Epidemiology of Homebound Population Among Beneficiaries of a Large National Medicare Advantage Plan.

BACKGROUND: Interest in home-based care is increasing among Medicare Advantage (MA) plans. The epidemiology of homebound MA beneficiaries is unknown. OBJECTIVE: To determine the prevalence, characteristics, predictors, health service use, and mortality outcomes of homebound beneficiaries of a large national MA plan. DESIGN: Cross-sectional. SETTING: National MA plan. PARTICIPANTS: Humana MA beneficiaries in 2022 (n = 2 435 519). MEASUREMENTS: Homebound status was assessed via in-home assessment using previously defined categories: homebound (never or rarely left home in the past month), semihomebound (left home with assistance, had difficulty, or needed help leaving home), and not homebound. Demographic, clinical, health service use, and mortality outcomes were compared by homebound status. RESULTS: In 2022, the overall prevalence of homebound beneficiaries was 22.0% (8.4% of beneficiaries were homebound, and 13.6% were semihomebound). In adjusted models, female sex (odds ratio [OR], 1.36 [95% CI, 1.35 to 1.37), low-income status or dual eligibility for Medicare and Medicaid (OR, 1.56 [CI, 1.55 to 1.57]), dementia (OR, 2.36 [CI, 2.33 to 2.39]), and moderate to severe frailty (OR, 4.32 [CI, 4.19 to 4.45]) were predictive of homebound status. In multivariable logistic regression, homebound status was associated with increased odds of any emergency department visit (OR, 1.14 [ CI, 1.14 to 1.15]), any inpatient hospital admission (OR, 1.44 [CI, 1.42 to 1.46]), any skilled-nursing facility admission (OR, 2.18 [CI, 2.13 to 2.23]), and death (OR, 2.55 [CI, 2.52 to 2.58]). LIMITATION: The study period overlapped the tail end of the COVID-19 pandemic, and data were derived from a single national MA plan, which limits generalizability. CONCLUSION: Overall homebound prevalence in a national MA plan was 22.0% and was independently associated with increased health service use and mortality. Study findings can inform strategic initiatives to identify and manage care for homebound beneficiaries. PRIMARY FUNDING SOURCE: Humana, under a collaborative research agreement with Johns Hopkins University.

A Comparison of Home Health Utilization, Outcomes, and Cost Between Medicare Advantage and Traditional Medicare.

BACKGROUND: Home health use is rising rapidly in the United States as the population ages, the prevalence of chronic disease increases, and older Americans express their desire to age at home. Enrollment in Medicare Advantage (MA) plans rather than Traditional Medicare (TM) has grown as well, from 13% of total Medicare enrollment in 2004 to 39% in 2020. Despite these shifts, little is known about outcomes and costs following home health in MA as compared with TM. OBJECTIVE: The objective of this study was to measure the association of MA enrollment with outcomes and costs for patients using home health. DESIGN: This was a retrospective cohort study. PARTICIPANTS: Patients enrolled in plans offered by 1 large, national MA organization and patients enrolled in TM, with at least 1 home health visit between January 1, 2017, and June 30, 2018. EXPOSURE: MA enrollment. MAIN MEASURES: We compared the intensity of home health services and types of care delivered. The main outcome measures were hospitalization, the proportion of days in the home, and total allowed costs during the 180-day period following the first qualifying home health visit during the study period. KEY RESULTS: Among patients who used home health, our models demonstrated enrollment in MA was associated with 14%, and 6% decreased odds of 60- and 180-day hospitalization, respectively, a 12.8% and 14.7% decrease in medical costs exclusive and inclusive of home health costs, respectively, and a 0.27% increase in the proportion of days at home during the 180-day follow-up, equivalent to an additional half-day at home. There were few differences in home health care delivered for MA and TM [mean number of visits in the first episode of care (17.1 vs. 17.3) and mean visits per week (3.2 vs. 3.3)]. The mean number of visits by visit type and percent of patients with each type was similar between MA and TM as well. CONCLUSIONS: Compared with enrollment in TM, enrollment in MA was associated with improved patient-centered outcomes and lower cost and utilization, despite few differences in the way home health was delivered. These findings might be explained by structural components of MA that encourage better care management, but further investigation is needed to clarify the mechanisms by which MA enrollment may lead to higher value home health care.

Long-term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Choline is critical for normative function of 3 major pathways in the brain, including acetylcholine biosynthesis, being a key mediator of epigenetic regulation, and serving as the primary substrate for the phosphatidylethanolamine N-methyltransferase pathway. Sufficient intake of dietary choline is critical for proper brain function and neurodevelopment. This is especially important for brain development during the perinatal period. Current dietary recommendations for choline intake were undertaken without critical evaluation of maternal choline levels. As such, recommended levels may be insufficient for both mother and fetus. Herein, we examined the impact of perinatal maternal choline supplementation (MCS) in a mouse model of Down syndrome and Alzheimer's disease, the Ts65Dn mouse relative to normal disomic littermates, to examine the effects on gene expression within adult offspring at ∼6 and 11 mo of age. We found MCS produces significant changes in offspring gene expression levels that supersede age-related and genotypic gene expression changes. Alterations due to MCS impact every gene ontology category queried, including GABAergic neurotransmission, the endosomal-lysosomal pathway and autophagy, and neurotrophins, highlighting the importance of proper choline intake during the perinatal period, especially when the fetus is known to have a neurodevelopmental disorder such as trisomy.-Alldred, M. J., Chao, H. M., Lee, S. H., Beilin, J., Powers, B. E., Petkova, E., Strupp, B. J., Ginsberg, S. D. Long-term effects of maternal choline supplementation on CA1 pyramidal neuron gene expression in the Ts65Dn mouse model of Down syndrome and Alzheimer's disease.

Subgroups of High-Cost Medicare Advantage Patients: an Observational Study.

BACKGROUND: There is a growing focus on improving the quality and value of health care delivery for high-cost patients. Compared to fee-for-service Medicare, less is known about the clinical composition of high-cost Medicare Advantage populations. OBJECTIVE: To describe a high-cost Medicare Advantage population and identify clinically and operationally significant subgroups of patients. DESIGN: We used a density-based clustering algorithm to group high-cost patients (top 10% of spending) according to 161 distinct demographic, clinical, and claims-based variables. We then examined rates of utilization, spending, and mortality among subgroups. PARTICIPANTS: Sixty-one thousand five hundred forty-six Medicare Advantage beneficiaries. MAIN MEASURES: Spending, utilization, and mortality. KEY RESULTS: High-cost patients (n = 6154) accounted for 55% of total spending. High-cost patients were more likely to be younger, male, and have higher rates of comorbid illnesses. We identified ten subgroups of high-cost patients: acute exacerbations of chronic disease (mixed); end-stage renal disease (ESRD); recurrent gastrointestinal bleed (GIB); orthopedic trauma (trauma); vascular disease (vascular); surgical infections and other complications (complications); cirrhosis with hepatitis C (liver); ESRD with increased medical and behavioral comorbidity (ESRD+); cancer with high-cost imaging and radiation therapy (oncology); and neurologic disorders (neurologic). The average number of inpatient days ranged from 3.25 (oncology) to 26.09 (trauma). Preventable spending (as a percentage of total spending) ranged from 0.8% (oncology) to 9.5% (complications) and the percentage of spending attributable to prescription medications ranged from 7.9% (trauma and oncology) to 77.0% (liver). The percentage of patients who were persistently high-cost ranged from 11.8% (trauma) to 100.0% (ESRD+). One-year mortality ranged from 0.0% (liver) to 25.8% (ESRD+). CONCLUSIONS: We identified clinically distinct subgroups of patients within a heterogeneous high-cost Medicare Advantage population using cluster analysis. These subgroups, defined by condition-specific profiles and illness trajectories, had markedly different patterns of utilization, spending, and mortality, holding important implications for clinical strategy.

Applying Machine Learning Algorithms to Segment High-Cost Patient Populations.

BACKGROUND: Efforts to improve the value of care for high-cost patients may benefit from care management strategies targeted at clinically distinct subgroups of patients. OBJECTIVE: To evaluate the performance of three different machine learning algorithms for identifying subgroups of high-cost patients. DESIGN: We applied three different clustering algorithms-connectivity-based clustering using agglomerative hierarchical clustering, centroid-based clustering with the k-medoids algorithm, and density-based clustering with the OPTICS algorithm-to a clinical and administrative dataset. We then examined the extent to which each algorithm identified subgroups of patients that were (1) clinically distinct and (2) associated with meaningful differences in relevant utilization metrics. PARTICIPANTS: Patients enrolled in a national Medicare Advantage plan, categorized in the top decile of spending (n = 6154). MAIN MEASURES: Post hoc discriminative models comparing the importance of variables for distinguishing observations in one cluster from the rest. Variance in utilization and spending measures. KEY RESULTS: Connectivity-based, centroid-based, and density-based clustering identified eight, five, and ten subgroups of high-cost patients, respectively. Post hoc discriminative models indicated that density-based clustering subgroups were the most clinically distinct. The variance of utilization and spending measures was the greatest among the subgroups identified through density-based clustering. CONCLUSIONS: Machine learning algorithms can be used to segment a high-cost patient population into subgroups of patients that are clinically distinct and associated with meaningful differences in utilization and spending measures. For these purposes, density-based clustering with the OPTICS algorithm outperformed connectivity-based and centroid-based clustering algorithms.

Prioritizing Primary Care Patients for a Communication Intervention Using the "Surprise Question": a Prospective Cohort Study.

BACKGROUND: Communication about priorities and goals improves the value of care for patients with serious illnesses. Resource constraints necessitate targeting interventions to patients who need them most. OBJECTIVE: To evaluate the effectiveness of a clinician screening tool to identify patients for a communication intervention. DESIGN: Prospective cohort study. SETTING: Primary care clinics in Boston, MA. PARTICIPANTS: Primary care physicians (PCPs) and nurse care coordinators (RNCCs) identified patients at high risk of dying by answering the Surprise Question (SQ): "Would you be surprised if this patient died in the next 2 years?" MEASUREMENTS: Performance of the SQ for predicting mortality, measured by the area under receiver operating curve (AUC), sensitivity, specificity, and likelihood ratios. RESULTS: Sensitivity of PCP response to the SQ at 2 years was 79.4% and specificity 68.6%; for RNCCs, sensitivity was 52.6% and specificity 80.6%. In univariate regression, the odds of 2-year mortality for patients identified as high risk by PCPs were 8.4 times higher than those predicted to be at low risk (95% CI 5.7-12.4, AUC 0.74) and 4.6 for RNCCs (3.4-6.2, AUC 0.67). In multivariate analysis, both PCP and RNCC prediction of high risk of death remained associated with the odds of 2-year mortality. LIMITATIONS: This study was conducted in the context of a high-risk care management program, including an initial screening process and training, both of which affect the generalizability of the results. CONCLUSION: When used in combination with a high-risk algorithm, the 2-year version of the SQ captured the majority of patients who died, demonstrating better than expected performance as a screening tool for a serious illness communication intervention in a heterogeneous primary care population.

Three members of a peptide family are differentially distributed and elicit differential state-dependent responses in a pattern generator-effector system.

C-type allatostatins (AST-Cs) are pleiotropic neuropeptides that are broadly conserved within arthropods; the presence of three AST-C isoforms, encoded by paralog genes, is common. However, these peptides are hypothesized to act through a single receptor, thereby exerting similar bioactivities within each species. We investigated this hypothesis in the American lobster, Homarus americanus, mapping the distributions of AST-C isoforms within relevant regions of the nervous system and digestive tract, and comparing their modulatory influences on the cardiac neuromuscular system. Immunohistochemistry showed that in the pericardial organ, a neuroendocrine release site, AST-C I and/or III and AST-C II are contained within distinct populations of release terminals. Moreover, AST-C I/III-like immunoreactivity was seen in midgut epithelial endocrine cells and the cardiac ganglion (CG), whereas AST-C II-like immunoreactivity was not seen in these tissues. These data suggest that AST-C I and/or III can modulate the CG both locally and hormonally; AST-C II likely acts on the CG solely as a hormonal modulator. Physiological studies demonstrated that all three AST-C isoforms can exert differential effects, including both increases and decreases, on contraction amplitude and frequency when perfused through the heart. However, in contrast to many state-dependent modulatory changes, the changes in contraction amplitude and frequency elicited by the AST-Cs were not functions of the baseline parameters. The responses to AST-C I and III, neither of which is COOH-terminally amidated, are more similar to one another than they are to the responses elicited by AST-C II, which is COOH-terminally amidated. These results suggest that the three AST-C isoforms are differentially distributed in the lobster nervous system/midgut and can elicit distinct behaviors from the cardiac neuromuscular system, with particular structural features, e.g., COOH-terminal amidation, likely important in determining the effects of the peptides. NEW & NOTEWORTHY Multiple isoforms of many peptides exert similar effects on neural circuits. In this study we show that each of the three isoforms of C-type allatostatin (AST-C) can exert differential effects, including both increases and decreases in contraction amplitude and frequency, on the lobster cardiac neuromuscular system. The distribution of effects elicited by the nonamidated isoforms AST-C I and III are more similar to one another than to the effects of the amidated AST-C II.

CA1 pyramidal neuron gene expression mosaics in the Ts65Dn murine model of Down syndrome and Alzheimer's disease following maternal choline supplementation.

Although there are changes in gene expression and alterations in neuronal density and afferent inputs in the forebrain of trisomic mouse models of Down syndrome (DS) and Alzheimer's disease (AD), there is a lack of systematic assessments of gene expression and encoded proteins within individual vulnerable cell populations, precluding translational investigations at the molecular and cellular level. Further, no effective treatment exists to combat intellectual disability and basal forebrain cholinergic neurodegeneration seen in DS. To further our understanding of gene expression changes before and following cholinergic degeneration in a well-established mouse model of DS/AD, the Ts65Dn mouse, we assessed RNA expression levels from CA1 pyramidal neurons at two adult ages (∼6 months of age and ∼11 months of age) in both Ts65Dn and their normal disomic (2N) littermates. We further examined a therapeutic intervention, maternal choline supplementation (MCS), which has been previously shown to lessen dysfunction in spatial cognition and attention, and have protective effects on the survival of basal forebrain cholinergic neurons in the Ts65Dn mouse model. Results indicate that MCS normalized expression of several genes in key gene ontology categories, including synaptic plasticity, calcium signaling, and AD-associated neurodegeneration related to amyloid-beta peptide (Aß) clearance. Specifically, normalized expression levels were found for endothelin converting enzyme-2 (Ece2), insulin degrading enzyme (Ide), Dyrk1a, and calcium/calmodulin-dependent protein kinase II (Camk2a), among other relevant genes. Single population expression profiling of vulnerable CA1 pyramidal neurons indicates that MCS is a viable therapeutic for long-term reprogramming of key transcripts involved in neuronal signaling that are dysregulated in the trisomic mouse brain which have translational potential for DS and AD.

Maternal choline supplementation programs greater activity of the phosphatidylethanolamine N-methyltransferase (PEMT) pathway in adult Ts65Dn trisomic mice.

Maternal choline supplementation (MCS) induces lifelong cognitive benefits in the Ts65Dn mouse, a trisomic mouse model of Down syndrome and Alzheimer's disease. To gain insight into the mechanisms underlying these beneficial effects, we conducted a study to test the hypothesis that MCS alters choline metabolism in adult Ts65Dn offspring. Deuterium-labeled methyl-d9-choline was administered to adult Ts65Dn and disomic (2N) female littermates born to choline-unsupplemented or choline-supplemented Ts65Dn dams. Enrichment of d9-choline metabolites (derived from intact choline) and d3 + d6-choline metabolites [produced when choline-derived methyl groups are used by phosphatidylethanolamine N-methyltransferase (PEMT)] was measured in harvested tissues. Adult offspring (both Ts65Dn and 2N) of choline-supplemented (vs. choline-unsupplemented) dams exhibited 60% greater (P≤0.007) activity of hepatic PEMT, which functions in de novo choline synthesis and produces phosphatidylcholine (PC) enriched in docosahexaenoic acid. Higher (P<0.001) enrichment of PEMT-derived d3 and d6 metabolites was detected in liver, plasma, and brain in both genotypes but to a greater extent in the Ts65Dn adult offspring. MCS also yielded higher (P<0.05) d9 metabolite enrichments in liver, plasma, and brain. These data demonstrate that MCS exerts lasting effects on offspring choline metabolism, including up-regulation of the hepatic PEMT pathway and enhanced provision of choline and PEMT-PC to the brain.

Maternal choline supplementation improves spatial mapping and increases basal forebrain cholinergic neuron number and size in aged Ts65Dn mice.

Down syndrome (DS) is marked by intellectual disability (ID) and early-onset of Alzheimer's disease (AD) neuropathology, including basal forebrain cholinergic neuron (BFCN) degeneration. The present study tested the hypothesis that maternal choline supplementation (MCS) improves spatial mapping and protects against BFCN degeneration in the Ts65Dn mouse model of DS and AD. During pregnancy and lactation, dams were assigned to either a choline sufficient (1.1g/kg choline chloride) or choline supplemented (5.0g/kg choline chloride) diet. Between 13 and 17months of age, offspring were tested in the radial arm water maze (RAWM) to examine spatial mapping followed by unbiased quantitative morphometry of BFCNs. Spatial mapping was significantly impaired in unsupplemented Ts65Dn mice relative to normal disomic (2N) littermates. Additionally, a significantly lower number and density of medial septum (MS) hippocampal projection BFCNs was also found in unsupplemented Ts65Dn mice. Notably, MCS significantly improved spatial mapping and increased number, density, and size of MS BFCNs in Ts65Dn offspring. Moreover, the density and number of MS BFCNs correlated significantly with spatial memory proficiency, providing support for a functional relationship between these behavioral and morphometric effects of MCS for trisomic offspring. Thus, increasing maternal choline intake during pregnancy may represent a safe and effective treatment approach for expectant mothers carrying a DS fetus, as well as a possible means of BFCN neuroprotection during aging for the population at large.

Reduced Cost Sharing and Medication Management Services for COPD: A Randomized Clinical Trial.

Importance: High out-of-pocket costs and improper use of maintenance inhalers contribute to poor outcomes among patients with chronic obstructive pulmonary disease (COPD). There is limited evidence for how addressing these barriers could improve adherence and affect COPD exacerbations, spending, or racial disparities in these outcomes. Objective: To examine the effect of a national program to reduce beneficiary cost sharing for COPD maintenance inhalers and provide medication management services that included education on proper technique for inhaler use. Design, Setting, and Participants: This randomized clinical trial included individuals with COPD. All individuals were enrolled in Medicare Advantage. Data were collected from January 2019 to December 2021, and data were analyzed from January 2023 to May 2024. Intervention: Invitation to enroll in a program that reduced cost sharing for maintenance inhalers to $0 or $10 and provided medication management services. The random assignment of the invitation was used to estimate the effects of the invitation and program enrollment, overall and by race. Main Outcomes and Measures: Inhaler adherence measured as proportion of days covered (PDC), moderate-to-severe exacerbations, short-acting inhaler fills, total spending, and as an exploratory outcome, out-of-pocket spending. Results: Of 19 113 included patients, 55.2% were female; 9.5% were Black, 81.1% were White, and 9.4% were another or unknown race; and the median (IQR) age was 74 (69-80) years. Program enrollment was higher in the invited group (29.4%) than the control group (5.1%). The PDC for maintenance inhalers was higher in the invited group than the control group (32.0% vs 28.4%; adjusted invitation effect, 3.8 percentage points; 95% CI, 3.1-4.5); the adjusted effect of the program (the local average treatment effect) was 15.5 percentage points (95% CI, 12.8-18.1), a 55% relative increase in adherence. Mean (SD) out-of-pocket spending for prescriptions was lower in the invited group ($619.5 [$863.1]) than the control group ($675.0 [$887.3]; adjusted invitation effect, -$49.5; 95% CI, -68.9 to -30.0; adjusted program effect, -$203.0; 95% CI, -282.8 to -123.2), but there was no statistically significant difference in exacerbations, short-acting inhaler fills, or total spending. Among Black individuals, the adjusted invitation effect on maintenance inhaler PDC was 5.5 percentage points (95% CI, 3.3-7.7), and the adjusted program effect was 19.5 percentage points (95% CI, 12.4-26.7). Among White individuals, the adjusted invitation effect was 3.7 percentage points (95% CI, 2.9-4.4), and the adjusted program effect was 15.1 percentage points (95% CI, 12.1-18.1). The difference between the invitation effects by race was not statistically significant (1.8 percentage points; 95% CI, -0.5 to 4.1; P = .13). Conclusions and Relevance: Individuals in Medicare Advantage who received an invitation to enroll in a program that reduced cost sharing for maintenance inhalers and provided medication management services had higher inhaler adherence compared with the control group. The difference in the program's effect on inhaler adherence between Black and White individuals was substantial but not statistically significant. Trial Registration: ClinicalTrials.gov Identifier: NCT05497999.

Senior-Focused Primary Care Organizations Increase Access For Medicare Advantage Members, Especially Underserved Groups.

Population-based payment in Medicare Advantage (MA) can foster innovation in care delivery by giving risk-bearing providers flexibility and strong incentives to enhance care and engage patients. This may particularly benefit historically underserved groups for whom payments often exceed costs. In this study, using data from Humana MA plans, we examined "senior-focused" primary care organizations that are supported predominantly by population-based payments in contracts with MA plans. We explored whether such organizations supported by such payment are associated with better care and improved equity compared with other primary care organizations receiving other forms of payment in MA. Analyses of data from 462,872 MA beneficiaries in 2021 showed that senior-focused primary care organizations served more Black and dually eligible beneficiaries than other primary care organizations serving MA beneficiaries, and regression-adjusted analysis showed that senior-focused primary care patients received 17 percent more primary care visits. Differences were largest among Black and dual-eligible beneficiaries. These findings suggest that risk-bearing organizations in MA are responding to current payment dynamics and providing enhanced care and access to patients, particularly historically underserved populations.

HEXIM1 is correlated with Alzheimer's disease pathology and regulates immediate early gene dynamics in neurons.

Impaired memory formation and recall is a distinguishing feature of Alzheimer's disease, and memory requires de novo gene transcription in neurons. Rapid and robust transcription of many genes is facilitated by the formation of a poised basal state, in which RNA polymerase II (RNAP2) has initiated transcription, but is paused just downstream of the gene promoter. Neuronal depolarization releases the paused RNAP2 to complete the synthesis of messenger RNA (mRNA) transcripts. Paused RNAP2 release is controlled by positive transcription elongation factor b (P-TEFb), which is sequestered into a larger inactive complex containing Hexamethylene bisacetamide inducible protein 1 (HEXIM1) under basal conditions. In this work, we find that neuronal expression of HEXIM1 mRNA is highly correlated with human Alzheimer's disease pathologies. Furthermore, P-TEFb regulation by HEXIM1 has a significant impact on the rapid induction of neuronal gene transcription, particularly in response to repeated depolarization. These data indicate that HEXIM1/P-TEFb has an important role in inducible gene transcription in neurons, and for setting and resetting the poised state that allows for the robust activation of genes necessary for synaptic plasticity.

Maternal choline supplementation improves spatial learning and adult hippocampal neurogenesis in the Ts65Dn mouse model of Down syndrome.

In addition to intellectual disability, individuals with Down syndrome (DS) exhibit dementia by the third or fourth decade of life, due to the early onset of neuropathological changes typical of Alzheimer's disease (AD). Deficient ontogenetic neurogenesis contributes to the brain hypoplasia and hypocellularity evident in fetuses and children with DS. A murine model of DS and AD (the Ts65Dn mouse) exhibits key features of these disorders, notably deficient ontogenetic neurogenesis, degeneration of basal forebrain cholinergic neurons (BFCNs), and cognitive deficits. Adult hippocampal (HP) neurogenesis is also deficient in Ts65Dn mice and may contribute to the observed cognitive dysfunction. Herein, we demonstrate that supplementing the maternal diet with additional choline (approximately 4.5 times the amount in normal rodent chow) dramatically improved the performance of the adult trisomic offspring in a radial arm water maze task. Ts65Dn offspring of choline-supplemented dams performed significantly better than unsupplemented Ts65Dn mice. Furthermore, adult hippocampal neurogenesis was partially normalized in the maternal choline supplemented (MCS) trisomic offspring relative to their unsupplemented counterparts. A significant correlation was observed between adult hippocampal neurogenesis and performance in the water maze, suggesting that the increased neurogenesis seen in the supplemented trisomic mice contributed functionally to their improved spatial cognition. These findings suggest that supplementing the maternal diet with additional choline has significant translational potential for DS.