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.

PCSK9 Inhibitor Use and Outcomes Using Concomitant Lipid-Lowering Therapies in the Veterans Health Administration.

Background: Real-world data on use of PCSK9 inhibitors (PCSK9-Is), with or without statins and/or ezetimibe, and associated outcomes, can inform more effective prescribing. The objective was to evaluate clinical effectiveness and safety of PCSK9-Is within the Veterans Health Administration (VHA). Methods: In this retrospective cohort study, we included Veterans who had at least one outpatient prescription for alirocumab and/or evolocumab filled within VHA between August 21, 2015, and September 30, 2020. Analyses included 4 mutually exclusive subgroups: PCSK9-I alone, PCSK9-I+statin, PCSK9-I+ezetimibe, and PCSK9-I+statin+ezetimibe subgroups. Primary outcomes included medication possession ratio, persistence, and low-density lipoprotein (LDL). Results: Among Veterans in the analytical cohort (n = 2428), 36.2% were on PCSK9-I monotherapy; 24.0% received a PCSK9-I+statin; 27.4% were on a PCSK9-I+ezetimibe; and 12.4% received triple therapy, that is, PCSK9-I+statin+ezetimibe. The mean medication possession ratio (standard deviation [SD]) for PCSK9-I monotherapy was 83.8% (13.3) compared to 84.3% (11.2) with PCSK9-I+statin therapy, 87.1% (10.1) with PCSK9-I+ezetimibe therapy, and 85.8% (11.7) with triple therapy. The percentage of patients who discontinued PCSK9-I in the monotherapy subgroup was 12.3% vs 9.5%, 6.6%, and 7.4% in the concomitant statin, ezetimibe, and triple-therapy subgroups, respectively (p = .002 among the groups). Mean LDL level was greater in the PCSK9-I monotherapy subgroup (85.6 mg/dL) compared with the concomitant statin (66.5 mg/dL), ezetimibe (65.7 mg/dL), and triple-therapy subgroups (68.1 mg/dL). Conclusions: Veterans showed good adherence and/or persistence with PCSK9-I regimens. On average, those receiving concomitant therapy with a statin and/or ezetimibe achieved significantly lower LDL levels.

Effect of Deintensifying Diabetes Medications on Negative Events in Older Veteran Nursing Home Residents.

OBJECTIVE: Guidelines advocate against tight glycemic control in older nursing home (NH) residents with advanced dementia (AD) or limited life expectancy (LLE). We evaluated the effect of deintensifying diabetes medications with regard to all-cause emergency department (ED) visits, hospitalizations, and death in NH residents with LLE/AD and tight glycemic control. RESEARCH DESIGN AND METHODS: We conducted a national retrospective cohort study of 2,082 newly admitted nonhospice veteran NH residents with LLE/AD potentially overtreated for diabetes (HbA1c ≤7.5% and one or more diabetes medications) in fiscal years 2009-2015. Diabetes treatment deintensification (dose decrease or discontinuation of a noninsulin agent or stopping insulin sustained ≥7 days) was identified within 30 days after HbA1c measurement. To adjust for confounding, we used entropy weights to balance covariates between NH residents who deintensified versus continued medications. We used the Aalen-Johansen estimator to calculate the 60-day cumulative incidence and risk ratios (RRs) for ED or hospital visits and deaths. RESULTS: Diabetes medications were deintensified for 27% of residents. In the subsequent 60 days, 28.5% of all residents were transferred to the ED or acute hospital setting for any cause and 3.9% died. After entropy weighting, deintensifying was not associated with 60-day all-cause ED visits or hospitalizations (RR 0.99 [95% CI 0.84, 1.18]) or 60-day mortality (1.52 [0.89, 2.81]). CONCLUSIONS: Among NH residents with LLE/AD who may be inappropriately overtreated with tight glycemic control, deintensification of diabetes medications was not associated with increased risk of 60-day all-cause ED visits, hospitalization, or death.

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.

Effectiveness of a Calculation-Free Weight-Based Unfractionated Heparin Nomogram With Anti-Xa Level Monitoring Compared With Activated Partial Thromboplastin Time.

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.

Antihypertensive Deprescribing in Older Adult Veterans at End of Life Admitted to Veteran Affairs Nursing Homes.

OBJECTIVES: Geriatric palliative care approaches support deprescribing of antihypertensives in older nursing home (NH) residents with limited life expectancy and/or advanced dementia (LLE/AD) who are intensely treated for hypertension (HTN), but information on real-world deprescribing patterns in this population is limited. We examined the incidence and factors associated with antihypertensive deprescribing. DESIGN: National, retrospective cohort study. SETTING AND PARTICIPANTS: Older Veterans with LLE/AD and HTN admitted to VA NHs in fiscal years 2009-2015 with potential overtreatment of HTN at admission, defined as receiving at least 1 antihypertensive class of medications and mean daily systolic blood pressure (SBP) <120 mm Hg. MEASURES: Deprescribing was defined as subsequent dose reduction or discontinuation of an antihypertensive for ≥7 days. Competing risk models assessed cumulative incidence and factors associated with deprescribing. RESULTS: Within our sample (n = 10,574), cumulative incidence of deprescribing at 30 days was 41%. Veterans with the greatest level of overtreatment (ie, multiple antihypertensives and SBP <100 mm Hg) had an increased likelihood (hazard ratio 1.75, 95% confidence interval 1.59, 1.93) of deprescribing vs those with the lowest level of overtreatment (ie, one antihypertensive and SBP ≥100 to <120 mm Hg). Several markers of poor prognosis (ie, recent weight loss, poor appetite, dehydration, dependence for activities of daily living, pain) and later admission year were associated with increased likelihood of deprescribing, whereas cardiovascular risk factors (ie, diabetes, congestive heart failure, obesity), shortness of breath, and admission source from another NH or home/assisted living setting (vs acute hospital) were associated with decreased likelihood. CONCLUSIONS AND IMPLICATIONS: Real-world deprescribing patterns of antihypertensives among NH residents with HTN and LLE/AD appear to reflect variation in recommendations for HTN treatment intensity and individualization of patient care in a population with potential overtreatment. Factors facilitating deprescribing included treatment intensity and markers of poor prognosis. Comparative effectiveness and safety studies are needed to guide clinical decisions around deprescribing and HTN management.

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.

Serious cardiovascular adverse events with fluoroquinolones versus other antibiotics: A self-controlled case series analysis.

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.

Discontinuation of Statins in Veterans Admitted to Nursing Homes near the End of Life.

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.

Incidence and Predictors of Aspirin Discontinuation in Older Adult Veteran Nursing Home Residents at End of Life.

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.

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.

Deintensification of Diabetes Medications among Veterans at the End of Life in VA Nursing Homes.

OBJECTIVES: Many older adults with limited life expectancy and/or advanced dementia (LLE/AD) are potentially overtreated for diabetes and may benefit from deintensification. Our aim was to examine the incidence and predictors of diabetes medication deintensification in older Veterans with LLE/AD who were potentially overtreated at admission to Veterans Affairs (VA) nursing homes (community living centers [CLCs]). DESIGN: Retrospective cohort study using linked VA and Medicare clinical/administrative data and Minimum Data Set assessments. SETTING: VA CLCs. PARTICIPANTS: A total of 6960 Veterans with diabetes and LLE/AD admitted to VA CLCs in fiscal years 2009 to 2015 with hemoglobin (Hb)A1c measured within 90 days of admission. MEASUREMENTS: We evaluated treatment deintensification (discontinuation or dose reduction for a consecutive 7-day period) among residents who were potentially overtreated (HbA1c ≤7.5% and receiving hypoglycemic medications). Competing risk models assessed 90-day cumulative incidence of deintensification. RESULTS: More than 40% (n = 3056) of Veteran CLC residents with diabetes were potentially overtreated. The cumulative incidence of deintensification at 90 days was 45.5%. Higher baseline HbA1c values were associated with a lower likelihood of deintensification (e.g., HbA1c 7.0-7.5% vs <6.0%; adjusted risk ratio [aRR] = .57; 95% confidence interval [CI] = .50-.66). Compared with non-sulfonylurea oral agents (e.g., metformin), other treatment regimens were more likely to be deintensified (aRR = 1.31-1.88), except for basal insulin (aRR = .59; 95% CI = .52-.66). The only resident factor associated with increased likelihood of deintensification was documented end-of-life status (aRR = 1.12; 95% CI = 1.01-1.25). Admission from home/assisted living (aRR = .85; 95% CI = .75-.96), obesity (aRR = .88; 95% CI = .78-.99), and peripheral vascular disease (aRR = .90; 95% CI = .81-.99) were associated with decreased likelihood of deintensification. CONCLUSION: Deintensification of treatment regimens occurred in less than one-half of potentially overtreated Veterans and was more strongly associated with low HbA1c values and use of medications with high risk for hypoglycemia, rather than other resident characteristics. J Am Geriatr Soc 68:736-745, 2020.

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.

Reporting of adverse drug events in the Veterans Health Administration for patients whose treatment with empagliflozin or apixaban was discontinued.

PURPOSE: To examine the reporting rates of adverse drug events (ADEs) with apixaban and empagliflozin as reports move up to the next level of spontaneous reporting. METHODS: This 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. RESULTS: From 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. CONCLUSION: We found substantial underreporting of apixaban and empagliflozin ADEs that became worse at each higher level of spontaneous reporting.

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.

Use of targeted therapies for advanced renal cell carcinoma in the Veterans Health Administration.

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.