The Living Alone with Cognitive Impairment Project's Policy Advisory Group on Long-Term Services and Supports: Setting a Research Equity Agenda.

(1) Background: A United States national policy advisory group (PAG) was convened to identify barriers and facilitators to expand formal long-term services and support (LTSS) for people living alone with cognitive impairment (PLACI), with a focus on equitable access among diverse older adults. The PAG's insights will inform the research activities of the Living Alone with Cognitive Impairment Project, which is aimed at ensuring the equitable treatment of PLACI. (2) Methods: The PAG identified barriers and facilitators of providing effective and culturally relevant LTSS to PLACI via one-on-one meetings with researchers, followed by professionally facilitated discussions among themselves. (3) Results: The PAG identified three factors that were relevant to providing effective and culturally relevant LTSS to PLACI: (i) better characterization of PLACI, (ii) leveraging the diagnosis of cognitive impairment, and (iii) expanding and enhancing services. For each factor, the PAG identified barriers and facilitators, as well as directions for future research. (4) Conclusions: The barriers and facilitators the PAG identified inform an equity research agenda that will help inform policy change.

Identifying and Understanding Transfusion Reactions in the Oncology Population.

OBJECTIVES: To provide an overview of transfusion reactions, their underlying pathophysiology, clinical presentation, and recommendations for nursing management. DATA SOURCES: We researched peer-reviewed journal articles, book chapters, Internet, and lecture proceedings. CONCLUSION: Transfusion reactions are adverse reactions to blood products frequently seen in the oncology population and can significantly vary in severity and etiology. Oncology nurses are in a critical position to assist with prevention, early detection, and time-sensitive treatment of transfusion reactions. IMPLICATIONS FOR NURSING PRACTICE: The oncology nurse's comprehensive understanding of possible transfusion reactions and management recommendations is key for optimal care of the oncology patient.

Emerging Approaches for Fluorescence-Based Newborn Screening of Mucopolysaccharidoses.

Interest in newborn screening for mucopolysaccharidoses (MPS) is growing, due in part to ongoing efforts to develop new therapies for these disorders and new screening assays to identify increased risk for the individual MPSs on the basis of deficiency in the cognate enzyme. Existing tests for MPSs utilize either fluorescence or mass spectrometry detection methods to measure biomarkers of disease (e.g., enzyme function or glycosaminoglycans) using either urine or dried blood spot (DBS) samples. There are currently two approaches to fluorescence-based enzyme function assays from DBS: (1) manual reaction mixing, incubation, and termination followed by detection on a microtiter plate reader; and (2) miniaturized automation of these same assay steps using digital microfluidics technology. This article describes the origins of laboratory assays for enzyme activity measurement, the maturation and clinical application of fluorescent enzyme assays for MPS newborn screening, and considerations for future expansion of the technology.

Fluorimetric assay with a novel substrate for quantification of galactocerebrosidase activity in dried blood spot specimens.

BACKGROUND: Decreased galactocerebrosidase (GALC) enzyme activity is causative for Krabbe disease, a lysosomal storage disorder with devastating neurodegenerative consequences. Quantitative fluorimetric assays for GALC activity in isolated blood and skin cells have been described; however, no such assay has been described using dried blood spot (DBS) specimens. METHODS: GALC enzyme activity was measured quantitatively using fluorescence from a novel glycosidic substrate: carboxy derived from 6-hexadecanoylamino-4-methylumbelliferone. GALC activity was demonstrated on newborn DBS specimens, known Krabbe disease patient specimens, proficiency testing and quality control samples. RESULTS: We present data on characterization of the novel substrate and assay, including pH optimization and enzyme kinetics using a fluorimetric profile. Single and multi-day precision analyses revealed tight analytical measurements with %CV ranging from 5.2% to 14.1%. GALC enzyme activity was linear over the range of 0.31 - 12.04 µmol/l/h with a limit of detection of 0.066 µmol/l/h. Our results with this assay show a clear discrimination between GALC activities in samples from Krabbe disease patients versus presumed normal newborn samples. CONCLUSIONS: A fluorimetric assay for GALC enzyme activity measurement on dried blood spot specimens is feasible. Improvements to the assay including novel substrate design, increased substrate concentration and removal of sodium chloride maximize the specificity of the assay and minimize interference from ß-galactosidase.

Antifungal Activity of the Enterococcus faecalis Peptide EntV Requires Protease Cleavage and Disulfide Bond Formation.

Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a polymorphic fungus, are common constituents of the microbiome as well as increasingly problematic causes of infections. Interestingly, we previously showed that these two species antagonize each other's virulence and that E. faecalis inhibition of C. albicans was specifically mediated by EntV. EntV is a bacteriocin encoded by the entV (ef1097) locus that reduces C. albicans virulence and biofilm formation by inhibiting hyphal morphogenesis. In this report, we studied the posttranslational modifications necessary for EntV antifungal activity. First, we show that the E. faecalis secreted enzyme gelatinase (GelE) is responsible for cleaving EntV into its 68-amino-acid, active form and that this process does not require the serine protease SprE. Furthermore, we demonstrate that a disulfide bond that forms within EntV is necessary for antifungal activity. Abrogating this bond by chemical treatment or genetic modification rendered EntV inactive against C. albicans Moreover, we identified the likely catalyst of this disulfide bond, a previously uncharacterized thioredoxin within the E. faecalis genome called DsbA. Loss of DsbA, or disruption of its redox-active cysteines, resulted in loss of EntV antifungal activity. Finally, we show that disulfide bond formation is not a prerequisite for cleavage; EntV cleavage proceeded normally in the absence of DsbA. In conclusion, we present a model in which following secretion, EntV undergoes disulfide bond formation by DsbA and cleavage by GelE in order to generate a peptide capable of inhibiting C. albicansIMPORTANCEEnterococcus faecalis and Candida albicans are among the most important and problematic pathobionts, organisms that normally are harmless commensals but can cause dangerous infections in immunocompromised hosts. In fact, both organisms are listed by the Centers for Disease Control and Prevention as serious global public health threats stemming from the increased prevalence of antimicrobial resistance. The rise in antifungal resistance is of particular concern considering the small arsenal of currently available therapeutics. EntV is a peptide with antifungal properties, and it, or a similar compound, could be developed into a therapeutic alternative, either alone or in combination with existing agents. However, to do so requires understanding what properties of EntV are necessary for its antifungal activity. In this work, we studied the posttranslational processing of EntV and what modifications are necessary for inhibition of C. albicans in order to fill this gap in knowledge.

Phase II Study of Systemic High-dose Methotrexate and Intrathecal Liposomal Cytarabine for Treatment of Leptomeningeal Carcinomatosis From Breast Cancer.

Metastatic breast cancer frequently leads to brain metastases and, less commonly, leptomeningeal carcinomatosis (LC). Once cerebrospinal fluid involvement occurs, the prognosis is poor. There are limited treatment options available, but none offer significant survival benefit. Methotrexate, given systemically at high doses (3.5-8 gm/m2), achieves cytotoxic concentrations in the CSF and has been shown to prolong survival in patients with LC. Intrathecal liposomal cytarabine has been shown to increase time to neurologic progression in patients with breast cancer and LC. The combination of these 2 agents in LC has not been studied extensively. Here, we present the results of the phase II study with this combination showing promising efficacy and very good tolerability.

Organizational Characteristics Associated With the Predicted Sustainability of Villages.

Guided by resource dependence theory, this mixed-methods study examined organizational characteristics contributing to the perceived sustainability of Villages, a rapidly proliferating grassroots approach for promoting social participation and service access for community-dwelling older adults. Surveys conducted with leaders of 86% of Villages in the United States in 2012 found that higher predicted confidence in their Village's 10-year survival was associated with greater financial reserves, human resources, number of Village members, formal policies and procedures, and formal collaboration agreements. Respondents' explanations of their confidence ratings revealed additional themes of organizational leadership and perceived community need. Member resource inputs were not found to be as salient for Village leaders' perceptions of sustainability as was anticipated given the Village model's emphasis on consumer involvement. Despite the lack of longitudinal prospective data, study findings suggest potential limitations of consumer-driven organizational models such as Villages, including the need for a more stable resource base.

Assessing the Quality of Nursing Homes in Managed Care Organizations: Integrating LTSS for Dually Eligible Beneficiaries.

Little is known about the quality of nursing homes in managed care organizations (MCOs) networks. This study (1) described decision-making criteria for selecting nursing home networks and (2) compared selected quality indicators of network and nonnetwork nursing homes. The sample was 17 MCOs participating in a California demonstration that provided integrated long-term services and supports to dually eligible enrollees in 2017. The findings showed that the MCOs established a broad network of nursing homes, with only limited attention to using quality criteria. Network nursing homes (602) scored significantly lower on 6 selected quality measures than nonnetwork (117) nursing homes. Low registered nurse and total nurse staffing were strong predictors of network nursing homes controlling for facility characteristics. Managed care organizations should consider greater transparency about the quality of their nursing homes and use specific quality criteria to improve the quality of their networks.

Beneficiaries Respond To California's Program To Integrate Medicare, Medicaid, And Long-Term Services.

In 2014 California implemented a demonstration project called Cal MediConnect, which used managed care organizations to integrate Medicare and Medicaid, including long-term services and supports for beneficiaries dually eligible for Medicare and Medicaid. Postenrollment telephone surveys assessed how enrollees adjusted to Cal MediConnect over time. Results showed increased satisfaction with benefits, improved ratings of quality of care, fewer acute care visits, and increased personal care assistance hours over time. Enrollees also had somewhat better prescription medication access and lower unmet needs for personal care, compared to the comparison group. The lack of improvement in care coordination raises concerns about the implementation of the care coordination benefit, a key feature of the program. The Bipartisan Budget Act of 2018 contains provisions that permanently certify the use of managed care (such as Dual Eligible Special Needs Plans) to integrate Medicare and Medicaid, which makes the lessons learned from California's duals demonstration especially relevant for informing other integrated programs for seniors and people with disabilities.

Do Villages Promote Aging in Place? Results of a Longitudinal Study.

Villages are a new, grassroots, consumer-directed model that aims to promote aging in place and prevent unwanted relocations for older adults. In exchange for a yearly membership fee, Villages provide seniors with opportunities for social engagement (social events and classes), civic engagement (member-to-member volunteer opportunities), and an array of support services. In total, 222 Village members were surveyed at intake and 12-month follow-up to examine changes in their confidence aging in place, social connectedness, and health. The strongest positive results were in the domain of confidence, including significantly greater confidence aging in place, perceived social support, and less intention to relocate after 1 year in the Village. As most seniors were in good health and well connected at the time they joined the Village, there were not improvements in health or social connectedness. Authors discuss the importance of longer term, longitudinal studies to examine the effectiveness of Villages in preventing institutionalization over time.

Integration of Medicare and Medicaid for dually eligible beneficiaries: A focus group study examining beneficiaries' early experiences in California's dual financial alignment demonstration.

BACKGROUND: In 2014 California implemented a federal dual alignment demonstration used a capitated managed healthcare model called Cal MediConnect (CMC) to integrate medical care and long term services and supports (LTSS) for beneficiaries with both Medicare and Medicaid. These beneficiaries often have complex care needs, including multiple chronic conditions and disabilities. By 2016, 120,000 eligible beneficiaries were enrolled in the program. OBJECTIVES: Focus groups with enrolled beneficiaries were conducted to gather rich data about their early experiences with quality of care, access to care, and coordination of care in CMC plans and to identify recommendations for program improvement. METHODS: Evaluators conducted 14 focus groups with 104 beneficiaries enrolled in CMC plans in 6 demonstration counties. RESULTS: The passive enrollment process did not provide adequate information about certain aspects of CMC, leaving many beneficiaries unaware of new benefits such as care coordination, transportation, and managed LTSS. Most beneficiaries who were using the CMC care coordination benefit reported increased access to specialty care, medical equipment, and other LTSS. Changing providers and having trouble with authorization for specialty services, prescriptions, or medical equipment were common reasons for dissatisfaction. Many beneficiaries reported that early disruptions in care due to the transition of delivery system improved with time. CONCLUSION: Similar to other studies that examine beneficiaries' experiences with delivery system change, participants were confused about the passive enrollment process and demonstrated a lack of understanding of many aspects of Cal MediConnect. Analysis identified areas where beneficiaries noted improvement in their quality of care, access, and coordination of care, but also areas for improvement. Streamlining the authorization processes and extending continuity of care provisions would improve access to providers. Increasing beneficiaries' awareness of CMC plans' role in LTSS is key to improving their access to home- and community-based services.

Impact of the Village Model: Results of a National Survey.

Villages are a relatively new, consumer-directed model that brings together older adults in a community who have a mutual interest in aging in place. These membership organizations provide social and civic engagement opportunities, volunteer provided support services, and referral to vetted community providers to achieve their primary goals of promoting independence and preventing undesired relocations. This cross sectional survey of 1,753 active Village members from 28 Villages across the US measured members' perceived impacts in the areas of social connection, civic engagement, service access, health and well-being, and ability to age in place. Results showed that involvement in the Village was a key factor associated with greater perceived impacts. Over half of members perceive that the Village has improved their sense of connection to others and their feeling that they have someone to count on. Though younger members in better health were more likely to perceive impacts in social connections, results suggest older women, living alone with some disability may be the most likely to experience improved health, quality of life, and mobility. The implications for social work practice are discussed.

Enterococcus faecalis bacteriocin EntV inhibits hyphal morphogenesis, biofilm formation, and virulence of Candida albicans.

Enterococcus faecalis, a Gram-positive bacterium, and Candida albicans, a fungus, occupy overlapping niches as ubiquitous constituents of the gastrointestinal and oral microbiome. Both species also are among the most important and problematic, opportunistic nosocomial pathogens. Surprisingly, these two species antagonize each other's virulence in both nematode infection and in vitro biofilm models. We report here the identification of the E. faecalis bacteriocin, EntV, produced from the entV (ef1097) locus, as both necessary and sufficient for the reduction of C. albicans virulence and biofilm formation through the inhibition of hyphal formation, a critical virulence trait. A synthetic version of the mature 68-aa peptide potently blocks biofilm development on solid substrates in multiple media conditions and disrupts preformed biofilms, which are resistant to current antifungal agents. EntV68 is protective in three fungal infection models at nanomolar or lower concentrations. First, nematodes treated with the peptide at 0.1 nM are completely resistant to killing by C. albicans The peptide also protects macrophages and augments their antifungal activity. Finally, EntV68 reduces epithelial invasion, inflammation, and fungal burden in a murine model of oropharyngeal candidiasis. In all three models, the peptide greatly reduces the number of fungal cells present in the hyphal form. Despite these profound effects, EntV68 has no effect on C. albicans viability, even in the presence of significant host-mimicking stresses. These findings demonstrate that EntV has potential as an antifungal agent that targets virulence rather than viability.

Seniors' and People with Disabilities' Experiences with Mandatory Medicaid Managed Care in California: Populations to Target for Additional Support during Transitions.

With more states moving people with disabilities and complex care needs into managed care, it is important to target beneficiaries for additional anticipated support before specific needs arise. In a survey of 1,521 seniors and people with disabilities in California who moved into Medicaid managed care six-16 months previously, the majority reported neutral or positive experiences with managed care continuity, access, and quality, compared with fee-for-service. Beneficiaries most likely to have negative experiences included those with poor self-rated health, functional impairment, cognitive impairment, frequent ED visits, and claims for back / osteoarthritis and cancer. Those with no specialty visits and those who had been continuously enrolled in Medicaid longer term before the transition also were more likely to report negative experiences. These populations can be targeted for assistance by health plans and Medicaid agencies. More specialty visits and longer time in Medicaid managed care also seems to improve beneficiaries' experiences.

Primary central nervous system lymphoma treated with high-dose methotrexate and rituximab: A single-institution experience.

Rituximab (RTX) improves the outcome in patients with systemic diffuse large B-cell lymphoma (DLBCL), but its benefit in primary central nervous system lymphoma (PCNSL) is unclear. In the present study, a single-institution retrospective analysis was performed for 12 patients with newly diagnosed PCNSL treated with combined high-dose methotrexate (HD-MTX) and RTX. MTX was administered biweekly at 8 g/m2/dose until a complete response (CR) was achieved or for a maximum of eight doses. RTX was provided for a total of eight weekly doses at 375 mg/m2/dose. Following a median of 11 cycles of MTX, the radiographic overall response rate was 91% and the CR rate was 58%. A CR was achieved after a median 6 cycles of MTX. The median progression-free survival time was 22 months and the median overall survival time has not yet been attained. These results compare favorably to single-agent HD-MTX and suggest a role for immunochemotherapy in the treatment of PCNSL.

Medicaid beneficiaries in california reported less positive experiences when assigned to a managed care plan.

In 2011 California began transitioning approximately 340,000 seniors and people with disabilities from Medicaid fee-for-service (FFS) to Medicaid managed care plans. When beneficiaries did not actively choose a managed care plan, the state assigned them to one using an algorithm based on their previous FFS primary and specialty care use. When no clear link could be established, beneficiaries were assigned by default to a managed care plan based on weighted randomization. In this article we report the results of a telephone survey of 1,521 seniors and people with disabilities enrolled in Medi-Cal (California Medicaid) and who were recently transitioned to a managed care plan. We found that 48 percent chose their own plan, 11 percent were assigned to a plan by algorithm, and 41 percent were assigned to a plan by default. People in the latter two categories reported being similarly less positive about their experiences compared to beneficiaries who actively chose a plan. Many states in addition to California are implementing mandatory transitions of Medicaid-only beneficiaries to managed care plans. Our results highlight the importance of encouraging beneficiaries to actively choose their health plan; when beneficiaries do not choose, states should employ robust intelligent assignment algorithms.

An Integrated Model of Co-ordinated Community-Based Care.

PURPOSE OF THE STUDY: Co-ordinated approaches to community-based care are a central component of current and proposed efforts to help vulnerable older adults obtain needed services and supports and reduce unnecessary use of health care resources. DESIGN AND METHODS: This study examines ElderHelp Concierge Club, an integrated community-based care model that includes comprehensive personal and environmental assessment, multilevel care co-ordination, a mix of professional and volunteer service providers, and a capitated, income-adjusted fee model. Evaluation includes a retrospective study (n = 96) of service use and perceived program impact, and a prospective study (n = 21) of changes in participant physical and social well-being and health services utilization. RESULTS: Over the period of this study, participants showed greater mobility, greater ability to meet household needs, greater access to health care, reduced social isolation, reduced home hazards, fewer falls, and greater perceived ability to obtain assistance needed to age in place. IMPLICATIONS: This study provides preliminary evidence that an integrated multilevel care co-ordination approach may be an effective and efficient model for serving vulnerable community-based elders, especially low and moderate-income elders who otherwise could not afford the cost of care. The findings suggest the need for multisite controlled studies to more rigorously evaluate program impacts and the optimal mix of various program components.

The impact of the "Village" model on health, well-being, service access, and social engagement of older adults.

BACKGROUND: Villages represent an emerging consumer-driven social support model that aims to enhance the social engagement, independence, and well-being of community-dwelling seniors through a combination of social activities, volunteer opportunities, service referral, and direct assistance. This study aimed to assess the perceived impact of Village membership on factors associated with the likelihood of aging in place. Additionally, the research examines the characteristics and service use of members who benefit the most. METHOD: Perceived impacts of Village membership in the areas of social engagement, service access, health and well-being, and self-efficacy for maintaining independence were assessed through a survey of 282 active Village members from five sites in California. Bivariate and multivariate analyses examined associations between member characteristics, volunteerism, service use, and self-reported impacts. RESULTS: Villages have the strongest impact in the area of promoting social engagement and facilitating access to services. Three quarters of the participants report that the Village increases their ability to age in place. Positive impacts were associated with level of Village involvement, but less likely among members who had worse self-reported health. CONCLUSION: Villages represent a promising new model designed to support community-dwelling seniors with a number of positive impacts that may reduce social isolation, improve well-being, and increase confidence aging in place. Villages appear to have the greatest benefit for members who are most involved and fewer positive impacts for members in poor health, prompting questions about the long-term effectiveness of the Village model in helping more frail seniors to age in place.

Does the Village model help to foster age-friendly communities?

This article explores the potential role of the Village model, a social initiative that emphasizes member involvement and service access, in helping communities to become more age-friendly. A survey of 86.3% of operational Villages examined activities designed to help members access a variety of supports and services consistent with the World Health Organization's (WHO) Global Network of Age-Friendly Cities and Communities program model, as well as other potential contributions to community age friendliness. Analysis revealed that 85.5% of Villages provided assistance with at least six of the eight WHO domains, but only 10.1% implemented features of all eight; more than one-third were engaged in direct or indirect efforts to improve community physical or social infrastructures or improve community attitudes toward older persons. These findings suggest that Villages and other social organizations may have untapped potential for enhancing their members' ability to age in place consistent with the goals of age-friendly initiatives while also promoting constructive changes in the overall community.

Novel application of digital microfluidics for the detection of biotinidase deficiency in newborns.

OBJECTIVE: Newborn screening for biotinidase deficiency can be performed using a fluorometric enzyme assay on dried blood spot specimens. As a pre-requisite to the consolidation of different enzymatic assays onto a single platform, we describe here a novel analytical method for detecting biotinidase deficiency using the same digital microfluidic cartridge that has already been demonstrated to screen for five lysosomal storage diseases (Pompe, Fabry, Gaucher, Hurler and Hunter) in a multiplex format. METHODS: A novel assay to quantify biotinidase concentration in dried blood spots (DBS) was developed and optimized on the digital microfluidic platform using proficiency testing samples from the Centers for Disease Control and Prevention. The enzymatic assay uses 4-methylumbelliferyl biotin as the fluorogenic substrate. Biotinidase deficiency assays were performed on normal (n=200) and deficient (n=7) newborn DBS specimens. RESULTS: Enzymatic activity analysis of biotinidase deficiency revealed distinct separation between normal and affected DBS specimens using digital microfluidics and these results matched the expected activity. CONCLUSIONS: This study has demonstrated performance of biotinidase deficiency assays by measurement of 4-methylumbelliferyl product on a digital microfluidic platform. Due to the inherent ease in multiplexing on such a platform, consolidation of other fluorometric assays onto a single cartridge may be realized.