Events In Older Adults Research Articles

Risk prediction models for adverse drug reactions and adverse drug events in older adults—a systematic review and meta-analysis

Risk prediction models for adverse drug reactions and adverse drug events in older adults—a systematic review and meta-analysis

Higher dose antiviral therapy for herpes infections is associated with a risk of serious adverse events in older adults with chronic kidney disease.

Antiviral use has been linked to encephalopathy and elevated serum creatinine concentrations in individuals with chronic kidney disease (CKD) in case reports. Using linked healthcare data in Ontario, we conducted a population-based cohort study on adults aged ≥66 years not receiving dialysis and newly prescribed oral acyclovir, valacyclovir, or famciclovir in the outpatient setting (2008-2022) at higher versus lower doses. The primary composite outcome, a hospital visit with encephalopathy or acute kidney injury (AKI) within 14 days of initiating antiviral treatment, was examined in a primary cohort. AKI was assessed in a secondary cohort of older adults with CKD with available linked hospital-based laboratory (lab) data. We used inverse probability of treatment weighting on the propensity score to balance comparison groups on baseline health. Weighted risk ratios (RR) and risk differences (RD) were obtained using modified Poisson and binomial regression. In the primary cohort, higher- versus lower-dose antiviral was not associated with an increased 14-day risk of hospital visit with encephalopathy or AKI. However, Higher- versus lower-dose antiviral was associated with a higher risk of a hospital visit with AKI when assessed using lab values (weighted number of events, 70 of 8407 [0.83%] versus 18 of 8230 [0.22%], respectively; weighted RR, 3.83 [95% CI, 1.87-7.87]; weighted RD, 0.62% [95% CI, 0.37%-0.86%]). In older adults with CKD, starting an antiviral at a higher versus lower dose was associated with a higher risk of AKI, although the absolute risk of this event was <1%.

Predictors of non-adherence to an early in-hospital rehabilitation program after surgery for hip fracture in a co-managed orthogeriatric unit

BackgroundHip fracture is a common event in older adults, leading to an increased risk of mortality, disability, and higher healthcare costs. Early in-hospital rehabilitation after surgery within orthogeriatric units may improve outcomes with limited incident complications even in the oldest old. We aimed to determine the prevalence and predictors of non-adherence to early rehabilitation in the orthogeriatric unit of an Italian tertiary hospital and its impact on outcomes and setting at discharge.MethodsRetrospective observational single-centered cohort study. Patients aged ≥ 65 years admitted to the orthogeriatric unit for hip fracture who underwent surgery between April 2019 and October 2020 were considered eligible if able to walk autonomously or with assistance and independent in at least 2 Basic Activities of Daily Living. Along with sociodemographic and geriatric variables, characteristics of surgery and rehabilitation, in-hospital complications and functional outcomes at discharge were collected. The primary outcome was non-adherence to the early in-hospital rehabilitation program.ResultsAmong 283 older patients (mean age 82.7 years, 28.6% male), non-compliance with physical therapy was assessed in 49 cases (17.3%), characterized by worse pre-fracture clinical, cognitive, and functional status and showing worse outcomes in terms of mobilization at discharge. After multivariable analysis, non-adherence was independently associated with the onset of delirium (OR 5.26, 95%CI 2.46–11.26; p < 0.001) or infections after surgery (OR 3.26, 95%CI 1.54–6.89; p < 0.001) and a systolic blood pressure at admission < 120 mmHg (OR 4.52, 95%CI 1.96–10.43, p < 0.001).ConclusionsPre-fracture poor cognitive and functional status, along with lower systolic blood pressure, seem to make some patients more vulnerable to in-hospital complications (mainly delirium and infections) and negatively affect the adherence to physical therapy and, by consequence, clinical outcomes of rehabilitation.

Risk Prediction Models for Adverse Drug Reactions and Adverse Drug Events in Older Adults – A Systematic Review and Meta-analysis

Abstract Background Adverse drug reactions (ADRs) and adverse drug events (ADEs) are common and result in significant morbidity, mortality and healthcare costs. As the world’s population ages, the consumption of medications and healthcare will increase. Models predicting ADR risks in older adults have previously been found to lack reliability and validity. The aim of this systematic review and meta-analysis is to provide an updated, comprehensive quality assessment and analysis of ADR-risk prediction tools in older adults. Methods Standard computerised-databases and citations were searched (2012 to 2023) to identify relevant peer-reviewed studies. Studies which developed and/or validated an ADR/ADE prediction model for use in older adults were included. Four studies from a previous systematic review were also included. The TRIPOD (transparent reporting of a multivariable prediction model for individual prognosis or diagnosis) guidelines were used to evaluate each of the included studies. Random effects models were used to derive a pooled discrimination estimate (area under the receiver operation curve; AUROC) for model development studies and model validation studies. The prediction model risk of bias assessment tool (PROBAST) was applied to evaluate bias. Results Five out of 11,481 titles, plus four previous studies, met all inclusion criteria and underwent TRIPOD evaluation. Meta-analysis resulted in a favourable pooled AUROC 0.75 (95% CI 0.57, 0.87; I-squared= 96.65%) for model development studies and 0.70 (95% CI 0.57, 0.80; I-squared= 90.53%) for model validation studies but there was substantial heterogeneity. Studies had poor adherence (range 32-50%; median 44%; IQR 11.5%) to TRIPOD guidelines. The overall risk of bias was high for all included studies. Conclusion Seven risk prediction models were identified, all exhibiting poor adherence to TRIPOD guidelines which may question the investigational rigor of the studies and their usability. This underscores the need for the development of a validated, robust and reliable tool worthy of implementation and testing in a real-world setting.

Association between antidepressant use and delirium in older adults: an analysis of the World Health Organization’s global pharmacovigilance database

BackgroundPsychoactive drugs frequently cause delirium adverse events in older adults. However, few data on the relationship between antidepressants and delirium are available. Here, we investigated the association between antidepressant prescription and pharmacovigilance reports of delirium in older adults.MethodsUsing the World Health Organization’s VigiBase® global pharmacovigilance database from 1967 to 2022, we performed a disproportionality analysis in order to probe the putative associations between each antidepressant class (non-selective monoamine reuptake inhibitors (NSMRIs), selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors (MAOIs), alpha-2-adrenergic receptor antagonists, and other antidepressants) and reports of delirium in people aged 65 or over. We calculated the reporting odds ratios (r-OR) and their 95% confidence interval ([95%CI]) with logistic regression models before and after adjustment for confounding factors. Secondary analyses were performed for each drug and within each class by age group (65-74, and 75 and over). We also studied the reports of concomitant delirium and hyponatremia.ResultsOur main analysis included 87,524 cases of delirium. After adjustment for confounders, a significant association was found between delirium and all antidepressant classes other than SNRIs. Intraclass disparities were found for the association between the most frequently prescribed antidepressants and reports of delirium. An elevated risk of reports of concomitant delirium and hyponatremia was found for SSRIs (4.46 [4.01-4.96]), SNRIs (1.25 [1.07-1.46]), MAOIs (1.72 [1.41-2.09]), and the “other antidepressants” class (1.47 [1.30-1.65]).ConclusionsThere was a significant association between reports of delirium and antidepressant classes (other than SNRIs). However, this association varied from one drug to another within a given antidepressant class. Moreover, this association could not always be explained by antidepressant-induced hyponatremia.

Real-World Prevalence and Tolerability of Immune-Related Adverse Events in Older Adults with Non-Small Cell Lung Cancer: A Multi-Institutional Retrospective Study.

With cancer diagnosis occurring at older ages, the use of immune checkpoint inhibitors (ICIs) has extended to older adults. However, the safety of immune-related adverse events (irAEs) in this population remains unclear and relies on data extrapolated from younger adults. This multicenter retrospective study aimed to examine irAE prevalence and tolerability in older adults. We included 436 patients with non-small lung cancer undergoing ICI therapy and dichotomized them into two age groups (< or ≥75 years). Incidence of any irAE grade, grade ≥3 irAEs, and steroid usage after irAE occurrence was similar between younger (n = 332) and older groups (n = 104). While the younger patients with irAEs showed prolonged overall survival in the 12-month landmark Kaplan-Meier analysis (Hazard ratio (HR) 0.59, 95% confidence interval (CI) 0.38-0.89, p = 0.013), the older cohort did not (HR 0.80, 95% CI 0.36-1.78, p = 0.588). Although no differences were observed with ICI continuation or re-challenge after irAE onset, the elderly cohort had double the irAE cases that required a transition to best supportive care (BSC) (11.3% vs. 22.4%, p = 0.026). In conclusion, although irAE prevalence remains consistent regardless of age, the increased conversion to BSC post-irAE onset in older adults suggests diminished tolerability and the potential absence of favorable prognosis associated with irAEs in this population.

Medicare Fee-For-Service Spending for Fall Injury and Nonfall Events: The Health, Aging, and Body Composition Study.

Fall injuries are prevalent in older adults, yet whether higher spending occurs after nonfracture (NFFI) and fracture is unknown. We examined whether incident fall injuries, including NFFI and fractures, were associated with higher Medicare spending in 12 months after incident events in older adults. The Health, Aging, and Body Composition Study included 1595 community-dwelling adults (53% women, 37% Black; 76.7 ± 2.9 years) with linked Medicare Fee-For-Service (FFS) claims at 2000/01 exam. Incident outpatient and inpatient fall injuries (N = 448) from 2000/01 exam to December 31, 2008 were identified using the first claim with a nonfracture injury diagnosis code with a fall E-code, or a fracture diagnosis code with/without an E-code. Up to 3 participants without fall injuries (N = 1147) were matched on nonfall events to 448 participants in the fall injury month. We calculated the change in monthly FFS spending in 12 months before versus after index events in both groups. Generalized linear regression with centered outcomes and gamma distributions examined the association of prepost expenditure changes with fall injuries (including NFFI and fractures) adjusting for related covariates. Monthly spending increased after versus before fall injuries (USD$2261 vs $981), nonfracture (N = 105; USD$2083 vs $1277), and fracture (N = 343; USD$2315 vs $890) injuries (all p < .0001). However, after adjusting for covariates in final models, fall injuries were not significantly associated with larger increases in spending/month versus nonfall events (differential increase: USD$399.58 [95% CI: -USD$44.95 to $844.11]). Fracture prepost change in monthly spending was similar versus NFFI (differential increase: USD$471.93 [95% CI: -USD$21.17 to $965.02]). Although substantial increases occurred after injuries, with fracture and NFFI increasing similarly, changes in monthly spending after fall injury were not different compared to nonfall events. Our results contribute to the understanding of subsequent spending after fall injury that may inform further research on fall injury-related health care spending.

Strategies aiming to improve statin therapy adherence in older adults: a systematic review

BackgroundRandomized clinical trials have shown that, under optimal conditions, statins reduce the risk of cardiovascular events in older adults. Given the prevalence and consequences of suboptimal adherence to statin among older adults, it is essential to document strategies designed to increase statin adherence in this population. The objective of this systematic review is to describe and summarize the effectiveness of interventions to improve statin adherence in older adults (≥ 65 years old).MethodsThis review followed PRISMA guidelines. Studies were identified from PubMed, PsycINFO, Embase, CINAHL and Web of Science. Study selection was conducted independently by four reviewers working in pairs. Included studies reported data on interventions designed to increase adherence to statin therapy in older adults and were original trials or observational studies. Interventions were pragmatically regrouped into 8 different categories going from patient to administrative level. Two reviewers extracted study data and assessed study quality independently. Given the heterogeneity between the included studies, a narrative critique and summary was conducted.ResultsTwelve out of the 2889 identified articles were included in the review. Our review showed that simplifying patients’ drug regimen, administrative improvements and large-scale pharmacy-led automated telephone interventions show positive effects on patient adherence to statin therapy, with odds ratios between > 1.0 and 3.0, while education-based strategies and intensified patient care showed mixed results.ConclusionsCurrent evidence suggests that some interventions can increase statin adherence in older adults, which could help in the reduction of the risk of a cardiovascular event in this population.

Real-world outcomes of ponatinib treatment in 724 patients with CML and Ph+ ALL: a post-marketing surveillance study with a special interest in arterial occlusive events in Japan.

In September 2016, ponatinib was approved in Japan for the treatment of patients with chronic myeloid leukemia with resistance/intolerance to prior tyrosine kinase inhibitors and patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoblastic leukemia. We conducted a post-marketing all-case surveillance to study the safety and efficacy of ponatinib in clinical practice, focusing on arterial occlusive events. Data from 724 patients were collected for 2years from the initiation of ponatinib. The arterial occlusive events were reported in 6.49% (47/724) with an exposure-adjusted incidence rate of 6.8/100 person-years. The risks associated with arterial occlusive events were age and comorbidities including hypertension and diabetes. At 104weeks, the cumulative major molecular response rate in patients with chronic-phase chronic myeloid leukemia was 67.2% and the complete cytogenetic response in patients with Philadelphia chromosome-positive acute lymphoblastic leukemia was 80.0%. Furthermore, the estimated 1-year overall survival rate was 98.5% for chronic-phase chronic myeloid leukemia and 68.6% for Philadelphia chromosome-positive acute lymphoblastic leukemia. This surveillance demonstrated that ponatinib has a favorable safety and efficacy profile in Japanese patients and also showed the necessity of closely monitoring arterial occlusive events in older adults and patients with predisposing factors for atherosclerosis.

Predictive Value of Plasma PCSK9 Levels for Degree of Atherosclerosis and Major Adverse Cardiovascular and Cerebrovascular Events in Older Adult Patients with Non-Alcoholic Fatty Liver Disease.

This study investigated the influence of plasma proprotein convertase subtilisin/kexin 9 (PCSK9) levels on the degree of atherosclerosis and major adverse cardiovascular and cerebrovascular events (MACCE) in older adults with non-alcoholic fatty liver disease. The degree of atherosclerosis severity was assessed by the standard Gensini score quartile method. According to the degree of atherosclerosis, patients were divided into mild (0-24 points; n=84), moderate (25-53 points; n=86), and severe groups (≥54 points; n=84) and then categorized as MACCE (n=30) or non-MACCE (n=224) according to 6-month follow-up data. The patients' age, sex, smoking history, medical history, and early morning fasting venous blood, for measuring biochemical indexes, were collected. Clinical data were compared between groups and the relationship between Gensini scores and PCSK9 was evaluated. Compared with the mild group, the moderate and severe groups had higher high-sensitivity C-reactive protein(hs-CRP), PCSK9, triglycerides(TG), low-density lipoprotein cholesterol (LDL-C), and lipoprotein(a)[Lp(a)] levels and lower high-density lipoprotein cholesterol(HDL-C) levels (all P<0.05). Moreover, PCSK9 positively correlated with Gensini scores (r=0.657, P<0.01). The MACCE and non-MACCE groups had significantly different ages, statin use, Gensini scores, PCSK9, and LDL-C (all P<0.05). Multi-factorial Cox risk regression analysis showed the Gensini score (HR=1.018, 95% CI: 1.006~1.029) and PCSK9 (HR=1.147, 95% CI: 1.038~1.287) were independent risk factors for MACCE. The Gensini score and PCSK9 levels can be used as predictive indicators for the degree of illness and occurrence of MACCE in older NAFLD patients.

Usability of the 4Ms Worksheet in the Emergency Department for Older Patients: A Qualitative Study.

Older adults often have multiple comorbidities; therefore, they are at high risk for adverse events after discharge. The 4Ms framework-what matters, medications, mentation, mobility-has been used in acute and ambulatory care settings to identify risk factors for adverse events in older adults, although it has not been used in the emergency department (ED). We aimed to determine whether 1)use of the 4Ms worksheet would help emergency clinicians understand older adult patients' goals of care and 2)use of the worksheet was feasible in the ED. We conducted a qualitative, descriptive study among patients aged ≥60years and emergency clinicians from January-June 2022. Patients were asked to fill out a 4Ms worksheet; following this, semi-structured interviews were conducted with patients and clinicians separately. We analysed data to create codes, which were divided into categories and sub-categories. A total of 20 older patients and 19 emergency clinicians were interviewed. We identified two categories based on our aims: understanding patient goals of care (sub-categories: clinician/ patient concordance; understanding underlying goals of care; underlying goals of care discrepancy) and use of 4Ms Worksheet (sub-categories: worksheet to discussion discrepancy; challenges using worksheet; challenge completing worksheet before discharge). Rates of concordance between patient and clinician on main concern/goal of care and underlying goals of care were 82.4% and 15.4%, respectively. We found that most patients and emergency clinicians agreed on the main goal of care, although clinicians often failed to elicit patients' underlying goal(s) of care. Additionally, many patients preferred to have the interviewer fill out the worksheet for them. There was often discrepancy between what was written and what was discussed with the interviewer. More research is needed to determine the best way to integrate the 4Ms framework within emergency care.

Predicting the incidence of mild cognitive impairment with a computer-based cognitive assessment tool in community-dwelling older adults: The Otassha study.

This study examined the ability of a computer-based cognitive assessment tool (CompBased-CAT) to predict mild cognitive impairment (MCI) in community-dwelling older adults. A two-year longitudinal study was conducted using data from 2016 to 2018 from the Otassha study cohort of community-dwelling older adults. MCI was defined as a Mini-Mental Status Examination (MMSE) score of <27. The CompBased-CAT was used at baseline, with each subtest score converted into a Z-score. Subsequently, the total Z-scores were calculated. Participants were divided into robust and MCI groups, and all variables were compared using the t-test or χ2 test. Receiver operating characteristic (ROC) curves and logistic regression analyses were conducted, with MCI and total Z-scores as dependent and independent variables, respectively. Among the 455 participants (median age, 72 years; range, 65-89 years; 282 women and 173 men), 32 developed MCI after two years. The participants in the MCI group were significantly older. They had lower maximal gait speed, baseline MMSE scores, subtest Z-scores, and total Z-scores than those in the robust group. The area under the ROC curve was 0.79 (95% confidence interval: 0.70-0.87; P <0.01). The sensitivity was 0.76, and the specificity was 0.75. The logistic regression analysis showed an odds ratio of 1.34 (95% confidence interval: 1.18-1.52; P <0.01). This study showed that CompBased-CAT can detect MCI, which is an early stage of dementia. Thus, CompBased-CAT can be used in future community health checkups and events for older adults.

Usability of the 4Ms Worksheet in the Emergency Department for Older Patients: A Qualitative Study

Introduction: Older adults often have multiple comorbidities; therefore, they are at high risk for adverse events after discharge. The 4Ms framework—what matters, medications, mentation, mobility—has been used in acute and ambulatory care settings to identify risk factors for adverse events in older adults, although it has not been used in the emergency department (ED).Weaimed to determine whether 1) use of the 4Ms worksheet would help emergency clinicians understand older adult patients’ goals of care and 2) use of the worksheet was feasible in the ED. Methods: We conducted a qualitative, descriptive study among patients aged ≥60 years and emergency clinicians from January–June 2022. Patients were asked to fill out a 4Ms worksheet; following this, semi-structured interviews were conducted with patients and clinicians separately. We analysed data to create codes, which were divided into categories and sub-categories. Results: A total of 20 older patients and 19 emergency clinicians were interviewed. We identified two categories based on our aims: understanding patient goals of care (sub-categories: clinician/ patient concordance; understanding underlying goals of care; underlying goals of care discrepancy) and use of 4Ms Worksheet (sub-categories: worksheet to discussion discrepancy; challenges using worksheet; challenge completing worksheet before discharge). Rates of concordance between patient and clinician on main concern/goal of care and underlying goals of care were 82.4% and 15.4%, respectively. Conclusion: We found that most patients and emergency clinicians agreed on the main goal of care, although clinicians often failed to elicit patients’ underlying goal(s) of care. Additionally, many patients preferred to have the interviewer fill out the worksheet for them. There was often discrepancy between what was written and what was discussed with the interviewer. More research is needed to determine the best way to integrate the 4Ms framework within emergency care.

Polypharmacy and Elevated Risk of Severe Adverse Events in Older Adults Based on the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database.

Older adults are at a higher risk of severe adverse drug events (ADEs) because of multimorbidity, polypharmacy, and lower physiological function. This study aimed to determine whether polypharmacy, defined as the use of ≥ 5 active drug ingredients, was associated with severe ADEs in this population. We used ADE reports from the Korea Institute of Drug Safety and Risk Management-Korea Adverse Event Reporting System Database, a national spontaneous ADE report system, from 2012 to 2021 to examine and compare the strength of association between polypharmacy and severe ADEs in older adults (≥ 65 years) and younger adults (20-64 years) using disproportionality analysis. We found a significant association between severe ADEs of cardiac and renal/urinary Medical Dictionary for Regulatory Activities System Organ Classes (MedDRA SOC) with polypharmacy in older adults. Regarding individual-level ADEs included in these MedDRA SOCs, acute cardiac arrest and renal failure were more significantly associated with polypharmacy in older adults compared with younger adults. The addition of new drugs to the regimens of older adults warrants close monitoring of renal and cardiac symptoms.

GLP-1 AGONISTS: EFFECT IN MANAGEMENT OF DIABETES AND WEIGHT LOSS IN OLDER ADULTS WITH OVERWEIGHT AND OBESITY

Abstract Prevalence of Diabetes Mellitus Type 2 in older adults in the US is 33%, incidence of newly diagnosed diabetes is highest among those aged 65-79 years. Obesity in older adults impacts not only the morbidity and mortality, but importantly impacts quality of life and risk of institutionalization. Treatment for diabetes with glucagon like peptide 1 (GLP-1) agonists have demonstrated to reduce weight, control glucose, and reduce major adverse cardiovascular events in older adults. This study aims to describe outcomes in the management of older adults with diabetes and obesity with GLP-1 agonists. A retrospective study of 30 older adults with uncontrolled diabetes, overweight and obesity at a local practice that were started on treatment with GLP-1 agonists, since 2022, with ages 65-84 with diabetes mellitus type 2 with initial HbA1C 9.6%-12.6%, and BMI 27-48.2 that were started on GLP-1 agonists with improved results during treatment with current reduction of HbA1C 5.8%-7.7% and BMI reduction 23-39.8. In conclusion GLP-1 agonists have demonstrated significantly improved management of uncontrolled Diabetes Mellitus in older adults as well as a significant reduction in weight improving outcomes.

In older adults, postoperative oral haloperidol vs. antipsychotics was linked to similar risk for in-hospital adverse events.

Kim DH, Lee SB, Park CM, et al. Comparative safety analysis of oral antipsychotics for in-hospital adverse clinical events in older adults after major surgery: a nationwide cohort study. Ann Intern Med. 2023;176:1153-1162. 37665998.

Major cardiovascular adverse events in older adults with early-stage triple-negative breast cancer treated with adjuvant taxane + anthracycline versus taxane-based chemotherapy regimens: A SEER-medicare study

BackgroundTriple-negative breast cancer (TNBC) is more aggressive as compared to other subtypes of breast cancer with characteristic metastatic patterns and a poor prognosis. The standard of care for early-stage TNBC is historically anthracycline and taxane-based chemotherapy (ATAX). Despite the effectiveness of this regimen, anthracyclines carry a small but important risk of cardiotoxicity, which is specifically a concern in the older population. This study evaluates major adverse cardiovascular events (MACE) in older women with TNBC treated with ATAX compared to taxane-based chemotherapy (TAX). MethodsUsing the Surveillance, Epidemiology, and End Results (SEER)-Medicare database, we identified women aged 66 and older with TNBC diagnosed between 2010 and 2015 (N = 2215). We compared patient and clinical characteristics according to adjuvant chemotherapy regimen (chemotherapy versus no chemotherapy and ATAX versus TAX). Logistic regression was performed to estimate the odds ratios (OR) and 95% confidence intervals (CIs), Kaplan-Meier survival curves were generated to estimate three-year overall survival (OS) and cancer specific survival (CSS). Cox proportional hazards models were used to analyze OS and CSS while controlling for patient and tumor characteristics. MACE was defined as acute myocardial infarction, heart failure, potentially fatal arrhythmia, and cerebral vascular incidence. Few patients experienced a cardiac death and therefore this was excluded in the analysis. ResultsOf the 2215 patients in our cohort, most patients (n = 1334; 60.26%) received TAX compared to ATAX (n = 881; 39.78%). Patients who received ATAX were not statistically significantly more likely than those who received TAX to experience acute myocardial infarction, cerebral vascular accident (CVA), or potentially fatal arrhythmia when controlling for traditional risk factors. Among patients who experienced MACE, there was no difference in OS or CSS in patients who received TAX vs ATAX. Patients who received ATAX were less likely to develop heart failure than those who received TAX (OR 0.63, 95% CI [0.45–0.88], p < 0.01). Patients who developed MACE and who were > 76 years old had worse OS compared to those who experienced MACE and were age 66–75 years old (HR 1.67, 95% CI [1.07–2.62], p = 0.02). ConclusionAmong older women with TNBC, receipt of adjuvant chemotherapy with ATAX was not associated with increased risk of major adverse cardiac events. For those who experienced a cardiac event, there was no difference in survival amongst those who received TAX vs ATAX. Other factors including additional chemotherapy toxicities should be investigated as a potential etiology for the inferior OS previously observed with ATAX vs TAX in older women with node negative or 1–3 positive lymph nodes.

Deprescribing electronic case reviews for older veterans at risk for falls: Effects on drug burden and falls.

Falls are the most common medication-related safety event in older adults. Deprescribing fall risk-increasing drugs (FRIDs) may mitigate fall risk. This study assesses the effects of an innovative deprescribing program in reducing FRID burden and falls-related acute visits over 1 year. The Falls Assessment of Medications in the Elderly (FAME) Program is a pilot deprescribing program designed to improve medication safety in Veterans aged ≥65, screening positive for high fall risk at the Durham Veterans Affairs Health Care System. Central case finding and electronic case reviews with deprescribing recommendations were completed by an interdisciplinary team, forwarded to prescribers for approval, then implemented during follow-up telephone visits by FAME team. Primary outcome was change in FRID burden calculated by modified Drug Burden Index (DBI) at 1 year and an exploratory outcome was 1-year fall-related acute visits. Overall, 472 patients (236 intervention cases, 236 matched controls) were included in the study. Of the 236 patients receiving a FAME deprescribing plan, 147 had recommendations approved by prescriber and patient. In the intention-to-treat analysis, the 1-year change in modified DBI was -0.15 (95% CI -0.23, -0.08) in the intervention cohort and -0.11 (-0.21, -0.00) in the matched control cohort (p = 0.47). The odds of increasing DBI by a clinically important threshold of 0.5 was significantly lower in the FAME cohort (OR 0.37, 0.21, 0.66). Fall-related acute events occurred in 6.3% of patients in the intervention group versus 11.0% in control patients over a one-year period (p = 0.10). The program was associated with a significantly lower odds of further increasing FRID burden at 1 year compared to matched controls. An electronic case review and telephone counseling program has the potential to reduce drug-related falls in high-risk older adults.

Epigenetic and inflammatory markers in older adults with cancer: A Young International Society of Geriatric Oncology narrative review

The number of adults aged ≥ 65 years with cancer is rapidly increasing. Older adults with cancer are susceptible to treatment-related acute and chronic adverse events, resulting in loss of independence, reduction in physical function, and decreased quality of life. Nevertheless, evidence-based interventions to prevent or treat acute and chronic adverse events in older adults with cancer are limited. Several promising blood-based biomarkers related to inflammation and epigenetic modifications are available to identify older adults with cancer who are at increased risk of accelerated aging and physical, functional, and cognitive impairments caused by the cancer and its treatment. Inflammatory changes and epigenetic modifications can be reversible and targeted by lifestyle changes and interventions. Here we discuss ways in which changes in inflammatory and epigenetic pathways influence the aging process and how these pathways can be targeted by interventions aimed at reducing inflammation and aging-associated biological markers. As the number of older adults with cancer entering survivorship continues to increase, it is becoming progressively more important to understand ways in which the benefit from treatment can be enhanced while reducing the effects of accelerated aging.

Kidney function estimators for drug dose adjustment of direct oral anticoagulants in older adults with atrial fibrillation.

The Cockcroft-Gault equation (CrClC-G) is recommended for dose adjustment of direct oral anticoagulant drugs (DOACs) to kidney function. We aimed to assess whether defining DOAC dose appropriateness according to various kidney function estimators changed the associations between dose appropriateness and adverse events in older adults with atrial fibrillation (AF). Participants of the Berlin Initiative Study with AF and treated with DOACs were included. We investigated CrClC-G and estimated glomerular filtration rate (eGFR) using the Chronic Kidney Disease Epidemiology Collaboration and European Kidney Function Consortium equations based on creatinine and/or cystatin C. Marginal structural Cox models yielded confounder-adjusted hazard ratios for the risk of mortality, thromboembolism and bleeding associated with dose status. A total of 224 patients were included in the analysis (median age 87years). Using CrClC-G, 154 (69%) had an appropriate dose of DOACs, 52 (23%) were underdosed and 18 (8%) were overdosed. During a 39-month median follow-up period, 109 (14.9/100 person-years) participants died, 25 (3.6/100 person-years) experienced thromboembolism and 60 (9.8/100 person-years) experienced bleeding. Dose status was not associated with mortality and thromboembolism, independent of the equation. Underdose status was associated with a lower risk of bleeding with all the equations compared with the appropriate dose group. In participants with discrepancies in dose status using CrClC-G and eGFR equations, the occurrence of endpoints did not differ between participants having an appropriate dose using CrClC-G or eGFR. In older adults with AF, the association of DOAC dose status with adverse events did not differ when using CrClC-G or eGFR. Our results suggest that eGFR equations are not inferior to CrClC-G within this context.