorouracil/leucovorin (5-FU/LV), capecitabine, and the combination of each with oxaliplatin. The analysis was performed from a US Veterans Affairs perspective via retrospectively collected data, over a 5-year model time horizon. Outcome and cost data were used to calculate cost per quality adjusted life year (QALY), and one-way and probabilistic sensitivity analyses were performed. In the base case analysis, capecitabine and capecitabine plus oxaliplatin both cost more and were less effective than other regimens, and 5-FU/LV plus oxaliplatin, compared to 5-FU/LV alone, resulted in a cost of $25,997 per QALY gained. Model results were generally robust to parameter variation. Capecitabine plus oxaliplatin could be economically reasonable if full dosing occurred ≥76% of the time (base case 42%). In a real-world setting, the addition of oxaliplatin to 5-FU/LV is more effective but also more costly than 5-FU/LV alone. If full dosing of capecitabine-containing regimens can be assured, they may also be cost-effective strategies.

Objectives To describe the prevalence of and factors associated with drug–disease interactions (DDIs) in older nursing home residents according to the American Geriatrics Society 2012 Beers Criteria. Design Cross-sectional. Setting Fifteen Veterans Affairs Community Living Centers. Participants Individuals aged 65 and older with a diagnosis of dementia or cognitive impairment, a history of falls or hip fracture, heart failure (HF), a history of peptic ulcer disease (PUD), or Stage IV or V chronic kidney disease (CKD). Measurements Medications that could exacerbate the above conditions (DDIs). Results Three hundred sixty-one of 696 (51.9%) eligible residents had one or more DDIs. None involved residents with a history of PUD, one involved a resident with CKD, and four occurred in residents with HF. Of 540 residents with dementia or cognitive impairment, 50.7% took a drug that could exacerbate these conditions; the most commonly involved medications were antipsychotics (35.4%) and benzodiazepines (14.4%). Of 267 with a history of falls or hip fracture, 67.8% received an interacting medication, with selective serotonin reuptake inhibitors (33.1%), antipsychotics (30.7%), and anticonvulsants (25.1%) being most commonly involved. Using separate multivariable logistic regression models, factors associated with DDIs in dementia or cognitive impairment and falls or fractures included age 85 and older (adjusted odds ratio (aOR) = 0.38, 95% confidence interval (CI) = 0.24–0.60 and aOR = 0.48, 95% CI = 0.24–0.96, respectively), taking five to eight medications (aOR = 2.06, 95% CI = 1.02–4.16 and aOR = 4.76, 95% CI = 1.68–13.5, respectively), taking nine or more medications (aOR = 1.99, 95% CI = 1.03–3.85 and aOR = 3.68, 95% CI = 1.41–9.61, respectively), and being a long-stay resident (aOR = 1.80, 95% CI = 1.04–3.12 and aOR = 2.35, 95% CI = 1.12–4.91, respectively). Conclusion DDIs were common in older nursing home residents with dementia or cognitive impairment or a history of falls or fractures.

To determine the utility (i.e., positive predictive value [PPV] and time requirement) of an adverse drug event (ADE) trigger tool in Veterans Affairs (VA) nursing facilities and to describe the most common types of potential ADEs detected with the trigger tool.Retrospective chart review.Veterans residing in three VA nursing facilities between September 29, 2010, and October 29, 2010.We used the Institute for Healthcare Improvement-endorsed nursing facility ADE trigger tool, modified to enhance its clinical relevance to detect potential ADEs. Electronic medical records were screened to identify residents with one or more abnormal laboratory values specified in the trigger tool.A potential ADE was defined as the concurrent administration of medication that could cause the abnormal laboratory value. An overall PPV, or proportion of residents with an abnormal laboratory value who had a potential ADE, and average time required to complete each trigger tool assessment, were calculated.Among 321 veterans, 50.5% (n = 162) had at least one abnormal laboratory value contained in the trigger tool. Ninety-nine potential ADEs involving 146 medications were detected in 65 veterans. The overall PPV of the ADE trigger tool was 40.1% (65/162), and the average time to complete resident assessments was 8.8 (standard deviation ± 5.7) minutes. The most common potential ADEs were acute kidney injury (n = 30 residents), hypokalemia (n = 18), hypoglycemia (n = 13), and hyperkalemia (n = 10).The modified nursing facility trigger tool was shown to be an effective and efficient method for detecting potential ADEs.

Objectives The objectives of this study were to describe changes in glyburide prescribing in cohorts that were and were not targeted by a risk reduction project, assess factors associated with glyburide discontinuation, and evaluate changes in glycated hemoglobin (ie, HbA 1c ) levels and rates of serious hypoglycemia. Methods This historical cohort study included a targeted cohort of 4368 outpatient veterans aged ≥65 years with active prescriptions for glyburide between April 1, 2007 and June 30, 2007 and serum creatinine (SCr) ≥2 mg/dL and a nontargeted cohort of 1886 outpatients meeting these same criteria between July 1, 2007 and September 3, 2007. The intervention in the risk reduction project took place on September 4, 2007 and entailed giving regional pharmacy leaders information about the increased risk of hypoglycemia with glyburide and the list of targeted patients for follow up with providers. For each patient, the study period was the time between the date they first met the eligibility criteria and March 31, 2008. All data were obtained from Veterans Affairs (VA) administrative databases. The primary outcome was the discontinuation of glyburide. Secondary outcomes were the change in HbA 1c after stopping glyburide and the rate of serious hypoglycemia after intervention. Results Incidence rate ratios (IRRs) for glyburide discontinuation in targeted versus nontargeted cohorts were statistically significantly elevated in September (IRR 2.1; 95% CI 1.7–2.5), October (IRR 1.3; 95% CI 1.1–1.6), and November 2007 (IRR 1.4; 95% CI 1.1–1.7). The intervention, black race, SCr, Charlson comorbidity score, new glyburide use, and VA region were independently associated with discontinuation. Among patients in the targeted cohort who discontinued glyburide, mean (SD) HbA 1c at baseline and after discontinuation were 7.17% (1.35%), and 7.22% (1.34%), respectively ( P = 0.36). The hypoglycemia rates/1000 person-days were 0.093 before the intervention and 0.070 afterwards ( P = 0.10). Conclusion A one-time intervention in a risk reduction project decreased glyburide use over a 3-month period in elderly outpatients with renal insufficiency without compromising glucose control.

Objective To compare the cost-effectiveness of four, six, and eight doses per month of vardenafil in the context of pharmacy benefit decision making. Methods A Markov model was used to estimate the incremental cost-effectiveness of zero, four, six, or eight doses of vardenafil per month in hypothetical cohorts of 60-year-old male veterans with erectile dysfunction. Efficacy values for vardenafil were obtained from the literature, and vardenafil costs were obtained from Veterans Affairs pharmacy data. The analysis was conducted from a third-party payer perspective with a lifetime horizon, and the effect of parameter uncertainty was explored in one-way and probabilistic sensitivity analyses. Results In the base case analysis, the cost per quality-adjusted life-year gained for four doses of vardenafil per month compared with no therapy was $576. Six doses per month compared with four cost $2585/quality-adjusted life-year gained, and eight doses per month compared with six cost $5169/quality-adjusted life-year gained. In one-way sensitivity analyses of six doses per month compared with four, variation of two parameters caused the incremental cost-effectiveness ratio to cross a willingness-to-pay threshold of $20,000: when the increased utility associated with giving two additional doses/month was less than 0.001 (baseline 0.01) and when the cost per dose increased to $15.00 (baseline $1.69). Conclusion Although four doses per month of vardenafil was the most cost-effective strategy, the use of six or eight doses per month also compares favorably with other accepted medical treatments. The results were stable across a range of inputs and help to support the current Veterans Affairs policy on the number of vardenafil doses provided per month for erectile dysfunction.

Article-at-a-Glance Background A mixed-methods quality improvement (QI) project for patients with pneumonia hospitalized from the emergency department (ED) was undertaken to (1) delineate the basic steps in the flow of patient care from presentation in the ED to time to first antibiotic dose (TFAD), (2) identify perceived barriers to and facilitators of reduced TFAD within these steps, (3) describe QI strategies to improve TFAD rates, and (4) identify perceived strategies for facilities to enhance performance. Methods The QI project was conducted at 10 lower- and 10 higher-performing Veterans Affairs hospitals on the basis of the proportion of patients whose TFAD was within four hours of presentation. An ED physician, an ED nurse, a radiologist, a pharmacist, and a quality manager from each site were invited to participate in a survey and focus group. Results Of the 82 survey participants, 59 (72%) perceived that ordering and performing the chest radiograph was the step most frequently resulting in TFAD delays. Medical provider assessment, chest radiograph interpretation, ordering/obtaining blood cultures, and ordering/administering initial antibiotic therapy also caused TFAD delays. The most commonly perceived barriers were patient and x-ray equipment transportation delays and communication delays between providers. The most frequently used strategies to reduce TFAD were stocking antibiotics in the ED and physician education. Focus groups emphasized the importance of multifaceted QI approaches and a top-down hospital leadership style to improve TFAD performance. Discussion TFAD relies on a series of complex, stepwise processes of care that involve numerous hospital departments and is often delayed by well-described barriers. Addressing these barriers, as well as involving facility leadership in setting institutional QI goals, could possibly improve performance on this pneumonia quality measure.

Background. Although gatifloxacin is no longer available, other fluoroquinolones may significantly interfere with glucose homeostasis. The objective of the present study was to compare the risk of severe hypo- and hyperglycemia in a cohort of patients treated with gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin. Methods. This was a retrospective inception cohort study of outpatients with a new prescription for gatifloxacin, levofloxacin, ciprofloxacin, or azithromycin from 1 October 2000 through 30 September 2005 in the Veterans Affairs health care system. For patients who received one of these antibiotics, we identified outcomes of hospitalization with a primary diagnosis of hypo- or hyperglycemia. Multivariable logistic regression was used to determine the odds of hypo- and hyperglycemia with the individual fluoroquinolones versus azithromycin. Results. The crude incidence rates for severe hypo- and hyperglycemia among those who received gatifloxacin, levofloxacin, ciprofloxacin, and azithromycin were 0.35 and 0.45, 0.19 and 0.18, 0.10 and 0.12, and 0.07 and 0.10 cases per 1000 patients, respectively. Among patients with diabetes, the odds ratios for hypoglycemia compared with azithromycin were 4.3 (95% confidence interval [CI], 2.7‐6.6) for gatifloxacin, 2.1 (95% CI, 1.4‐3.3) for levofloxacin, and 1.1 (95% CI, 0.6‐2.0) for ciprofloxacin. The odds ratios for hyperglycemia were 4.5 (95% CI, 3.0‐6.9) for gatifloxacin, 1.8 (95% CI, 1.2‐2.7) for levofloxacin, and 1.0 (95% CI, 0.6‐1.8) for ciprofloxacin. Conclusions. The odds of severe hypo- and hyperglycemia were significantly greater with gatifloxacin and levofloxacin, but not ciprofloxacin, than with azithromycin. Thus, the risk of a clinically relevant dysglycemic event appears to vary among the fluoroquinolones. The fluoroquinolone antibiotics are widely used because they are generally well tolerated and have a broad spectrum of activity. However, gatifloxacin—which had been used in the treatment of a variety of infections, including those involving the skin and the respiratory and genitourinary tracts [1, 2]—was withdrawn from the market because of concerns about severe glucose disturbances. Although hypoglycemia and hyperglycemia were reported only rarely during clinical trials with gatifloxacin, severe dysglycemic events, typically in elderly patients and in patients with diabetes, were re

The objective of the study was to identify patient and provider factors associated with prescribing antibiotics for outpatients with acute respiratory tract infections of likely nonbacterial etiology.We identified outpatients who were diagnosed in the emergency department with nonspecific upper respiratory tract infections (URIs) and acute bronchitis at the VA Pittsburgh Healthcare System from June 15, 2003, to June 14, 2004, and the Philadelphia VA Medical Center from November 30, 2003, to March 31, 2004. Stepwise logistic regression was used to identify factors independently associated with antibiotic prescribing.Overall, 26% of the 667 eligible patients with URIs and/or acute bronchitis received antibiotics. Antibiotics were prescribed significantly more frequently for acute bronchitis at one site (97% vs 65%, P.001). Using multivariable analysis, the following factors were independently associated with antibiotic prescribing (odds ratio, 95% confidence interval): presence of 1 or more comorbidities (2.1, 1.2-3.5), fever (2.5, 1.4-4.4), purulent sputum (2.5, 1.5-4.4), shortness of breath (2.8, 1.4-5.4), altered breath sounds (4.6, 2.4-8.6), diagnosis of acute bronchitis (15.9, 8.0-31.8), provider ageor = 30 years (2.6, 1.1-6.3), and noninternal medicine specialty (2.7, 1.2-6.0).Antibiotic use was high and varied substantially for URIs and acute bronchitis. Specific signs and symptoms, a diagnosis of acute bronchitis, and provider age and specialty were associated with antibiotic prescribing. Interventions to decrease inappropriate prescribing should address the perceived utility of antibiotics in acute bronchitis and the accuracy of signs and symptoms in diagnosing a bacterial respiratory infection.

Objective: This paper reviews recent articles examining medication errors in the elderly. Methods: MEDLINE and International Pharmaceutical Abstracts were searched for articles published in 2006 using a combination of the terms medication errors, medication adherence, medication compliance, suboptimal prescribing , and aged . A manual search of the reference lists of the identified articles and the authors' article files, book chapters, and recent reviews was conducted to identify additional publications. Those studies that described new measures of medication errors or had a randomized controlled design, evaluated the impact of an intervention on ≥1 measure of medication errors, and involved the community-dwelling elderly were included in the review. Results: The search identified 5 studies and a new set of explicit criteria for prescribing problems in nursing homes from the Centers for Medicare and Medicaid Services (CMS). One of the studies found a new instrument, the Medication Management Instrument for Deficiencies in the Elderly, to be a reliable and valid measure of medication management in older adults. A study in the ambulatory elderly found that 13.0% reported cost-related medication nonadherence. A randomized controlled trial of a pharmacist intervention in elderly patients at high risk for coronary events found the intervention was associated with improvements in both medication adherence and systolic blood pressure control. The report from the CMS described new explicit criteria for unnecessary drug use in elderly patients in long-term care facilities, including drugs to avoid, drugs that should be limited in dose or duration, drugs to be monitored, and drug-drug interactions. A modified Delphi survey of an expert panel reached consensus on 28 drug-disease interactions in older adults. Finally, a randomized controlled trial of computerized feedback in a health maintenance organization found improvements in inappropriate prescribing of target drugs in older adults. Conclusion: Data from recently published studies may provide guidance to practitioners and help direct future research.

The Outpatient Bleeding Risk Index (BRI) prospectively classified patients who were at high, intermediate, or low risk for warfarin-related major bleeding. However, there are only 2 published validation studies of the index and neither included veterans.To determine the accuracy of the BRI in patients attending a Veterans Affairs (VA) anticoagulation clinic and to specifically evaluate the accuracy of the BRI in patients with atrial fibrillation.Retrospective cohort study.Using the BRI, all patients managed by the Anticoagulation Clinic between January 1, 2001 and December 31, 2002 were classified as high, intermediate, or low risk for major bleeding. Bleeds were identified via quality-assurance reports. Poisson regression was used to determine whether there was an association between the index and the development of bleeding.The rate of major bleeding was 10.6%, 2.5%, and 0.8% per patient-year of warfarin in the high-, intermediate-, and low-risk groups, respectively. Patients in the high-risk category had 14 times the rate of major bleeding of those in the low-risk group (incidence rate ratio (IRR) 14; 95% confidence interval (CI), 1.9 to 104.7). The rate of major bleeding was significantly different between the high- and intermediate-risk categories (P.001). Among those with atrial fibrillation, patients in the high-risk category had 6 times the major bleeding rate of those in the intermediate- and low-risk groups combined (IRR=6; 95% CI, 2.4 to 15.3).The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic, including those with atrial fibrillation.

Programs have targeted individual patient and physician behaviors to reduce the use of antibiotics for upper respiratory infections (URIs), but such efforts have had limited success to date.The aim of this study was to measure the extent of variation in antibiotic prescribing patterns at the hospital-facility level to determine whether organizational factors may be associated with patterns of antibiotic prescribing.This was a cross-sectional study using linked pharmacy and encounter data to measure hospital-level variation in patterns of antibiotic prescribing at US Department of Veterans Affairs (VA) medical centers between October 1, 2000, and September 30, 2001. The main outcome measure was the proportion of visits for URIs or acute bronchitis with an antibiotic dispensed within 1 day before to 3 days after the encounter, restricted to primary-care and emergency/urgent care clinics at VA medical centers withor =100 annual visits for URIs.A median of 523 visits for URIs occurred across 108 medical centers. The median proportion of visits with an antibiotic dispensed was 52% (range, 14%-88%). Hospitals in the South had increased odds of prescribing antibiotics for veterans with URIs compared with hospitals in the Northeast (odds ratio, 1.8 [95% CI, 1.2-2.5]). Among facilities with200,000 visits per year, an increase in the percentage of unscheduled outpatient visits increased the odds of prescribing antibiotics for veterans with URIs (odds ratio per 10% increase, 1.3 [95% CI, 1.1-1.5]).Our results suggest variation in antibiotic prescribing for URIs at the hospital-facility level within the VA health care system. Organizational factors, such as time pressure, may be important targets for future interventions designed to reduce inappropriate antibiotic use in ambulatory care settings.

The detection of adverse drug reactions (ADRs) by a traditional passive reporting system and by a method involving patient and provider interviews was studied. The study sample consisted of randomly selected outpatients seen by their primary care provider during scheduled appointments in January and February 2001 at a Veterans Affairs medical center. After ambulatory care clinic sessions, patients and providers were asked (by telephone and in person, respectively) to identify potential ADRs. Also obtained were demographic data, information about drug regimens, and the severity and management of each ADR. A standardized ADR-assessment tool was used to determine the severity of each reported reaction and its causal relationship with the medication. A total of 198 patients were included. Of these, 51 (26%) had one or more ADRs. The patient and provider interviews identified a total of 83 ADRs, compared with 1 ADR identified by the passive reporting system. When providers were made aware of the ADRs they had not identified, changes were made to the patient's medication regimen in 34% of cases. The risk of an ADR was not associated with age, number of medications, or provider type. Direct patient and provider interviews yielded a significantly higher rate of ADR detection in an ambulatory care setting than did a passive ADR-reporting system.

OBJECTIVE: To report three cases of a suspected interaction between warfarin and fluvastatin. CASE SUMMARIES: Three patients receiving stable warfarin dosages with therapeutic international normalized ratios (INRs) exhibited increased INRs when fluvastatin was added to their maintenance regimens. While none of the patients experienced a bleeding episode, they did require a reduction in their weekly warfarin dosage to achieve an appropriate level of anticoagulation. DISCUSSION: Reports of an interaction between warfarin and lovastatin have been described previously; however, to our knowledge, this is the first published report of a possible interaction between warfarin and fluvastatin. These cases were chosen because other factors that could potentially increase the INR were ruled out as significant contributors. CONCLUSIONS: The exact mechanism for the potential interaction between warfarin and fluvastatin is unknown. Until more is known, it is advisable to monitor patients more frequently when fluvastatin is initiated, discontinued, or adjusted in patients taking warfarin.

Objective: To report on a patient with recurrent methicillin-resistant Staphylococcus aureus (MRSA) osteomyelitis and bacteremia successfully treated with combination antibiotic therapy. Case Summary: Two sets of blood cultures from a 55-year-old man with fever, malaise, and low back pain grew MRSA. Radiologic studies of the spine showed bony changes consistent with osteomyelitis. Soon after completing 6 weeks of vancomycin, the patient experienced a recurrence of back pain. Laboratory values included an increase in the sedimentation rate to 53 mm/h and positive blood cultures for MRSA. Vancomycin, gentamicin, and rifampin were administered for 8 weeks. Serum inhibitory and bactericidal titers were more than 1:1024 for both the peak and trough concentrations. Radiologic studies of the spine showed healing osteomyelitis. Two years after completion of antibiotic therapy, the infection has not recurred. Discussion: Antibiotic therapy alone was attempted because the patient was considered a risky surgical candidate. Serum inhibitory and bactericidal titers documented the high in vivo activity of the vancomycin, gentamicin, and rifampin combination. Initiation of vancomycin therapy led to disappearance of the fever and back pain. Cure was documented by sustained normalization of the erythrocyte sedimentation rate and radiologic evidence of healing. Conclusions: Combination antibiotic therapy with vancomycin, rifampin, and low-dose gentamicin (1 mg/kg q12h) may be useful for deep-seated tissue infection caused by MRSA.