Characterizing PRN Use of Psychotropic Medications for Acute Agitation in Canadian Long-Term Care Residents with Dementia Before and During COVID-19.

Background: Agitation is a disabling neuropsychiatric symptom of dementia. Pro re nata (PRN) injections of psychotropics can be administered for severe acute agitation, but little is known about the frequency of their actual use. Objective: Characterize actual use of injectable PRN psychotropics for severe acute agitation in Canadian long-term care (LTC) residents with dementia and compare use before and during the COVID-19 pandemic. Methods: Residents from two Canadian LTC facilities with orders for PRN haloperidol, olanzapine, or lorazepam between January 1, 2018- May 1, 2019 (i.e., pre-COVID-19) and January 1, 2020- May 1, 2021 (i.e., COVID-19) were identified. Electronic medical records were reviewed to document PRN injections of psychotropic medications and collect data on reason and demographic characteristics. Descriptive statistics were used to characterize frequency, dose, and indications of use, and multivariate regression models were used to compare use between time periods. Results: Of the 250 residents, 45 of 103 (44%) people in the pre-COVID-19 period and 85 of 147 (58%) people in the COVID-19 period with standing orders for PRN psychotropics received ≥1 injections. Haloperidol was the most frequently used agent in both time periods (74% (155/209 injections) pre-COVID-19; 81% (323/398 injections) during COVID-19). Residents in the COVID-19 period were almost two times more likely to receive injections compared with those in the pre-COVID-19 period (odds ratio = 1.96; 95% CI = 1.15-3.34; p = 0.01). Conclusion: Our results suggest that use of PRN injections increased in LTC during the pandemic and contribute to the mounting evidence that agitation worsened during that time.

The relationship between indoleamine 2,3-dioxygenase activity and post-stroke cognitive impairment.

BACKGROUND: Activation of indoleamine 2,3-dioxygenase (IDO) and higher concentrations of several kynurenine metabolites have been observed post-stroke, where they have been associated with increased mortality. While lower tryptophan or a higher ratio of kynurenine/tryptophan (K/T) in peripheral blood have been associated with dementia and the severity of cognitive symptoms in Alzheimer's disease, the association between K/T ratios and post-stroke cognitive impairment (PSCI) has not been investigated. METHODS: Patients were recruited from the acute stroke unit of a general hospital within 1 month post-stroke. Assessments included the Standardized Mini-Mental State Examination (sMMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Tryptophan and kynurenine concentrations were determined by high-performance liquid chromatography. RESULTS: A total of 41 patients with ischemic stroke ([mean ± SD] age 72.3 ± 12.2 years, 53.7% male, sMMSE 25.6 ± 4.1, NIHSS 7.27 ± 5.55) were recruited. Higher K/T ratios were associated with lower post-stroke global cognition (i.e. sMMSE scores; ß = -.327, P = .037). A backward stepwise elimination linear regression (F1,40=6.15, P=.005, adjusted R2=.205) showed that the highest K/T ratio tertile (ß = -.412, P = .006) predicted lower sMMSE scores, controlling for age (ß = -.253, p = .081), with NIHSS (ß = -.027, P = 0.859), and lesion volume (ß = -.066, P = 0.659) removed from the model. In receiver operating characteristic analysis, a K/T ratio of 78.3 µmol/mmol (top tertile) predicted significant cognitive impairment (sMMSE score ≤ 24) with 67% sensitivity and 86% specificity (area under the curve = 0.730, p = .022). CONCLUSIONS: These data suggest an inflammatory response characterized by IDO activation may be relevant to the development of PSCI. Since the neuroactivity of kynurenine metabolites may be amenable to pharmacotherapeutic intervention, the K/T ratio may be a clinically important biomarker.

Are vascular risk factors associated with post-stroke depressive symptoms?

OBJECTIVE: Vascular risk factors (VRFs) have been associated with stroke and cognitive impairment, however, the role of VRFs in predicting post-stroke depression (PSD) has not been assessed. The objective of the current study was to determine whether VRFs are associated with the risk of PSD in an acute stroke population. METHODS: In this observational study, patients meeting World Health Organization MONICA Project and National Institute of Neurological Disorders and Stroke criteria for stroke were eligible. Patients were assessed for depression, cognition, and stroke severity, and VRF and demographic information were obtained. RESULTS: A total of 102 patients were recruited within 4 months post-stroke. Using a score of ≥16 on the Center for Epidemiological Studies Depression scale to determine depressive symptoms, 38 patients (age 72.1 ± 15.6, 44.7% male) screened positive for depressive symptoms and 64 (age 70.1 ± 13.6, 51.6% male) screened negative. Analysis of VRFs showed that only hypertension (P = .044) independently predicted the presence of depressive symptoms (χ(2) = 4.742, P = .029, Nagelkerke R (2) = .062). CONCLUSIONS: Hypertension was associated with post-stroke depressive symptoms, while there was no relationship between PSD and other VRFs. Hypertension may have a greater impact than other VRFs on mood following stroke and may have a role in prevention and treatment of PSD.

The relationship between inflammatory markers and post stroke cognitive impairment.

OBJECTIVE: To determine whether there is a relationship between inflammatory markers (serum C-reactive protein (CRP) and cytokines) and post stroke cognitive impairment (PSCI). METHODS: This was a cross-sectional observational study. Patients were recruited from 4 sources: (1) the acute stroke unit of a general hospital, (2) an outpatient stroke prevention clinic, (3) a stroke rehabilitation unit in a specialized geriatric hospital, or (4) a stroke rehabilitation unit of a rehabilitation hospital. Patients meeting National Institute of Neurological and Communicative Disorders and Stroke (NINCDS) and World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (WHO-MONICA) project criteria for stroke were invited to participate in this study within the first 5 to 31 days post stroke. Patients with subarachnoid or intracranial hemorrhage, decreased level of consciousness, severe aphasia or dysarthria, or a significant acute medical, neurological, or psychiatric illness were excluded. Clinical assessments included the Mini-Mental State Examination (MMSE) for cognition, the National Institutes of Health Stroke Scale (NIHSS) for stroke severity, and the Center for Epidemiological Studies-Depression Scale (CES-D) for depressive symptoms. Enzyme-linked immunosorbent assay (ELISA) was used to measure serum concentrations of CRP, interleukin 6 (IL-6), and interferon gamma (IFN-gamma). RESULTS: A total of 48 patients with ischemic stroke (age [mean +/- SD] 71.6 +/- 13.2 years, 54.2% male, MMSE 26.4 +/- 3.8, NIHSS 6.8 +/- 4.0) were recruited within their first month post stroke. Backward stepwise elimination linear regression showed that higher concentrations of serum CRP (beta(CRP) = -0.46, p( CRP) = 0.002) predicted lower post stroke global cognition ([MMSE], F1,44 = 11.31, P = .002), with age (P = .92), level of education (P = .22), infarct side (P = 0.49), IL-6 (P = 0.36), and IFN-gamma (P = .57) removed from the final model. CONCLUSIONS: A post stroke inflammatory response may be important in subacute, PSCI.

Mortality in medical-surgical inpatients referred for psychiatric consultation.

OBJECTIVE: The purpose of this study is to calculate the 1-year mortality rate of medical-surgical inpatients referred for psychiatric consultation and to determine factors associated with mortality in this population. METHOD: We conducted a retrospective chart review of medical-surgical inpatients referred for psychiatric consultation (N=454). Patients who died within 1 year of psychiatric consultation were compared to age-matched patients from the same group who survived on demographic and clinical domains. RESULTS: Sixty-nine patients (15.2%) died within 1 year of referral for psychiatric consultation. Delirium was the only psychiatric diagnosis significantly associated with 1-year mortality [52.2% vs. 29.9%, P=.01; hazard ratio (HR), 1.7]. Cancer was the only medical condition associated with 1-year mortality (24.6% vs. 6.0%, P<.0001; HR, 3.03). Having both delirium and cancer shortened mean survival time significantly. Mortality risk was also associated with time duration between admission and psychiatric consultation. CONCLUSION: The 1-year mortality rate in this group of medical-surgical inpatients referred for psychiatric consultation was 15.2%. Mortality was independently associated with delirium and cancer. Mortality was also associated with greater length of time from admission to consultation, which raises a question about whether earlier psychiatry consultation may have a positive impact on survival.

Toward defining the scope of psychosomatic medicine practice: psychosomatic medicine in an outpatient, tertiary-care practice setting.

BACKGROUND: Because psychosomatic medicine (PM) is increasingly practiced in outpatient settings, the scope of practice needs to be delineated from community psychiatry and inpatient psychiatry work. OBJECTIVE: The authors sought to address the question of whether outpatient activities are a definably part the scope of practice of PM. METHOD: Three clinical groups were compared: 200 PM outpatients, 200 consultation-liaison (CL) inpatients, and 200 community-psychiatry (CP) outpatients. RESULTS: The groups differed significantly in 49 of 112 demographic and clinical comparisons (43.8%). Analysis of individual measures validated the concept that PM outpatient practice requires traditional PM/CL expertise with medical-psychiatric differential diagnosis, unexplained physical symptoms, pain, and psychopharmacological management in medically ill and geriatric patients. CONCLUSION: Outpatient PM experiences may also enhance training opportunities, given an expanded case-mix.