Serum proteomic analysis in esophagectomy patients with postoperative delirium: A case-control study.

BACKGROUND: Postoperative delirium occurs in up to 80% of patients undergoing esophagectomy. We performed an exploratory proteomic analysis to identify protein pathways that may be associated with delirium post-esophagectomy. OBJECTIVES: Identify proteins associated with delirium and delirium severity in a younger and higher-risk surgical population. METHODS: We performed a case-control study using blood samples collected from patients enrolled in a negative, randomized, double-blind clinical trial. English speaking adults aged 18 years or older, undergoing esophagectomy, who had blood samples obtained were included. Cases were defined by a positive delirium screen after surgery while controls were patients with negative delirium assessments. Delirium was assessed using Richmond Agitation Sedation Scale and Confusion Assessment Method for the Intensive Care Unit, and delirium severity was assessed by Delirium Rating Scale-Revised-98. Blood samples were collected pre-operatively and on post-operative day 1, and discovery proteomic analysis was performed. Between-group differences in median abundance ratios were reported using Wilcoxon-Mann-Whitney Odds (WMWodds1) test. RESULTS: 52 (26 cases, 26 controls) patients were included in the study with a mean age of 64 (SD 9.6) years, 1.9% were females and 25% were African American. The median duration of delirium was 1 day (IQR: 1-2), and the median delirium/coma duration was 2.5 days (IQR: 2-4). Two proteins with greater relative abundance ratio in patients with delirium were: Coagulation factor IX (WMWodds: 1.89 95%CI: 1.0-4.2) and mannosyl-oligosaccharide 1,2-alpha-mannosidase (WMWodds: 2.4 95%CI: 1.03-9.9). Protein abundance ratios associated with mean delirium severity at postoperative day 1 were Complement C2 (Spearman rs = -0.31, 95%CI [-0.55, -0.02]) and Mannosyl-oligosaccharide 1,2-alpha-mannosidase (rs = 0.61, 95%CI = [0.29, 0.81]). CONCLUSIONS: We identified changes in proteins associated with coagulation, inflammation, and protein handling; larger, follow-up studies are needed to confirm our hypothesis-generating findings.

Association between Change in the peripheral biomarkers of inflammation, astrocyte activation, and neuroprotection at one week of critical illness and hospital mortality in patients with delirium: A prospective cohort study.

OBJECTIVE: In critically ill adults with delirium, biomarkers of systemic inflammation, astrocyte activation, neuroprotection, and systemic inflammation measured at one week of critical illness may be associated with mortality. DESIGN: Prospective observational study. SETTING: Intensive care unit (ICU). PATIENTS: 178 ICU patients with delirium, alive and remaining in ICU at one week. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Blood samples collected for a pair of previously published, negative, clinical trials were utilized. Samples were collected at study enrollment/ICU admission (Day 1 sample) and one week later (Day 8 sample), and analyzed for interleukins (IL)-6, 8, 10, Insulin-like Growth Factor (IGF), S100 Binding Protein (S100B), Tumor Necrosis Factor Alpha (TNF-A) and C-Reactive Protein (CRP). Delirium, delirium severity, and coma were assessed twice daily using Confusion Assessment Method for the Intensive Care Unit (CAM-ICU), CAM-ICU-7, and Richmond Agitation-Sedation Scale (RASS), respectively. Mortality was assessed until discharge using the electronic medical record. Logistic regression models adjusting for age, sex, severity of illness, comorbidities, sepsis, and randomization status, were used to assess the relationship among biomarkers and mortality. Higher IL-10 quartiles at day 8 were associated with increased odds of hospital mortality (IL-10: OR 2.00 95%CI: 1.1-3.65, p = 0.023). There was a significant interaction between day 1 and day 8 biomarker quartiles only for IL-6. Patients with IL-6 values in the first three quartiles on admission to the ICU that transitioned to higher IL-6 quartiles at day 8 had increased probability of hospital mortality. CONCLUSION: In this hypothesis-generating study, higher IL-6 and IL-10 quartiles at one week, and increase in IL-6 from day 1 to day 8 were associated with increased hospital mortality. Studies with larger sample sizes are needed to confirm the mechanisms for these observations.

Serum Biomarkers in Postoperative Delirium After Esophagectomy.

BACKGROUND: Esophagectomy is associated with postoperative delirium, but its pathophysiology is not well defined. We conducted this study to measure the relationship among serum biomarkers of inflammation and neuronal injury and delirium incidence and severity in a cohort of esophagectomy patients. METHODS: Blood samples were obtained from patients preoperatively and on postoperative days 1 and 3 and were analyzed for S100 calcium-binding protein B, C-reactive protein (CRP), interleukin (IL) 8 and IL-10, tumor necrosis factor-α, and insulin-like growth factor 1. Delirium was assessed twice daily using the Richmond Agitation Sedation Scale and Confusion Assessment Method for Intensive Care Unit. Delirium severity was assessed once daily with the Delirium Rating Scale-Revised-98. RESULTS: Samples from 71 patients were included. Preoperative biomarker concentrations were not associated with postoperative delirium. Significant differences in change in concentrations from preoperatively to postoperative day 1 were seen in IL-8 (delirium, 38.6; interquartile range [IQR], 29.3-69.8; no delirium, 24.8; IQR, 16.0-41.7, P = .022), and IL-10 (delirium, 26.1; IQR, 13.9-36.7; no delirium, 12.4; IQR, 7.7-25.7; P = .025). Greater postoperative increase in S100 calcium-binding protein B (Spearman r = 0.289, P = .020) and lower levels of insulin-like growth factor 1 were correlated with greater delirium severity (Spearman r = -0.27, P = .040). Greater CRP change quartiles were associated with higher delirium incidence adjusting for severity of illness (odds ratio, 1.68; 95% confidence interval, 1.03-2.75; P = .037) or comorbidities (odds ratio, 1.70; 95% confidence interval, 1.05-2.76, P = .030). CONCLUSIONS: Differences in change in serum CRP, IL-8, and IL-10 concentrations were associated with postoperative delirium, suggesting biomarker measurement early in the postoperative course is associated with delirium.

Pre-Existing Anxiety and Depression in Injured Older Adults: An Under-Recognized Comorbidity With Major Health Implications.

To compare differences in baseline depression and anxiety screenings between older injured patients with pre-existing diagnoses and those without. Background: Little is known about the prevalence and impact of psychiatric comorbidities on early postinjury depression and anxiety in nonneurologically injured older adults. Methods: This was a retrospective post-hoc analysis of data from the Trauma Medical Home, a multicenter randomized controlled trial (R01AG052493-01A1) that explored the effect of a collaborative care model on postinjury recovery for older adults compared to usual care. Results: Nearly half of the patients screened positive for at least mild depressive symptoms as measured by the Patient Health Questionnaire-9. Forty-one percent of the patients screened positive for at least mild anxiety symptoms as measured by the Generalized Anxiety Disorder Scale. Female patients with a history of concurrent anxiety and depression, greater injury severity scores, and higher Charlson scores were more likely to have mild anxiety at baseline assessment. Patients with a history of depression only, a prior history of depression and concurrent anxiety, and higher Charlson scores (greater medical comorbidity) had greater odds of at least mild depression at the time of hospital discharge after traumatic injury. Conclusions: Anxiety and depression are prevalent in the older adult trauma population, and affect women disproportionately. A dual diagnosis of depression and anxiety is particularly morbid. Mental illness must be considered and addressed with the same importance as other medical diagnoses in patients with injuries.

Time trends of delirium rates in the intensive care unit.

BACKGROUND: Effects of clinical practice changes on ICU delirium are not well understood. OBJECTIVES: Determine ICU delirium rates over time. METHODS: Data from a previously described screening cohort of the Pharmacological Management of Delirium trial was analyzed. Richmond Agitation-Sedation Scale (RASS) and Confusion Assessment Method for the ICU (CAM-ICU) were assessed twice daily. We defined: Any delirium (positive CAM-ICU at any time during ICU stay) and ICU-acquired delirium (1st CAM-ICU negative with a subsequent positive CAM-ICU). Mixed-effects logistic regression models were used to test for differences. RESULTS: 2742 patient admissions were included. Delirium occurred in 16.5%, any delirium decreased [22.7% to 10.2% (p < 0.01)], and ICU-acquired delirium decreased [8.4% to 4.4% (p = 0.01)]. Coma decreased from 24% to 17.4% (p = 0.04). Later ICU years and higher mean RASS scores were associated with lower odds of delirium. CONCLUSIONS: Delirium rates were not explained by the measured variables and further prospective research is needed.

Colorectal polyp prevalence and aspirational detection targets determined using high definition colonoscopy and a high level detector in 2017.

BACKGROUND: Colorectal adenoma prevalence can be determined by autopsy studies, or imaging studies such as colonoscopy. We describe the prevalence of colorectal adenomas determined by a single high detecting colonoscopist using high definition colonoscopes. METHODS: We conducted a cross-sectional study of consecutive patients aged ≥18 years undergoing colonoscopy with a high level detector for the indications of screening, surveillance, and diagnostic reasons from December 29, 2016 to January 12, 2018. RESULTS: During the study period, 1172 eligible patients underwent colonoscopy. Women comprised 55% (n = 646) and the majority (89%, n = 1038) were aged ≥50 years (mean age, 62.1 years). In persons aged ≥50 years undergoing screening, the prevalence of ≥1 conventional adenoma was 48.5% and ≥1 sessile serrated polyp was 15.3%. Diminutive polyps (1-5 mm in size) comprised three-quarters of all resected polyps (2236/2986). Among 246 patients (21%), 1050 hyperplastic appearing polyps were not resected from the recto-sigmoid. Adenoma prevalence was strongly associated with age and indication but serrated lesion prevalence was not. CONCLUSIONS: The true prevalence of precancerous lesions in the colorectum determined by modern colonoscopy exceeds determination by autopsy studies. These data help define aspirational detection targets for colonoscopy. The economic burden associated with colonoscopic resection of tiny lesions is substantial.

Risks and Benefits of Screening for Dementia in Primary Care: The Indiana University Cognitive Health Outcomes Investigation of the Comparative Effectiveness of Dementia Screening (IU CHOICE)Trial.

BACKGROUND/OBJECTIVE: The benefits and harms of screening of Alzheimer disease and related dementias (ADRDs) are unknown. This study addressed the question of whether the benefits outweigh the harms of screening for ADRDs among older adults in primary care. DESIGN, SETTING, AND PARTICIPANTS: Single-blinded, two-arm, randomized controlled trial (October 2012-September 2016) in urban, suburban, and rural primary care settings in Indiana. A total of 4005 primary care patients (aged ≥65 years) were randomized to ADRD screening (n = 2008) or control (n = 1997). INTERVENTION: Patients were screened using the Memory Impairment Screen or the Mini-Cog and referred for a voluntary follow-up diagnostic assessment if they screened positive on either or both screening tests. MEASUREMENTS: Primary measures were health-related quality of life (HRQOL; Health Utilities Index) at 12 months, depressive symptoms (Patient Health Questionnaire-9), and anxiety symptoms (Generalized Anxiety Disorder seven-item scale) at 1 month. RESULTS: The mean age was 74.2 years (SD = 6.9 years); 2257 (66%) were female and 2301 (67%) were white. At 12 months, we were unable to detect differences in HRQOL between the groups (effect size = 0.009 [95% confidence interval {CI} = -0.063 to 0.080]; P = .81). At 1 month, differences in mean depressive symptoms (mean difference = -0.23 [90% CI = -0.42 to -0.039]) and anxiety symptoms (mean difference = -0.087 [90% CI = -0.246 to 0.072]) were within prespecified equivalency range. Scores for depressive and anxiety symptoms were similar between the groups at all time points. No differences in healthcare utilization, advance care planning, and ADRD recognition by physicians were detected at 12 months. CONCLUSION: We were unable to detect a difference in HRQOL for screening for ADRD among older adults. We found no harm from screening measured by symptoms of depression or anxiety. Missing data, low rates of dementia detection, and high rate of refusal for follow-up diagnostic assessments after a positive screen may explain these findings. J Am Geriatr Soc 68:535-543, 2020.

Biomarkers of Delirium Duration and Delirium Severity in the ICU.

OBJECTIVES: Both delirium duration and delirium severity are associated with adverse patient outcomes. Serum biomarkers associated with delirium duration and delirium severity in ICU patients have not been reliably identified. We conducted our study to identify peripheral biomarkers representing systemic inflammation, impaired neuroprotection, and astrocyte activation associated with delirium duration, delirium severity, and in-hospital mortality. DESIGN: Observational study. SETTING: Three Indianapolis hospitals. PATIENTS: Three-hundred twenty-one critically ill delirious patients. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We analyzed the associations between biomarkers collected at delirium onset and delirium-/coma-free days assessed through Richmond Agitation-Sedation Scale/Confusion Assessment Method for the ICU, delirium severity assessed through Confusion Assessment Method for the ICU-7, and in-hospital mortality. After adjusting for age, gender, Acute Physiology and Chronic Health Evaluation II score, Charlson comorbidity score, sepsis diagnosis and study intervention group, interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were negatively associated with delirium-/coma-free days by 1 week and 30 days post enrollment. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium-/coma-free days at both time points. Interleukin-6, -8, and -10, tumor necrosis factor-α, C-reactive protein, and S-100ß levels in quartile 4 were also associated with delirium severity by 1 week. At hospital discharge, interleukin-6, -8, and -10 retained the association but tumor necrosis factor-α, C-reactive protein, and S-100ß lost their associations with delirium severity. Insulin-like growth factor-1 levels in quartile 4 were not associated with delirium severity at both time points. Interleukin-8 and S-100ß levels in quartile 4 were also associated with higher in-hospital mortality. Interleukin-6 and -10, tumor necrosis factor-α, and insulin-like growth factor-1 were not found to be associated with in-hospital mortality. CONCLUSIONS: Biomarkers of systemic inflammation and those for astrocyte and glial activation were associated with longer delirium duration, higher delirium severity, and in-hospital mortality. Utility of these biomarkers early in delirium onset to identify patients at a higher risk of severe and prolonged delirium, and delirium related complications during hospitalization needs to be explored in future studies.

Perioperative Risk Factors for Postoperative Delirium in Patients Undergoing Esophagectomy.

BACKGROUND: Postoperative delirium affects up to 50% of patients undergoing esophagectomy and is associated with negative outcomes. The perioperative risk factors for delirium in this population are not well understood. We conducted this study to assess perioperative risk factors for postoperative delirium among esophagectomy patients. METHODS: We performed a secondary data analysis of patients enrolled in a randomized controlled trial evaluating the efficacy of haloperidol prophylaxis postoperatively in reducing delirium among esophagectomy patients. Postoperative delirium was assessed twice daily using the Confusion Assessment Method for the ICU. Univariate and logistic regression analyses were performed to examine the association between perioperative variables and development of postoperative delirium. RESULTS: Of 84 consecutive esophagectomy patients, postoperative delirium developed in 27 (32%). These patients had higher Acute Physiology and Chronic Health Evaluation II scores (22.1 [SD, 6.5] vs 17.4 [SD, 6.8]; p = 0.003), longer mechanical ventilation days (1.7 [SD, 1.4] days vs 1.0 [SD, 1.1] days; p = 0.001), and longer intensive care unit (ICU) days (5.1 [SD, 2.6] days vs 2.6 [SD, 1.6] days; p < 0.001). In a logistic regression model, only ICU length of stay had a significant association with postoperative delirium (odds ratio, 1.65; 95% confidence interval, 1.21 to 2.25). CONCLUSIONS: ICU length of stay was significantly associated with postoperative delirium. Other perioperative factors, including duration of procedure, blood loss, and hemoglobin levels, were not significantly associated with postoperative delirium.

Association Between Antithrombotic Medication Use After Bioprosthetic Aortic Valve Replacement and Outcomes in the Veterans Health Administration System.

Importance: The recommendations about antithrombotic medication use after bioprosthetic aortic valve replacement (bAVR) vary. Objectives: To describe the post-bAVR antithrombotic medication practice across the Veterans Health Administration (VHA) and to assess the association between antithrombotic strategies and post-bAVR outcomes. Design, Setting, and Participants: Retrospective cohort study. Multivariable modeling with propensity scores was conducted to adjust for differences in patient characteristics across the 3 most common antithrombotic medication strategies (aspirin plus warfarin sodium, aspirin only, and dual antiplatelets). Text mining of notes was used to identify the patients with bAVR (fiscal years 2005-2015). Main Outcomes and Measures: This study used VHA and non-VHA outpatient pharmacy data and text notes to classify the following antithrombotic medications prescribed within 1 week after discharge from the bAVR hospitalization: aspirin plus warfarin, aspirin only, dual antiplatelets, no antithrombotics, other only, and warfarin only. The 90-day outcomes included all-cause mortality, thromboembolism risk, and bleeding events. Outcomes were identified using primary diagnosis codes from emergency department visits or hospital admissions. Results: The cohort included 9060 veterans with bAVR at 47 facilities (mean [SD] age, 69.3 [8.8] years; 98.6% male). The number of bAVR procedures per year increased from 610 in fiscal year 2005 to 1072 in fiscal year 2015. The most commonly prescribed antithrombotic strategy was aspirin only (4240 [46.8%]), followed by aspirin plus warfarin (1638 [18.1%]), no antithrombotics (1451 [16.0%]), dual antiplatelets (1010 [11.1%]), warfarin only (439 [4.8%]), and other only (282 [3.1%]). Facility variation in antithrombotic prescription patterns was observed. During the 90-day post-bAVR period, adverse events were uncommon, including all-cause mortality in 127 (1.4%), thromboembolism risk in 142 (1.6%), and bleeding events in 149 (1.6%). No differences in 90-day mortality or thromboembolism were identified across the 3 antithrombotic medication groups in either the unadjusted or adjusted models. Patients receiving the combination of aspirin plus warfarin had higher odds of bleeding than patients receiving aspirin only in the unadjusted analysis (odds ratio, 2.58; 95% CI, 1.71-3.89) and after full risk adjustment (adjusted odds ratio, 1.92; 95% CI, 1.17-3.14). Conclusions and Relevance: These data demonstrate that bAVR procedures are increasingly being performed in VHA facilities and that aspirin only was the most commonly used antithrombotic medication strategy after bAVR. The risk-adjusted results suggest that the combination of aspirin plus warfarin does not improve either all-cause mortality or thromboembolism risk but increases the risk of bleeding events compared with aspirin only.

Preventing Postoperative Delirium After Major Noncardiac Thoracic Surgery-A Randomized Clinical Trial.

OBJECTIVES: To assess the efficacy of haloperidol in reducing postoperative delirium in individuals undergoing thoracic surgery. DESIGN: Randomized double-blind placebo-controlled trial. SETTING: Surgical intensive care unit (ICU) of tertiary care center. PARTICIPANTS: Individuals undergoing thoracic surgery (N=135). INTERVENTION: Low-dose intravenous haloperidol (0.5 mg three times daily for a total of 11 doses) administered postoperatively. MEASUREMENTS: The primary outcome was delirium incidence during hospitalization. Secondary outcomes were time to delirium, delirium duration, delirium severity, and ICU and hospital length of stay. Delirium was assessed using the Confusion Assessment Method for the ICU and delirium severity using the Delirium Rating Scale-Revised. RESULTS: Sixty-eight participants were randomized to receive haloperidol and 67 placebo. No significant differences were observed between those receiving haloperidol and those receiving placebo in incident delirium (n=15 (22.1%) vs n=19 (28.4%); p = .43), time to delirium (p = .43), delirium duration (median 1 day, interquartile range (IQR) 1-2 days vs median 1 day, IQR 1-2 days; p = .71), delirium severity, ICU length of stay (median 2.2 days, IQR 1-3.3 days vs median 2.3 days, IQR 1-4 days; p = .29), or hospital length of stay (median 10 days, IQR 8-11.5 days vs median 10 days, IQR 8-12 days; p = .41). In the esophagectomy subgroup (n = 84), the haloperidol group was less likely to experience incident delirium (n=10 (23.8%) vs n=17 (40.5%); p = .16). There were no differences in time to delirium (p = .14), delirium duration (median 1 day, IQR 1-2 days vs median 1 day, IQR 1-2 days; p = .71), delirium severity, or hospital length of stay (median 11 days, IQR 10-12 days vs median days 11, IQR 10-15 days; p = .26). ICU length of stay was significantly shorter in the haloperidol group (median 2.8 days, IQR 1.1-3.8 days vs median 3.1 days, IQR 2.1-5.1 days; p = .03). Safety events were comparable between the groups. CONCLUSION: Low-dose postoperative haloperidol did not reduce delirium in individuals undergoing thoracic surgery but may be efficacious in those undergoing esophagectomy. J Am Geriatr Soc 66:2289-2297, 2018.

Patient characteristics associated with screening positive for Alzheimer's disease and related dementia.

INTRODUCTION: Screening all older adults for Alzheimer's disease and related dementias (ADRD) in primary care may not be acceptable or feasible. The goal of this study was to identify factors that could optimize screening in primary care and enhance its feasibility. METHODS: This is a cross-sectional study in rural, suburban, and urban primary care practices in Indiana. A total of 1,723 patients ≥65 years of age were screened for ADRD using the Memory Impairment Screen. Logistic regression was used to identify patient-specific factors associated with screening positive for ADRD. RESULTS: The positive screening rate was 4.9%. Rates varied significantly across the three study sites. The rural site had the lowest rate (2.8%), which was significantly lower than the rates at the suburban (5.6%) and urban (6.6%) sites (P<0.01). Patient age, sex, and education were significantly (P<0.05) associated with screening positive for ADRD. CONCLUSION: Targeted screening of patients at risk for ADRD may represent a more optimal and feasible screening alternative to population screening.

Acceptability and Results of Dementia Screening Among Older Adults in the United States.

OBJECTIVES: To measure older adults acceptability of dementia screening and assess screening test results of a racially diverse sample of older primary care patients in the United States. DESIGN: Cross-sectional study of primary care patients aged 65 and older. SETTING: Urban and suburban primary care clinics in Indianapolis, Indiana, in 2008 to 2009. PARTICIPANTS: Nine hundred fifty-four primary care patients without a documented diagnosis of dementia. MEASUREMENTS: Community Screening Instrument for Dementia, the Mini-Mental State Examination, and the Telephone Instrument for Cognitive Screening. RESULTS: Of the 954 study participants who consented to participate, 748 agreed to be screened for dementia and 206 refused screening. The overall response rate was 78.4%. The positive screen rate of the sample who agreed to screening was 10.2%. After adjusting for demographic differences the following characteristics were still associated with increased likelihood of screening positive for dementia: age, male sex, and lower education. Patients who believed that they had more memory problems than other people of their age were also more likely to screen positive for dementia. CONCLUSION: Age and perceived problems with memory are associated with screening positive for dementia in primary care.

Cross-over study of novice intubators performing endotracheal intubation in an upright versus supine position.

There are a number of potential physical advantages to performing orotracheal intubation in an upright position. The objective of this study was to measure the success of intubation of a simulated patient in an upright versus supine position by novice intubators after brief training. This was a cross-over design study in which learners (medical students, physician assistant students, and paramedic students) intubated mannequins in both a supine (head of the bed at 0°) and upright (head of bed elevated at 45°) position. The primary outcome of interest was successful intubation of the trachea. Secondary outcomes included log time to intubation, Cormack-Lehane view obtained, Percent of Glottic Opening score, provider assessment of difficulty, and overall provider satisfaction with the position. There were a total of 126 participants: 34 medical students, 84 physician assistant students, and 8 paramedic students. Successful tracheal intubation was achieved in 114 supine attempts (90.5 %) and 123 upright attempts (97.6 %; P = 0.283). Upright positioning was associated with significantly faster log time to intubation, higher likelihood of achieving Grade I Cormack-Lehane view, higher Percent of Glottic Opening score, lower perceived difficulty, and higher provider satisfaction. A subset of 74 participants had no previous intubation training or experience. For these providers, there was a non-significant trend toward improved intubation success with upright positioning vs supine positioning (98.6 % vs. 87.8 %, P = 0.283). For all secondary outcomes in this group, upright positioning significantly outperformed supine positioning.

Association of Anticholinergic Burden with Cognitive Impairment and Health Care Utilization Among a Diverse Ambulatory Older Adult Population.

STUDY OBJECTIVE: To determine the association between Anticholinergic Cognitive Burden (ACB) score and both cognitive impairment and health care utilization among a diverse ambulatory older adult population. DESIGN: Retrospective cohort study. DATA SOURCE: Medication exposure and other clinical data were extracted from the Regenstrief Medical Record System (RMRS), and cognitive diagnosis was derived from a dementia screening and diagnosis study. PATIENTS: A total of 3344 community-dwelling older adults (age 65 yrs and older) who were enrolled in a previously published dementia screening and diagnosis study; of these, 3127 were determined to have no cognitive impairment, and 217 were determined to have cognitive impairment. MEASUREMENTS AND MAIN RESULTS: The study followed a two-phase screening and comprehensive neuropsychiatric examination to determine a cognitive diagnosis, which defined cognitive impairment as dementia or mild cognitive impairment. The ACB scale was used to identify anticholinergics dispensed in the 12 months prior to screening. A total daily ACB score was calculated by using pharmacy dispensing data from RMRS; each anticholinergic was multiplied by 1, 2, or 3 consistent with anticholinergic burden defined by the ACB scale. The sum of all ACB medications was divided by the number of days with any medication dispensed to achieve the total daily ACB score. Health care utilization included visits to inpatient, outpatient, and the emergency department, and it was determined by using visit data from the RMRS. The overall population had a mean age of 71.5 years, 71% were female, and 58% were African American. Each 1-point increase in mean total daily ACB score was associated with increasing risk of cognitive impairment (odds ratio [OR] 1.13, 95% confidence interval [CI] 1.004-1.27, p=0.043). Each 1-point increase in mean total daily ACB score increased the likelihood of inpatient admission (OR 1.11, 95% CI 1.02-1.29, p=0.014) and number of outpatient visits after adjusting for demographic characteristics, number of chronic conditions, and prior visit history (estimate 0.382, standard error [SE] 0.113; p=0.001). The number of visits to the emergency department was also significantly different after similar adjustments (estimate 0.046, SE 0.023, p=0.043). CONCLUSION: Increasing total ACB score was correlated with an increased risk for cognitive impairment and more frequent health care utilization. Future work should study interventions that safely reduce ACB and evaluate the impact on brain health and health care costs.

Older primary care patients' attitudes and willingness to screen for dementia.

Objective. To understand older primary care patients' perceptions of the risks and benefits of dementia screening and to measure the association between attitudes and screening behaviors. Methods. Eligible patients completed the Perceptions Regarding Investigational Screening for Memory in Primary Care (PRISM-PC) questionnaire and then were asked to undergo dementia screening by a telephone screening instrument. Results. Higher scores on the PRISM-PC questionnaire items that measure attitudes about benefits of screening were associated with decreased odds of refusing screening. Participants who refused screening had significantly lower PRISM-PC questionnaire scores on the items that measure perceived benefits compared to those who agreed to screening. Participants who refused screening were less likely to agree on screening for other conditions, such as depression and cancer. Participants who know someone with Alzheimer's disease (AD) were less likely to refuse screening. Discussion. Patients' attitudes about the benefits of dementia screening are associated with their acceptance of dementia screening.

Characterization of hepatic enzyme activity in older adults with dementia: potential impact on personalizing pharmacotherapy.

OBJECTIVE: To determine the frequency of pharmacogenomic variants and concurrent medications that may alter the efficacy and tolerability of acetylcholinesterase inhibitors (AChEIs). MATERIALS AND METHODS: A multisite cross-sectional study was carried out across four memory care practices in the greater Indianapolis area. Participants were adults aged 65 years and older with a diagnosis of probable or possible Alzheimer's disease (AD) (n=105). Blood samples and self-reported medication data were collected. Since two of the three AChEIs are metabolized by cytochrome P450 (CYP)-2D6, we determined the frequency of functional genetic variants in the CYP2D6 gene and calculated their predicted CYP2D6-activity scores. Concurrent medication data were collected from self-reported medication surveys, and their predicted effect on the pharmacokinetics of AChEIs was determined based on their known effects on CYP2D6 and CYP3A4/5 enzyme activities. RESULTS: Among the 105 subjects enrolled, 72% were female and 36% were African American. Subjects had a mean age of 79.6 years. The population used a mean of eight medications per day (prescription and nonprescription). The CYP2D6 activity score frequencies were 0 (3.8%), 0.5 (4.8%), 1.0 (36.2%), 1.5-2.0 (51.4%), and >2.0 (3.8%). Nineteen subjects (18.1%) used a medication considered a strong or moderate inhibitor of CYP2D6, and eight subjects (7.6%) used a medication considered a strong or moderate inhibitor of CYP3A4/5. In total, 28.6% of the study population was predicted to have reduced activity of the CYP2D6 or CYP3A4/5 enzymes due to either genetic variants or concomitant medications. CONCLUSION: Both pharmacogenetic variants and concurrent drug therapies that are predicted to alter the pharmacokinetics of AChEIs should be evaluated in older adults with AD. Pharmacogenetic and drug-interaction data may help personalize AD therapy and increase adherence by improving tolerability.

A statewide collaboration to initiate mental health screening and assess services for detained youths in Indiana.

OBJECTIVES: We describe a statewide effort to implement detention-based mental health screening and assess follow-up services offered to detained youths in Indiana. METHODS: A total of 25,265 detention stays (15,461 unique youths) occurred between January 1, 2008, and December 31, 2011, across 16 detention centers participating in the Indiana Juvenile Mental Health Screening Project. We collected screening results and reports of detention-based follow-up mental health services and referrals from justice system records. RESULTS: Approximately 21% of youths screened positive for mental health issues requiring follow-up. A positive screen significantly predicted that youths would receive a follow-up mental health service or referral while detained or upon detention center discharge, compared with youths who did not screen positive (61% vs 39%). Logistic regression models indicated that a positive screen was associated with (1) contact with a mental health clinician within 24 hours of detention center intake and (2) a mental health referral upon discharge. White youths were more likely than minorities to receive both follow-up services. CONCLUSIONS: Future statewide efforts to improve the mental health of detained youths should incorporate standards for providing appropriate follow-up services in detention centers.

The Indiana University Cognitive Health Outcomes Investigation of the Comparative Effectiveness of dementia screening (CHOICE) study: study protocol for a randomized controlled trial.

BACKGROUND: Dementia affects over 4 million people in the US and is frequently unrecognized and underdiagnosed in primary care. Routine dementia screening in primary care is not recommended by the US Preventive Services Task Force due to lack of empirical data on the benefits and harms of screening. This trial seeks to fill this gap and contribute information about the benefits, harms, and costs of routine screening for dementia in primary care. METHODS/DESIGN: Single-blinded, parallel, randomized controlled clinical trial with 1:1 allocation. A total of 4,000 individuals aged ≥65 years without a diagnosis of dementia, cognitive impairment, or serious mental illness receiving care at primary care practices within two cities in Indiana. Subjects will be randomized to either i) screening for dementia using the Memory Impairment Screen Telephone version or ii) no screening for dementia. Subjects who screen positive for dementia will be referred to the local Aging Brain Care program that delivers an evidence-based collaborative care model for dementia and depression. Research assistants will administer the 15-item Health Utility Index, Patient Health Questionnaire, Generalized Anxiety Disorder Scale, and Medical Outcomes Study at baseline, 1, 6, and 12 months. Information about advanced care planning will be collected at baseline and 12 months. All enrollees' medical records will be reviewed to collect data on health care utilization and costs. DISCUSSION: We have two primary hypotheses; first, in comparison to non-screened subjects, those who are screened and referred to a dementia collaborative care program will have a higher health-related quality of life as measured by the Health Utility Index at 12 months post-screening. Second, in comparison to non-screened subjects, those who are screened and referred to a dementia collaborative care program will not have higher depression or anxiety at one month post-screening as measured by the Patient Health Questionnaire and Generalized Anxiety Disorder Scale scales. Our secondary hypothesis is that screened subjects will have an Incremental Cost-Effectiveness Ratio below the maximum acceptable threshold of $60,000 per quality adjusted life year saved at 12 months. TRIAL REGISTRATION: Ongoing; registered on September 19, 2012. ClinicalTrials.gov Identifier: 2012 NCT01699503.

Medication adherence and tolerability of Alzheimer's disease medications: study protocol for a randomized controlled trial.

BACKGROUND: The class of acetylcholinesterase inhibitors (ChEI), including donepezil, rivastigmine, and galantamine, have similar efficacy profiles in patients with mild to moderate Alzheimer's disease (AD). However, few studies have evaluated adherence to these agents. We sought to prospectively capture the rates and reasons for nonadherence to ChEI and determine factors influencing tolerability and adherence. METHODS/DESIGN: We designed a pragmatic randomized clinical trial to evaluate the adherence to ChEIs among older adults with AD. Participants include AD patients receiving care within memory care practices in the greater Indianapolis area. Participants will be followed at 6-week intervals up to 18 weeks to measure the primary outcome of ChEI discontinuation and adherence rates and secondary outcomes of behavioral and psychological symptoms of dementia. The primary outcome will be assessed through two methods, a telephone interview of an informal caregiver and electronic medical record data captured from each healthcare system through a regional health information exchange. The secondary outcome will be measured by the Healthy Aging Brain Care Monitor and the Neuropsychiatric Inventory. In addition, the trial will conduct an exploratory evaluation of the pharmacogenomic signatures for the efficacy and the adverse effect responses to ChEIs. We hypothesized that patient-specific factors, including pharmacogenomics and pharmacokinetic characteristics, may influence the study outcomes. DISCUSSION: This pragmatic trial will engage a diverse population from multiple memory care practices to evaluate the adherence to and tolerability of ChEIs in a real world setting. Engaging participants from multiple healthcare systems connected through a health information exchange will capture valuable clinical and non-clinical influences on the patterns of utilization and tolerability of a class of medications with a high rate of discontinuation. TRIAL REGISTRATION: Clinicaltrials.gov: NCT01362686.