Relationship Between Pain and Delirium in Critically Ill Adults.

OBJECTIVES: Although opioids are frequently used to treat pain, and are an important risk for ICU delirium, the association between ICU pain itself and delirium remains unclear. We sought to evaluate the relationship between ICU pain and delirium. DESIGN: Prospective cohort study. SETTING: A 32-bed academic medical-surgical ICU. PATIENTS: Critically ill adults (n = 4,064) admitted greater than or equal to 24 hours without a condition hampering delirium assessment. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Daily mental status was classified as arousable without delirium, delirium, or unarousable. Pain was assessed six times daily in arousable patients using a 0-10 Numeric Rating Scale (NRS) or the Critical Care Pain Observation Tool (CPOT); daily peak pain score was categorized as no (NRS = 0/CPOT = 0), mild (NRS = 1-3/CPOT = 1-2), moderate (NRS = 4-6/CPOT = 3-4), or severe (NRS = 7-10/CPOT = 5-8) pain. To address missingness, a Multiple Imputation by Chained Equations approach that used available daily pain severity and 19 pain predictors was used to generate 25 complete datasets. Using a first-order Markov model with a multinomial logistic regression analysis, that controlled for 11 baseline/daily delirium risk factors and considered the competing risks of unarousability and ICU discharge/death, the association between peak daily pain and next-day delirium in each complete dataset was evaluated. RESULTS: Among 14,013 ICU days (contributed by 4,064 adults), delirium occurred on 2,749 (19.6%). After pain severity imputation on 1,818 ICU days, mild, moderate, and severe pain were detected on 2,712 (34.1%), 1,682 (21.1%), and 894 (11.2%) of the no-delirium days, respectively, and 992 (36.1%), 513 (18.6%), and 27 (10.1%) of delirium days (p = 0.01). The presence of any pain (mild, moderate, or severe) was not associated with a transition from awake without delirium to delirium (aOR 0.96; 95% CI, 0.76-1.21). This association was similar when days with only mild, moderate, or severe pain were considered. All results were stable after controlling for daily opioid dose. CONCLUSIONS: After controlling for multiple delirium risk factors, including daily opioid use, pain may not be a risk factor for delirium in the ICU. Future prospective research is required.

Comparing Lookback Periods to Ascertain Alzheimer's Disease and Related Dementias.

Claims data are a valuable resource for studying Alzheimer's disease and related dementias (ADRD). Alzheimer's disease and related dementias is often identified using a list of claims codes and a fixed lookback period of 3 years of data. However, a 1-year lookback or an approach using all-available lookback data could be beneficial based on different research questions. Thus, the purpose of this study was to compare 1-year and all-available lookback approaches to ascertaining ADRD compared to the standard 3-year approach. Using a cohort of Veterans hospitalized for heart failure (N = 373, 897), our results suggested high agreement (93% or greater) between the lookback periods. The 1-year lookback period had lower sensitivity (60%) and underestimated the prevalence of ADRD. These results suggest that 1-year and all-available lookback periods are viable approaches when using claims data.

Incidence of New Dementia Diagnosis in Veterans Admitted to Nursing Homes After Heart Failure Hospitalization.

BACKGROUND: Hospitalization with heart failure (HF) may signal an increased risk of Alzheimer's disease and related dementias (ADRD). Nursing homes routinely assess cognition but the association of these results with new ADRD diagnosis in a population at high risk of ADRD is not known. OBJECTIVE: To determine the association between nursing home cognitive assessment results and new diagnosis of dementia after heart failure hospitalization. METHODS: This retrospective cohort study included Veterans hospitalized for HF and discharged to nursing homes, from 2010 to 2015, without a prior diagnosis of ADRD. We determined mild, moderate, or severe cognitive impairment using multiple items of the nursing home admission assessment. We used Cox regression to determine the association of cognitive impairment with new ADRD diagnosis during 365 days of follow-up. RESULTS: The cohort included 7,472 residents, new diagnosis of ADRD occurred in 4,182 (56%). The adjusted hazard ratio of ADRD diagnosis was 4.5 (95% CI 4.2, 4.8) for the mild impairment group, 5.4 (95% CI 4.8, 5.9) for moderate impairment, and 4.0 (95% CI 3.2, 5.0) for severe impairment compared to the cognitively intact group. CONCLUSION: New ADRD diagnoses occurred in more than half of Veterans with HF admitted to nursing homes for post-acute care.

Acute Antipsychotic Use and Presence of Dysphagia Among Older Veterans with Heart Failure.

OBJECTIVE: Examine whether new antipsychotic (AP) exposure is associated with dysphagia in hospitalized patients with heart failure (HF). DESIGN: Retrospective cohort. SETTINGS AND PARTICIPANTS: AP-naïve Veterans hospitalized with HF and subsequently discharged to a skilled nursing facility (SNF) between October 1, 2010, and November 30, 2019. METHODS: We linked Veterans Health Administration (VHA) electronic medical records with Centers for Medicare & Medicaid (CMS) Minimum Data Set (MDS) version 3.0 assessments and CMS claims. The exposure variable was administration of ≥1 dose of a typical or atypical AP during hospitalization. Our main outcome measure was dysphagia presence defined by (1) inpatient dysphagia diagnosis codes and (2) the SNF admission MDS 3.0 swallowing-related items to examine post-acute care dysphagia status. Inverse probability of treatment weighting was used for risk adjustment. RESULTS: The analytic cohort consisted of 29,591 Veterans (mean age 78.5 ± 10.0 years; female 2.9%; n = 865). Acute APs were administered to 9.9% (n = 2941). Those receiving APs had differences in prior dementia [37.1%, n = 1091, vs 22.3%, n = 5942; standardized mean difference (SMD) = 0.33] and hospital delirium diagnoses (7.7%, n = 227 vs 2.8%, n = 754; SMD = 0.22). Acute AP exposure was associated with nearly double the risk for hospital dysphagia diagnosis codes [adjusted (adj.) relative risk (RR) 1.9, 95% CI 1.8, 2.1]. At the SNF admission MDS assessment, acute AP administration during hospitalization was associated with an increased dysphagia risk (adj. RR 1.2, 95% CI 1.0, 1.5) both in the oral (adj. RR 1.7, 95% CI 1.2, 2.0) and pharyngeal phases (adj. RR 1.3, 95% CI 1.0, 1.7). CONCLUSIONS AND IMPLICATIONS: In this retrospective study, AP medication exposure was associated with increased dysphagia coding and MDS assessment. Considering other adverse effects, acute AP should be cautiously administered during hospitalization, particularly in those with dementia. Swallowing function is critical to hydration, nutrition, and medical management of HF; therefore, when acute APs are initiated, a swallow evaluation should be considered.

Prevalence of Comorbid Depression and Insomnia Among Veterans Hospitalized for Heart Failure with Alzheimer Disease and Related Disorders.

OBJECTIVE: To examine prevalence of Alzheimer Disease and related dementias (ADRD) and patient characteristics as a function of comorbid insomnia and/or depression among heart failure (HF) patients discharged from hospitals. DESIGN: Retrospective cohort descriptive epidemiology study. SETTING: VA Hospitals. PARTICIPANTS: N = 373,897 Veterans hospitalized with heart failure from October 1, 2011 until September 30, 2020. MEASUREMENTS: We examined VA and Center for Medicare & Medicaid Services (CMS) coding in the year prior to admission using published ICD-9/10 codes for dementia, insomnia, and depression. The primary outcome was the prevalence of ADRD and the secondary outcomes were 30-day and 365-day mortality. RESULTS: The cohort were predominantly older adults (mean age = 72 years, SD = 11), male (97%), and White (73%). Dementia prevalence in participants without insomnia or depression was 12%. In those with both insomnia and depression, dementia prevalence was 34%. For insomnia alone and depression alone, dementia prevalence was 21% and 24%, respectively. Mortality followed a similar pattern with highest 30-day and 365-day mortality higher in those with both insomnia and depression. CONCLUSIONS: These results suggest that persons with both insomnia and depression are at an increased risk of ADRD and mortality compared to persons with one or neither condition. Screening for both insomnia and depression, especially in patients with other ADRD risk factors, could lead to earlier identification of ADRD. Understanding comorbid conditions which may represent earlier signs of ADRD may be critical in the identification of ADRD risk.

Development and validation of the fall-related injury risk in nursing homes (INJURE-NH) prediction tool.

BACKGROUND: Existing models to predict fall-related injuries (FRI) in nursing homes (NH) focus on hip fractures, yet hip fractures comprise less than half of all FRIs. We developed and validated a series of models to predict the absolute risk of FRIs in NH residents. METHODS: Retrospective cohort study of long-stay US NH residents (≥100 days in the same facility) between January 1, 2016 and December 31, 2017 (n = 733,427) using Medicare claims and Minimum Data Set v3.0 clinical assessments. Predictors of FRIs were selected through LASSO logistic regression in a 2/3 random derivation sample and tested in a 1/3 validation sample. Sub-distribution hazard ratios (HR) and 95% confidence intervals (95% CI) were estimated for 6-month and 2-year follow-up. Discrimination was evaluated via C-statistic, and calibration compared the predicted rate of FRI to the observed rate. To develop a parsimonious clinical tool, we calculated a score using the five strongest predictors in the Fine-Gray model. Model performance was repeated in the validation sample. RESULTS: Mean (Q1, Q3) age was 85.0 (77.5, 90.6) years and 69.6% were women. Within 2 years of follow-up, 43,976 (6.0%) residents experienced ≥1 FRI. Seventy predictors were included in the model. The discrimination of the 2-year prediction model was good (C-index = 0.70), and the calibration was excellent. Calibration and discrimination of the 6-month model were similar (C-index = 0.71). In the clinical tool to predict 2-year risk, the five characteristics included independence in activities of daily living (ADLs) (HR 2.27; 95% CI 2.14-2.41) and a history of non-hip fracture (HR 2.02; 95% CI 1.94-2.12). Performance results were similar in the validation sample. CONCLUSIONS: We developed and validated a series of risk prediction models that can identify NH residents at greatest risk for FRI. In NH, these models should help target preventive strategies.

Comparing Resident, Proxy, and Staff Respondents for Nursing Home Residents' Preferences for Everyday Living.

To encourage person-centered care, the Centers for Medicare and Medicaid require nursing homes to measure resident preferences using the Preferences Assessment Tool (PAT). No known research has examined the implications of respondent type (i.e., resident, proxy, staff) on preference importance; therefore, the purpose of this study was to compare the importance of preferences depending on which respondent completed the PAT. Participants included 16,111 Veterans discharged to community-based skilled nursing facilities after hospitalization for heart failure. A majority (95%) of residents completed the PAT compared to proxy (3%) and staff (2%). Proxy responders were both more and less likely to indicate individual preferences as important compared to residents. Staff members were consistently less likely to indicate all preferences as important compared to residents. Findings from this study emphasize the need for proxy and staff to find methods to better understand residents' preferences when residents are not able to participate in assessments.

Adverse events following third dose of mRNA COVID-19 vaccination among nursing home residents who received the primary series.

BACKGROUND: We sought to compare rates of adverse events among nursing home residents who received an mRNA COVID-19 vaccine booster dose with those who had not yet received their booster. METHODS: We assessed a prospective cohort of 11,200 nursing home residents who received a primary COVID-19 mRNA vaccine series at least 6 months prior to September 22, 2021 and received a third "booster dose" between September 22, 2021 and February 2, 2022. Residents lived in 239 nursing homes operated by Genesis HealthCare, spanning 21 U.S. states. We screened electronic health records for 20 serious vaccine-related adverse events that are monitored following receipt of COVID-19 vaccination by the CDC's Vaccine Safety Datalink. We matched boosted and yet-to-be boosted residents during the same time period, comparing rates of events occurring 14 days after booster administration with those occurring 14 days prior to booster administration. To supplement previously reported background rates of adverse events, we report background rates of medical conditions among nursing home residents during 2020, before COVID-19 vaccines were administered in nursing homes. Events occurring in 2021-2022 were confirmed by physician chart review. We report unadjusted rates of adverse events and used a false discovery rate procedure to adjust for multiplicity of events tested. RESULTS: No adverse events were reported during the 14 days post-booster. A few adverse events occurred prior to booster (ischemic stroke: 49.4 per 100,000 residents, 95% CI: 21.2, 115.7; venous thromboembolism: 9.9 per 100,000 residents, 95% CI: 1.7, 56.0), though differences in event rates pre- versus post-booster were not statistically significant (p < 0.05) after adjusting for multiple comparisons. No significant differences were detected between post-booster vaccination rates and prior year 14-day background rates of medical conditions. CONCLUSIONS: No safety signals were detected following a COVID-19 mRNA vaccine booster dose in this large multi-state sample of nursing home residents.

Diarrhea during critical illness: a multicenter cohort study.

PURPOSE: To study the incidence, predictors, and outcomes of diarrhea during the stay in the intensive care unit (ICU). METHODS: Prospective cohort of consecutive adults in the ICU for > 24 h during a 10-week period across 12 intensive care units (ICUs) internationally. The explored outcomes were: (1) incidence of diarrhea, (2) Clostridioides difficile-associated diarrhea (CDAD); (3) ICU and hospital length of stay (LOS) and mortality in patients with diarrhea. We fit generalized linear models to evaluate the predictors, management, morbidity and mortality associated with diarrhea. RESULTS: Among 1109 patients aged 61.4 (17.5) [mean (standard deviation)] years, 981(88.5%) were medical and 645 (58.2%) were mechanically ventilated. The incidence was 73.8% (818 patients, 73.8%, 95% confidence interval [CI] 71.1-76.6) using the definition of the World Health Organisation (WHO). Incidence varied across definitions (Bristol 53.5%, 95% CI 50.4-56.7; Bliss 37.7%, 95% CI 34.9-40.4). Of 99 patients with diarrhea undergoing CDAD testing, 23 tested positive (2.2% incidence, 95% CI 1.5-3.4). Independent predictors included enteral nutrition (RR 1.23, 95% CI 1.16-1.31, p < 0.001), antibiotic days (RR 1.02, 95% CI 1.02-1.03, p < 0.001), and suppositories (RR 1.14 95% CI 1.06-1.22, p < 0.001). Opiates decreased diarrhea risk (RR 0.76, 95% CI 0.68-0.86, p < 0.001). Diarrhea prompted management modifications (altered enteral nutrition or medications: RR 10.25, 95% CI 5.14-20.45, p < 0.001) or other consequences (fecal management device or CDAD testing: RR 6.16, 95% CI 3.4-11.17, p < 0.001). Diarrhea was associated with a longer time to discharge for ICU or hospital stay, but was not associated with hospital mortality. CONCLUSION: Diarrhea is common, has several predictors, and prompts changes in patient care, is associated with longer time to discharge but not mortality.

Naloxegol to Prevent Constipation in ICU Adults Receiving Opioids: A Randomized Double-Blind Placebo-Controlled Pilot Trial.

Background: Constipation is frequent in critically ill adults receiving opioids. Naloxegol (N), a peripherally acting mu-receptor antagonist (PAMORA), may reduce constipation. The objective of this trial was to evaluate the efficacy and safety of N to prevent constipation in ICU adults receiving opioids. Methods and Patients. In this single-center, double-blind, randomized trial, adults admitted to a medical ICU receiving IV opioids (≥100 mcg fentanyl/day), and not having any of 17 exclusion criteria, were randomized to N (25 mg) or placebo (P) daily randomized to receive N (25mg) or placebo (P) and docusate 100 mg twice daily until ICU discharge, 10 days, or diarrhea (≥3 spontaneous bowel movement (SBM)/24 hours) or a serious adverse event related to study medication. A 4-step laxative protocol was initiated when there was no SBM ≥3 days. Results: Only 318 (20.6%) of the 1542 screened adults during the 1/17-10/19 enrolment period met all inclusion criteria. Of these, only 19/381 (4.9%) met all eligibility criteria. After 7 consent refusals, 12 patients were randomized. The study was stopped early due to enrolment futility. The N (n = 6) and P (n = 6) groups were similar. The time to first SBM (N 41.4 ± 31.7 vs. P 32.5 ± 25.4 hours, P = 0.56) was similar. The maximal daily abdominal pressure was significantly lower in the N group (N 10 ± 4 vs. P 13 ± 5, P = 0.002). The median (IQR) daily SOFA scores were higher in N (N 7 (4, 8) vs. P 4 (3, 5), P < 0.001). Laxative protocol use was similar (N 83.3% vs. P 66.6%; P = 0.51). Diarrhea prevalence was high but similar (N 66.6% vs. P 66.6%; P = 1.0). No patient experienced opioid withdrawal. Conclusions: Important recruitment challenges exist for ICU trials evaluating the use of PAMORAs for constipation prevention. Despite being underpowered, our results suggest time to first SBM with naloxegol, if different than P, may be small. The effect of naloxegol on abdominal pressure, SOFA, and the interaction between the two requires further research.

Association Between Perioperative Medication Use and Postoperative Delirium and Cognition in Older Adults Undergoing Elective Noncardiac Surgery.

BACKGROUND: Postoperative delirium is frequent in older adults and is associated with postoperative neurocognitive disorder (PND). Studies evaluating perioperative medication use and delirium have generally evaluated medications in aggregate and been poorly controlled; the association between perioperative medication use and PND remains unclear. We sought to evaluate the association between medication use and postoperative delirium and PND in older adults undergoing major elective surgery. METHODS: This is a secondary analysis of a prospective cohort study of adults ≥70 years without dementia undergoing major elective surgery. Patients were interviewed preoperatively to determine home medication use. Postoperatively, daily hospital use of 7 different medication classes listed in guidelines as risk factors for delirium was collected; administration before delirium was verified. While hospitalized, patients were assessed daily for delirium using the Confusion Assessment Method and a validated chart review method. Cognition was evaluated preoperatively and 1 month after surgery using a neurocognitive battery. The association between prehospital medication use and postoperative delirium was assessed using a generalized linear model with a log link function, controlling for age, sex, type of surgery, Charlson comorbidity index, and baseline cognition. The association between daily postoperative medication use (when class exposure ≥5%) and time to delirium was assessed using time-varying Cox models adjusted for age, sex, surgery type, Charlson comorbidity index, Acute Physiology and Chronic Health Evaluation (APACHE)-II score, and baseline cognition. Mediation analysis was utilized to evaluate the association between medication use, delirium, and cognitive change from baseline to 1 month. RESULTS: Among 560 patients enrolled, 134 (24%) developed delirium during hospitalization. The multivariable analyses revealed no significant association between prehospital benzodiazepine (relative risk [RR], 1.44; 95% confidence interval [CI], 0.85-2.44), beta-blocker (RR, 1.38; 95% CI, 0.94-2.05), NSAID (RR, 1.12; 95% CI, 0.77-1.62), opioid (RR, 1.22; 95% CI, 0.82-1.82), or statin (RR, 1.34; 95% CI, 0.92-1.95) exposure and delirium. Postoperative hospital benzodiazepine use (adjusted hazard ratio [aHR], 3.23; 95% CI, 2.10-4.99) was associated with greater delirium. Neither postoperative hospital antipsychotic (aHR, 1.48; 95% CI, 0.74-2.94) nor opioid (aHR, 0.82; 95% CI, 0.62-1.11) use before delirium was associated with delirium. Antipsychotic use (either presurgery or postsurgery) was associated with a 0.34 point (standard error, 0.16) decrease in general cognitive performance at 1 month through its effect on delirium (P = .03), despite no total effect being observed. CONCLUSIONS: Administration of benzodiazepines to older adults hospitalized after major surgery is associated with increased postoperative delirium. Association between inhospital, postoperative medication use and cognition at 1 month, independent of delirium, was not detected.

Effects of dipeptidyl peptidase-4 inhibitors and sulphonylureas on cognitive and physical function in nursing home residents.

AIMS: Dipeptidyl peptidase-4 inhibitors (DPP4Is) may mitigate hypoglycaemia-mediated declines in cognitive and physical functioning compared with sulphonylureas (SUs), yet comparative studies are unavailable among older adults, particularly nursing home (NH) residents. We evaluated the effects of DPP4Is versus SUs on cognitive and physical functioning among NH residents. MATERIALS AND METHODS: This new-user cohort study included long-stay NH residents aged ≥65 years from the 2007-2010 national US Minimum Data Set (MDS) clinical assessments and linked Medicare claims. We measured cognitive decline from the validated 6-point MDS Cognitive Performance Scale, functional decline from the validated 28-point MDS Activities of Daily Living scale, and hospitalizations or emergency department visits for altered mental status from Medicare claims. We compared 180-day outcomes in residents who initiated a DPP4I versus SU after 1:1 propensity score matching using Cox regression models. RESULTS: The matched cohort (N = 1784) had a mean ± SD age of 80 ± 8 years and 73% were women. Approximately 46% had no or mild cognitive impairment and 35% had no or mild functional impairment before treatment initiation. Compared with SU users, DPP4I users had lower 180-day rates of cognitive decline [hazard ratio (HR) = 0.61, 95% confidence interval (CI) 0.31-1.19], altered mental status events (HR = 0.71, 95% CI 0.39-1.27), and functional decline (HR = 0.89, 95% CI 0.51-1.56), but estimates were imprecise. CONCLUSIONS: Rates of cognitive and functional decline may be reduced among older NH residents using DPP4Is compared with SUs, but larger studies with greater statistical power should resolve the remaining uncertainty by providing more precise effect estimates.

Identification of Fall-Related Injuries in Nursing Home Residents Using Administrative Claims Data.

BACKGROUND: Fall-related injuries (FRIs) are a leading cause of morbidity, mortality, and costs among nursing home (NH) residents. Carefully defining FRIs in administrative data is essential for improving injury-reduction efforts. We developed a series of novel claims-based algorithms for identifying FRIs in long-stay NH residents. METHODS: This is a retrospective cohort of residents of NH residing there for at least 100 days who were continuously enrolled in Medicare Parts A and B in 2016. FRIs were identified using 4 claims-based case-qualifying (CQ) definitions (Inpatient [CQ1], Outpatient and Provider with Procedure [CQ2], Outpatient and Provider with Fall [CQ3], or Inpatient or Outpatient and Provider with Fall [CQ4]). Correlation was calculated using phi correlation coefficients. RESULTS: Of 153 220 residents (mean [SD] age 81.2 [12.1], 68.0% female), we identified 10 104 with at least one FRI according to one or more CQ definition. Among 2 950 residents with hip fractures, 1 852 (62.8%) were identified by all algorithms. Algorithm CQ4 (n = 326-2 775) identified more FRIs across all injuries while CQ1 identified less (n = 21-2 320). CQ2 identified more intracranial bleeds (1 028 vs 448) than CQ1. For nonfracture categories, few FRIs were identified using CQ1 (n = 20-488). Of the 2 320 residents with hip fractures identified by CQ1, 2 145 (92.5%) had external cause of injury codes. All algorithms were strongly correlated, with phi coefficients ranging from 0.82 to 0.99. CONCLUSIONS: Claims-based algorithms applied to outpatient and provider claims identify more nonfracture FRIs. When identifying risk factors, stakeholders should select the algorithm(s) suitable for the FRI and study purpose.

Impact of the 2018 Society of Critical Care Medicine Pain, Agitation/Sedation, Delirium, Immobility, and Sleep Guidelines on Nonopioid Analgesic Use and Related Outcomes in Critically Ill Adults After Major Surgery.

We compared ICU nonopioid analgesic use, opioid use, and pain before and after Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication at one academic center among critically ill adults receiving an opioid infusion and greater than or equal to 24 hours of mechanical ventilation after major surgery. The 2017 (n = 77) and 2019 (n = 57) groups were similar at baseline. The 2019 (vs 2017) patients were more likely to receive scheduled IV/oral acetaminophen (84% vs 69%; p = 0.05), less likely to receive a lidocaine patch (33% vs 50%; p = 0.05), and just as likely to receive ketamine (4% vs 3%; p = 1.0), an nonsteroidal anti-inflammatory drug (7% vs 3%; p = 0.26), or gabapentin/pregabalin (16% vs 9%; p = 0.23). Daily average opioid exposure (in IV morphine milligram equivalent) was not different (70 [42-99] [2017] vs 78 mg [49-109 mg]; p = 0.94). The 2019 (vs 2017) group spent more ICU days with severe pain (p = 0.04). At our center, Pain, Agitation/Sedation, Delirium, Immobility, and Sleep guideline publication had little effect on nonopioid analgesic or opioid prescribing practices in critically ill surgical adults.

Comparative safety of dipeptidyl peptidase-4 inhibitors and sulfonylureas among frail older adults.

BACKGROUND: Studies comparing dipeptidyl peptidase-4 inhibitors (DPP4Is) to sulfonylureas (SUs) are unavailable for frail older adults, especially nursing home (NH) residents. We examined the effects of DPP4Is versus SUs on severe adverse glycemic events, cardiovascular events, and death among NH residents. METHODS: We conducted a national retrospective cohort study of long-stay NH residents aged ≥65 years using 2008-2010 national US Minimum Data Set clinical assessment data and linked Medicare claims. Exposure was new DPP4I versus new SU use assessed via Medicare Part D drug claims. One-year outcomes were severe hypoglycemia, severe hyperglycemia, acute myocardial infarction (AMI), heart failure (HF), major adverse cardiovascular events plus HF (MACE+HF), and death. We compared outcomes after propensity score matching using Cox proportional hazards regression models. RESULTS: The cohort (N = 2016) had a mean (SD) age of 81 (8.1) years and was 72% female. Compared with SU users, DPP4I users had a lower 1-year rate of severe hypoglycemic events (HR = 0.57, 95% CI 0.34-0.94), but statistically similar rates of severe hyperglycemic events (HR = 0.94, 95% CI 0.52-1.72), AMI (HR = 0.76, 95% CI 0.44-1.30), HF (HR = 1.01, 95% CI 0.79-1.30), MACE+HF (HR = 0.90, 95% CI 0.72-1.12), and death (HR = 0.97, 95% CI 0.86-1.10). CONCLUSIONS: DPP4Is should be a preferred treatment option over SUs for NH residents and other frail older adults given the importance of avoiding hypoglycemia.