Objective There is a high prevalence of delirium in older medical intensive care unit (ICU) patients and delirium is associated with adverse outcomes. We need to identify modifiable risk factors for delirium in the ICU, such as medication use. The objective of this study was to examine the impact of benzodiazepine or opioid use on the duration of ICU delirium in an older medical population. Design Prospective cohort study. Setting Fourteen-bed medical intensive care unit in an urban university teaching hospital. Patients 304 consecutive admissions age 60 and older. Interventions None Main Outcome Measurements The main outcome measure was duration of ICU delirium, specifically the first episode of ICU delirium. Patients were assessed daily for delirium with the Confusion Assessment Method for the ICU (CAM-ICU) and a validated chart review method. Our main predictor was the receipt of benzodiazepines or opioids during ICU stay. A multivariable model was developed using Poisson rate regression. Results Delirium occurred in 239 of 304 patients (79%). The median duration of ICU delirium was 3 days with a range of 1-33 days. In a multivariable regression model receipt of a benzodiazepine or opioid (RR, 1.64, 95% CI, 1.27-2.10) was associated with increased delirium duration. Other variables associated with delirium duration in this analysis include preexisting dementia (RR, 1.19, 95% CI 1.07-1.33), receipt of haloperidol (RR, 1.35, 95% CI, 1.21-1.50), and severity of illness (RR, 1.01, 95% CI, 1.00-1.02). Conclusions The use of benzodiazepines or opioids in the ICU is associated with longer duration of a first episode of delirium. Receipt of these medications may represent modifiable risk factors for delirium. Clinicians caring for ICU patients should carefully evaluate the need for benzodiazepines, opioids and haloperidol.

No abstract

Falls are an important health concern among older adults due to age-related changes in the body. Having a medical history of chronic health condition may pose even higher risk of falling. Only few studies have assessed a number of chronic health conditions as risk factor for falls over a large nationally representative sample of US older adults. In this study, Behavioral Risk Factor Surveillance System (BRFSS) 2014 participants aged 65 years and older (n = 159,336) were evaluated. It was found that 29.7% (n = 44,550) of the sample experienced at least one fall and 16.3% (n = 20,444) experienced more than one fall in the past 12 months. According to the study findings, having a medical history of stroke, CKD, arthritis, depression, and diabetes independently predict the risk of first-time falling as well as the risk of recurrent falling in older adult population while controlling for other factors. On the other hand, having a medical history of the heart attack, angina, asthma, and COPD did not predict the risk of first-time falling, but did predict the risk of recurrent falling after experiencing the first fall in this population.

Fall-related medical conditions affect a substantial number of the community-dwelling elderly and result in direct medical costs of dollar 6 to dollar 8 billion per year in the United States. The total economic burden of falls is significantly higher because this estimate does not include direct nonmedical, intangible, and indirect costs. The results of this study highlight the importance of research aimed at decreasing the incidence and severity of falls in the elderly.

Background & Aims:Postoperative cognitive dysfunction (POCD) is a decline in cognitive function that occurs after surgery. The purpose of this study was to estimate the incidence and identify potential risk factors of POCD in older adults undergoing major noncardiac surgery.Materials and Methods:A total of 69 patients aged 65 years or older undergoing major noncardiac surgery were enrolled. Patients’ cognitive function was assessed before and 3 months after surgery using a computerized neurocognitive battery. A nonsurgical control group of 54 older adults was recruited to adjust for learning effects from repeated administration of neurocognitive tests. Data about potential risk factors for POCD were collected before, during, and after surgery, including patient, medication, and surgery factors. The incidence of POCD was calculated using the Z-score method. A multivariable logistic regression model was used to identify risk factors for POCD.Results:POCD was present in eleven patients (15.9%, 95% confidence interval [CI] = 7.3-24.6) 3 months after major noncardiac surgery. Carrying the apolipoprotein E4 (APOE4) genotype (odds ratio [OR] = 4.74, 95% CI = 1.09-22.19), using one or more highly anticholinergic or sedative-hypnotic drugs at home prior to surgery (OR = 5.64, 95% CI = 1.35-30.22), and receiving sevoflurane for anesthesia (OR = 6.43, 95% CI = 1.49-34.66) were associated with the development of POCD.Conclusions:POCD was observed in 15.9% of older adults after major noncardiac surgery. Risk factors for POCD in these patients were carrying the APOE4 genotype, using one or more highly anticholinergic or sedative-hypnotic drugs prior to surgery, and receiving sevoflurane for anesthesia.

Introduction Epigenetics is the study of reversible modifications to chromatin and their extensive and profound effects on gene regulation. To date, the role of epigenetics in personalized medicine has been under-explored. Therefore, this review aims to highlight the vast potential that epigenetics holds. Areas covered We first review the cell-specific nature of epigenetic states and how these can vary with developmental stage and in response to environmental factors. We then summarize epigenetic biomarkers of disease, with a focus on diagnostic tests, followed by a detailed description of current and pipeline drugs with epigenetic modes of action. Finally, we discuss epigenetic biomarkers of drug response. Expert commentary Epigenetic variation can yield information on cellular states and developmental histories in ways that genotype information cannot. Furthermore, in contrast to fixed genome sequence, epigenetic patterns are plastic, so correcting aberrant, disease-causing epigenetic marks holds considerable therapeutic promise. While just six epigenetic drugs are currently approved for use in the United States, a larger number is being developed. However, a drawback to current therapeutics is their non-specific effects. Development of locus-specific epigenetic modifiers, used in conjunction with epigenetic biomarkers of response, will enable truly precision interventions.

Changes that accompany older age can alter the pharmacokinetics (PK), pharmacodynamics (PD), and likelihood of adverse effects (AEs) of a drug. However, older adults, especially the oldest or those with multiple chronic health conditions, polypharmacy, or frailty, are often under‐represented in clinical trials of new drugs. Deficits in the current conduct of clinical evaluation of drugs for older adults and potential steps to fill those knowledge gaps are presented in this communication. The most important step is to increase clinical trial enrollment of older adults who are representative of the target treatment population. Unnecessary eligibility criteria should be eliminated. Physical and financial barriers to participation should be removed. Incentives could be created for inclusion of older adults. Enrollment goals should be established based on intended treatment indications, prevalence of the condition, and feasibility. Relevant clinical pharmacology data need to be obtained early enough to guide dosing and reduce risk for participation of older adults. Relevant PK and PD data as well as patient‐centered outcomes should be measured during trials. Trial data should be analyzed for differences in PK, PD, effectiveness, and safety arising from differences in age or from the presence of conditions common in older adults. Postmarket evaluations with real‐world evidence and drug labeling updates throughout the product lifecycle reflecting new knowledge are also needed. A comprehensive plan is needed to ensure adequate evaluation of the safety and effectiveness of drugs in older adults.

Background. Very few studies have assessed the impact of poor sleep and sleep medication use on the risk of falls among community-dwelling older adults. The objective of this study was to evaluate the association between sleep problems, sleep medication use, and falls in community-dwelling older adults. Methods. The study population comprised a nationally representative sample of noninstitutionalized older adults participating in the 2010 Health and Retirement Study. Proportion of adults reporting sleep problems, sleep medication use, and fall was calculated. Multiple logistic regression models were constructed to examine the impact of sleep problems and sleep medication use on the risk of falls after controlling for covariates. Results. Among 9,843 community-dwelling older adults, 35.8% had reported a fall and 40.8% had reported sleep problems in the past two years. Sleep medication use was reported by 20.9% of the participants. Older adults who do have sleep problems and take sleep medications had a significant high risk of falls, compared to older adults who do not have sleep problems and do not take sleep medications. The other two groups also had significantly greater risk for falls. Conclusion. Sleep problems added to sleep medication use increase the risk of falls. Further prospective studies are needed to confirm these observed findings.