Association of the Comprehensive End-Stage Renal Disease Care Model With Medicare Payments and Quality of Care for Beneficiaries With End-Stage Renal Disease.

Importance: Medicare beneficiaries with end-stage renal disease (ESRD) are a medically complex group accounting for less than 1% of the Medicare population but more than 7% of Medicare fee-for-service payments. Objective: To evaluate the association of the Comprehensive End-Stage Renal Disease Care (CEC) model with Medicare payments, health care use, and quality of care. Design, Setting, and Participants: In this economic evaluation, a difference-in-differences design estimated the change in outcomes for 73 094 Medicare fee-for-service beneficiaries aligned to CEC dialysis facilities between the baseline (from January 2014 to March 2015) and intervention periods (from October 2015 to December 2017) relative to 60 464 beneficiaries at matched dialysis facilities. In the CEC model, dialysis facilities, nephrologists, and other providers partner to form ESRD Seamless Care Organizations (ESCOs), specialty-oriented accountable care organizations that coordinate care for beneficiaries with ESRD. ESCOs with expenditures below a benchmark set by the Centers for Medicare & Medicaid Services are eligible to share in savings if they meet quality thresholds. A total of 685 dialysis facilities affiliated with 37 ESCOs participated in the CEC model as of January 2017. Thirteen ESCOs joined the CEC model on October 1, 2015 (wave 1), and 24 ESCOs joined on January 1, 2017 (wave 2). Patients with ESRD who were aligned with CEC dialysis facilities were compared with patients at matched dialysis facilities. Main Outcomes and Measures: Medicare total and service-specific payments per beneficiary per month; hospitalizations, readmissions, and emergency department visits; and select quality measures. Results: Relative to the comparison group (n = 60 464; 55% men; mean [SD] age, 63.5 [14.4] years), total Medicare payments for CEC beneficiaries (n = 73 094; 56% men; mean [SD] age, 63.0 [14.4] years) decreased by $114 in payments per beneficiary per month (95% CI, -$202 to -$26; P = .01), associated primarily with decreases in payments for hospitalizations and readmissions. Payment reductions were offset by shared savings payments to ESCOs, resulting in net losses of $78 in payments per beneficiary per month (95% CI, -$8 to $164; P = .07). Relative to the comparison group, CEC beneficiaries had 5.01 fewer hospitalizations per 1000 beneficiaries per month (95% CI, -8.45 to -1.56; P = .004), as well as fewer catheter placements (CEC beneficiaries with catheter as vascular access for periods longer than 90 days decreased by 0.78 percentage points [95% CI, -1.36 to -0.19; P = .01]) and fewer hospitalizations for ESRD complications (CEC beneficiaries were 0.11 percentage points less likely [95% CI, -0.20 to -0.02; P = .01] to be hospitalized in a given month). Total dialysis sessions and payments increased, suggesting improved adherence to dialysis treatments. Conclusions and Relevance: Early findings from the CEC model demonstrate that a specialty accountable care organization model focused on a particular population was associated with reduced payments and improved quality of care. Future research can assess the longer-term outcomes of the CEC model and its applicability to populations with other complex chronic conditions.

Novel Mechanism for Nicotinamide Phosphoribosyltransferase Inhibition of TNF-α-mediated Apoptosis in Human Lung Endothelial Cells.

Nicotinamide phosphoribosyltransferase (NAMPT) exists as both intracellular NAMPT and extracellular NAMPT (eNAMPT) proteins. eNAMPT is secreted into the blood and functions as a cytokine/enzyme (cytozyme) that activates NF-κB signaling via ligation of Toll-like receptor 4 (TLR4), further serving as a biomarker for inflammatory lung disorders such as acute respiratory distress syndrome. In contrast, intracellular NAMPT is involved in nicotinamide mononucleotide synthesis and has been implicated in the regulation of cellular apoptosis, although the exact mechanisms for this regulation are poorly understood. We examined the role of NAMPT in TNF-α-induced human lung endothelial cell (EC) apoptosis and demonstrated that reduced NAMPT expression (siRNA) increases EC susceptibility to TNF-α-induced apoptosis as reflected by PARP-1 cleavage and caspase-3 activation. In contrast, overexpression of NAMPT served to reduce degrees of TNF-α-induced EC apoptosis. Inhibition of nicotinamide mononucleotide synthesis by FK866 (a selective NAMPT enzymatic inhibitor) failed to alter TNF-α-induced human lung EC apoptosis, suggesting that NAMPT-dependent NAD+ generation is unlikely to be involved in regulation of TNF-α-induced EC apoptosis. We next confirmed that TNF-α-induced EC apoptosis is attributable to NAMPT secretion into the EC culture media and subsequent eNAMPT ligation of TLR4 on the EC membrane surface. Silencing of NAMPT expression, direct neutralization of secreted eNAMPT by an NAMPT-specific polyclonal antibody (preventing TLR4 ligation), or direct TLR4 antagonism all served to significantly increase EC susceptibility to TNF-α-induced EC apoptosis. Together, these studies provide novel insights into NAMPT contributions to lung inflammatory events and to novel mechanisms of EC apoptosis regulation.

Case report: Pseudotumor associated with corrosion of a femoral component with a modular neck and a ceramic-on-polyethylene bearing.

Pseudotumor is a rare complication that can occur following hip arthroplasty. This complication may present with pain, swelling, and decreased function and may lead to bone and soft-tissue destruction. We report a case of pseudotumor formation resulting from corrosion of a modular neck in a hip replacement with a ceramic-on-polyethylene bearing. The patient underwent successful revision surgery using an extended trochanteric osteotomy, removal of the entire stem, and implantation of a new femoral stem and ceramic-polyethylene bearing without a modular neck.

Nicotinamide phosphoribosyltransferase inhibitor is a novel therapeutic candidate in murine models of inflammatory lung injury.

We previously identified the intracellular nicotinamide phosphoribosyltransferase (iNAMPT, aka pre-B-cell colony enhancing factor) as a candidate gene promoting acute respiratory distress syndrome (ARDS) and ventilator-induced lung injury (VILI) with circulating nicotinamide phosphoribosyltransferase potently inducing NF-κB signaling in lung endothelium. iNAMPT also synthesizes intracellular nicotinamide adenine dinucleotide (iNAD) in response to extracellular oxidative stress, contributing to the inhibition of apoptosis via ill-defined mechanisms. We now further define the role of iNAMPT activity in the pathogenesis of ARDS/VILI using the selective iNAMPT inhibitor FK-866. C57/B6 mice were exposed to VILI (40 ml/kg, 4 h) or LPS (1.5 mg/kg, 18 h) after osmotic pump delivery of FK-866 (100 mg/kg/d, intraperitoneally). Assessment of total bronchoalveolar lavage (BAL) protein, polymorphonuclear neutrophil (PMN) levels, cytokine levels (TNF-α, IL-6, IL-1α), lung iNAD levels, and injury scores revealed that FK-866-mediated iNAMPT inhibition successfully reduced lung tissue iNAD levels, BAL injury indices, inflammatory cell infiltration, and lung injury scores in LPS- and VILI-exposed mice. FK-866 further increased lung PMN apoptosis, as reflected by caspase-3 activation in BAL PMNs. These findings support iNAMPT inhibition via FK-866 as a novel therapeutic agent for ARDS via enhanced apoptosis in inflammatory PMNs.