Beneficiary Experience of Care by Level of Integration in Dual Eligible Special Needs Plans.

Importance: Dual Eligible Special Needs Plans (D-SNPs) are private managed care plans designed to promote Medicare and Medicaid integration for full-benefit, dually eligible beneficiaries. Currently, the highest level of D-SNP integration occurs in plans with exclusively aligned enrollment (EAE). Objective: To compare patient experience of care, out-of-pocket spending, and satisfaction among dually enrolled Medicaid beneficiaries in D-SNPs with EAE, those in D-SNPs without EAE, and those with traditional Medicare. Design, Setting, and Participants: This cross-sectional study included respondents to a mail survey fielded to a stratified random sample of full-benefit, community-dwelling, dual-eligible Medicaid beneficiaries who qualified for receipt of home and community-based services in the Virginia Medicaid Commonwealth Coordinated Care Plus program between March and October 2022. Exposure: Enrollment in a D-SNP with EAE or a D-SNP without EAE vs traditional Medicare. Main Outcomes and Measures: The main outcomes were self-reported measures of access and delays in receiving plan approvals, out-of-pocket spending, and satisfaction with health plans' customer service and choice of primary care and specialist physicians. Results: Of 7200 surveys sent, 2226 were completed (response rate, 30.9%). The analytic sample consisted of 1913 Medicaid beneficiaries with nonmissing data on covariates (mean [SD] age, 70.8 [15.6] years; 1367 [71.5%] female). Of these, 583 (30.5%) were enrolled in D-SNPs with EAE, 757 (39.6%) in D-SNPs without EAE, and 573 (30.0%) in traditional Medicare. Compared with respondents enrolled in D-SNPs without EAE, those in D-SNPs with the highest level of integration (EAE) were 6.77 percentage points (95% CI, 8.81-12.66 percentage points) more likely to report being treated with courtesy and respect and 5.83 percentage points (95% CI, 0.21-11.46 percentage points) more likely to know who to call when they had a health problem. No statistically significant differences were found between members in either type of D-SNP and between those in D-SNPs and traditional Medicare in terms of their difficulty accessing care, delays in care, and satisfaction with care coordination and physician choice. Conclusions and Relevance: This cross-sectional study found some benefits of integrating administrative processes under Medicare and Medicaid but suggests that care coordination and access improvements under full integration require additional time and/or efforts to achieve.

Neurological injury following peripheral nerve blocks: a narrative review of estimates of risks and the influence of ultrasound guidance.

BACKGROUND: Peripheral nerve injury or post-block neurological dysfunction (PBND) are uncommon but a recognized complications of peripheral nerve blocks (PNB). A broad range of its incidence is noted in the literature and hence a critical appraisal of its occurrence is needed. OBJECTIVE: In this review, we wanted to know the pooled estimates of PBND and further, determine its pooled estimates following various PNB over time. Additionally, we also sought to estimate the incidence of PBND with or without US guidance. EVIDENCE REVIEW: A literature search was conducted in six databases. For the purposes of the review, we defined PBND as any new-onset sensorimotor disturbances in the distribution of the performed PNB either attributable to the PNB (when reported) or reported in the context of the PNB (when association with a PNB was not mentioned). Both prospective and retrospective studies which provided incidence of PBND at timepoints of interest (>48 hours to <2 weeks; >2 weeks to 6 weeks, 7 weeks to 5 months, 6 months to 1 year and >1 year durations) were included for review. Incidence data were used to provide pooled estimates (with 95% CI) of PBND at these time periods. Similar estimates were obtained to know the incidence of PBND with or without the use of US guidance. Additionally, PBND associated with individual PNB were obtained in a similar fashion with upper and lower limb PNB classified based on the anatomical location of needle insertion. FINDINGS: The overall incidence of PBND decreased with time, with the incidence being approximately 1% at <2 weeks' time (Incidence per thousand (95% CI)= 9 (8; to 11)) to approximately 3/10 000 at 1 year (Incidence per thousand (95% CI)= 0. 3 (0.1; to 0.5)). Incidence of PBND differed for individual PNB with the highest incidence noted for interscalene block. CONCLUSIONS: Our review adds information to existing literature that the neurological complications are rarer but seem to display a higher incidence for some blocks more than others. Use of US guidance may be associated with a lower incidence of PBND especially in those PNBs reporting a higher pooled estimates. Future studies need to standardize the reporting of PBND at various timepoints and its association to PNB.

A novel long intergenic non-coding RNA, Nostrill, regulates iNOS gene transcription and neurotoxicity in microglia.

BACKGROUND: Microglia are resident immunocompetent and phagocytic cells in the CNS. Pro-inflammatory microglia, stimulated by microbial signals such as bacterial lipopolysaccharide (LPS), viral RNAs, or inflammatory cytokines, are neurotoxic and associated with pathogenesis of several neurodegenerative diseases. Long non-coding RNAs (lncRNA) are emerging as important tissue-specific regulatory molecules directing cell differentiation and functional states and may help direct proinflammatory responses of microglia. Characterization of lncRNAs upregulated in proinflammatory microglia, such as NR_126553 or 2500002B13Rik, now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus) increases our understanding of molecular mechanisms in CNS innate immunity. METHODS: Microglial gene expression array analyses and qRT-PCR were used to identify a novel long intergenic non-coding RNA, Nostrill, upregulated in LPS-stimulated microglial cell lines, LPS-stimulated primary microglia, and LPS-injected mouse cortical tissue. Silencing and overexpression studies, RNA immunoprecipitation, chromatin immunoprecipitation, chromatin isolation by RNA purification assays, and qRT-PCR were used to study the function of this long non-coding RNA in microglia. In vitro assays were used to examine the effects of silencing the novel long non-coding RNA in LPS-stimulated microglia on neurotoxicity. RESULTS: We report here characterization of intergenic lncRNA, NR_126553, or 2500002B13Rik now termed Nostrill (iNOS Transcriptional Regulatory Intergenic LncRNA Locus). Nostrill is induced by LPS stimulation in BV2 cells, primary murine microglia, and in cortical tissue of LPS-injected mice. Induction of Nostrill is NF-κB dependent and silencing of Nostrill decreased inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production in BV2 and primary microglial cells. Overexpression of Nostrill increased iNOS expression and NO production. RNA immunoprecipitation assays demonstrated that Nostrill is physically associated with NF-κB subunit p65 following LPS stimulation. Silencing of Nostrill significantly reduced NF-κB p65 and RNA polymerase II recruitment to the iNOS promoter and decreased H3K4me3 activating histone modifications at iNOS gene loci. In vitro studies demonstrated that silencing of Nostrill in microglia reduced LPS-stimulated microglial neurotoxicity. CONCLUSIONS: Our data indicate a new regulatory role of the NF-κB-induced Nostrill and suggest that Nostrill acts as a co-activator of transcription of iNOS resulting in the production of nitric oxide by microglia through modulation of epigenetic chromatin remodeling. Nostrill may be a target for reducing the neurotoxicity associated with iNOS-mediated inflammatory processes in microglia during neurodegeneration.

Microglia induce neurogenic protein expression in primary cortical cells by stimulating PI3K/AKT intracellular signaling in vitro.

Emerging evidence suggests that microglia can support neurogenesis. Little is known about the mechanisms by which microglia regulate the cortical environment and stimulate cortical neurogenesis. We used an in vitro co-culture model system to investigate the hypothesis that microglia respond to soluble signals from cortical cells, particularly following mechanical injury, to alter the cortical environment and promote cortical cell proliferation, differentiation, and survival. Analyses of cortical cell proliferation, cell death, neurogenic protein expression, and intracellular signaling were performed on uninjured and injured cortical cells in co-culture with microglial cell lines. Microglia soluble cues enhanced cortical cell viability and proliferation cortical cells. Co-culture of injured cortical cells with microglia significantly reduced cell death of cortical cells. Microglial co-culture significantly increased Nestin + and α-internexin + cortical cells. Multiplex ELISA and RT-PCR showed decreased pro-inflammatory cytokine production by microglia co-cultured with injured cortical cells. Inhibition of AKT phosphorylation in cortical cells blocked microglial-enhanced cortical cell viability and expression of neurogenic markers in vitro. This in vitro model system allows for assessment of the effect of microglial-derived soluble signals on cortical cell viability, proliferation, and stages of differentiation during homeostasis or following mechanical injury. These data suggest that microglia cells can downregulate inflammatory cytokine production following activation by mechanical injury to enhance proliferation of new cells capable of neurogenesis via activation of AKT intracellular signaling. Increasing our understanding of the mechanisms that drive microglial-enhanced cortical neurogenesis during homeostasis and following injury in vitro will provide useful information for future primary cell and in vivo studies.

Evaluation for Primary Hyperparathyroidism in Patients Who Present With Nephrolithiasis.

BACKGROUND: The incidence of primary hyperparathyroidism (PHP) is likely underestimated. Nephrolithiasis may indicate PHP with indication for parathyroidectomy. We sought to determine the proportion of patients with an index diagnosis of nephrolithiasis that have serum calcium levels measured, parathyroid hormone (PTH) levels measured if hypercalcemic, and time to referral for definitive management if PHP is diagnosed. METHODS: A single-institution retrospective review was performed of adult patients presenting with nephrolithiasis between July 1, 2016 and December 31, 2018. Exclusion criteria included currently admitted patients, prior nephrolithiasis, congenital or acquired urinary tract anomalies, and patients on calciuretics. Records were assessed for serum calcium and PTH measurement, as well as referrals. Univariate statistical analysis was performed. RESULTS: Of 1782 patients with nephrolithiasis screened, 968 met inclusion criteria. Patients were 49.8% female, 88.9% white. Mean age was 53 y. Within this cohort, 620 (64.0%) patients had a calcium measured, with a mean elapsed time from presentation of 27 d (interquartile range [IQR] 0-8). Twelve patients (1.58%) with calcium measured were hypercalcemic and eight (66.7%) had PTH measured with a mean elapsed time from presentation of 183 d (IQR 72-310), all had elevated or non-suppressed PTH. Five (62.5%) were referred to surgeons with mean elapsed referral time of 270 d (IQR 95-492). CONCLUSIONS: Many with index nephrolithiasis are not assessed for hypercalcemia or hyperparathyroidism. Patients with serum calcium and PTH values indicating PHP diagnosis may have significant delay to parathyroidectomy. Targeted interventions with electronic health record alerts or automated reflex testing may improve care in this domain.