Association between potentially inappropriate medications prescription and health-related quality of life among US older adults.

BACKGROUND: Potentially inappropriate medications (PIMs) are associated with worse health outcomes among older adults. Our objective was to examine the association between PIM prescription and health-related quality of life (HRQoL) among older adults in the United States using nationally representative data. METHODS: This was a retrospective study utilizing 2011-2015 Medical Expenditure Panel Survey (MEPS) data. Community dwelling US adults aged 65 years or older were included. A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to define exposure to PIMs during the study period. The Physical Component Summary (PCS) and Mental Component Summary (MCS) of the Medical Outcomes Study 12-Item Short Form Health Survey (SF-12) were used to measure HRQoL. Survey-weighted linear regression models were constructed to investigate the association between PIM exposure and participants' PCS and MCS scores. Analyses were stratified across three age cohorts (65-74, 75-85, and ≥85 years). RESULTS: Unadjusted analysis showed poorer scores in the PIM exposed group for both PCS and MCS (all p < 0.001). PIM exposure was associated with poorer PCS scores across all age groups with those aged 65-74 years (adjusted regression coefficient = -1.60 [95% CI = -2.27, -0.93; p < 0.001]), those 75-84 years (adjusted regression coefficient: -1.49 [95% CI = -2.45, -0.53; p = 0.003]), and those 85 years and older (adjusted regression coefficient = -1.65 [95% CI = -3.03, -0.27; p = 0.02]). PIM exposure was also associated with poorer MCS scores in participants aged 65-74 years (adjusted regression coefficient = -0.69 [95% CI = -1.16, -0.22; p = 0.004]) and 85 years and older (adjusted regression coefficient = -2.01 [95% CI = -3.25, -0.78; p = 0.002]). CONCLUSIONS: Our results suggest that patients' exposure to PIMs is associated with poorer HRQoL. Further work is needed to assess whether interventions to deprescribe PIMs may help to improve patients' HRQoL.

Neural Net Modeling of Checkpoint Inhibitor Related Myocarditis and Steroid Response.

Background: Serious but rare side effects associated with immunotherapy pose a difficult problem for regulators and practitioners. Immune checkpoint inhibitors (ICIs) have come into widespread use in oncology in recent years and are associated with rare cardiotoxicity, including potentially fatal myocarditis. To date, no comprehensive model of myocarditis progression and outcomes integrating time-series based laboratory and clinical signals has been constructed. In this paper, we describe a time-series neural net (NN) model of ICI-related myocarditis derived using supervised machine learning. Methods: We extracted and modeled data from electronic medical records of ICI-treated patients who had an elevation in their troponin. All data collection was performed using an electronic case report form, with approximately 300 variables collected on as many occasions as available, yielding 6000 data elements per patient over their clinical course. Key variables were scored 0-5 and sequential assessments were used to construct the model. The NN model was developed in MatLab and applied to analyze the time course and outcomes of treatments. Results: We identified 23 patients who had troponin elevations related to their ICI therapy, 15 of whom had ICI-related myocarditis, while the remaining 8 patients on ICIs had other causes for troponin elevation, such as myocardial infarction. Our model showed that troponin was the most predictive biomarker of myocarditis, in line with prior studies. Our model also identified early and aggressive use of steroid treatment as a major determinant of survival for cases of grade 3 or 4 ICI-related myocarditis. Conclusion: Our study shows that a supervised learning NN can be used to model rare events such as ICI-related myocarditis and thus provide clinical insight into drivers of progression and treatment outcomes. These findings direct attention to early detection biomarkers and clinical symptoms as the best means of implementing early and potentially life-saving steroid treatment.

Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis.

BACKGROUND: Immune checkpoint inhibitors (ICI) have emerged as a front-line therapy for a variety of solid tumors. With the widespread use of these agents, immune-associated toxicities are increasingly being recognized, including fatal myocarditis. There are limited data on the outcomes and prognostic utility of biomarkers associated with ICI-associated myocarditis. Our objective was to examine the associations between clinical biomarkers of cardiomyocyte damage and mortality in patients with cancer treated with ICIs. METHODS: We retrospectively studied 23 patients who developed symptomatic and asymptomatic troponin elevations while receiving ICI therapy at a National Cancer Institute-designated comprehensive cancer center. We obtained serial ECGs, troponin I, and creatine kinase-MD (CK-MB), in addition to other conventional clinical biomarkers, and compared covariates between survivors and non-survivors. RESULTS: Among patients with myocarditis, higher troponin I (p=0.037) and CK-MB (p=0.034) levels on presentation correlated with progression to severe myocarditis. Higher troponin I (p=0.016), CK (p=0.013), and CK-MB (p=0.034) levels were associated with increased mortality, while the presence of advanced atrioventricular block on presentation (p=0.088) trended toward increased mortality. Weekly troponin monitoring lead to earlier hospitalization for potential myocarditis (p=0.022) and was associated with decreased time to steroid initiation (p=0.053) and improved outcomes. CONCLUSIONS: Routine troponin surveillance may be helpful in predicting mortality in ICI-treated patients with cancer in the early phase of ICI therapy initiation. Early detection of troponin elevation is associated with earlier intervention and improved outcomes in ICI-associated myocarditis. The recommended assessment and diagnostic studies guiding treatment decisions are presented.

Trends in fall-related mortality and fall risk increasing drugs among older individuals in the United States,1999-2017.

BACKGROUND: Previous studies have demonstrated increasing mortality due to falls among older adults. The objective of this study was to determine whether there was an increase in fall risk increasing drug prescribing and if this is concurrent with an increase in fall-related mortality in persons 65 years and older in the United States. METHODS: The study is a serial cross-sectional analysis utilizing data from both the National Vital Statistics System (NVSS) and the medical expenditure panel survey (MEPS) for years 1999-2017. Adults aged 65 years and older were evaluated for death due to falls from the NVSS and for prescription fills of fall risk increasing drugs per the Stopping Elderly Accidents, Deaths, and Injuries-Rx (STEADI-Rx) fall checklist from the MEPS. RESULTS: The analysis included 374 972 fall-related mortalities and 7 858 177 122 fills of fall risk increasing drugs. 563 037 964 persons age 65 and older received at least one fall risk increasing drug. Age-adjusted mortality due to falls increased from 29.40 per 100 000 in 1999 to 63.27 per 100 000 in 2017. The percent of persons who received at least one prescription for a fall risk increasing drug increased from 57% in 1999 to 94% in 2017 (p for trend <.0001). CONCLUSIONS AND RELEVANCE: Both use of fall risk increasing drugs and mortality due to falls are on the rise. Fall risk increasing drugs may partially explain the increase in mortality due to falls; this cannot be firmly concluded from the current study. Future research examining the potential relationship between fall risk increasing drugs and fall-related mortality utilizing nationally representative person-level data are needed.

Potentially Inappropriate Medications Are Associated with Increased Healthcare Utilization and Costs.

BACKGROUND/OBJECTIVES: To examine the prevalence of potentially inappropriate medication (PIM) prescribing and its association with healthcare utilization and related expenditures utilizing nationally representative data from the United States. DESIGN: Retrospective cohort study. SETTING: The 2011-2015 Medical Expenditure Panel Survey (MEPS). PARTICIPANTS: Community-dwelling sample of U.S. adults aged 65 and older during the first round of each MEPS cycle. MEASUREMENTS: A qualified definition operationalized from the 2019 American Geriatrics Society Beers Criteria® was used to estimate the prevalence of PIM prescribing over the study period. Negative binomial models were assembled to examine associations between PIM exposure and healthcare utilization including hospitalizations, emergency department (ED) visits, and outpatient provider visits. Generalized linear models with the log link function and gamma distribution were used to analyze associations between PIM exposure and healthcare expenditures. Sensitivity analyses were conducted utilizing inverse probability treatment weighting using propensity scores for being prescribed a PIM. RESULTS: The period prevalence of PIM prescribing over the 5-year sample was 34.4%. PIM prescribing was positively associated with hospitalizations (adjusted incidence rate ratio [aIRR] = 1.17; 95 confidence interval [CI] = 1.08-1.26; P < .001), ED visits (aIRR = 1.26; 95% CI = 1.17-1.35; P < .001), and outpatient provider visits (aIRR = 1.18; 95% CI = 1.14-1.21; P < .001). PIM exposure was associated with higher marginal costs within outpatient visits ($116; 95% CI = $105-$243; P < .001), prescription medications ($128; 95% CI = $72-$199; P < .001), and total healthcare expenditures ($458; 95% CI = $295-$664; P < .001). Similar results were found in our propensity score analyses. CONCLUSION: PIMs continue to be prescribed at a high rate among older adults in the United States. Our results suggest that receipt of PIMs is associated with higher rates of healthcare utilization and increased costs across the healthcare continuum. Further work is needed to implement evidence-based deprescribing interventions that may in turn reduce unnecessary healthcare utilization.

Proton Pump Inhibitors and Risk of Acute and Chronic Kidney Disease: A Retrospective Cohort Study.

BACKGROUND: Proton pump inhibitors (PPIs) have been linked to acute kidney injury (AKI) and chronic kidney disease (CKD); however, current evidence has only been evaluated in a small number of studies with short follow-up periods. This study examined the association between PPI use and risk of incident AKI and CKD in a large population-based health maintenance organization (HMO) cohort. METHODS: Patients aged 18 years or older, without evidence of preexisting renal disease, started on PPI therapy, and those continuously enrolled for at least 12 months between July 1993 and September 2008 were identified in an HMO database. Incidences of AKI and CKD were defined using documented International Classification of Disease, Ninth Revision, Clinical Modification (ICD-9-CM) codes or a glomerular filtration rate less than 60 ml/min/1.73 m2 after initiation of PPI therapy. Patients with AKI were followed for up to 90 days (cohort 1), and patients with CKD required at least 1 year of follow-up (cohort 2). Multivariable logistic regression analyses were used to adjust for differences in demographics (excluding race), comorbidities, and medication use between groups. RESULTS: In 93,335 patients in the AKI cohort, 16,593 of whom were exposed to PPIs, the incidence rate of AKI was higher in the PPI group than nonusers (36.4 vs 3.54 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPI exposure was associated with an increased risk of AKI (adjusted odds ratio [aOR] 4.35, 95% confidence interval [CI] 3.14-6.04, p<0.0001). In 84,600 patients in the CKD cohort, 14,514 of whom were exposed to PPIs, the incidence rate of CKD was higher in the PPI group than nonusers (34.3 vs 8.75 per 1000 person-years, p<0.0001, respectively). In adjusted models, PPIs were associated with a higher risk of CKD compared with controls (aOR 1.20, 95% CI 1.12-1.28, p<0.0001). Associations between PPI use and AKI and CKD persisted in propensity score-matched analyses. CONCLUSION: The use of PPIs is associated with an increased risk of incident AKI and CKD. This relationship could have a considerable public health impact; therefore, health care provider education and deprescribing initiatives will be necessary to raise awareness and reduce health care burden.