Comparison of hospitalization costs for the same adverse reaction associated with different medications.

PURPOSE: Costs of hospitalization due to severe adverse drug reactions (ADRs) were previously estimated within the Veterans Health Administration (VHA), but additional analyses are needed to infer potential interventions to mitigate these negative outcomes. The objective of this study was to compare specific adverse reaction-related hospitalization costs between medications with similar indications. METHODS: Mean hospitalization costs associated with the same ADR symptom were compared for different drugs with similar indications using adjusted generalized linear models with a Bonferroni correction for multiple comparisons as well as a gamma distribution. RESULTS: Overall, hospitalization costs between medications with similar indications were not significantly different for specific adverse reactions. However, gastrointestinal hemorrhage-associated costs were higher for warfarin versus nonsteroidal anti-inflammatory drugs (model estimate of mean cost, $18,114 [range of lower and upper model estimates, $12,522-$26,202] vs $14,255 [estimate range, $9,710-$20,929]). Similarly, the estimated mean hospitalization cost associated with angioedema was higher for losartan versus lisinopril or lisinopril/hydrochlorothiazide: $14,591 (range, $9467-$22,488) versus $8,935 (range, $6,301-$12,669) and $8,022 (range, $5,424-$11,865), respectively. CONCLUSION: Although we found few differences in the cost of hospitalization when comparing drugs with similar indications and the same adverse reaction, there were specific drug-ADR pairs that merit attention and consideration of interventions to improve safe and appropriate medication use. Evaluation of the effect of those interventions on the incidence of ADRs is an area for future study.

Anticholinergic co-prescribing in nursing home residents using cholinesterase inhibitors: Potential deprescribing cascade.

BACKGROUND: Polypharmacy may result from inappropriate prescribing of medications to treat adverse drug reactions (ADRs), i.e., "prescribing cascade." A potentially harmful prescribing cascade affecting those with severe dementia can result when anticholinergics are prescribed to manage side effects of cholinesterase inhibitors (ChEIs). We investigated 1) factors associated with co-prescribing of anticholinergics and ChEIs and 2) whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics-a potentially beneficial reversal or "deprescribing cascade." METHODS: We conducted a retrospective analysis of linked Medicare Part A/B/D claims, Master Beneficiary Summary File, Minimum Data Set, Area Health Resource File, and Nursing Home Compare from 2015 to 2016. Subjects were Medicare beneficiaries residing in nursing homes, ≥65 years old with severe dementia admitted for non-skilled stays, who were prescribed ChEIs. Cross-sectional analysis evaluated factors associated with co-prescribing of anticholinergics with ChEIs. Longitudinal Cox proportional hazards regression examined whether discontinuation of ChEIs was associated with subsequent discontinuation of anticholinergics over a 1-year period. RESULTS: We found 15% of our sample experienced co-prescribing of anticholinergics and ChEIs. Several resident and facility-level factors were associated with co-prescribing anticholinergics. Advancing age, minority race or ethnicity, end-stage renal disease, heart failure, and poor appetite were associated with a decreased likelihood of co-prescribing. Female sex, polypharmacy, and non-geriatric prescriber-type were associated with a higher likelihood of co-prescribing. In longitudinal analyses, we observed that discontinuation of ChEIs was associated with a reduced likelihood (HR 0.58 [95% CI, 0.47-0.71]) of discontinuing any medications with anticholinergic properties, except for bladder antimuscarinics (HR 1.32 [95% CI, 0.83-2.09]). CONCLUSIONS: Younger, healthier older adults with dementia were more likely to experience co-prescribing anticholinergics and ChEIs. Discontinuation of anticholinergics was infrequent. Further research is needed to understand prescribers' ability to recognize and reverse potential prescribing cascades through deprescribing.

Patterns of oral bisphosphonate deprescribing in older nursing home residents with dementia.

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. INTRODUCTION: To determine incidence of deprescribing bisphosphonates among nursing home (NH) residents with dementia and identify factors associated with deprescribing. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Exploratory Cost-Effectiveness Analysis for Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections: Is Linezolid or Daptomycin Favored Over Vancomycin?

BACKGROUND AND OBJECTIVE: 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. Our objective was to compare the cost-effectiveness of vancomycin and other antibiotic regimens against MRSAB. METHODS: We estimated the cost-effectiveness of intravenous antibiotics (vancomycin, daptomycin, linezolid, ceftaroline/daptomycin) for Veterans Health Administration patients with MRSAB using an exploratory decision-tree model. Primary effectiveness outcome was composite of microbiological failure at 7 days and adverse drug event (ADE)-related discontinuation after at least 7 days. RESULTS: In base-case analyses, intravenous linezolid was the least expensive regimen at 4 and 6 weeks. Daptomycin was more expensive and more effective than linezolid, with an incremental cost-effectiveness ratio (ICER) of ~$13,000 (4 weeks) per composite failure avoided. With 6 weeks of treatment, daptomycin was more expensive and more effective than vancomycin (ICER ~$21,000 per composite failure avoided). Vancomycin and ceftaroline/daptomycin were dominated strategies at both 4 and 6 weeks. In one-way sensitivity analyses, vancomycin was favored when its microbiological failure risk was less than 20.1% (base-case: 27.2%), assuming a willingness to pay (WTP) threshold of $40,000/composite treatment failure avoided. In two-way sensitivity analyses, intravenous linezolid was favored if linezolid microbiological failure and ADE-related discontinuation rates were < 22.5% and < 17.3%, respectively. Daptomycin, vancomycin, and linezolid were favored in 50%, 31%, and 17% of 4-week probabilistic iterations, respectively, at $40,000 WTP. CONCLUSION: Daptomycin is likely less expensive and more effective than vancomycin or other initial regimens for MRSAB. More data are needed on the safety of linezolid against MRSAB.

Are Nursing Home Residents With Dementia Appropriately Treated for Fracture Prevention?

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) was >80 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.

Impact of deprescribing AChEIs on aggressive behaviors and antipsychotic prescribing.

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 <.001]). DISCUSSION: Deprescribing AChEIs was not associated with a worsening of aggressive behaviors or incident antipsychotic prescriptions.

Risk for Health Events After Deprescribing Acetylcholinesterase Inhibitors in Nursing Home Residents With Severe Dementia.

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.

Review of purchases of unapproved medications by the Veterans Health Administration.

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.

Factors Associated With Deprescribing Acetylcholinesterase Inhibitors in Older Nursing Home Residents With Severe Dementia.

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.

Anticholinergic Prescribing in Medicare Part D Beneficiaries Residing in Nursing Homes: Results from a Retrospective Cross-Sectional Analysis of Medicare Data.

BACKGROUND: 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. OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Pharmacy Benefits Management in the Veterans Health Administration Revisited: A Decade of Advancements, 2004-2014.

Over 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. DISCLOSURES: No 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.

Cost-Effectiveness Analysis of Adjuvant Stage III Colon Cancer Treatment at Veterans Affairs Medical Centers.

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.

Incremental cost effectiveness of pharmacist-managed erythropoiesis-stimulating agent clinics for non-dialysis-dependent chronic kidney disease patients.

BACKGROUND: Pharmacists successfully manage patients with anemia and chronic kidney disease (CKD), but the cost effectiveness of these programs is unknown. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Use of antipsychotics among older residents in VA nursing homes.

BACKGROUND: Antipsychotic medications are commonly prescribed to nursing home residents despite their well-established adverse event profiles. Because little is known about their use in Veterans Affairs (VA) nursing homes [ie, Community Living Centers (CLCs)], we assessed the prevalence and risk factors for antipsychotic use in older residents of VA CLCs. METHODS: This cross-sectional study included 3692 Veterans age 65 or older who were admitted between January 2004 and June 2005 to one of 133 VA CLCs and had a stay of ≥90 days. We used VA Pharmacy Benefits Management data to examine antipsychotic use and VA Medical SAS datasets and the Minimum Data Set to identify evidence-based indications for antipsychotic use (eg, schizophrenia, dementia with psychosis). We used multivariable logistic regression and generalized estimating equations to identify factors independently associated with antipsychotic receipt. RESULTS: Overall, 948/3692(25.7%) residents received an antipsychotic, of which 59.3% had an evidence-based indication for use. Residents with aggressive behavior [odds ratio (OR)=2.74, 95% confidence interval (CI), 2.04-3.67] and polypharmacy (9+ drugs; OR=1.84, 95% CI, 1.41-2.40) were more likely to receive antipsychotics, as were users of antidepressants (OR=1.37, 95% CI, 1.14-1.66), anxiolytic/hypnotics (OR=2.30, 95% CI, 1.64-3.23), or drugs for dementia (OR=1.52, 95% CI, 1.21-1.92). Those residing in Alzheimer/dementia special care units were also more likely to receive an antipsychotic (OR=1.66, 95% CI, 1.26-2.21). Veterans with dementia but no documented psychosis were as likely as those with an evidence-based indication to receive an antipsychotic (OR=1.10, 95% CI, 0.82-1.47). CONCLUSIONS: Antipsychotic use is common among VA nursing home residents aged 65 and older, including those without a documented evidence-based indication for use. Further quality improvement efforts are needed to reduce potentially inappropriate antipsychotic prescribing.

Incremental cost-effectiveness of various monthly doses of vardenafil.

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.

Bleeding Risk Index in an anticoagulation clinic. Assessment by indication and implications for care.

BACKGROUND: 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. OBJECTIVE: 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. DESIGN: Retrospective cohort study. PATIENTS AND MEASUREMENTS: 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. RESULTS: 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). CONCLUSIONS: The BRI discriminates between high- and intermediate-risk patients in a VA anticoagulation clinic, including those with atrial fibrillation.

The evolving use of cost-effectiveness analysis in formulary management within the Department of Veterans Affairs.

The Veterans Health Administration (VHA) runs the largest integrated healthcare system in the nation. Formulary management within VHA primarily involves 3 national groups: the Medical Advisory Panel, the Veterans Integrated Service Network Formulary Leaders, and the Pharmacy Benefits Management Strategic Healthcare Group. Together, these groups manage the VHA national drug formulary with a goal of providing a comprehensive, safe, and cost-effective pharmacy benefit for veterans. Traditionally, VHA has relied on cost-minimization analyses in formulary decisions. More recently, VHA has emphasized the use of cost-effectiveness data, especially for newer, costly drugs. In addition to including this data in drug monographs, the VHA has begun requiring formal cost-effectiveness analysis from manufacturers of selected pharmaceuticals. VHA has also requested that clinically relevant information such as quality of life plus mortality benefit be made available from industry so that internal cost analyses can be performed. It is hoped that by setting the expectation that cost-effectiveness will be formally considered in all VHA formulary decisions, the pharmaceutical industry and others will be stimulated to collect and report data that enables these analyses. We believe that if other organizations also place an emphasis on economic evaluations, industry and the public will be more accepting of decisions that incorporate cost considerations.

Equal effectiveness of older traditional antibiotics and newer broad-spectrum antibiotics in treating patients with acute exacerbations of chronic bronchitis.

BACKGROUND: Choice of antibiotic therapy for acute exacerbations of chronic bronchitis (AECB) is important because of cost and concerns about development of resistance. METHODS: A retrospective cohort study was conducted in outpatients with chronic obstructive pulmonary disease and documented AECB treated with antibiotics. RESULTS: We compared outcomes and costs of AECB treated with first-line antibiotics having partial coverage against organisms associated with AECB (eg, amoxicillin), first-line antibiotics with full coverage against organisms associated with AECB (eg, sulfamethoxazole-trimethoprim), and newer broad-spectrum antibiotics (eg, azithromycin). There were no significant differences among the three antibiotic groups in failure rate, hospitalization rate, or time until subsequent AECB. Pharmacy costs were significantly less with first-line antibiotics (3.18 dollars +/- 0.64, 3.00 dollars +/- 0.48, and 36.70 dollars +/- 16.29, respectively; P < 0.0001), but there was no significant difference among all three groups with regard to total costs. CONCLUSION: We found no difference in outcome between older traditional antibiotics with adequate coverage against organisms associated with AECB and newer broad-spectrum antibiotics.