Medicare eligibility and healthcare access,affordability, and financial strain for low- and higher-income adults in the United States: A regression discontinuity analysis

BackgroundUS policymakers are debating whether to expand the Medicare program by lowering the age of eligibility. The goal of this study was to determine the association of Medicare eligibility and enrollment with healthcare access, affordability, and financial strain from medical bills in a contemporary population of low- and higher-income adults in the US.Methods and findingsWe used cross-sectional data from the National Health Interview Survey (2019) to examine the association of Medicare eligibility and enrollment with outcomes by income status using a local randomization-based regression discontinuity approach. After weighting to account for survey sampling, the low-income group consisted of 1,660,188 adults age 64 years and 1,488,875 adults age 66 years, with similar baseline characteristics, including distribution of sex (59.2% versus 59.7% female) and education (10.8% versus 12.5% with bachelor’s degree or higher). The higher-income group consisted of 2,110,995 adults age 64 years and 2,167,676 adults age 66 years, with similar distribution of baseline characteristics, including sex (40.0% versus 49.4% female) and education (41.0% versus 41.6%). The share of adults age 64 versus 66 years enrolled in Medicare differed within low-income (27.6% versus 87.8%, p < 0.001) and higher-income groups (8.0% versus 85.9%, p < 0.001). Medicare eligibility at 65 years was associated with a decreases in the percentage of low-income adults who delayed (14.7% to 6.2%; −8.5% [95% CI, −14.7%, −2.4%], P = 0.007) or avoided medical care (15.5% to 5.9%; −9.6% [−15.9%, −3.2%], P = 0.003) due to costs, and a larger decrease in the percentage who were worried about (66.5% to 51.1%; −15.4% [−25.4%, −5.4%], P = 0.003) or had problems (33.9% to 20.6%; −13.3% [−23.0%, −3.6%], P = 0.007) paying medical bills. In contrast, there were no significant associations between Medicare eligibility and measures of cost-related barriers to medication use. For higher-income adults, there was a large decrease in worrying about paying medical bills (40.5% to 27.5%; −13.0% [−21.4%, −4.5%], P = 0.003), a more modest decrease in avoiding medical care due to cost (3.5% to 0.6%; −2.9% [−5.3%, −0.5%], P = 0.02), and no significant association between eligibility and other measures of healthcare access and affordability. All estimates were stronger when examining the association of Medicare enrollment with outcomes for low and higher-income adults. Additional analyses that adjusted for clinical comorbidities and employment status were largely consistent with the main findings, as were analyses stratified by levels of educational attainment. Study limitations include the assumption adults age 64 and 66 would have similar outcomes if both groups were eligible for Medicare or if eligibility were withheld from both.ConclusionsMedicare eligibility and enrollment at age 65 years were associated with improvements in healthcare access, affordability, and financial strain in low-income adults and, to a lesser extent, in higher-income adults. Our findings provide evidence that lowering the age of eligibility for Medicare may improve health inequities in the US.

Rahul Aggarwal and colleagues explore the association of Medicare eligibility and enrollment with health care access, affordability, and financial strain from medical bills in low- and higher-income adults in the US.     

Bystander killing of breast cancer MCF-7 cells by MDA-MB-231 cells exposed to 5-fluorouracil is mediated via Fas

The major drawback with cancer therapy is the development of resistant cells within tumors due to their heterogeneous nature and due to inadequate drug delivery during chemotherapy. Therefore, the propagation of injury ("bystander effect" (BE)) from directly damaged cells to other cells may have great implications in cancer chemotherapy. The general advantage of the bystander cell killing phenomenon is the large therapeutic index that can be achieved. Experiments suggest that this phenomenon is detected in radiation therapy as well as in gene therapy in conjunction with chemotherapy. In the present study, we developed an original in vitro model dedicated to the exploration of bystander cytotoxicity induced during breast carcinoma chemotherapy. In brief, we investigated this perpetuation of injury on untreated bystander MCF-7 breast cancer cells which were coplated with 5-fluorouracil (5-FU)-treated MDA-MB-231 breast cancer cells. To achieve this goal, a specific in vitro coculture model which involved mixing of aggressive MDA-MB-231 breast cancer cells with enhanced green fluorescent protein (EGFP) expressing stable clone of non-metastatic MCF-7 breast cancer cells (MCF-EGFP), was used. A bystander killing effect was observed in MCF-EGFP cells cocultured with MDA-MB-231 cells pretreated with 5-FU. The striking decrease in MCF-EGFP cells, as detected by assaying for total GFP intensity, is mediated by activation of Fas/FasL system. The implication of Fas in MCF-EGFP cell death was confirmed by using antagonistic anti-FasL antibody that reverses bystander cell death by blocking FasL on MDA-MB-231 cells. In addition, inhibition of CD95/Fas receptor on the cell surface of MCF-EGFP cells by treatment with Pifithrin-alpha, a p53 specific transactivation inhibitor, partially abrogated the sensitivity of bystander MCF-EGFP cells. Our data, therefore, demonstrates that the Fas/FasL system could be considered as a new determinant for chemotherapy-induced bystander cell death in breast cancers.     

Somatostatin receptor-2 negatively regulates β-adrenergic receptor mediated Ca dependent signaling pathways in H9c2 cells

In the present study, we report that somatostatin receptor 2 (SSTR2) plays a crucial role in modulation of β₁AR and β₂AR mediated signaling pathways that are associated with increased intracellular Ca^2 + and cardiac complications. In H9c2 cells, SSTR2 colocalizes with β₁AR or β₂AR in receptor specific manner. SSTR2 selective agonist inhibits isoproterenol and formoterol stimulated cAMP formation and PKA phosphorylation in concentration dependent manner. In the presence of SSTR2 agonist, the expression of PKCα and PKCβ was comparable to the basal condition, however SSTR2 agonist inhibits isoproterenol or formoterol induced PKCα and PKCβ expression, respectively. Furthermore, the activation of SSTR2 not only inhibits calcineurin expression and its activity, but also blocks NFAT dephosphorylation and its nuclear translocation. SSTR2 selective agonist abrogates isoproterenol mediated increase in cell size and protein content (an index of hypertrophy). Taken together, the results described here provide direct evidence in support of cardiac protective role of SSTR2 via modulation of Ca^2 + associated signaling pathways attributed to cardiac hypertrophy.     

Design and evaluation of multifunctional nanocarriers for selective delivery of coenzyme Q10 to mitochondria

Impairments of mitochondrial functions have been associated with failure of cellular functions in different tissues, leading to various pathologies. We report here a mitochondria-targeted nanodelivery system for coenzyme Q10 (CoQ10) that can reach mitochondria and deliver CoQ10 in adequate quantities. Multifunctional nanocarriers based on ABC miktoarm polymers (A = poly(ethylene glycol (PEG), B = polycaprolactone (PCL), and C = triphenylphosphonium bromide (TPPBr)) were synthesized using a combination of click chemistry with ring-opening polymerization, self-assembled into nanosized micelles, and were employed for CoQ10 loading. Drug loading capacity (60 wt %), micelle size (25-60 nm), and stability were determined using a variety of techniques. The micelles had a small critical association concentration and were colloidally stable in solution for more than 3 months. The extraordinarily high CoQ10 loading capacity in the micelles is attributed to good compatibility between CoQ10 and PCL, as indicated by the low Flory-Huggins interaction parameter. Confocal microscopy studies of the fluorescently labeled polymer analog together with the mitochondria-specific vital dye label indicated that the carrier did indeed reach mitochondria. The high CoQ10 loading efficiency allowed testing of micelles within a broad concentration range and provided evidence for CoQ10 effectiveness in two different experimental paradigms: oxidative stress and inflammation. Combined results from chemical, analytical, and biological experiments suggest that the new miktoarm-based carrier provides a suitable means of CoQ10 delivery to mitochondria without loss of drug effectiveness. The versatility of the click chemistry used to prepare this new mitochondria-targeting nanocarrier offers a widely applicable, simple, and easily reproducible procedure to deliver drugs to mitochondria or other intracellular organelles.     

Withaferin a inhibits the proteasome activity in mesothelioma in vitro and in vivo

The medicinal plant Withania somnifera has been used for over centuries in Indian Ayurvedic Medicine to treat a wide spectrum of disorders. Withaferin A (WA), a bioactive compound that is isolated from this plant, has anti-inflammatory, immuno-modulatory, anti-angiogenic, and anti-cancer properties. Here we investigated malignant pleural mesothelioma (MPM) suppressive effects of WA and the molecular mechanisms involved. WA inhibited growth of the murine as well as patient-derived MPM cells in part by decreasing the chymotryptic activity of the proteasome that resulted in increased levels of ubiquitinated proteins and pro-apoptotic proteasome target proteins (p21, Bax, IκBα). WA suppression of MPM growth also involved elevated apoptosis as evidenced by activation of pro-apoptotic p38 stress activated protein kinase (SAPK) and caspase-3, elevated levels of pro-apoptotic Bax protein and cleavage of poly-(ADP-ribose)-polymerase (PARP). Our studies including gene-array based analyses further revealed that WA suppressed a number of cell growth and metastasis-promoting genes including c-myc. WA treatments also stimulated expression of the cell cycle and apoptosis regulatory protein (CARP)-1/CCAR1, a novel transducer of cell growth signaling. Knock-down of CARP-1, on the other hand, interfered with MPM growth inhibitory effects of WA. Intra-peritoneal administration of 5 mg/kg WA daily inhibited growth of murine MPM cell-derived tumors in vivo in part by inhibiting proteasome activity and stimulating apoptosis. Together our in vitro and in vivo studies suggest that WA suppresses MPM growth by targeting multiple pathways that include blockage of proteasome activity and stimulation of apoptosis, and thus holds promise as an anti-MPM agent.     

Development of novel peptide inhibitor of Lipoxygenase based on biochemical and BIAcore evidences

Lipoxygenase (LOX) are enzymes implicated in a broad range of inflammatory diseases, cancer, asthma and atherosclerosis. These diverse biological properties lead to the interesting target for the inhibition of this metabolic pathway of LOX. The drugs available in the market against LOX reported to have various side effects. To develop potent and selective therapeutic agents against LOX, it is essential to have the knowledge of its active site. Due to the lack of structural data of human LOX, researchers are using soybean LOX (sLOX) because of their availability and similarities in the active site structure. Based on the crystal structure of sLOX-3 and its complex with known inhibitors, we have designed a tripeptide, FWY which strongly inhibits sLOX-3 activity. The inhibition by peptide has been tested with purified sLOX-3 and with LOX present in blood serum of breast cancer patients in the presence of substrate linoleic acid and arachidonic acid respectively. The dissociation constant (K(D)) of the peptide with sLOX-3 as determined by Surface Plasmon Resonance (SPR) was 3.59x10(-9) M. The kinetic constant (K(i)) and IC(50), as determined biochemical methods were 7.41x10(-8) M and 0.15x10(-6) M respectively.     

Characterization of T cell responses to the RgpA-Kgp proteinase-adhesin complexes of Porphyromonas gingivalis in BALB/c mice

Porphyromonas gingivalis is a Gram-negative bacterium strongly associated with chronic periodontitis, an inflammatory oral disease. A major virulence factor common to all characterized strains of P. gingivalis is the RgpA-Kgp proteinase-adhesin complexes (RgpA-Kgp complexes). In this study, we investigated T cell proliferative and cytokine responses to the RgpA-Kgp complexes and identified T cell epitopes in BALB/c mice utilizing Pepscan methodology. T cell proliferative responses were found to be predominantly directed toward the proteinase catalytic domains. Eleven T cell epitopes were identified using RgpA-Kgp-primed lymph node T cells (IL-4 dominant) and 21 using an RgpA-Kgp-specific T cell line (IFN-gamma dominant), with 5 T cell epitopes, including the immunodominant epitope peptide 22, common to both T cell populations. Peptide 22 ((439)ANYTAHGSETAWADP(453)) from the Kgp proteinase catalytic domain induced a Th2 cytokine response in mice, and peptide 22-primed T cells had a Th2 cytokine profile when stimulated with the RgpA-Kgp complexes. Truncation and alanine scanning of peptide 22 identified the minimum epitope ((442)TAHGSETAWA(451)), and residues His(444), Glu(447), and Trp(450) as critical for T cell proliferation. With a view to vaccine development, peptide 22 was incorporated into a synthetic peptide polymer. Peptide 22 polymer induced strong T cell proliferation and crossreactivity to native RgpA-Kgp complexes. In conclusion, we have identified a major T cell epitope of P. gingivalis and established that antigenicity of the T cell epitope is retained when delivered as a peptide polymer. The strategies employed here may have potential in the development of a synthetic peptide vaccine for P. gingivalis.