Overall survival associated with CDK4/6 inhibitors in patients with HR+/HER2- metastatic breast cancer in the United States: A SEER-Medicare population-based study.

BACKGROUND: Evidence on overall survival (OS) with cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitors is generally limited to data from clinical trials or a few observational studies with limited generalizability to Medicare population. The aim of this study was to determine OS benefits associated with CDK4/6 inhibitors in older Medicare patients with hormone receptor (HR)-positive and human epidermal growth factor receptor-2 overexpressing (HER2-) metastatic breast cancer (MBC). METHODS: In a retrospective cohort design, female patients aged ≥65 years with diagnosis of HR+/HER2- MBC from 2015 to 2017 who initiated first-line systemic therapy within 12 months of MBC diagnosis were selected from the Survey Epidemiology and End Results-Medicare database. The effect of treatment type (endocrine therapy [ET]+CDK4/6 inhibitor vs. ET alone) on OS was analyzed using Kaplan-Meier methods and multivariable Cox regression models. Adjusted hazard ratio (aHR) and 95% CIs were estimated. RESULTS: A total of 630 eligible patients were identified (169 patients treated with ET+CDK4/6 inhibitor and 461 patients treated with ET alone). In the Kaplan-Meier analysis, OS rate at 3 years after first-line treatment initiation was 73.0% for ET+CDK4/6 inhibitor versus 49.1% for ET alone (log-rank p < .0001). In Cox regression analysis, first-line ET+CDK4/6 inhibitor therapy was associated with 41% lower rate of mortality versus ET alone (aHR, 0.590; 95% CI, 0.423-0.823). CONCLUSIONS: The findings of this real-world study demonstrate significant OS benefit associated with ET+CDK4/6 inhibitor therapy over ET alone in an older Medicare population of patients with HR+/HER2- MBC, largely consistent with the evidence from clinical trials.

The Association Between Medication Use in Older Women with Early-Stage Operable Primary Breast Cancer and Decision Regarding Primary Treatment.

BACKGROUND: Polypharmacy is one factor contributing to increased mortality, hospitalization, and adverse drug reactions in older adults. The aim of this study was to measure the prevalence of polypharmacy in a cohort of older women with early-stage operable primary breast cancer and the relationship of polypharmacy to primary treatment decision and functional status. METHODS: A total of 139 patients with a new diagnosis of early-stage operable primary breast cancer proven histologically were recruited as part of a prospective study. The average age was 77 years. Assessment using a cancer-specific Comprehensive Geriatric Assessment (CGA) tool was conducted within 6 weeks of diagnosis of breast cancer. Association was determined between number of medications and treatment decision and physical status as measured by the CGA outcomes. Additional analysis was performed to determine the associations above with polypharmacy defined by ≥5 daily medications, and if cardiovascular-related diseases have a role in the treatment decision. RESULTS: Polypharmacy was present in 48% of patients (n = 139). CGA determined that polypharmacy was associated with greater comorbidity (P < .001), reduced physical status rated by physicians (P = .009) and patients (P = .019), and reduced ability to perform activities of instrumental ADLs (P = .008). Similar findings were present in the analysis of cardiovascular-related diseases. CONCLUSIONS: This work suggests that patients with polypharmacy are more likely to be frail. The number of medications could help us screen patients who should go on to receive full CGA.

Impact of CDK4/6 inhibitors on chemotherapy utilization in earlier therapy lines for HR+/HER2- metastatic breast cancer in the United States.

PURPOSE: Delaying chemotherapy remains a vital goal in therapeutic management of HR+/HER2- metastatic breast cancer (MBC). However, recent reports continue to highlight substantially high chemotherapy utilization in earlier therapy lines. In this study, we explored the impact of cyclin-dependent kinase 4 and 6 (CDK4/6) inhibitor therapy class, introduced in 2015, on early chemotherapy utilization in an older population of patients with HR+/HER2- MBC in the United States (US). METHODS: Using an interrupted time series design, patients with a confirmed diagnosis of MBC aged ≥ 65 years initiating systemic therapy during 2010-2019 were selected from the SEER-Medicare database. The proportion of chemotherapy use was summarized quarterly based on the date of treatment initiation separately in the first, second, and third lines. Segmented regression models adjusted for autocorrelation over time were fitted to estimate trends before and after the availability of CDK4/6 inhibitors in the first quarter of 2015. RESULTS: Of the 3244 eligible women (median age at diagnosis: 74 years), all initiated first-line therapy; 47.9% (n = 1581) initiated second-line therapy, and 50.1% (n = 792) initiated third-line therapy. Overall utilization of chemotherapy (alone or in combination) during the study period was 15.7% for the first line, 19.6% for the second line, and 24.8% for the third line. Chemotherapy utilization in the period immediately after introduction of CDK4/6 inhibitor therapy decline by estimated 2.5% in the first line (P = 0.408), 15.5% in the second line (P = 0.005), and 16.3% in the third line (P = 0.003). CONCLUSIONS: This population-based study illustrates that chemotherapy utilization in earlier therapy lines for HR+/HER2- MBC declined steadily between 2010 and 2019. These declines were significantly accelerated by the introduction of CDK4/6 therapy class in 2015, notably in the second- and third-line settings.

How do we define high and low dose intensity of heart failure medications: a scoping review.

BACKGROUND: Older adults with heart failure often experience adverse drug events with high doses of heart failure medications. Recognizing whether a patient is on a high or low dose intensity heart failure medication can be helpful for daily practice, since it could potentially guide the physician on which symptoms to look for, whether from overdosing or underdosing. However, the current guideline does not provide sufficient information about the dose intensity below the target dose. Furthermore, the definition of high or low-intensity heart failure medication is unclear, and there is no consensus. METHODS: To close the knowledge gap, we conducted a scoping review of the current literature to identify the most frequently used definition of high versus low doses of heart failure medications. We searched Pubmed, Embase, CINAHL, and Cochrane Library using comprehensive search terms that can capture the intensity of heart failure medications. RESULTS: We reviewed 464 articles, including 144 articles that had information about beta-blockers (BB), 179 articles about angiotensin-converting enzyme inhibitors (ACEi), 75 articles about angiotensin receptor blockers (ARB), 80 articles about diuretics, 37 articles about mineralocorticoid receptor antagonists (MRA), and 33 articles about angiotensin receptor-neprilysin inhibitor (ARNI). For hydralazine with isosorbide dinitrate or ivabradine, we could not identify any eligible articles. We identified 40 medications with most frequently used definitions of dose intensity. Four medications (nadolol, pindolol, cilazapril, and torsemide) did not reach consensus in definitions. Most of the BBs, ACEis, or ARBs used the definition of low being < 50% of the target dose and high being ≥ 50% of the target dose from the guideline. However, for lisinopril and losartan, the most commonly used definitions of high or low were from pivotal clinical trials with a pre-defined definition of high or low. CONCLUSION: Our comprehensive scoping review studies identified the most frequently used definition of dose intensity for 40 medications but could not identify the definitions for 4 medications. The results of the current scoping review will be helpful for clinicians to have awareness whether the currently prescribed dose is considered high - requiring close monitoring of side effects, or low - requiring more aggressive up-titration.

Emotional barriers and facilitators of deprescribing for older adults with cancer and polypharmacy: a qualitative study.

PURPOSE: To describe emotional barriers and facilitators to deprescribing (the planned reduction or discontinuation of medications) in older adults with cancer and polypharmacy. METHODS: Virtual focus groups were conducted over Zoom with 5 key informant groups: oncologists, oncology nurses, primary care physicians, pharmacists, and patients. All groups were video- and audio-recorded and transcribed verbatim. Focus group transcripts were analyzed using inductive content analysis, and open coding was performed by two coders. A codebook was generated based on the initial round of open coding and updated throughout the analytic process. Codes and themes were discussed for each transcript until consensus was reached. Emotion coding (identifying text segments expressing emotion, naming the emotion, and assigning a label of positive or negative) was performed by both coders to validate the open coding findings. RESULTS: All groups agreed that polypharmacy is a significant problem. For clinicians, emotional barriers to deprescribing include fear of moral judgment from patients and colleagues, frustration toward patients, and feelings of incompetence. Oncologists and patients expressed ambivalence about deprescribing due to role expectations that physicians "heal with med[ication]s." Emotional facilitators of deprescribing included the involvement of pharmacists, who were perceived to be neutral, discerning experts. Pharmacists described emotionally aware communication strategies when discussing deprescribing with other clinicians and expressed increased awareness of patient context. CONCLUSION: Deprescribing can elicit strong and predominantly negative emotions among clinicians and patients which could inhibit deprescribing interventions. The involvement of pharmacists in deprescribing interventions could mitigate these emotional barriers. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05046171 . Date of registration: September 16, 2021.

Prescribing trends of proton pump inhibitors, antipsychotics and benzodiazepines of medicare part d providers.

BACKGROUND: Proton pump inhibitors, benzodiazepines, and antipsychotics are considered potentially inappropriate medications in older adults according to the American Geriatric Society Beers Criteria, and deprescribing algorithms have been developed to guide use of these drug classes. The objective of this study was to describe the number of beneficiaries prescribed these medications, provider specialty and regional trends in prescribing, and the aggregate costs for these claims in Medicare Part D. METHODS: This was a retrospective cross-sectional study using publicly available Medicare Provider Utilization and Payment Data: Part D Prescriber data for years 2013-2019. Descriptive statistics and the Cochrane-Armitage test were used to summarize the trends. RESULTS: Overall, 30.1%, 25.6%, 4.6% of Medicare Part D beneficiaries had a proton pump inhibitor, benzodiazepine, and antipsychotic claim in 2013, respectively. These rates decreased to 27.5%, 17.5%, 4.1% in 2019 (p-value < 0.0001). However, the number of standardized 30-day claims increased from 63 million in 2013 to 84 million in 2019 for proton pump inhibitors, remained steady for benzodiazepines and slightly increased (10 million to 13 million) for antipsychotics. Total aggregate costs decreased by almost $1.5 billion for proton pump inhibitor, $100 million for benzodiazepine, and $700 million for antipsychotic from 2013 to 2019 (p-value < 0.0001). Almost 93% of gastroenterologists prescribed a proton pump inhibitor, and 60% of psychiatrists prescribed benzodiazepines and antipsychotics all seven years. The Other region had the highest percentage of providers prescribing all three classes and the highest number of standardized 30-day benzodiazepine claims. CONCLUSIONS: The overall rate of use of proton pump inhibitors, benzodiazepines, and antipsychotics decreased from 2013-2019 among Medicare Part D beneficiaries. Despite the increase in raw number of standardized 30-day claims, the costs decreased which is likely due to generics made available. These prescribing trends may aid in identifying and targeting potential deprescribing interventions.

Prevalence of potential interactions of medications, including herbs and supplements, before, during, and after chemotherapy in patients with breast and prostate cancer.

BACKGROUND: The use of herbs and supplements (HS) is common among patients with cancer, yet limited information exists about potential medication interactions (PMIs) with HS use around chemotherapy. METHODS: Patients with breast or prostate cancer who had recently finished chemotherapy at 2 academic medical centers were surveyed by telephone. Interviewers inquired about all medications, including HS, before, during, and after chemotherapy. Micromedex, Lexicomp, and Natural Medicines Comprehensive Database interaction software programs were used to determine PMIs. RESULTS: A total of 67 subjects (age range, 39-77 years) were evaluated in this study. Participants were primarily White patients (73%) with breast cancer (87%). The median number of medications was 11 (range, 2-28) during the entire study and was highest during chemotherapy (7; range, 2-22). Approximately four-fifths (84%) used HS. A total of 1747 PMIs were identified, and they represented 635 unique PMIs across all 3 timeframes, with most occurring during chemotherapy. Prescription-related PMIs (70%) were the most common type, and they were followed by HS-related (56%) and anticancer treatment-related PMIs (22%). Approximately half of the PMIs (54%) were categorized as moderate interactions, and more than one-third (38%) were categorized as major interactions. Patient use of HS increased from 51% during chemotherapy to 66% after chemotherapy, and this correlated with an increased prevalence of HS PMIs (46% to 60%). HS users were more likely to be at risk for a major PMI than non-HS users (92% vs 70%; P = .038). CONCLUSIONS: The use of HS remains prevalent among patients with cancer and may place them at risk for PMIs both during chemotherapy and after the completion of treatment. LAY SUMMARY: This study evaluates the risk of potential medication interactions for patients with breast or prostate cancer undergoing chemotherapy. The results show that patients often use herbs and supplements during treatment. Prescription medications are most often associated with medication interactions, which are followed by herb and supplement-related interactions. More than one-third of potential medication interactions are considered major. Patients should be educated about the risk of herb and supplement-related medication interactions during treatment.

Delirium Among Hospitalized Older Adults With Acute Heart Failure Exacerbation.

BACKGROUND: Delirium among older adults hospitalized with acute heart failure is associated with increased mortality. However, studies concomitantly assessing the association of delirium with both clinical and economic outcomes in this population, such as mortality, hospital cost, or length of stay, are lacking. METHODS AND RESULTS: We conducted a retrospective observational study using National Inpatient Sample data from 2011 to 2014. Using multivariable logistic regression, we assessed the association of delirium with in-hospital mortality, then estimated the incremental hospital cost and excessive length of stay adjusting for demographic and clinical factors using multivariable generalized linear regression. The association of other medical complications on clinical and economic outcomes was also assessed. A total of 568,565 (weighted N = 2,826,131) hospitalizations of patients 65 years or older with acute heart failure from 2011 to 2014 were included in the final analysis. The reported prevalence of delirium was 4.53%. After multivariable adjustment, delirium was associated with a 2.35-fold increase in the odds of in-hospital mortality (95% confidence interval [CI] 2.23-2.47), which was lower than the odds ratio for sepsis/septicemia (5.36; 95% CI, 5.02-5.72) or respiratory failure (4.53; 95% CI, 4.38-4.69), but similar to that for acute kidney injury (2.39; 95% CI, 2.31-2.48) and higher than for non-ST elevation myocardial infarct (1.57; 95% CI, 1.46-1.68). Delirium increased the total hospital cost by $4,262 (95% CI, $4,002-4,521) and the length of stay by 1.73 days (95% CI, 1.68-1.78), which was slightly lower than, but similar to, acute kidney injury ($4,771; 95% CI, $4,644-4,897) and 1.82 days (95% CI, 1.79-1.84), and higher than non-ST elevation myocardial infarct ($1,907; 95% CI, $1,629-2,185) and 0.31 days (95% CI, 0.25-0.37). CONCLUSIONS: Delirium was associated with increased in-hospital mortality, total hospital cost, and length of stay, and the magnitude of the effect was similar to that for acute kidney injury. Enhanced efforts to prevent delirium are needed to decrease its adverse impact on clinical and economic outcomes for hospitalized older adults with acute heart failure.

Quality of Life Assessment in Older Adults with Dementia: A Systematic Review.

INTRODUCTION: In the absence of a cure, dementia is often managed by minimizing risk factors contributing to quality of life (QOL). Attitudes to dementia in older adults may differ from those in relatively younger adults. The aim was to conduct a systematic review of the literature to determine how QOL was assessed in adults, 65 years and older with dementia, and identify factors that influence the reported scores. METHODS: A systematic review of full-text articles addressing QOL in older adults with dementia, published in English from January 1995 to September 2020, was conducted using PubMed and PsycINFO. We included studies that assessed QOL and involved participants 65 years and older. Studies were evaluated for inclusion by 2 independent pairs of reviewers. We assessed the quality of the studies using the Joanna Briggs Institute's Critical Appraisal Checklist. Study characteristics and findings were summarized. Analysis was by narrative synthesis. We identified social and clinical factors influencing QOL scores. RESULTS: Of the 1,010 articles identified, 19 met the inclusion criteria. These 19 studies involved 6,279 persons with dementia, with sample sizes from 32 to 1,366. Mean age of participants ranged from 77.1 to 86.6 years. Five measurement tools were identified; Quality of Life in Alzheimer Disease (QOL-AD), Alzheimer Disease-Related Quality of Life (ADRQL), Quality of Life in Late-Stage Dementia (QUALID), QUALIDEM (a dementia-specific QOL tool), and DEMQOL (health-related QOL for people with dementia). Self-ratings of QOL were higher than proxy ratings. Factors commonly influencing self-ratings of QOL included depression, functional impairment, and polypharmacy. Common factors that influenced proxy ratings included functional impairment, presence of neuropsychiatric symptoms, cognitive impairment, and caregiver burden. CONCLUSION: In evaluating QOL in dementia, self- and proxy reports may complement each other to ensure that all perspectives are addressed.

Comparative risk of adverse outcomes associated with nonselective and selective antimuscarinic medications in older adults with dementia and overactive bladder.

OBJECTIVE: The differential muscarinic receptor selectivity could cause selective antimuscarinics to offer advantages over nonselective agents with respect to adverse effects. The objective was to examine the comparative risk of falls/fractures and all-cause hospitalizations among older adults with dementia and overactive bladder (OAB) using nonselective and selective antimuscarinics METHODS/DESIGN: A retrospective cohort study design was conducted among older patients with dementia and OAB using incident antimuscarinics. The primary exposure was classified as nonselective (oxybutynin, tolterodine, trospium, and fesoterodine) and selective (solifenacin and darifenacin). Cox proportional-hazards regression using inverse probability of treatment weighting (IPTW) evaluated the risk of falls/fractures and all-cause hospitalizations within 6 months of nonselective and selective antimuscarinic use. RESULTS: The study cohort consisted of 13,896 (76.9%) nonselective and 4,179 (23.1%) selective antimuscarinic incident users. The unadjusted falls/fractures rate was 27.14% (3,772) for nonselective and 24.55% (1,026) for selective users (p-value< 0.01). The unadjusted all-cause hospitalizations rate was 24.14% (3,354) for nonselective and 21.58% (902) for selective users (p-value <0.01). The IPTW models did not find a significant difference in the risk of falls/fractures (Hazard Ratio [HR] 1.03; 95% Confidence Interval [CI] 0.99-1.07) and risk of all-cause hospitalizations (HR 1.04; 95% CI 0.99-1.08) between nonselective and selective antimuscarinics. Several sensitivity analyses corroborated the main findings. CONCLUSIONS: The study did not find a differential risk of falls/fractures and all-cause hospitalizations in older adults with dementia and OAB using nonselective and selective antimuscarinics. More research is needed to understand the role of pharmacodynamics and pharmacokinetics in the safety profile of antimuscarinics in dementia.

Identifying Geriatric Oncology Competencies for Medical Oncology Trainees: A Modified Delphi Consensus Study.

BACKGROUND: Most oncology trainees are not taught about the needs of older patients, who make up the majority of patients with cancer. Training of health care providers is critical to improve the care of older adults with cancer. There is no consensus about which geriatric oncology (GO) competencies are important for medical oncology trainees. Our objective was to identify GO competencies medical oncology trainees should acquire during training. MATERIALS AND METHODS: A modified Delphi consensus of experts in oncology medical education and GO was conducted. Experts categorized at what training stage proposed competencies should be attained: internal medicine, oncology, or GO training. Consensus was obtained if two thirds of experts agreed on the training stage at which the competency should be attained. RESULTS: A total of 78 potential competencies were identified, of which 35 (44.9%) proposed competencies were felt to be appropriate to be acquired during oncology training. The majority of the identified competencies pertained to prescribing of systemic therapy (n = 12) and psychosocial and supportive care (n = 13). No competencies related to geriatric assessment were identified for acquisition during oncology training. CONCLUSION: Experts in oncology education and geriatric oncology agreed upon a set of GO competencies appropriate for oncology trainees. These results provide the foundation for developing a GO curriculum for medical oncology trainees and will hopefully lead to better care of older adults with cancer. IMPLICATIONS FOR PRACTICE: The aging population will drive the projected rise in cancer incidence. Although aging patients make up the majority of patients diagnosed with cancer, oncologists rarely receive training on how to care for them. Training of health care providers is critical to improving the care of older adults with cancer. The results of this study will help form the foundation of developing a geriatric oncology curriculum for medical oncology trainees.

Associations of Polypharmacy and Inappropriate Medications with Adverse Outcomes in Older Adults with Cancer: A Systematic Review and Meta-Analysis.

BACKGROUND: Polypharmacy (PP) and potentially inappropriate medications (PIM) are highly prevalent in older adults with cancer. This study systematically reviews the associations of PP and/or PIM with outcomes and, through a meta-analysis, obtains estimates of postoperative outcomes associated with PP in this population. MATERIALS AND METHODS: We searched PubMed, Embase, Web of Science, and Cochrane Register of Clinical Trials using standardized terms for concepts of PP, PIM, and cancer. Eligible studies included cohort studies, cross-sectional studies, meta-analyses, and clinical trials which examined outcomes associated with PP and/or PIM and included older adults with cancer. A random effects model included studies in which definitions of PP were consistent to examine the association of PP with postoperative complications. RESULTS: Forty-seven articles met the inclusion criteria. PP was defined as five or more medications in 57% of the studies. Commonly examined outcomes included chemotherapy toxicities, postoperative complications, functional decline, hospitalization, and overall survival. PP was associated with chemotherapy toxicities (4/9 studies), falls (3/3 studies), functional decline (3/3 studies), and overall survival (2/11 studies). A meta-analysis of four studies indicated an association between PP (≥5 medications) and postoperative complications (overall odds ratio, 1.3; 95% confidence interval [1.3-2.8]). PIM was associated with adverse outcomes in 3 of 11 studies. CONCLUSION: PP is associated with postoperative complications, chemotherapy toxicities, and physical and functional decline. Only three studies showed an association between PIM and outcomes. However, because of inconsistent definitions, heterogeneous populations, and variable study designs, these associations should be further investigated in prospective studies. IMPLICATIONS FOR PRACTICE: Polypharmacy and potentially inappropriate medications (PIM) are prevalent in older adults with cancer. This systematic review summarizes the associations of polypharmacy and PIM with health outcomes in older patients with cancer. Polypharmacy and PIM have been associated with postoperative complications, frailty, falls, medication nonadherence, chemotherapy toxicity, and mortality. These findings emphasize the prognostic importance of careful medication review and identification of PIM by oncology teams. They also underscore the need to develop and test interventions to address polypharmacy and PIM in older patients with cancer, with the goal of improving outcomes in these patients.

Risk of Mortality Associated with Non-selective Antimuscarinic medications in Older Adults with Dementia: a Retrospective Study.

BACKGROUND: Selective antimuscarinics may offer a favorable safety profile over non-selective antimuscarinics for the management of overactive bladder (OAB) in patients with dementia. OBJECTIVE: To test the hypothesis that non-selective antimuscarinics are associated with increased risk of mortality compared to selective antimuscarinics in older adults with dementia and OAB. DESIGN: Propensity score-matched retrospective new-user cohort design among Medicare beneficiaries in community settings. PATIENTS: Older adults with dementia and OAB with incident antimuscarinic use. MAIN MEASURES: The primary exposure was antimuscarinic medications classified as non-selective (oxybutynin, tolterodine, trospium, fesoterodine) and selective (solifenacin, darifenacin) agents. All-cause mortality within 180 days of incident antimuscarinic use formed the outcome measure. New users of non-selective and selective antimuscarinics were matched on propensity scores using the Greedy 5 → 1 matching technique. Cox proportional-hazards model stratified on matched pairs was used to evaluate the risk of mortality associated with the use of non-selective versus selective antimuscarinics in the sample. KEY RESULTS: The study identified 16,955 (77.6%) non-selective antimuscarinic users and 4893 (22.4%) selective antimuscarinic users. Propensity score matching yielded 4862 patients in each group. The unadjusted mortality rate at 180 days was 2.6% (126) for non-selective and 1.6% (78) for selective antimuscarinic users in the matched cohort (p value < 0.01). The Cox model stratified on matched pairs found 50% higher risk of 180-day mortality with non-selective antimuscarinics as compared to selective ones (hazard ratio (HR) 1.50; 95% confidence interval (CI) 1.04-2.16). The study findings remained consistent across multiple sensitivity analyses. CONCLUSIONS: Use of non-selective antimuscarinics was associated with a 50% increase in mortality risk among older adults with dementia and OAB. Given the safety concerns regarding non-selective antimuscarinic agents, there is a significant need to optimize their use in the management of OAB for older patients with dementia.

Risk of Mortality Associated With Atypical Antipsychotic use: A National Cohort Study of Older Adults With Depression and Parkinson's Disease.

OBJECTIVES: This study examined the risk of all-cause-mortality in patients with Parkinson's Disease (PD) and comorbid depression using inappropriate atypical antipsychotics (AAPs), based on the 2015 American Geriatrics Society Beers criteria. METHODS: A retrospective analysis of 2007-2010 Minimum Data Set linked Medicare data was conducted using a propensity-matched approach. The cohort included PD patients aged 65 years or older without schizophrenia or bipolar disorder who started AAPs. All patients had a diagnosis of comorbid depression. Risk of 6-month all-cause-mortality was compared across appropriate AAPs (aripiprazole, clozapine, or quetiapine) and inappropriate AAPs (olanzapine, asenapine, brexpiprazole, iloperidone, lurasidone, paliperidone, risperidone, or ziprasidone) using robust Cox regression models involving the matched cohort. RESULTS: All-cause mortality rate was 15.65% in appropriate AAP group (n = 6,038) and 16.91% in inappropriate AAP group (n = 6,038) over 6-month follow-up in the matched cohort. The robust Cox proportional hazards models revealed increased risk of all-cause mortality (hazard ratio [HR] 1.13 [95% confidence interval {CI}: 1.01-1.28)] for patients who used inappropriate compared to appropriate AAPs. Risk of death was also higher for risperidone compared to quetiapine (HR: 1.20 [95% CI: 1.03-1.40]) in sensitivity analysis. However, there was a significant relationship between pneumonia and death in all analyses. The impact of inappropriate AAP use on mortality was not significant when pneumonia was modeled as a mediator. CONCLUSIONS: Inappropriate AAP use is associated with a higher risk of all-cause-mortality in older patients with PD which is mainly mediated by pneumonia. Therefore, inappropriate AAP use should be avoided to improve quality of care in PD.

The concomitant use of tyrosine kinase inhibitors and proton pump inhibitors: Prevalence, predictors, and impact on survival and discontinuation of therapy in older adults with cancer.

BACKGROUND: The concomitant use of tyrosine kinase inhibitors (TKIs) and proton pump inhibitors (PPIs) is a significant concern because of potential drug-drug interaction that reduces TKI absorption, thus potentially reducing the effectiveness of TKIs. The objective of this study was to evaluate the prevalence and predictors of concomitant TKI-PPI receipt and its impact on survival and therapy discontinuation in older adults with cancer. METHODS: This retrospective study used linked Surveillance, Epidemiology, and End Results-Medicare data for the years 2007 through 2012. In total, 12,538 patients with lung cancer, renal cell cancer, chronic myelogenous leukemia, liver cancer, or pancreatic cancer were included. The primary exposure variable was concomitant receipt of TKI-PPI, defined as at least 30 days of PPI use in the first 90 days from the start of the TKI (exposure period). The outcomes measured were overall survival and discontinuation of therapy in 90 days and 1 year after the end of the exposure period. Cox proportional-hazards regression with inverse probability of treatment weighting was used to evaluate the association between exposure and outcome. RESULTS: The overall prevalence of TKI-PPI receipt was 22.7%. Predictors that were associated with increased use included polypharmacy and prior PPI receipt. TKI-PPI use decreased survival in 90 days (hazard ratio, 1.16; 95% confidence interval, 1.05-1.28) and in 1 year (hazard ratio, 1.10; 95% confidence interval, 1.04-1.18) but was not associated with discontinuation. CONCLUSIONS: Nearly 1 in 4 older adults with cancer who receive TKIs also receive PPIs concomitantly, and concomitant use is associated with an increased risk of death. Concerted efforts to manage medications are needed to identify and reduce the receipt of PPIs when TKIs are initiated.

Use of Nonpalliative Medications Following Burdensome Health Care Transitions in Hospice Patients: A Matched Cohort Analysis.

BACKGROUND: Limited benefit medications (LBMs), those medications with questionable benefit at the end of life, are often recommended for discontinuation in hospice patients. Transitions in care are associated with inappropriate prescribing in older and terminally ill populations. OBJECTIVES: To evaluate the association between burdensome health care transitions and subsequent receipt of LBMs in older hospice patients. METHODS: We conducted a matched cohort analysis of patients admitted to hospice between 2008 and 2013 using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database. The prevalence of post-health care transition LBM use was assessed. Adjusted incidence rate ratios (IRRs) were estimated for the association between transitions and subsequent receipt of LBMs. RESULTS: In total, 17.9% of 7064 hospice patients received at least 1 LBM following their first burdensome health care transition. Posttransition continuation of a medication class used before hospice admission was most common for antidementia medications (14.2%) and antihypertensives (11.2%). Transitions were associated with a 33% increase in the risk of receiving at least 1 LBM [IRR, 1.33; 95% confidence interval (CI), 1.25-1.42], increasing to 56% when evaluating only hospitalization transitions (IRR, 1.56; 95% CI, 1.39-1.76). Medication classes more likely to be dispensed after a transition included antihyperlipidemics (IRR, 1.38; 95% CI, 1.13-1.70), antihypertensives (IRR, 1.28; 95% CI, 1.16-1.40), and proton-pump inhibitors (IRR, 1.40; 95% CI, 1.20-1.63). CONCLUSIONS: Burdensome health care transitions were associated with the receipt of nonpalliative medications in older hospice patients. Interventions aimed at improving provider communication and reducing fragmentation in care may help reduce unnecessary medication use in this vulnerable population.

Older Medicare Beneficiaries Frequently Continue Medications with Limited Benefit Following Hospice Admission.

BACKGROUND: The use of medications not relieving symptoms or maximizing quality of life should be minimized following hospice enrollment. OBJECTIVE: To evaluate the frequency of and predictive factors for continuation of medications with limited benefit after hospice admission among those admitted for cancer- and non-cancer-related causes. DESIGN: Cohort study using the Surveillance, Epidemiology and End Results-Medicare linked database. PATIENTS: Medicare Part D-enrolled beneficiaries 66 years and older who were admitted to and died under hospice care between January 1, 2008, and December 31, 2013 (N = 70,035). MAIN MEASURES: Patients were followed from hospice enrollment through death for Part D dispensing of limited benefit medications (LBMs) they had used in the 6 months prior to hospice admission, including anti-hyperlipidemics, anti-hypertensives, oral anti-diabetics, anti-platelets, anti-dementia medications, anti-osteoporotic medications, and proton pump inhibitors. The proportion of patients continuing an LBM after hospice admission was evaluated. Adjusted relative risks (RRs) were estimated for factors associated with LBM continuation. KEY RESULTS: Overall, 29.8% and 30.5% of patients admitted to hospice for a cancer- and non-cancer-related cause, respectively, continued at least one LBM after hospice admission. Anti-dementia medications were continued most frequently (29.3%) while anti-osteoporotic medications were continued least often (14.1%). Compared to home hospice, LBM continuation was greater in hospice patients residing in skilled nursing (RR 1.25, 95% CI 1.20-1.29), non-skilled nursing (RR 1.29, 95% CI 1.25-1.32), and assisted living facilities (RR 1.28, 95% CI 1.24-1.32). Patients with hospice stays ≥ 180 days were more likely to continue at least one LBM compared to those with stays of 1 week or less (RR 13.11, 95% CI 12.25-14.02). CONCLUSIONS: A substantial proportion of Medicare hospice beneficiaries continued to receive LBMs following hospice enrollment. Providers should evaluate the necessity of continuing non-palliative medications at the end of life through a careful, patient-centric consideration of their potential risks and benefits.

Potentially inappropriate medication use in older patients with breast and colorectal cancer.

BACKGROUND: The objective of this study was to determine patient characteristics associated with potentially inappropriate medication (PIM) use and its impact on outcomes for patients with breast or colorectal cancer receiving adjuvant chemotherapy. METHODS: The Surveillance, Epidemiology, and End Results database, linked to Medicare claims, was used. The cohort included patients who were 66 years old or older and were diagnosed with stage II or III breast or colorectal cancer between July 1, 2007, and December 31, 2009. The Drugs to Avoid in the Elderly (DAE) list and the Beers criteria were used to identify PIM use. Univariate/multivariate logistic regression determined the association of baseline PIMs with covariates. Event-free survival (EFS) was defined as the time from chemotherapy initiation to the first emergency room (ER) visit, hospitalization, death, or a composite until 3 months after chemotherapy. Cox proportional hazards modeling determined the association of PIMs with EFS. RESULTS: The analysis included 1595 patients with breast cancer and 1528 patients with colorectal cancer. The baseline PIM frequencies were 22.2% (according to the DAE list) and 27.6% (according to the Beers criteria) in the breast cohort and 15.5% (according to the DAE list) and 24.8% (according to the Beers criteria) in the colorectal cohort. Among patients with breast cancer, 37.5% had at least 1 adverse outcome; associations included the use of ≥5 medications, an advanced stage, higher comorbidity, and prior ER visits/hospitalizations. Baseline PIM use according to the DAE list was associated with an increased risk of death in patients with breast cancer. Among patients with colorectal cancer, 45% had at least 1 adverse outcome, and associations included the use of ≥5 medications, older age, female sex, and higher comorbidity. A time-to-event analysis revealed no association between baseline PIM use and most outcomes. CONCLUSIONS: These findings require further prospective confirmation, but they support a correlation between polypharmacy and adverse outcomes for cancer patients and call into question the association with PIMs. Cancer 2018;124:3000-7. © 2018 American Cancer Society.

Missed opportunities: unnecessary medicine use in patients with lung cancer at the end of life - an international cohort study.

AIMS: The aims of the current study were: (i) to examine the prescribing of preventative medication in a cohort of people with advanced lung cancer on hospital admission and discharge across different healthcare systems; and (ii) to explore the factors that influence preventative medication prescribing at hospital discharge. METHODS: A retrospective cohort study was conducted across two centres in the UK and the US. The prescribing of preventative medication was examined at hospital admission and discharge for patients who died of lung cancer. A zero-inflated negative binomial regression model was used to examine the association between preventative medications at discharge and patient- and hospital-based factors. The classes of preventative medication prescribed included were: vitamins and minerals, and antidiabetic, antihypertensive, antihyperlipidaemic and antiplatelet medications. RESULTS: In the UK site (n = 125), the mean number of preventative medications prescribed was 1.9 [standard deviation (SD) 1.7) on admission, and 1.7 (SD 1.7) on discharge, and in the US site (n = 191) the mean was 2.6 (SD 2.2) on admission and 1.9 (SD 2.2) on discharge. The model found a significant association between the number of preventative drugs prescribed on admission and the number on discharge; it also found a significant association between the total number of drugs prescribed on discharge and the number of preventative medications on discharge. Other indicators related to patient and hospital factors were not significantly associated with the number of preventative medications supplied on discharge. CONCLUSIONS: The use of preventative medication was common in lung cancer patients, despite undergoing discharge. Patient- and hospital-based factors did not influence the prescribing of preventative medication.

Fractures frequently occur in older cancer patients: the MD Anderson Cancer Center experience.

PURPOSE AND INTRODUCTION: A growing number of cancer patients are older adults aged 65 years and older. Patients with cancer are at increased risk for developing osteoporosis, falls, and fractures. We sought to identify the incidence of fractures in older adults who underwent cancer care between January 2013 and December 2015. METHODS: A comprehensive geriatric assessment was performed, and bone densitometry was measured at baseline, with a 2-year follow-up. RESULTS: In this study, among 304 patients with gastrointestinal, urologic, breast, lung, and gynecologic cancers we evaluated, and who completed the bone density testing (n = 199), 80% had osteoporosis or low bone mass (osteopenia). There was a higher prevalence of osteoporosis in cancer patients (40 vs. 16%, p = 0.05) than in population studies. Vitamin D insufficiency (< 30 ng/ml) was identified in 49% of tested cases (n = 245). Risk factors for low bone mass or osteoporosis were advanced age (p = 0.05), malnutrition (p = 0.04), and frailty (p = 0.01). Over the following 2 years (median follow-up 18 months), there was an incidence of fractures of 110 per 1000 person-years, or 2.8 times higher than reported in individuals without cancer. Risk factors for fractures included advanced age (70-79 vs. 60-69 years, p = 0.05) and frailty (p = 0.03). CONCLUSION: Most older cancer patients studied have osteoporosis or low bone mass, resulting in an almost 3-fold increase in fracture risk as compared to epidemiologic studies. Bone health issues are commonly seen in older cancer patients, we recommend universal bone density testing. The initiation of antiresorptive treatment when findings are of osteopenia or osteoporosis will reduce the risk of fractures.