Willingness of older people living with dementia and mild cognitive impairment and their caregivers to have medications deprescribed.

BACKGROUND: people living with cognitive impairment commonly take multiple medications including potentially inappropriate medications (PIMs), which puts them at risk of medication related harms. AIMS: to explore willingness to have a medication deprescribed of older people living with cognitive impairment (dementia or mild cognitive impairment) and multiple chronic conditions and assess the relationship between willingness, patient characteristics and belief about medications. METHODS: cross-sectional study using results from the revised Patients' Attitudes Towards Deprescribing questionnaire (rPATDcog) collected as baseline data in the OPTIMIZE study, a pragmatic, cluster-randomised trial educating patients and clinicians about deprescribing. Eligible participants were 65+, diagnosed with dementia or mild cognitive impairment, and prescribed at least five-long-term medications. RESULTS: the questionnaire was mailed to 1,409 intervention patients and 553 (39%) were returned and included in analysis. Participants had a mean age of 80.1 (SD 7.4) and 52.4% were female. About 78.5% (431/549) of participants said that they would be willing to have one of their medications stopped if their doctor said it was possible. Willingness to deprescribe was negatively associated with getting stressed when changes are made and with previously having a bad experience with stopping a medication (P < 0.001 for both). CONCLUSION: most older people living with cognitive impairment are willing to deprescribe. Addressing previous bad experiences with stopping a medication and stress when changes are made to medications may be key points to discuss during deprescribing conversations.

Adults With Asthma Experience No Increase in Asthma-related Exacerbations When Digital Communication Technology Tools Are Employed to Offset Provider Workload: A Pragmatic Randomized Trial.

BACKGROUND: Challenges to health care efficiency are increasingly addressed with the help of digital communication technology tools (DCTs). OBJECTIVE: The objective of this study was to test whether DCT, compared with Usual Care, can reduce health care clinician burden without increasing asthma-related exacerbations among patients with asthma in a large integrated health care system. RESEARCH DESIGN: The (Breathewell) program was a pragmatic, randomized trial at (Kaiser Permanente Colorado), where asthma nurses screen patients for poor symptom control when beta2-agonist refill requests came within 60 days of previous fill or in the absence of a controller medication fill within 4 months (beta2-agonist overfill). A total of 14,978 adults with asthma were randomized to Usual Care or 1 of 2 DCT intervention groups (Text/Phone call or Email). SUBJECTS: Participants included adults 18 and older with an asthma diagnosis at the time of randomization and no history of chronic obstructive pulmonary disease. MEASURES: Primary outcome measures included asthma-related health care resource utilization (eg, asthma nurse contacts), medication use, and exacerbations. RESULTS: A total of 1933 patients had 4337 events which met beta2-agonist overfill criteria. Of the 2874 events in the intervention arm, 1188 (41%) were resolved by DCT contact and did not require additional clinician contact. Asthma medication use and exacerbations over 12 months did not differ among the 3 groups. CONCLUSIONS: DCT tools can successfully contact adult asthma patients to screen for symptoms and facilitate intervention. The absence of differences in medication fills and health care utilization indicates that the strategic replacement of nursing interventions by digital outreach did not reduce treatment adherence or compromise health care outcomes.

Predictors of Hyperkalemia and Hypokalemia in Individuals with Diabetes: a Classification and Regression Tree Analysis.

BACKGROUND: Both hyperkalemia and hypokalemia can lead to cardiac arrhythmias and are associated with increased mortality. Information on the predictors of potassium in individuals with diabetes in routine clinical practice is lacking. OBJECTIVE: To identify predictors of hyperkalemia and hypokalemia in adults with diabetes. DESIGN: Retrospective cohort study, with classification and regression tree (CART) analysis. PARTICIPANTS: 321,856 individuals with diabetes enrolled in four large integrated health care systems from 2012 to 2013. MAIN MEASURES: We used a single serum potassium result collected in 2012 or 2013. Hyperkalemia was defined as a serum potassium ≥ 5.5 mEq/L and hypokalemia as < 3.5 mEq/L. Predictors included demographic factors, laboratory measurements, comorbidities, medication use, and health care utilization. KEY RESULTS: There were 2556 hypokalemia events (0.8%) and 1517 hyperkalemia events (0.5%). In univariate analyses, we identified concordant predictors (associated with increased probability of both hyperkalemia and hypokalemia), discordant predictors, and predictors of only hyperkalemia or hypokalemia. In CART models, the hyperkalemia "tree" had 5 nodes and a c-statistic of 0.76. The nodes were defined by prior potassium results and eGFRs, and the 5 terminal "leaves" had hyperkalemia probabilities of 0.2 to 7.2%. The hypokalemia tree had 4 nodes and a c-statistic of 0.76. The hypokalemia tree included nodes defined by prior potassium results, and the 4 terminal leaves had hypokalemia probabilities of 0.3 to 17.6%. Individuals with a recent potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no hypokalemia in the previous year had a < 1% rate of either hypokalemia or hyperkalemia. CONCLUSIONS: The yield of routine serum potassium testing may be low in individuals with a recent serum potassium between 4.0 and 5.0 mEq/L, eGFR ≥ 45 mL/min/1.73m2, and no recent history of hypokalemia. We did not examine the effect of recent changes in clinical condition or medications on acute potassium changes.

Randomized Clinical Trial of a Clinical Decision Support Tool for Improving the Appropriateness Scores for Ordering Imaging Studies in Primary and Specialty Care Ambulatory Clinics.

OBJECTIVE. The objective of our study was to evaluate whether the use of a clinical decision support (CDS) tool improved the appropriateness scores of orders for advanced imaging in clinical practice. MATERIALS AND METHODS. We used a stepped-wedge, cluster randomized clinical trial to evaluate the effectiveness of a CDS tool in an integrated health care system. Clinicians entered structured indications for each CT and MRI order, and the indications were electronically scored against appropriateness criteria to assign an appropriateness score. We compared the proportion of orders with adjusted appropriateness scores of 7 or greater (on a 1-9 scale) before and after activation of best practice alerts (BPAs) triggered for orders with low or marginal appropriateness scores. Secondary outcomes included the rate per month of orders for advanced imaging and the proportion of orders for which the radiology department requested changes. RESULTS. Between October 2015 and February 2016, 941 clinicians ordered 22,279 CT or MRI studies that met eligibility criteria. Before activation of the BPA, the mean proportion of appropriate orders (adjusted for time and clinic effect) was 77.0% (95% CI, 75.5-78.4%), which increased to 80.1% (95% CI, 78.7-81.5%) after activation (p = 0.001). There was no significant change in the rate of orders per month for advanced imaging. The proportion of order changes requested by the radiology department decreased from 5.7% (95% CI, 5.6-5.9%) before CDS implementation to 5.3% (95% CI, 5.1-5.5%) after CDS implementation (p < 0.001). CONCLUSION. Using an evidence-based CDS tool in clinical practice was associated with a modest but significant improvement in the appropriateness scores of advanced imaging orders.

Diagnosis-based cohort augmentation using laboratory results data: The case of chronic kidney disease.

PURPOSE: In this report, we use data from FDA's Sentinel System to focus on how augmenting a diagnosis-based chronic kidney disease cohort with patients identified through laboratory results impacts cohort characteristics and outcomes. METHODS: We used data from 2 Data Partners. Patients were eligible if they were health plan members on January 1, 2012. We classified chronic kidney disease patients into mutually exclusive categories according to the hierarchy of (1) ICD-9-CM diagnosis (DXGroup), or (2) two estimated glomerular filtration rates <60 mL/min/1.73m2 , separated by at least 90 days (2-LabGroup), or (3) a single estimated glomerular filtration rates <60 mL/min/1.73m2 (1-LabGroup). We compared the groups on demographic, clinical, and health care utilization characteristics using pairwise standardized differences. We used Cox regression to compare the groups on mortality, adjusting for baseline covariates. RESULTS: We identified 209 864 patients: 107 607 in DxGroup (51%) and 102 257 (49%) from laboratory data alone. For every characteristic, the DxGroup was the sickest, followed by the 2-LabGroup and then the 1-LabGroup. The DxGroup was more likely to die than 2-LabGroup (hazard ratio [HR], 1.47; 95% CI, 1.22-1.77) at Site 1; that effect was observed, but attenuated, at Site 2 (HR, 1.16; 95% CI, 1.07-1.25). The DxGroup was more likely to die than the 1-LabGroup at Site 1 (HR, 1.36; 95% CI, 1.20-1.55), but not at Site 2 (HR, 0.94; 95% CI, 0.89-1.00). CONCLUSIONS: We suggest that drug safety researchers consider whether the method of cohort identification contributes to generalizability of safety findings.

Risk of Breast Cancer With Long-Term Use of Calcium Channel Blockers or Angiotensin-Converting Enzyme Inhibitors Among Older Women.

Controversy exists about breast cancer risk associated with long-term use of calcium channel blockers (CCBs) or angiotensin-converting enzyme inhibitors (ACEis), respectively. Our objective in this study was to separately evaluate associations between duration of CCB or ACEi use and breast cancer in hypertensive women aged ≥55 years at 3 sites in the Kaiser Permanente health-care system (1997­2012). Exposures included CCB or ACEi use of 1­12 years' duration, determined from pharmacy dispensings. Outcomes included invasive lobular or ductal carcinoma. Statistical methods included discrete-time survival analyses. The cohort included 19,674 (17.9%) CCB users and 90,078 (82.1%) ACEi users. Two percent (n = 397) of CCB users and 1.9% (n = 1,733) of ACEi users developed breast cancer. Compared with 1­<2 years of use, in adjusted analysis, there was no association between CCB use for 2­<12 years and breast cancer: All 95% confidence intervals included 1. Increasing duration of ACEi use was associated with reduced breast cancer risk: Compared with 1­<2 years of use, the adjusted hazard ratio was 0.76 (95% confidence interval: 0.63, 0.92) for 5­<6 years of use and 0.63 (95% confidence interval: 0.43, 0.93) for 9­<10 years of use. We conclude that among older women with hypertension, long-term CCB use does not increase breast cancer risk and long-term treatment with ACEis may confer protection against breast cancer.

The Contemporary Safety and Effectiveness of Lower Extremity Bypass Surgery and Peripheral Endovascular Interventions in the Treatment of Symptomatic Peripheral Arterial Disease.

BACKGROUND: Treatment for symptomatic peripheral artery disease includes lower extremity bypass surgery (LEB) and peripheral endovascular interventions (PVIs); however, limited comparative effectiveness data exist between the 2 therapies. We assessed the safety and effectiveness of LEB and PVI in patients with symptomatic claudication and critical limb ischemia. METHODS AND RESULTS: In a community-based clinical registry at 2 large integrated healthcare delivery systems, we compared 883 patients undergoing PVI and 975 patients undergoing LEB between January 1, 2005 and December 31, 2011. Rates of target lesion revascularization were greater for PVI than for LEB in patients presenting with claudication (12.3±2.7% and 19.0±3.5% at 1 and 3 years versus 5.2±2.4% and 8.3±3.1%, log-rank P<0.001) and critical limb ischemia (19.1±4.8% and 31.6±6.3% at 1 and 3 years versus 10.8±2.5% and 16.0±3.2%, log-rank P<0.001). However, in comparison with PVI, LEB was associated with increased rates of complications up to 30 days following the procedure (37.1% versus 11.9%, P<0.001). There were no differences in amputation rates between the 2 groups. Findings remained consistent in sensitivity analyses by using propensity methods to account for treatment selection. CONCLUSIONS: In patients with symptomatic peripheral artery disease, in comparison with LEB, PVI was associated with fewer 30-day procedural complications, higher revascularization rates at 1 and 3 years, and no difference in subsequent amputations.

Evaluation of propensity scores, disease risk scores, and regression in confounder adjustment for the safety of emerging treatment with group sequential monitoring.

PURPOSE: The objective of this study was to evaluate regression, matching, and stratification on propensity score (PS) or disease risk score (DRS) in a setting of sequential analyses where statistical hypotheses are tested multiple times. METHODS: In a setting of sequential analyses, we simulated incident users and binary outcomes with different confounding strength, outcome incidence, and the adoption rate of treatment. We compared Type I error rate, empirical power, and time to signal using the following confounder adjustments: (i) regression; (ii) treatment matching (1:1 or 1:4) on PS or DRS; and (iii) stratification on PS or DRS. We estimated PS and DRS using lookwise and cumulative methods (all data up to the current look). We applied these confounder adjustments in examining the association between non-steroidal anti-inflammatory drugs and bleeding. RESULTS: Propensity score and DRS methods had similar empirical power and time to signal. However, DRS methods yielded Type I error rates up to 17% for 1:4 matching and 15.3% for stratification methods when treatment and outcome were common and confounding strength with treatment was stronger. When treatment and outcome were not common, stratification on PS and DRS and regression yielded 8-10% Type I error rates and inflated empirical power. However, when outcome and treatment were common, both regression and stratification on PS outperformed other matching methods with Type I error rates close to 5%. CONCLUSIONS: We suggest regression and stratification on PS when the outcomes and/or treatment is common and use of matching on PS with higher ratios when outcome or treatment is rare or moderately rare.

Methods for using clinical laboratory test results as baseline confounders in multi-site observational database studies when missing data are expected.

PURPOSE: Our purpose was to quantify missing baseline laboratory results, assess predictors of missingness, and examine performance of missing data methods. METHODS: Using the Mini-Sentinel Distributed Database from three sites, we selected three exposure-outcome scenarios with laboratory results as baseline confounders. We compared hazard ratios (HRs) or risk differences (RDs) and 95% confidence intervals (CIs) from models that omitted laboratory results, included only available results (complete cases), and included results after applying missing data methods (multiple imputation [MI] regression, MI predictive mean matching [PMM] indicator). RESULTS: Scenario 1 considered glucose among second-generation antipsychotic users and diabetes. Across sites, glucose was available for 27.7-58.9%. Results differed between complete case and missing data models (e.g., olanzapine: HR 0.92 [CI 0.73, 1.12] vs 1.02 [0.90, 1.16]). Across-site models employing different MI approaches provided similar HR and CI; site-specific models provided differing estimates. Scenario 2 evaluated creatinine among individuals starting high versus low dose lisinopril and hyperkalemia. Creatinine availability: 44.5-79.0%. Results differed between complete case and missing data models (e.g., HR 0.84 [CI 0.77, 0.92] vs. 0.88 [0.83, 0.94]). HR and CI were identical across MI methods. Scenario 3 examined international normalized ratio (INR) among warfarin users starting interacting versus noninteracting antimicrobials and bleeding. INR availability: 20.0-92.9%. Results differed between ignoring INR versus including INR using missing data methods (e.g., RD 0.05 [CI -0.03, 0.13] vs 0.09 [0.00, 0.18]). Indicator and PMM methods gave similar estimates. CONCLUSION: Multi-site studies must consider site variability in missing data. Different missing data methods performed similarly. Copyright © 2016 John Wiley & Sons, Ltd.

Anatomic runoff score predicts cardiovascular outcomes in patients with lower extremity peripheral artery disease undergoing revascularization.

BACKGROUND: Although the presence, extent, and severity of obstruction in patients with lower extremity peripheral artery disease (LE PAD) affect their functional status, quality of life, and treatment, it is not known if these factors are associated with future cardiovascular events. We empirically created an anatomic runoff score (ARS) to approximate the burden of LE PAD and determined its association with clinical outcomes. METHODS: We evaluated all patients with LE PAD and bilateral angiography undergoing revascularization in a community-based clinical study. Primary clinical outcomes of interest were (1) a composite of all-cause death, myocardial infarction (MI), and stroke and (2) amputation-free survival. Cox proportional hazards models were created to identify predictors of clinical outcomes. RESULTS: We evaluated 908 patients undergoing angiography, and a total of 260 (28.0%) patients reached the composite end point (45 MI, 63 stroke, and 152 death) during the study period. Anatomic runoff score ranged from 0 to 15 (mean 4.7; SD 2.5) with higher scores indicating a higher burden of disease, and an optimal cutpoint analysis classified patients into low ARS (<5) and high ARS (≥5). The unadjusted rates of the primary composite end point and amputation-free survival were nearly 2-fold higher in patients with a high ARS when compared with patients with a low ARS. The most significant predictors of the composite end point (death/MI/stroke) were age (δ 10 years; hazard ratio [HR] 1.53; CI 1.32-1.78; P < .001), diabetes mellitus (HR 1.65; CI 1.26-2.18; P < .001), glomerular filtration rate <30 (HR 2.23; CI 1.44-3.44; P < .001), statin use (HR 0.66; CI 0.48-0.88; P < .001), and ARS (δ 2 points; HR 1.21; CI 1.08-1.35; P < .001). CONCLUSIONS: After adjustment for clinical factors, the LE PAD ARS was an independent predictor of future cardiovascular morbidity and mortality in a broadly representative patient population undergoing revascularization for symptomatic PAD. A clinically useful anatomic scoring system, if validated, may assist clinicians in risk stratification during the course of clinical decision making.

PCSK9 inhibition fails to alter hepatic LDLR, circulating cholesterol, and atherosclerosis in the absence of ApoE.

LDL cholesterol (LDL-C) contributes to coronary heart disease. Proprotein convertase subtilisin/kexin type 9 (PCSK9) increases LDL-C by inhibiting LDL-C clearance. The therapeutic potential for PCSK9 inhibitors is highlighted by the fact that PCSK9 loss-of-function carriers exhibit 15-30% lower circulating LDL-C and a disproportionately lower risk (47-88%) of experiencing a cardiovascular event. Here, we utilized pcsk9(-/-) mice and an anti-PCSK9 antibody to study the role of the LDL receptor (LDLR) and ApoE in PCSK9-mediated regulation of plasma cholesterol and atherosclerotic lesion development. We found that circulating cholesterol and atherosclerotic lesions were minimally modified in pcsk9(-/-) mice on either an LDLR- or ApoE-deficient background. Acute administration of an anti-PCSK9 antibody did not reduce circulating cholesterol in an ApoE-deficient background, but did reduce circulating cholesterol (-45%) and TGs (-36%) in APOE*3Leiden.cholesteryl ester transfer protein (CETP) mice, which contain mouse ApoE, human mutant APOE3*Leiden, and a functional LDLR. Chronic anti-PCSK9 antibody treatment in APOE*3Leiden.CETP mice resulted in a significant reduction in atherosclerotic lesion area (-91%) and reduced lesion complexity. Taken together, these results indicate that both LDLR and ApoE are required for PCSK9 inhibitor-mediated reductions in atherosclerosis, as both are needed to increase hepatic LDLR expression.

Privacy-preserving analytic methods for multisite comparative effectiveness and patient-centered outcomes research.

BACKGROUND: For privacy and practical reasons, it is sometimes necessary to minimize sharing of individual-level information in multisite studies. However, individual-level information is often needed to perform more rigorous statistical analysis. OBJECTIVES: To compare empirically 3 analytic methods for multisite studies that only require sharing of summary-level information to perform statistical analysis that have traditionally required access to detailed individual-level data from each site. RESEARCH DESIGN, SUBJECTS, AND MEASURES: We analyzed data from a 7-site study of bariatric surgery outcomes within the Scalable Partnering Network. We compared the long-term risk of rehospitalization between adjustable gastric banding and Roux-en-y gastric bypass procedures using a stratified analysis of propensity score (PS)-defined strata, a case-centered analysis of risk set data, and a meta-analysis of site-specific effect estimates. Their results were compared with the result from a pooled individual-level data analysis. RESULTS: The study included 1327 events (18.1%) among 7342 patients. The adjusted hazard ratio was 0.71 (95% CI, 0.59, 0.84) comparing adjustable gastric banding with Roux-en-y gastric bypass in the individual-level data analysis. The corresponding effect estimate was 0.70 (0.59, 0.83) in the PS-stratified analysis, 0.71 (0.59, 0.84) in the case-centered analysis, and 0.71 (0.60, 0.84) in both the fixed-effect and random-effects meta-analysis. CONCLUSIONS: In this empirical study, PS-stratified analysis, case-centered analysis, and meta-analysis produced results that are identical or highly comparable with the result from a pooled individual-level data analysis. These methods have the potential to be viable analytic alternatives when sharing of individual-level information is not feasible or not preferred in multisite studies.

Estimating the effects of time-varying exposures in observational studies using Cox models with stabilized weights adjustment.

PURPOSE: Assessing the safety and effectiveness of medical products with observational electronic medical record data is challenging when the treatment is time-varying. The objective of this paper is to develop a Cox model stratified by event times with stabilized weights (SWs) adjustment to examine the effect of time-varying treatment in observational studies. METHODS: Time-varying SWs are calculated at unique event times and are used in a Cox model stratified by event times to estimate the effect of time-varying treatment. We applied this method in examining the effect of an antiplatelet agent, clopidogrel, on events, including bleeding, myocardial infarction, and death after a drug-eluting stent was implanted in coronary artery. Clopidogrel use may change over time on the basis of patients' behavior (e.g., non-adherence) and physicians' recommendations (e.g., end of duration of therapy). We also compared the results with those from a Cox model for counting processes adjusting for all covariates used in creating SWs. RESULTS: We demonstrate that the (i) results from the stratified Cox model without SWs adjustment and the Cox model for counting processes without covariate adjustment are identical in analyzing the clopidogrel data; and (ii) the effects of clopidogrel on bleeding, myocardial infarction, and death are larger in the stratified Cox model with SWs adjustment compared with those from the Cox model for counting processes with covariate adjustment. CONCLUSIONS: The Cox model stratified by event times with time-varying SWs adjustment is useful in estimating the effect of time-varying treatments in observational studies while balancing for known confounders.

Evaluating the Safety of an Educational Deprescribing Intervention: Lessons from the Optimize Trial.

BACKGROUND: Patients, family members, and clinicians express concerns about potential adverse drug withdrawal events (ADWEs) following medication discontinuation or fears of upsetting a stable medical equilibrium as key barriers to deprescribing. Currently, there are limited methods to pragmatically assess the safety of deprescribing and ascertain ADWEs. We report the methods and results of safety monitoring for the OPTIMIZE trial of deprescribing education for patients, family members, and clinicians. METHODS: This was a pragmatic cluster randomized trial with multivariable Poisson regression comparing outcome rates between study arms. We conducted clinical record review and adjudication of sampled records to assess potential causal relationships between medication discontinuation and outcomes. This study included adults aged 65+ with dementia or mild cognitive impairment, one or more additional chronic conditions, and prescribed 5+ chronic medications. The intervention included an educational brochure on deprescribing that was mailed to patients prior to primary care visits, a clinician notification about individual brochure mailings, and an educational tip sheets was provided monthly to primary care clinicians. The outcomes of the safety monitoring were rates of hospitalizations and mortality during the 4 months following brochure mailings and results of record review and adjudication. The adjudication process was conducted throughout the trial and included classifications: likely, possibly, and unlikely. RESULTS: There was a total of 3012 (1433 intervention and 1579 control) participants. There were 420 total hospitalizations involving 269 (18.8%) people in the intervention versus 517 total hospitalizations involving 317 (20.1%) people in the control groups. Adjusted risk ratios comparing intervention to control groups were 0.92 [95% confidence interval (CI) 0.72, 1.16] for hospitalization and 1.19 (95% CI 0.67, 2.11) for mortality. Both groups had zero deaths "likely" attributed to a medication change prior to the event. A total of 3 out of 30 (10%) intervention group hospitalizations and 7 out of 35 (20%) control group hospitalizations were considered "likely" due to a medication change. CONCLUSIONS: Population-based deprescribing education is safe in the older adult population with cognitive impairment in our study. Pragmatic methods for safety monitoring are needed to further inform deprescribing interventions. TRIAL REGISTRATION: NCT03984396. Registered on 13 June 2019.

Geographic variation in cardiovascular procedure use among Medicare fee-for-service vs Medicare Advantage beneficiaries.

IMPORTANCE: Little is known about how different financial incentives between Medicare Advantage and Medicare fee-for-service (FFS) reimbursement structures influence use of cardiovascular procedures. OBJECTIVE: To compare regional cardiovascular procedure rates between Medicare Advantage and Medicare FFS beneficiaries. DESIGN, SETTING, AND PARTICIPANTS: Cross-sectional study of Medicare beneficiaries older than 65 years between 2003-2007 comparing rates of coronary angiography, percutaneous coronary intervention (PCI), and coronary artery bypass graft (CABG) surgery across 32 hospital referral regions in 12 states. MAIN OUTCOMES AND MEASURES: Rates of coronary angiography, PCI, and CABG surgery. RESULTS: We evaluated a total of 878,339 Medicare Advantage patients and 5,013,650 Medicare FFS patients. Compared with Medicare FFS patients, Medicare Advantage patients had lower age-, sex-, race-, and income-adjusted procedure rates per 1000 person-years for angiography (16.5 [95% CI, 14.8-18.2] vs 25.9 [95% CI, 24.0-27.9]; P < .001) and PCI (6.8 [95% CI, 6.0-7.6] vs 9.8 [95% CI, 9.0-10.6]; P < .001) but similar rates for CABG surgery (3.1 [95% CI, 2.8-3.5] vs 3.4 [95% CI, 3.1-3.7]; P = .33). There were no significant differences between Medicare Advantage and Medicare FFS patients in the rates per 1000 person-years of urgent angiography (3.9 [95% CI, 3.6-4.2] vs 4.3 [95% CI, 4.0-4.6]; P = .24) or PCI (2.4 [95% CI, 2.2-2.7] vs 2.7 [95% CI, 2.5-2.9]; P = .16). Procedure rates varied widely across hospital referral regions among Medicare Advantage and Medicare FFS patients. For angiography, the rates per 1000 person-years ranged from 9.8 to 40.6 for Medicare Advantage beneficiaries and from 15.7 to 44.3 for Medicare FFS beneficiaries. For PCI, the rates ranged from 3.5 to 16.8 for Medicare Advantage and from 4.7 to 16.1 for Medicare FFS. The rates for CABG surgery ranged from 1.5 to 6.1 for Medicare Advantage and from 2.5 to 6.0 for Medicare FFS. Across regions, we found no statistically significant correlation between Medicare Advantage and Medicare FFS beneficiary utilization for angiography (Spearman r = 0.19, P = .29) and modest correlations for PCI (Spearman r = 0.33, P = .06) and CABG surgery (Spearman r = 0.35, P = .05). Among Medicare Advantage beneficiaries, adjustment for additional cardiac risk factors had little influence on procedure rates. CONCLUSIONS AND RELEVANCE: Although Medicare beneficiaries enrolled in capitated Medicare Advantage programs had lower angiography and PCI procedure rates than those enrolled in Medicare FFS, the degree of geographic variation in procedure rates was substantial among Medicare Advantage beneficiaries and was similar in magnitude to that observed among Medicare FFS beneficiaries.

Ethical Aspects of Physician Decision-Making for Deprescribing Among Older Adults With Dementia.

Importance: Physicians endorse deprescribing of risky or unnecessary medications for older adults (aged ≥65 years) with dementia, but there is a lack of information on what influences decisions to deprescribe in this population. Objective: To understand how physicians make decisions to deprescribe for older adults with moderate dementia and ethical and pragmatic concerns influencing those decisions. Design, Setting, and Participants: A cross-sectional national mailed survey study of a random sample of 3000 primary care physicians from the American Medical Association Physician Masterfile who care for older adults was conducted from January 15 to December 31, 2021. Main Outcomes and Measures: The study randomized participants to consider 2 clinical scenarios in which a physician may decide to deprescribe a medication for older adults with moderate dementia: 1 in which the medication could cause an adverse drug event if continued and the other in which there is no evidence of benefit. Participants ranked 9 factors related to possible ethical and pragmatic concerns through best-worst scaling methods (from greatest barrier to smallest barrier to deprescribing). Conditional logit regression quantified the relative importance for each factor as a barrier to deprescribing. Results: A total of 890 physicians (35.0%) returned surveys; 511 (57.4%) were male, and the mean (SD) years since graduation was 26.0 (11.7). Most physicians had a primary specialty in family practice (50.4% [449 of 890]) and internal medicine (43.5% [387 of 890]). A total of 689 surveys were sufficiently complete to analyze. In both clinical scenarios, the 2 greatest barriers to deprescribing were (1) the patient or family reporting symptomatic benefit from the medication (beneficence and autonomy) and (2) the medication having been prescribed by another physician (autonomy and nonmaleficence). The least influential factor was ease of paying for the medication (justice). Conclusions and Relevance: Findings from this national survey study of primary care physicians suggests that understanding ethical aspects of physician decision-making can inform clinician education about medication management and deprescribing decisions for older adults with moderate dementia.

Intervention design in cognitively impaired populations-Lessons learned from the OPTIMIZE deprescribing pragmatic trial.

BACKGROUND: Polypharmacy is common in older adults with cognitive impairment and multiple chronic conditions, increasing risks of adverse drug events, hospitalization, and death. Deprescribing, the process of reducing or stopping potentially inappropriate medications, may improve outcomes. The OPTIMIZE pragmatic trial examined whether educating and activating patients, family members and clinicians about deprescribing reduces number of chronic medications and potentially inappropriate medications. Acceptability and challenges of intervention delivery in cognitively impaired older adults are not well understood. METHODS: We explored mechanisms of intervention implementation through post hoc qualitative interviews and surveys with stakeholder groups of 15 patients, 7 caregivers, and 28 clinicians. We assessed the context in which the intervention was delivered, its implementation, and mechanisms of impact. RESULTS: Acceptance of the intervention was affected by contextual factors including cognition, prior knowledge of deprescribing, communication, and time constraints. All stakeholder groups endorsed the acceptability, importance, and delivery of the intervention. Positive mechanisms of impact included patients scheduling specific appointments to discuss deprescribing and providers being prompted to consider deprescribing. Recollection of intervention materials was inconsistent but most likely shortly after intervention delivery. Short visit times remained the largest provider barrier to deprescribing. CONCLUSIONS: Our work identifies key learnings in intervention delivery that can guide future scaling of deprescribing interventions in this population. We highlight the critical roles of timing and repetition in intervention delivery to cognitively impaired populations and the barrier posed by short consultation times. The acceptability of the intervention to patients and family members highlights the potential to incorporate deprescribing education into routine clinical practice and expand proven interventions to other vulnerable populations.

Characteristics of patients with primary non-adherence to medications for hypertension, diabetes, and lipid disorders.

BACKGROUND: Information comparing characteristics of patients who do and do not pick up their prescriptions is sparse, in part because adherence measured using pharmacy claims databases does not include information on patients who never pick up their first prescription, that is, patients with primary non-adherence. Electronic health record medication order entry enhances the potential to identify patients with primary non-adherence, and in organizations with medication order entry and pharmacy information systems, orders can be linked to dispensings to identify primarily non-adherent patients. OBJECTIVE: This study aims to use database information from an integrated system to compare patient, prescriber, and payment characteristics of patients with primary non-adherence and patients with ongoing dispensings of newly initiated medications for hypertension, diabetes, and/or hyperlipidemia. DESIGN: This is a retrospective observational cohort study. PARTICIPANTS (OR PATIENTS OR SUBJECTS): Participants of this study include patients with a newly initiated order for an antihypertensive, antidiabetic, and/or antihyperlipidemic within an 18-month period. MAIN MEASURES: Proportion of patients with primary non-adherence overall and by therapeutic class subgroup. Multivariable logistic regression modeling was used to investigate characteristics associated with primary non-adherence relative to ongoing dispensings. KEY RESULTS: The proportion of primarily non-adherent patients varied by therapeutic class, including 7% of patients ordered an antihypertensive, 11% ordered an antidiabetic, 13% ordered an antihyperlipidemic, and 5% ordered medications from more than one of these therapeutic classes within the study period. Characteristics of patients with primary non-adherence varied across therapeutic classes, but these characteristics had poor ability to explain or predict primary non-adherence (models c-statistics = 0.61-0.63). CONCLUSIONS: Primary non-adherence varies by therapeutic class. Healthcare delivery systems should pursue linking medication orders with dispensings to identify primarily non-adherent patients. We encourage conduct of research to determine interventions successful at decreasing primary non-adherence, as characteristics available from databases provide little assistance in predicting primary non-adherence.