White matter hyperintensity (WMH) burden is greater, has a frontal-temporal distribution, and is associated with proxies of exposure to repetitive head impacts (RHI) in former American football players. These findings suggest that in the context of RHI, WMH might have unique etiologies that extend beyond those of vascular risk factors and normal aging processes. The objective of this study was to evaluate the correlates of WMH in former elite American football players. We examined markers of amyloid, tau, neurodegeneration, inflammation, axonal injury, and vascular health and their relationships to WMH. A group of age-matched asymptomatic men without a history of RHI was included to determine the specificity of the relationships observed in the former football players.

240 male participants aged 45-74 (60 unexposed asymptomatic men, 60 male former college football players, 120 male former professional football players) underwent semi-structured clinical interviews, magnetic resonance imaging (structural T1, T2 FLAIR, and diffusion tensor imaging), and lumbar puncture to collect cerebrospinal fluid (CSF) biomarkers as part of the DIAGNOSE CTE Research Project. Total WMH lesion volumes (TLV) were estimated using the Lesion Prediction Algorithm from the Lesion Segmentation Toolbox. Structural equation modeling, using Full-Information Maximum Likelihood (FIML) to account for missing values, examined the associations between log-TLV and the following variables: total cortical thickness, whole-brain average fractional anisotropy (FA), CSF amyloid ß42, CSF p-tau181, CSF sTREM2 (a marker of microglial activation), CSF neurofilament light (NfL), and the modified Framingham stroke risk profile (rFSRP). Covariates included age, race, education, APOE z4 carrier status, and evaluation site. Bootstrapped 95% confidence intervals assessed statistical significance. Models were performed separately for football players (college and professional players pooled; n=180) and the unexposed men (n=60). Due to differences in sample size, estimates were compared and were considered different if the percent change in the estimates exceeded 10%.

In the former football players (mean age=57.2, 34% Black, 29% APOE e4 carrier), reduced cortical thickness (B=-0.25, 95% CI [0.45, -0.08]), lower average FA (B=-0.27, 95% CI [-0.41, -.12]), higher p-tau181 (B=0.17, 95% CI [0.02, 0.43]), and higher rFSRP score (B=0.27, 95% CI [0.08, 0.42]) were associated with greater log-TLV. Compared to the unexposed men, substantial differences in estimates were observed for rFSRP (Bcontrol=0.02, Bfootball=0.27, 994% difference), average FA (Bcontrol=-0.03, Bfootball=-0.27, 802% difference), and p-tau181 (Bcontrol=-0.31, Bfootball=0.17, -155% difference). In the former football players, rFSRP showed a stronger positive association and average FA showed a stronger negative association with WMH compared to unexposed men. The effect of WMH on cortical thickness was similar between the two groups (Bcontrol=-0.27, Bfootball=-0.25, 7% difference).

These results suggest that the risk factor and biological correlates of WMH differ between former American football players and asymptomatic individuals unexposed to RHI. In addition to vascular risk factors, white matter integrity on DTI showed a stronger relationship with WMH burden in the former football players. FLAIR WMH serves as a promising measure to further investigate the late multifactorial pathologies of RHI.

The International Psychogeriatric Association (IPA) published a provisional consensus definition of agitation in cognitive disorders in 2015. As proposed by the original work group, we summarize the use and validation of criteria in order to remove “provisional” from the definition.

This report summarizes information from the academic literature, research resources, clinical guidelines, expert surveys, and patient and family advocates on the experience of use of the IPA definition. The information was reviewed by a working group of topic experts to create a finalized definition.

We present a final definition which closely resembles the provisional definition with modifications to address special circumstances. We also summarize the development of tools for diagnosis and assessment of agitation and propose strategies for dissemination and integration into precision diagnosis and agitation interventions.

The IPA definition of agitation captures a common and important entity that is recognized by many stakeholders. Dissemination of the definition will permit broader detection and can advance research and best practices for care of patients with agitation.

To develop an agitation reduction and prevention algorithm is intended to guide implementation of the definition of agitation developed by the International Psychogeriatric Association (IPA)

Review of literature on treatment guidelines and recommended algorithms; algorithm development through reiterative integration of research information and expert opinion

IPA Agitation Workgroup

IPA panel of international experts on agitation

Integration of available information into a comprehensive algorithm

None

The IPA Agitation Work Group recommends the Investigate, Plan, and Act (IPA) approach to agitation reduction and prevention. A thorough investigation of the behavior is followed by planning and acting with an emphasis on shared decision-making; the success of the plan is evaluated and adjusted as needed. The process is repeated until agitation is reduced to an acceptable level and prevention of recurrence is optimized. Psychosocial interventions are part of every plan and are continued throughout the process. Pharmacologic interventions are organized into panels of choices for nocturnal/circadian agitation; mild-moderate agitation or agitation with prominent mood features; moderate-severe agitation; and severe agitation with threatened harm to the patient or others. Therapeutic alternatives are presented for each panel. The occurrence of agitation in a variety of venues—home, nursing home, emergency department, hospice—and adjustments to the therapeutic approach are presented.

The IPA definition of agitation is operationalized into an agitation management algorithm that emphasizes the integration of psychosocial and pharmacologic interventions, reiterative assessment of response to treatment, adjustment of therapeutic approaches to reflect the clinical situation, and shared decision-making.

Clinically significant weight gain (CSWG) is associated with increased morbidity and mortality. This study describes CSWG and comorbidities observed in patients with bipolar I disorder (BD-I) and schizophrenia (SZ) after initiating select second-generation antipsychotics (SGAs).

Percent change in weight, CSWG (=7% weight increase), and incident comorbidities within 12 months of treatment were assessed among patients initiating oral SGAs of moderate-to-high weight gain risk using medical records/claims (OM1 Real-World Data Cloud; January 2013-February 2020). Oral SGAs included clozapine (SZ), iloperidone (SZ), paliperidone (SZ), olanzapine, olanzapine/fluoxetine (BD-I), quetiapine, and risperidone. Outcomes were stratified by baseline body mass index and reported descriptively.

Among patients with BD-I (N = 9142) and SZ (N = 8174), approximately three-quarters were overweight/obese at baseline. During treatment (mean duration = 30 weeks), average percent weight increase was 3.7% (BD-I) and 3.3% (SZ). Average percent weight increase was highest for underweight/normal weight patients (BD-I = 5.5%; SZ = 4.8%), followed by overweight (BD-I = 3.8%; SZ = 3.4%) and obese patients (BD-I = 2.7%; SZ = 2.3%). Within 3 months of treatment, 12% of all patients experienced CSWG. A total of 11.3% (BD-I) and 14.7% (SZ) of patients developed coronary artery disease, hypertension, dyslipidemia, or type 2 diabetes within 12 months of treatment; development of comorbidities was highest among overweight/obese patients and those with CSWG.

Patients who were underweight/normal weight at baseline had the greatest percent change in weight during treatment. Increased comorbidities were observed within 12 months of treatment, specifically among overweight/obese patients and those with CSWG. The magnitude of weight gain and development of comorbidities were similar for patients with BD-I and SZ.

Alkermes, Inc.

The implementation of mandatory influenza vaccination policies among healthcare personnel (HCP) is controversial. Thus, we examined the affect of mandatory influenza vaccination policies among HCP working in outpatient settings.

Four Veterans’ Affairs (VA) health systems and three non-VA medical centers.

We analyzed rates of influenza and other viral causes of respiratory infections among HCP working in outpatient sites at 4 VA health systems without mandatory influenza vaccination policies and 3 non-VA health systems with mandatory influenza vaccination policies.

Influenza vaccination was associated with a decreased risk of influenza (odds ratio, 0.17; 95% confidence interval [CI], 0.13–0.22) but an increased risk of other respiratory viral infections (incidence rate ratio, 1.26; 95% CI, 1.02–1.57).

Our fitted regression models suggest that if influenza vaccination rates in clinics where vaccination was not mandated had equalled those where vaccine was mandated, HCP influenza infections would have been reduced by 52.1% (95% CI, 51.3%–53.0%). These observations, their possible causes, and additional strategies to reduce influenza and other viral respiratory illnesses among HCP working in ambulatory clinics warrant further investigation.