Aging precisely: Precision medicine through the lens of an older adult.

Precision medicine presents an opportunity to use novel, data-driven strategies to improve patient care. The field of precision medicine has undergone many advancements over the past few years. It has moved beyond incorporation of individualized genetic risk into medical decision-making to include multiple other factors such as unique social, demographic, behavioral, and clinical characteristics. Geriatric medicine stands to benefit heavily from the integration of precision medicine into its standard practices. Older adults, compared with other populations, have high clinical and biological heterogeneity that can alter the risks and benefits of different approaches to patient care. These factors have not been routinely considered previously by geriatricians. Yet, geriatricians' ability to address older adults' baseline heterogeneity is increasingly recognized as a cornerstone of delivering quality care in a geriatric medical practice. Given the shared focus of individualized decision-making, precision medicine is a natural fit for geriatric medicine. This manuscript provides, via cases and discussion, examples that illustrate how precision medicine can improve the care of our older patients today. We will share specific and existing tools and evidence, and review the existing multilevel barriers to further incorporate and implement these tools into clinical practice. We propose methods to address these barriers and to help realize the full potential of precision medicine for the care of older adults. We conclude with a brief discussion of potential future directions of research of precision medicine in the care of older adults.

American Delirium Society 2022 Year in Review: Highlighting the Year's Most Impactful Delirium Research.

Background: Since 2015, the American Delirium Society (ADS) Research Committee has conducted an annual survey of the delirium literature for presentation in its year-in-review session. Our objectives were to describe the review process used for the 2021-2022 and to summarise the selected publications. Methods: Each member of the ADS Research Committee nominated up to 6 publications considered to be the most impactful primary delirium research published from September 1, 2021, to July 31, 2022. The 24 nominated studies were divided into three categories balanced by number of articles: medical intervention trials, non-medical intervention trials, and delirium detection/basic science studies. Each ADS Research Committee member ranked all studies in their assigned category for methodological rigor and for impact, each being scored as 0-10, for a total score of 0-20. It was decided a priori to select the top three highest-scoring articles in each category for presentation, with ties adjudicated by Committee consensus. Results: Nineteen Research Committee members served as reviewers. Scores for each category were similar: medical interventions mean (standard deviation) 12.8 (1.1), non-medical interventions 13.1 (1.1), and detection/basic science 12.6 (1.0). We summarise the results of the papers presented in the 2022 ADS year-in-review session. Conclusion: The diversity of studies presented for the 2022 ADS year-in-review session illustrates the breadth of the delirium field and the growing number of clinical trials. The dissemination of publications across a broad, diverse array of journals provides further justification of the need for delirium-specific journals.

The Association of Selective Serotonin Reuptake Inhibitors With Delirium in Critically Ill Adults: A Secondary Analysis of the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors ICU Study.

OBJECTIVES: To assess the association between selective serotonin reuptake inhibitors (SSRI) and delirium in the subsequent 24 hours after drug administration in critically ill adults. DESIGN: Retrospective cohort study utilizing the Bringing to Light the Risk Factors and Incidence of Neuropsychologic Dysfunction in ICU Survivors dataset. SETTING: Two large U.S. ICUs. PATIENTS: Critically ill adults admitted to a medical or surgery ICU between March 2007 and May 2010 with respiratory failure or shock. INTERVENTIONS: Our primary outcome was the occurrence rate of delirium or coma during each day in the ICU. Our exposure variable was SSRI administration on the prior day in the ICU. As a secondary question, we assessed the association of SSRI administration and delirium the same day of SSRI administration in the ICU. MEASUREMENTS AND MAIN RESULTS: We analyzed 821 patients. The median age was 61.2 years old (interquartile range, 50.9-70.7), and 401 (48.8%) were female. A total of 233 patients (28.4%) received prescribed SSRIs at least once during their ICU admission. Delirium was present in 606 (74%) of the patients at some point during hospitalization in the ICU. Coma was present in 532 (64.8%) of the patients at some point during hospitalization in the ICU. After adjusting for multiple potential confounding factors, we found that SSRI administration in the ICU was associated with lower odds of delirium/coma (odds ratio [OR], 0.75; 95% CI, 0.57-1.00) the next day. An SSRI administered on the same day reduced the odds of delirium/coma as well (OR, 0.66; 95% CI, 0.50-0.87). CONCLUSIONS: SSRI administration is associated with decreased risk of delirium/coma in 24 hours and on the same day of administration in critically ill patients in a medical or surgical ICU.

The Pharmacogenetics of Opiates and Its Impact on Delirium in Mechanically Ventilated Adults: A Pilot Study.

Background: Pharmacogenetics may explain a substantial proportion of the variation seen in the efficacy and risk profile of analgesosedative drugs and the incidence of delirium in critically ill adults. Objectives: Conduct a feasibility study to demonstrate the reliability of collecting and analyzing pharmacogenetic information from critically ill patients and to assess the impact of pharmacogenetics on intensive care unit (ICU) outcomes. Methods: We prospectively enrolled subjects from the Medical ICU at the University of North Carolina (UNC). DNA was obtained via a buccal swab and evaluated using the DNA2Rx assay. We collected data on demographics, daily cumulative psychoactive medication exposure, and severity of illness. We performed daily delirium assessments via the CAM-ICU. We analyzed associations between select single nucleotide polymorphisms (SNPs) and delirium. Results: From June, 2018 through January, 2019, we screened 244 patients and enrolled 50. The median age was 62.0 years old (range: 28-82 years old), and 27 (54%) of the subjects were female. In all, 49 (98%) samples were both high quality and sufficient quantity. In secondary analyses, we found that 80% (12/15) of patients with two 2 copies of a G allele at rs4680 on COMT experienced delirium, whereas 44% (4/9) of patients with 2 copies of an A allele at this location had delirium. In all, 44% (4/9) of patients with 2 T allele copies at rs7439366 on UGT2B7 experienced delirium compared to 73% (11/15) of patients with 2 C allele copies at this location. Conclusions: We can feasibly collect genetic information from critically ill adults. We were able to efficiently collect high quality DNA of sufficient quantity to conduct pharmacogenetic analysis in this critically ill population. Although the sample size of our current study is too small to conduct robust inferential analyses, it suggests potential SNP targets for a future larger study.

Development and Implementation of a Multicomponent Protocol to Promote Sleep and Reduce Delirium in a Medical Intensive Care Unit.

BACKGROUND: Evidence suggests that poor sleep increases risk of delirium. Because delirium is associated with poor outcomes, institutions have developed protocols to improve sleep in critically ill patients. OBJECTIVE: To assess the impact of implementing a multicomponent sleep protocol. METHODS: In this prospective, preimplementation and postimplementation evaluation, adult patients admitted to the medical intensive care unit (ICU) over 42 days were included. Outcomes evaluated included median delirium-free days, median Richards-Campbell Sleep Questionnaire (RCSQ) score, median optimal sleep nights, duration of mechanical ventilation (MV), ICU and hospital length of stay (LOS), and in-hospital mortality. RESULTS: The preimplementation group included 78 patients and postimplementation group, 84 patients. There was no difference in median delirium-free days (1 day [interquartile range, IQR, = 0-2.5] vs 1 day [IQR = 0-2]; P = 0.48), median RCSQ score (59.4 [IQR = 43.2-71.6] vs 61.2 [IQR = 49.9-75.5]; P = 0.20), median optimal sleep nights (1 night [IQR = 0-2] vs 1 night [IQR = 0-2]; P = 0.95), and in-hospital mortality (16.7% vs 17.9%, P = 1.00). Duration of MV (8 days [IQR = 4-10] vs 4 days [IQR = 2-7]; P = 0.03) and hospital LOS (13 days [IQR = 7-22.3] vs 8 days [IQR = 6-17]; P = 0.05) were shorter in the postimplementation group, but both were similar between groups after adjusting for age and severity of illness. CONCLUSIONS AND RELEVANCE: This report demonstrates that implementation of a multicomponent sleep protocol in everyday ICU care is feasible, but limitations exist when evaluating impact on measurable outcomes. Additional evaluations are needed to identify the most meaningful interventions and best practices for quantifying impact on patient outcomes.

Association of Histamine-2 Blockers and Proton-Pump Inhibitors With Delirium Development in Critically Ill Adults: A Retrospective Cohort Study.

Histamine-2 receptor antagonists are commonly administered for stress ulcer prophylaxis in critically ill adults and may be associated with delirium development. We aimed to determine differential associations of histamine-2 receptor antagonist or proton-pump inhibitor administration with delirium development in patients admitted to a medical ICU. DESIGN: Retrospective observational study using a deidentified database sourced from the University of North Carolina Health Care system. Participants were identified as having delirium utilizing an International Classification of Diseases-based algorithm. Associations among histamine-2 receptor antagonist, proton-pump inhibitor, or no medication administration and delirium were identified using relative risk. Multiple logistic regression was used to control for potential confounders including mechanical ventilation and age. SETTING: Academic tertiary care medical ICU in the United States. PATIENTS: Adults admitted to the University of North Carolina medical ICU from January 2015 to December 2019, excluding those on concurrent histamine-2 receptor antagonists and proton-pump inhibitors in the same encounter. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified 6,645 critically ill patients, of whom 29% (n = 1,899) received mechanical ventilation, 45% (n = 3,022) were 65 or older, and 22% (n = 1,487) died during their medical ICU encounter. Of the 6,645 patients, 31% (n = 2,057) received an histamine-2 receptor antagonist and no proton-pump inhibitors, 40% (n = 2,648) received a proton-pump inhibitor and no histamine-2 receptor antagonists, and 46% (n = 3,076) had delirium. The histamine-2 receptor antagonist group had a greater association with delirium than the proton-pump inhibitor group compared with controls receiving neither medication, after controlling for mechanical ventilation and age (risk ratio, 1.36; 1.25-1.47; p < 0.001) and (risk ratio, 1.15; 1.07-1.24; p < 0.001, respectively). CONCLUSIONS: Histamine-2 receptor antagonists are more strongly associated with increased delirium than proton-pump inhibitors. Prospective studies are necessary to further elucidate this association and to determine if replacement of histamine-2 receptor antagonists with proton-pump inhibitors in ICUs decreases the burden of delirium in critically ill patients.

Association Between Postoperative Delirium and Long-term Cognitive Function After Major Nonemergent Surgery.

Importance: Postoperative delirium is associated with decreases in long-term cognitive function in elderly populations. Objective: To determine whether postoperative delirium is associated with decreased long-term cognition in a younger, more heterogeneous population. Design, Setting, and Participants: A prospective cohort study was conducted at a single academic medical center (≥800 beds) in the southeastern United States from September 5, 2017, through January 15, 2018. A total of 191 patients aged 18 years or older who were English-speaking and were anticipated to require at least 1 night of hospital admission after a scheduled major nonemergent surgery were included. Prisoners, individuals without baseline cognitive assessments, and those who could not provide informed consent were excluded. Ninety-day follow-up assessments were performed on 135 patients (70.7%). Exposures: The primary exposure was postoperative delirium defined as any instance of delirium occurring 24 to 72 hours after an operation. Delirium was diagnosed by the research team using the Confusion Assessment Method (CAM). Main Outcomes and Measures: The primary outcome was change in cognition at 90 days after surgery compared with baseline, preoperative cognition. Cognition was measured using a telephone version of the Montreal Cognitive Assessment (T-MoCA) with cognitive impairment defined as a score less than 18 on a scale of 0 to 22. Results: Of the 191 patients included in the study, 110 (57.6%) were women; the mean (SD) age was 56.8 (16.7) years. For the primary outcome of interest, patients with and without delirium had a small increase in T-MoCA scores at 90 days compared with baseline on unadjusted analysis (with delirium, 0.69; 95% CI, -0.34 to 1.73 vs without delirium, 0.67; 95% CI, 0.17-1.16). The initial multivariate linear regression model included age, preoperative American Society of Anesthesiologists Physical Status Classification System score, preoperative cognitive impairment, and duration of anesthesia. Preoperative cognitive impairment proved to be the only notable confounder: when adjusted for preoperative cognitive impairment, patients with delirium had a 0.70-point greater decrease in 90-day T-MoCA scores than those without delirium compared with their respective baseline scores (with delirium, 0.16; 95% CI, -0.63 to 0.94 vs without delirium, 0.86; 95% CI, 0.40-1.33). Conclusions and Relevance: Although a statistically significant association between 90-day cognition and postoperative delirium was not noted, patients with preoperative cognitive impairment appeared to have improvements in cognition 90 days after surgery; however, this finding was attenuated if they became delirious. Preoperative cognitive impairment alone should not preclude patients from undergoing indicated surgical procedures.

Tools to Promote Shared Decision Making in Serious Illness: A Systematic Review.

IMPORTANCE: Serious illness impairs function and threatens survival. Patients facing serious illness value shared decision making, yet few decision aids address the needs of this population. OBJECTIVE: To perform a systematic review of evidence about decision aids and other exportable tools that promote shared decision making in serious illness, thereby (1) identifying tools relevant to the treatment decisions of seriously ill patients and their caregivers, (2) evaluating the quality of evidence for these tools, and (3) summarizing their effect on outcomes and accessibility for clinicians. EVIDENCE REVIEW: We searched PubMed, CINAHL, and PsychInfo from January 1, 1995, through October 31, 2014, and identified additional studies from reference lists and other systematic reviews. Clinical trials with random or nonrandom controls were included if they tested print, video, or web-based tools for advance care planning (ACP) or decision aids for serious illness. We extracted data on the study population, design, results, and risk for bias using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) criteria. Each tool was evaluated for its effect on patient outcomes and accessibility. FINDINGS: Seventeen randomized clinical trials tested decision tools in serious illness. Nearly all the trials were of moderate or high quality and showed that decision tools improve patient knowledge and awareness of treatment choices. The available tools address ACP, palliative care and goals of care communication, feeding options in dementia, lung transplant in cystic fibrosis, and truth telling in terminal cancer. Five randomized clinical trials provided further evidence that decision tools improve ACP documentation, clinical decisions, and treatment received. CONCLUSIONS AND RELEVANCE: Clinicians can access and use evidence-based tools to engage seriously ill patients in shared decision making. This field of research is in an early stage; future research is needed to develop novel decision aids for other serious diagnoses and key decisions. Health care delivery organizations should prioritize the use of currently available tools that are evidence based and effective.