Effects of Texas State Agency Integration on Mental Health Service Use Among Individuals with Co-occurring Cognitive Disabilities and Mental Health Conditions.

This study uses Texas's 2017 integration of the state disability and mental health agencies as a case study, combining interviews with Texas agency and advocacy organization leaders to examine perceptions of agency integration and augmented synthetic control analyses of 2014-2020 Medical Expenditure Panel Survey to examine impacts on mental health service use among individuals with co-occurring cognitive disabilities (including intellectual and developmental disabilities) and mental health conditions. Interviewees described the intensive process of agency integration and identified primarily positive (e.g., decreased administrative burden) impacts of integration. Quantitative analyses indicated no effects of integration on receipt of mental health-related services among people with co-occurring conditions. While leaders identified some potentially beneficial impacts of state agency integration, the limited impact of integration beyond the agency suggests that interventions at multiple levels of the service system, including those targeting providers, are needed to better meet the mental health service needs for this population.

Racial/ethnic differences in neuropsychiatric disturbances associated with incident dementia.

INTRODUCTION: Neuropsychiatric symptoms (NPS) are nearly universal in dementia; some cross-sectional studies of NPS in dementia have found racial/ethnic differences, though it is unknown if NPS prevalence differs among racial/ethnic groups before and after dementia diagnosis. METHODS: Participants were followed annually at Alzheimer's Disease Centers and were assessed on the Neuropsychiatric Inventory-Questionnaire (NPI-Q) with at least one follow-up visit at which they were diagnosed with dementia. Descriptive statistics were generated by race/ethnicity. NPS were modeled over time as a function of race/ethnicity and with diagnosis date as the baseline. RESULTS: NPS were present in 95% in at least one time point. After adjusting for covariates, there were no statistically significant differences in NPI-Q total scores among racial/ethnic groups at the time of and after dementia diagnosis. DISCUSSION: Findings from our prospective cohort study suggest that when individuals are matched at the time of conversion to dementia, there are no racial/ethnic differences in NPS. Highlights: Neuropsychiatric symptoms of dementia are frequent and increase caregiver burden.Prior studies reported more neuropsychiatric symptoms (NPS) in Black compared to White individuals with dementia.National Alzheimer's Coordinating Center Black, White, and Hispanic participants did not differ in NPS at the time of dementia diagnosis.

Experiences of health care services among people with cognitive disabilities and mental health conditions.

BACKGROUND: People with cognitive disabilities such as intellectual and developmental disabilities face significant barriers to accessing high-quality health care services. Barriers may be exacerbated for those with co-occurring mental health conditions. OBJECTIVE: This study compares patient experiences of health care services between adults with and without cognitive disabilities and, among people with a cognitive disability, those with and without co-occurring mental health conditions. METHODS: Cross-sectional analyses were conducted using 2021 Medical Expenditure Panel Survey data, a national U.S. survey, to examine differences in Consumer Assessment of Healthcare Providers and Systems measures. RESULTS: Adults with cognitive disabilities reported lower satisfaction with health care services compared to the general population (7.62 (95% confidence interval (CI): 7.41-7.83) vs. 8.33 (95% CI: 8.29-8.38) on scale from 0 to 10). Adults with cognitive disabilities were less likely to report that providers listened carefully to them (odds ratio (OR): 0.55, 95% CI: 0.42-0.71), explained things in a way that was easy to understand (OR: 0.48, 95% CI: 0.35-0.66), showed respect for what they had to say (OR: 0.38, 95% CI: 0.29-0.51), spent enough time with them (OR: 0.52, 95% CI: 0.40-0.69), or gave advice that was easy to understand (OR: 0.40, 95% CI: 0.28-0.58) compared to the general population. Among adults with cognitive disabilities, there were no differences based on co-occurring mental health conditions. CONCLUSIONS: Adults with cognitive disabilities report lower satisfaction with health care services driven by worse experiences with the health care system. Policies to increase provider capacity to support this population should be prioritized.

Graphical methods for understanding changes in states: Understanding medication use pathways.

OBJECTIVES: As epidemiological studies become longer and larger, the field needs novel graphical methods to visualize complex longitudinal data. The aim of this study was to present the Slinkyplot, a longitudinal crosstabulation, to illustrate patterns of antidepressant use in a large prospective cohort of older adults with mild cognitive impairment. METHODS: Data from the National Alzheimer's Coordinating Center are used to track switches between different states and types of antidepressant use. A Slinkyplot is populated with rows representing the state of medication use at each timepoint and columns representing the state at each subsequent visit. RESULTS: The constructed Slinkyplots display the common practice of switching on and off different antidepressants over time, with citalopram, sertraline, and bupropion most commonly used followed by switching to another SSRI or SNRI as second-line treatment. CONCLUSIONS: Slinkyplots are an innovative graphical means of visualizing complex patterns of transitions between different states over time for large longitudinal studies.

Psychiatric Presentations and Medication Use in Older Adults With Intellectual and Developmental Disabilities.

OBJECTIVE: Adults with intellectual and developmental disabilities (IDD) are living longer, yet research about the medical and psychiatric needs of older adults still lags behind that of younger individuals with IDD. The aim of this study was to assess age-related differences in the mental health presentations of adults with IDD. METHODS: Fully deidentified data for adults 30 years and older were extracted from the START (Systemic, Therapeutic, Assessment, Resources, and Treatment) Information Reporting System, a deidentified database housed at the Center for START Services. Caregivers and START team documents reported psychiatric diagnoses, service use, recent stressors, and challenging behaviors. t Tests, Mann Whitney U tests, χ2 tests, and multinominal logistic regression models were used to compare the two age groups, 30-49 years (n = 1,188) versus 50 years and older (n = 464). RESULTS: Older adults had more medical conditions, fewer reported psychiatric conditions, and were more likely to be taking more psychiatric medications compared to younger adults, after adjusting for demographic variables, disability level, and number of recent stressors. CONCLUSION: Although older individuals reported fewer psychiatric diagnoses, they were more likely to take higher numbers of psychiatric medications and have more medical conditions. Clinicians and researchers ought to devote more attention to the healthcare needs of older adults with IDD, a vulnerable group exposed to polypharmacy and at risk of adverse events.

Aging in Autism Spectrum Disorder.

Most research on autism spectrum disorder (ASD) has focused on younger individuals, but there is increasing awareness that more must be known about the clinical needs and outcomes of older adults with ASD. This article reviews what is known about barriers to recognition in the elderly, the prevalence of ASD over the lifespan, outcomes in adulthood in comparison to the general population, co-occurring psychiatric diagnoses, and healthcare needs in this population.

Correlates of daily functioning in older adults with autism spectrum disorder.

Objectives: Studies of adults with autism spectrum disorder (ASD) have demonstrated poor outcomes related to independence and everyday living skills compared to the general population. In a sample of 74 adults with ASD who require a high level of support we sought to identify correlates of daily functioning.Methods: We administered questionnaires to residential staff and identified participants' independence level in basic and instrumental activities of daily living.Results: There was no association of age with daily functioning. Higher daily functioning was associated with a better general medical health rating. Functional independence was greater in participants with IQ range of 55 to 65 compared to those with IQ below 55. Language difficulties and behavioral disturbances were not significantly correlated with independence in daily living skills. In this sample, individual had held a median of three different types of jobs in supported employment.Conclusion: Daily functioning in adults with autism generally does not decline with age, but because this was cross-sectional data, this requires further confirmation. Community programs designed for adults with ASD who require a high level of support should focus on overall medical health and promotion of daily living skill building.

Trajectories of neuropsychiatric symptoms over time in healthy volunteers and risk of MCI and dementia.

OBJECTIVES: To identify subtypes of neuropsychiatric symptom (NPS) course among cognitively normal individuals and to assess the association between these subtypes and hazard of later mild cognitive impairment (MCI) or dementia diagnosis. METHODS: We modeled neuropsychiatric inventory questionnaire (NPI-Q) scores from 4184 volunteers over approximately 4 years using growth mixture models, generating latent classes of trajectory. We then fit Cox proportional hazard models to determine if membership in trajectory classes was associated with increased hazard of diagnosis of MCI or dementia. RESULTS: We identified four trajectory classes: the majority of the sample (65%) would be expected to belong to a class with consistently low or zero NPS. The next most prevalent class, (16%) showed a decrease over time in NPI-Q total score but, compared with the majority class had an almost threefold increase in hazard of MCI or dementia (HR: 2.92; 95% CI: 1.82-4.68). Another class (14%) showed an increase in NPS over time and was also associated with greater hazard of MCI or dementia (HR: 3.96; CI: 2.61-6.03). The smallest class (5%) had high and fluctuating NPI-Q total scores and had the greatest hazard (HR: 4.57; CI: 2.72-7.63). CONCLUSION: We have demonstrated that it is possible to identify meaningful groups of NPS trajectories and that trajectory of NPS can convey information beyond a single cross-sectional measure. While even those whose NPS improved were at increased hazard of MCI or dementia, hazard increased as a function of the severity of the NPS trajectory.

A genomics-informed computational biology platform prospectively predicts treatment responses in AML and MDS patients.

Patients with myelodysplastic syndromes (MDS) or acute myeloid leukemia (AML) are generally older and have more comorbidities. Therefore, identifying personalized treatment options for each patient early and accurately is essential. To address this, we developed a computational biology modeling (CBM) and digital drug simulation platform that relies on somatic gene mutations and gene CNVs found in malignant cells of individual patients. Drug treatment simulations based on unique patient-specific disease networks were used to generate treatment predictions. To evaluate the accuracy of the genomics-informed computational platform, we conducted a pilot prospective clinical study (NCT02435550) enrolling confirmed MDS and AML patients. Blinded to the empirically prescribed treatment regimen for each patient, genomic data from 50 evaluable patients were analyzed by CBM to predict patient-specific treatment responses. CBM accurately predicted treatment responses in 55 of 61 (90%) simulations, with 33 of 61 true positives, 22 of 61 true negatives, 3 of 61 false positives, and 3 of 61 false negatives, resulting in a sensitivity of 94%, a specificity of 88%, and an accuracy of 90%. Laboratory validation further confirmed the accuracy of CBM-predicted activated protein networks in 17 of 19 (89%) samples from 11 patients. Somatic mutations in the TET2, IDH1/2, ASXL1, and EZH2 genes were discovered to be highly informative of MDS response to hypomethylating agents. In sum, analyses of patient cancer genomics using the CBM platform can be used to predict precision treatment responses in MDS and AML patients.

Time course of neuropsychiatric symptoms and cognitive diagnosis in National Alzheimer's Coordinating Centers volunteers.

INTRODUCTION: Neuropsychiatric symptoms (NPSs) are nearly universal in cognitive disorders. The mild behavioral impairment construct postulates that NPS may be the first symptom of impending dementia. METHODS: Participants were cognitively normal volunteers followed up approximately annually at Alzheimer's Disease Centers, who were assessed on the Neuropsychiatric Inventory and had at least one follow-up visit during which they were diagnosed with mild cognitive impairment (MCI) or dementia. Descriptive statistics were used to determine sequencing of NPS presence with cognitive diagnoses. RESULTS: Data were available for 1998 participants who progressed to MCI or dementia. Over 59% developed NPS before the diagnosis of any cognitive disorder. Depression and irritability were the most common NPSs to precede cognitive diagnoses (24 and 21%, respectively). DISCUSSION: NPSs precede a cognitive diagnosis in most people who develop cognitive decline, both MCI and dementia. These individuals are an important group to focus clinical and research efforts.

Peripheral Blood Cytokine Levels After Acute Myocardial Infarction: IL-1ß- and IL-6-Related Impairment of Bone Marrow Function.

RATIONALE: Intracoronary infusion of bone marrow (BM) mononuclear cells after acute myocardial infarction (AMI) has led to limited improvement in left ventricular function. Although experimental AMI models have implicated cytokine-related impairment of progenitor cell function, this response has not been investigated in humans. OBJECTIVE: To test the hypothesis that peripheral blood (PB) cytokines predict BM endothelial progenitor cell colony outgrowth and cardiac function after AMI. METHODS AND RESULTS: BM and PB samples were collected from 87 participants 14 to 21 days after AMI and BM from healthy donors was used as a reference. Correlations between cytokine concentrations and cell phenotypes, cell functions, and post-AMI cardiac function were determined. PB interleukin-6 (IL-6) negatively correlated with endothelial colony-forming cell colony maximum in the BM of patients with AMI (estimate±SE, -0.13±0.05; P=0.007). BM from healthy individuals showed a dose-dependent decrease in endothelial colony-forming cell colony outgrowth in the presence of exogenous IL-1ß or IL-6 (P<0.05). Blocking the IL-1R or IL-6R reversed cytokine impairment. In AMI study participants, the angiogenic cytokine platelet-derived growth factor BB glycoprotein correlated positively with BM-derived colony-forming unit-endothelial colony maximum (estimate±SE, 0.01±0.002; P<0.001), multipotent mesenchymal stromal cell colony maximum (estimate±SE, 0.01±0.002; P=0.002) in BM, and mesenchymal stromal cell colony maximum in PB (estimate±SE, 0.02±0.005; P<0.001). CONCLUSIONS: Two weeks after AMI, increased PB platelet-derived growth factor BB glycoprotein was associated with increased BM function, whereas increased IL-6 was associated with BM impairment. Validation studies confirmed inflammatory cytokine impairment of BM that could be reversed by blocking IL-1R or IL-6R. Together, these studies suggest that blocking IL-1 or IL-6 receptors may improve the regenerative capacity of BM cells after AMI. CLINICAL TRIAL REGISTRATIONS: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00684060.

Aging and Autism Spectrum Disorder: A Naturalistic, Longitudinal Study of the Comorbidities and Behavioral and Neuropsychiatric Symptoms in Adults with ASD.

Little is known about Autism Spectrum Disorder (ASD) in persons over age 50. In a retrospective, naturalistic review of 74 individuals aged 30 and older meeting DSM-5 criteria for ASD, the point prevalence of behavioral and neuropsychiatric symptoms (BNPS) declined significantly for 12 of 13 BNPS over a mean of 25 years while many other features of ASD remained stable. GI disorders (68.9%) and seizure disorders (23%) were common, and 25.7% of the sample had a BMI >30. Females were more likely to engage in screaming (p < 0.05) and oppositional behavior (p < 0.05). Current age did not have a significant effect on BNPS prevalence.

Characteristics and Concerns of Caregivers of Adults With Traumatic Brain Injury.

OBJECTIVE: To describe the characteristics of caregivers of adults with traumatic brain injury (TBI) and their concerns in the first months after community discharge of the TBI survivor. DESIGN: Secondary analysis of data collected during a parallel-group randomized controlled trial. SETTING: Community. PARTICIPANTS: A total of 153 consecutively enrolled caregivers of adults with moderate to severe TBI discharged to the community following acute and/or rehabilitation care at a Level I trauma center with 71 caregivers in the treatment group identifying concerns as part of the intervention procedures. MAIN MEASURES: Caregiver demographics, caregiver-survivor relationship characteristics, caregiver activity changes, and concerns targeted by caregivers for education and problem-solving via biweekly phone calls. RESULTS: Thirty-nine percent of caregivers were spouses and 35% parents. Sixty-five percent lived in the same house as the survivor preinjury with 86% in touch daily to several times per week. Concerns targeted by more than one-third of caregivers related to managing their emotional adjustment, strategies for getting things done, managing survivor emotions and behaviors, and engaging in healthful habits. CONCLUSIONS: Caregivers of TBI survivors targeted personal concerns relating to their own emotional adjustment and participation as well as concerns relating to symptoms and recovery of the TBI survivor to address through education and problem-solving.

An injectable capillary-like microstructured alginate hydrogel improves left ventricular function after myocardial infarction in rats.

BACKGROUND: A new post-myocardial infarction (MI) therapy is injection of high-water-content polymeric biomaterial gels (hydrogels) into damaged myocardium to modulate cardiac negative remodeling and preserve heart function. METHODS: We investigated the therapeutic potential of a novel gelatinized alginate hydrogel with a unique microstructure of uniform capillary-like channels (termed Capgel). Shortly (48h) after induced anterior MI, Sprague Dawley rats received intramyocardial injection of Capgel directly into the antero-septal wall at the infarct border zone (n=12) or no injection (n=10, controls). Echocardiograms were performed at 48h (week 0) and 4weeks (week 4) to evaluate left ventricular function. RESULTS: Echocardiograms showed 27% improvement of left ventricular systolic function over time with gel injection: fractional shortening increased from 26±3% at week 0 to 33±2% at week 4 (p=0.001). Capgel was present at the injection site after 4weeks, but was minimal at 8weeks. The remaining gel was heavily populated by CD68(+) macrophages with CD206(+) clusters and blood vessels. An in vitro experiment was performed to assess Angiotensin-(1-7) released from Capgel. Angiotensin-(1-7) was released from the Capgel in a sustained manner for 90days. CONCLUSIONS: Use of Capgel, a degradable, bioactive hydrogel composed of gelatinized capillary-alginate gel, appears safe for intramyocardial injection, is associated with improved left ventricular function after MI in rats, and may provide a long-term supply of Angiotensin-(1-7).

Effectiveness of Occupation- and Activity-Based Interventions to Improve Everyday Activities and Social Participation for People With Traumatic Brain Injury: A Systematic Review.

This systematic review presents research on the effectiveness of occupation- and activity-based interventions to improve everyday activities and areas of occupation and social participation for people with traumatic brain injury (TBI). Nineteen studies identified through a comprehensive database search were reviewed and synthesized into five themes: (1) multidisciplinary and interdisciplinary treatment approaches, (2) community-based rehabilitation programs, (3) treatment approaches using client-centered goals and relevant contexts, (4) social skills training and peer mentoring interventions, and (5) community mobility interventions. Evidence supports the use of multidisciplinary and interdisciplinary approaches across a variety of settings, with no single treatment approach or setting clearly superior to another. The specific contributions of occupational therapy practitioners and the nature of occupational therapy interventions have not been well studied, making it difficult to determine the extent to which occupation- and activity-based interventions provided by occupational therapy practitioners improve occupational performance and social participation after TBI.

Ex vivo virotherapy with myxoma virus does not impair hematopoietic stem and progenitor cells.

BACKGROUND: Relapsing disease is a major challenge after hematopoietic cell transplantation for hematological malignancies. Myxoma virus (MYXV) is an oncolytic virus that can target and eliminate contaminating cancer cells from auto-transplant grafts. The aims of this study were to examine the impact of MYXV on normal hematopoietic stem and progenitor cells and define the optimal treatment conditions for ex vivo virotherapy. METHODS: Bone marrow (BM) and mobilized peripheral blood stem cells (mPBSCs) from patients with hematologic malignancies were treated with MYXV at various time, temperature and incubation media conditions. Treated BM cells from healthy normal donors were evaluated using flow cytometry for MYXV infection, long-term culture-initiating cell (LTC-IC) assay and colony-forming cell (CFC) assay. RESULTS: MYXV initiated infection in up to 45% of antigen-presenting monocytes, B cells and natural killer cells; however, these infections were uniformly aborted in >95% of all cells. Fresh graft sources showed higher levels of MYXV infection initiation than cryopreserved specimens, but in all cases less than 10% of CD34(+) cells could be infected after ex vivo MYXV treatment. MYXV did not impair LTC-IC colony numbers compared with mock treatment. CFC colony types and numbers were also not impaired by MYXV treatment. MYXV incubation time, temperature or culture media did not significantly change the percentage of infected cells, LTC-IC colony formation or CFC colony formation. CONCLUSIONS: Human hematopoietic cells are non-permissive for MYXV. Human hematopoietic stem and progenitor cells were not infected and thus unaffected by MYXV ex vivo treatment.

Chemosensitizing AML cells by targeting bone marrow endothelial cells.

Refractory disease is the greatest challenge in treating patients with acute myeloid leukemia (AML). Blood vessels may serve as sanctuary sites for AML. When AML cells were co-cultured with bone marrow endothelial cells (BMECs), a greater proportion of leukemia cells were in G0/G1. This led us to a strategy of targeting BMECs with tubulin-binding combretastatins, causing BMECs to lose their flat phenotype, degrade their cytoskeleton, cease growth, and impair migration despite unchanged BMEC viability and metabolism. Combretastatins also caused downregulation of BMEC adhesion molecules known to tether AML cells, including vascular cell adhesion molecule (VCAM)-1 and vascular endothelial (VE)-cadherin. When AML-BMEC co-cultures were treated with combretastatins, a significantly greater proportion of AML cells dislodged from BMECs and entered the G2/M cell cycle, suggesting enhanced susceptibility to cell cycle agents. Indeed, the combination of combretastatins and cytotoxic chemotherapy enhanced additive AML cell death. In vivo mice xenograft studies confirmed this finding by revealing complete AML regression after treatment with combretastatins and cytotoxic chemotherapy. Beyond highlighting the pathologic role of BMECs in the leukemia microenvironment as a protective reservoir of disease, these results support a new strategy for using vascular-targeting combretastatins in combination with cytotoxic chemotherapy to treat AML.

Identification of Bone Marrow Cell Subpopulations Associated With Improved Functional Outcomes in Patients With Chronic Left Ventricular Dysfunction: An Embedded Cohort Evaluation of the FOCUS-CCTRN Trial.

In the current study, we sought to identify bone marrow-derived mononuclear cell (BM-MNC) subpopulations associated with a combined improvement in left ventricular ejection fraction (LVEF), left ventricular end-systolic volume (LVESV), and maximal oxygen consumption (VO2 max) in patients with chronic ischemic cardiomyopathy 6 months after receiving transendocardial injections of autologous BM-MNCs or placebo. For this prospectively planned analysis, we conducted an embedded cohort study comprising 78 patients from the FOCUS-Cardiovascular Cell Therapy Research Network (CCTRN) trial. Baseline BM-MNC immunophenotypes and progenitor cell activity were determined by flow cytometry and colony-forming assays, respectively. Previously stable patients who demonstrated improvement in LVEF, LVESV, and VO2 max during the 6-month course of the FOCUS-CCTRN study (group 1, n = 17) were compared to those who showed no change or worsened in one to three of these endpoints (group 2, n = 61) and to a subset of patients from group 2 who declined in all three functional endpoints (group 2A, n = 11). Group 1 had higher frequencies of B-cell and CXCR4+ BM-MNC subpopulations at study baseline than group 2 or 2A. Furthermore, patients in group 1 had fewer endothelial colony-forming cells and monocytes/macrophages in their bone marrow than those in group 2A. To our knowledge, this is the first study to show that in patients with ischemic cardiomyopathy, certain bone marrow-derived cell subsets are associated with improvement in LVEF, LVESV, and VO2 max at 6 months. These results suggest that the presence of both progenitor and immune cell populations in the bone marrow may influence the natural history of chronic ischemic cardiomyopathy-even in stable patients. Thus, it may be important to consider the bone marrow composition and associated regenerative capacity of patients when assigning them to treatment groups and evaluating the results of cell therapy trials.

Endothelial cell derived angiocrine support of acute myeloid leukemia targeted by receptor tyrosine kinase inhibition.

In acute myeloid leukemia (AML), refractory disease is a major challenge and the leukemia microenvironment may harbor refractory disease. Human AML cell lines KG-1 and HL-60 expressed receptors also found on endothelial cells (ECs) such as VEGFRs, PDGFRs, and cKit. When human AML cells were co-cultured with human umbilical vein endothelial cells (HUVECs) and primary bone marrow endothelial cell (BMECs), the AML cells were more resistant to cytarabine chemotherapy, even in transwell co-culture suggesting angiocrine regulation. Primary BMECs secreted significantly increased levels of VEGF-A and PDGF-AB after exposure to cytarabine. Pazopanib, a receptor tyrosine kinase inhibitor (RTKI) of VEGFRs, PDGFRs, and cKit, removed EC protection of AML cells and enhanced AML cell sensitivity to cytarabine. Xenograft modeling showed significant regression of AML cells and abrogation of BM hypervascularity in RTKI treated cohorts. Together, these results show direct cytotoxicity of RTKIs on AML cells and reversal of EC protection. Combining RTKIs with chemotherapy may serve as promising therapeutic strategy for patients with AML.