Optimal Care for Kidney Health: Development of a Merit-based Incentive Payment System (MIPS) Value Pathway.

The Merit-based Incentive Payment System (MIPS) is a mandatory pay-for-performance program through the Centers for Medicare & Medicaid Services (CMS) that aims to incentivize high-quality care, promote continuous improvement, facilitate electronic exchange of information, and lower health care costs. Previous research has highlighted several limitations of the MIPS program in assessing nephrology care delivery, including administrative complexity, limited relevance to nephrology care, and inability to compare performance across nephrology practices, emphasizing the need for a more valid and meaningful quality assessment program. This article details the iterative consensus-building process used by the American Society of Nephrology Quality Committee from May 2020 to July 2022 to develop the Optimal Care for Kidney Health MIPS Value Pathway (MVP). Two rounds of ranked-choice voting among Quality Committee members were used to select among nine quality metrics, 43 improvement activities, and three cost measures considered for inclusion in the MVP. Measure selection was iteratively refined in collaboration with the CMS MVP Development Team, and new MIPS measures were submitted through CMS's Measures Under Consideration process. The Optimal Care for Kidney Health MVP was published in the 2023 Medicare Physician Fee Schedule Final Rule and includes measures related to angiotensin-converting enzyme inhibitor and angiotensin receptor blocker use, hypertension control, readmissions, acute kidney injury requiring dialysis, and advance care planning. The nephrology MVP aims to streamline measure selection in MIPS and serves as a case study of collaborative policymaking between a subspecialty professional organization and national regulatory agencies.

Kidney dysfunction requiring dialysis is a heterogeneous syndrome: we should treat it like one.

PURPOSE OF REVIEW: Advanced kidney failure requiring dialysis, commonly labeled end-stage kidney disease or chronic kidney disease stage 5D, is a heterogeneous syndrome -a key reason that may explain why: treating advanced kidney dysfunction is challenging and many clinical trials involving patients on dialysis have failed, thus far. Treatment with dialytic techniques - of which maintenance thrice-weekly hemodialysis is most commonly used - is broadly named kidney 'replacement' therapy, a term that casts the perception of a priori abandonment of intrinsic kidney function and subsumes patients into a single, homogeneous group. RECENT FINDINGS: Patients with advanced kidney failure necessitating dialytic therapy may have ongoing endogenous kidney function, and differ in their clinical manifestations and needs. Different terminology, for example, kidney dysfunction requiring dialysis (KDRD) with stages of progressive severity could better capture the range of phenotypes of patients who require kidney 'assistance' therapy. SUMMARY: Classifying patients with KDRD based on objective, quantitative levels of endogenous kidney function, as well as patient-reported symptoms and quality of life, would facilitate hemodialysis prescriptions tailored to level of kidney dysfunction, clinical needs, and personal priorities. Such classification would encourage clinicians to move toward personalized, physiological, and adaptive approach to hemodialysis therapy.

Perceptions of Home Dialysis Training and Experience Among US Nephrology Fellows.

RATIONALE & OBJECTIVE: Prior research suggests a lack of confidence among graduating US nephrology trainees in implementing both peritoneal dialysis (PD) and home hemodialysis (HHD). Gaps in fellowship training may represent an obstacle to achieving the Advancing American Kidney Health Initiative's goal of increasing the use of home dialysis. We sought to identify the strengths of and limitations in home dialysis training. DESIGN: A cross-sectional study surveying nephrology trainees regarding their confidence with home dialysis management and perceptions of home dialysis educational resources provided by their training program. SETTING & PARTICIPANTS: A paper survey was distributed to 110 nephrology trainees with at least 1 year of nephrology fellowship training who attended any 1 of 3 home dialysis conferences. ANALYTICAL APPROACH: Data were summarized as percentages. χ2, Fisher exact, and Kruskal-Wallis rank sum tests were used for statistical analysis. OUTCOME: Self-perception of readiness to manage PD and HHD patients. RESULTS: 76 of 110 (66%) attendees completed the survey. Most respondents were moderately confident regarding principles of PD. However, only 3% had initiated patients on "urgent-start PD" and 11% observed a PD catheter insertion. The level of confidence for HHD was low. Most trainees attended a home dialysis continuity clinic with mentorship from faculty. LIMITATIONS: A small number of participants and the inability to verify respondent-provided data for the number of PD and HHD patients seen and clinics attended. Potential lack of generalizability owing to inclusion of only trainees who attended a home dialysis conference. CONCLUSIONS: Nephrology trainees perceive low and moderate levels of preparedness for managing HHD and PD, respectively. Educational innovation and optimization of resources at both the institutional and national levels may improve confidence and promote public policy goals regarding home dialysis therapies.

Heat Shock Protein 27 Injection Leads to Caspase Activation in the Visual Pathway and Retinal T-Cell Response.

Heat shock protein 27 (HSP27) is one of the small molecular chaperones and is involved in many cell mechanisms. Besides the known protective and helpful functions of intracellular HSP27, very little is known about the mode of action of extracellular HSP27. In a previous study, we showed that intravitreal injection of HSP27 led to neuronal damage in the retina and optic nerve after 21 days. However, it was not clear which degenerative signaling pathways were induced by the injection. For this reason, the pathological mechanisms of intravitreal HSP27 injection after 14 days were investigated. Histological and RT-qPCR analyses revealed an increase in endogenous HSP27 in the retina and an activation of components of the intrinsic and extrinsic apoptosis pathway. In addition, an increase in nucleus factor-kappa-light-chain-enhancer of activated B cells (NFκB), as well as of microglia/macrophages and T-cells could be observed. In the optic nerve, however, only an increased apoptosis rate was detectable. Therefore, the activation of caspases and the induction of an incipient immune response seem to be the main triggers for retinal degeneration in this intravitreal HSP27 model.

Design Rationale for Stimuli-Responsive, Semi-interpenetrating Polymer Network Hydrogels-A Quantitative Approach.

Stimuli-responsive semi-interpenetrating polymer network (semi-IPN) hydrogels form an important class of polymers for their tunable properties via molecular design. They are widely investigated for a diverse range of applications including drug delivery, sensors, actuators, and osmotic agents. However, in-depth studies on some of the critical design principles affecting diffusion/leaching of linear polymer from semi-IPN hydrogels are lacking. Herein, for the first time, by preparing a series of model semi-IPN hydrogels based on thermally responsive poly (N-isopropyl acrylamide) (PNIPAM) network and linear poly(sodium acrylate) (PSA), a systematic and quantitative study concerning linear polymer chain retention and swelling/deswelling kinetics is reported. The study shows that PSA retention is significantly affected not only by PSA molecular weight and concentration, but also by polymerization temperature, which could be linked to homogeneity and internal morphology of the hydrogel. Surprisingly, there is no obvious influence of crosslinking density of PNIPAM network toward PSA retention, while faster swelling and deswelling at higher crosslinking density are observed in terms of swelling rate constant and deswelling activation energy. These findings offer new insights on the factors affecting structural and physicochemical properties of such semi-IPN hydrogels, which should in turn serve as a general guideline for materials design.

Sexually Transmitted Infections: Part I: Genital Bumps and Genital Ulcers.

Sexually transmitted infections (STIs) affect young people in a disproportionate way, with more than half of the infections occurring in 15- to 25-year-olds, although as an age group they constitute only 25% of the sexually active population. Pediatricians should be familiar with the social, behavioral, and biological factors that predispose adolescents to STIs. Preventive visits for teens and pre-teens should incorporate education and counseling about sexuality, safe sexual behavior, and STIs. Pediatricians should be able to identify, diagnose, and manage STIs presenting as genital "bumps" and genital "ulcers." Pediatricians should also offer human immunodeficiency virus testing and expedited partner treatment to all adolescents who are diagnosed as having an STI.

Sexually Transmitted Infections Part 2: Discharge Syndromes and Pelvic Inflammatory Disease.

Sexually transmitted infections (STIs) disproportionately affect young people, with more than half of the infections occurring in youth aged 15 to 25 years. (1)(2) This review, the second in a 2-part series on STIs, focuses on infections that may cause abnormal vaginal or penile discharge, including trichomonas, chlamydia, gonorrhea, and pelvic inflammatory disease (PID). Most infected persons, however, are asymptomatic. Nucleic acid amplification tests are the most sensitive and specific for the detection of chlamydia, gonorrhea, and trichomoniasis, and they can be performed on provider- or patient-collected swabs. Providers should have a low threshold for diagnosing and treating PID because untreated PID can have serious long-term complications for young women. Indications for hospitalization for PID include the presence of a tubo-ovarian abscess, severe illness with systemic symptoms, pregnancy, human immunodeficiency virus infection, and failure to respond to outpatient oral treatment (within 48-72 hours) or inability to tolerate the oral treatment.

Erythropoietin mimetic peptides and erythropoietin fusion proteins for treating anemia of chronic kidney disease.

PURPOSE OF REVIEW: First generation erythropoiesis stimulating agents (ESAs) have short duration of action which requires administration once weekly or greater. Second generation ESAs were developed which have longer duration of action and can be administered one to two times monthly. Erythropoietin (EPO) mimetic peptides (EMPs) activate the EPO receptor but have no structural analogy to EPO, offering the potential for lower cost as they are not biologic drugs. The first approved EMP, peginesatide, was withdrawn from the market within a year of its approval because of fatal anaphylactic reactions. In this review, we summarize recent progress regarding the development of newer, possibly less toxic, EMPs. We also summarize the development of EPO fusion proteins which fuse EPO with a portion of an immunoglobulin molecule or another EPO molecule, achieving a longer duration of action and less frequent dosing. RECENT FINDINGS: AGEM400(hydroxyethyl starch) and pegolsihematide are EMPs in phase II clinical trials. Three EPO fusion proteins are under development, two in phase I and one in phase II. SUMMARY: The future success of EMPs is limited by the prior experience with peginesatide and EPO fusion proteins do not offer cost savings or longer duration of action than currently available ESAs.

Infection with the Lyme disease pathogen suppresses innate immunity in mice with diet-induced obesity.

Obesity is a major global public health concern. Immune responses implicated in obesity also control certain infections. We investigated the effects of high-fat diet-induced obesity (DIO) on infection with the Lyme disease bacterium Borrelia burgdorferi in mice. DIO was associated with systemic suppression of neutrophil- and macrophage-based innate immune responses. These included bacterial uptake and cytokine production, and systemic, progressive impairment of bacterial clearance, and increased carditis severity. B. burgdorferi-infected mice fed normal diet also gained weight at the same rate as uninfected mice fed high-fat diet, toll-like receptor 4 deficiency rescued bacterial clearance defects, which greater in female than male mice, and killing of an unrelated bacterium (Escherichia coli) by bone marrow-derived macrophages from obese, B. burgdorferi-infected mice was also affected. Importantly, innate immune suppression increased with infection duration and depended on cooperative and synergistic interactions between DIO and B. burgdorferi infection. Thus, obesity and B. burgdorferi infection cooperatively and progressively suppressed innate immunity in mice.

Do current quality measures truly reflect the quality of dialysis?

The US End Stage Renal Disease (ESRD) Program, which came into existence in 1973, was initially envisioned to provide needed financial coverage for about 50 000 patients through Medicare. Over the past 45 years the evolution of the ESRD program has been quite different, and it now serves over one half million dialysis and transplant patients. The Medicare Improvements for Patients and Providers Act (MIPPA) of 2008 Section 153(c) requires the Centers for Medicare and Medicaid Services (CMS) to develop and implement quality measures for dialysis patients as part of the ESRD Quality Incentive Program (QIP) beginning in payment year (PY) 2012. The annual ESRD Prospective Payment System (PPS) rulemaking process allows CMS to create ESRD QIP rules that specify the measures, scoring methods, and payment reduction ranges applicable to the respective PY. CMS assesses each facility's performance and calculates a score for each measure, according to the method detailed for that PY. Scores for each measure are combined to create the Total Performance Score (TPS) for each facility. If a facility's TPS does not meet or exceed the performance standards established during the earlier comparison period, the facility will incur a payment reduction of up to 2% for the entire PY. The QIP program has evolved over the several years since its inception. There have been deletions and additions of various measures. CMS uses additional measures in its Dialysis Facility Compare (DFC) website which is available to the public and forms the basis of the 5-star rating system for dialysis facilities. The evidence underlying inclusion many of these measures in the QIP and DFC remains an area of debate. In this review, we discuss the evolution of these measures and their appropriateness. We recommend that some of the current QIP and DFC measures should not be used for public reporting and/or payment as unintended consequences may occur. Nonetheless, all the current QIP and DFC measures and others are suitable for internal quality review.

Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitors: A Potential New Treatment for Anemia in Patients With CKD.

Erythropoiesis-stimulating agents (ESAs) increase hemoglobin levels, reduce transfusion requirements, and have been the standard of treatment for anemia in patients with chronic kidney disease (CKD) since 1989. Many safety concerns have emerged regarding the use of ESAs, including an increased occurrence of cardiovascular events and vascular access thrombosis. Hypoxia-inducible factor (HIF) prolyl hydroxylase (PH) enzyme inhibitors are a new class of agents for the treatment of anemia in CKD. These agents work by stabilizing the HIF complex and stimulating endogenous erythropoietin production even in patients with end-stage kidney disease. HIF-PH inhibitors improve iron mobilization to the bone marrow. They are administered orally, which may be a more favorable route for patients not undergoing hemodialysis. By inducing considerably lower but more consistent blood erythropoietin levels than ESAs, HIF-PH inhibitors may be associated with fewer adverse cardiovascular effects at comparable hemoglobin levels, although this has yet to be proved in long-term clinical trials. One significant concern regarding the long-term use of these agents is their possible effect on tumor growth. There are 4 such agents undergoing phase 2 and 3 clinical trials in the United States; this report provides a focused review of HIF-PH inhibitors and their potential clinical utility in the management of anemia of CKD.

New Delhi metallo-ß-lactamase - type carbapenemases producing Escherichia coli isolates from hospitalized patients: A pilot study.

BACKGROUND & OBJECTIVES: Resistances to carbapenem group of antimicrobials among Escherichia coli due to production of carbapenemases, especially the New Delhi metallo-ß-lactamase (NDM) types, pose serious challenges in the treatment of infections in healthcare settings. This study was undertaken to detect NDM producing E. coli isolates from hospitalized patients with urinary tract infection (UTI). METHODS: A total of 30 non-repetitive isolates of E. coli from hospitalized patients with clinical suspicion of UTI were subjected to antimicrobial susceptibility testing. Screening for the production of extended-spectrum ß-lactamases (ESBL) was carried out by minimum inhibitory concentration (MIC) test strip ESBL followed by phenotypic confirmation by double-disc synergy test. Phenotypic confirmation of carbapenemase production was carried out by MIC test strip metallo-ß-lactamases. Molecular identification of the blaNDM gene was carried out by polymerase chain reaction (PCR) and sequencing of the amplified fragment. RESULTS: Seventeen of the 30 isolates were detected as ESBL producers, of which three were found to be carbapenemase producers. NDM genes were detected by PCR followed by gene sequencing in all three isolates positive for ESBL as well as carbapenemase. The amino acid sequence of the three isolates showed complete identity to the reference sequences of NDM-1, NDM-4 and NDM-8, respectively. INTERPRETATION & CONCLUSIONS: Our study showed the circulation of NDM variants among the clinical isolates of E. coli that were producers of ESBL as well as carbapenemase.

Opportunistic Pulmonary Infections in Immunocompromised Hosts.

Infections that are typically innocuous in immunocompetent persons may cause significant disease states in immunocompromised hosts. These individuals may be immunosuppressed secondary to many different causes such as drugs, malignancy, solid-organ or hematopoietic stem cell transplantation, HIV/AIDS, or anatomic reasons (asplenia). These immunocompromised hosts are at high risk for developing opportunistic infections. Here, we discuss some of these infections caused by bacteria, fungi, viruses, and parasites. Clinicians should be aware of the risk factors, common clinical presentations, diagnostic modalities, and treatment options for these potentially fatal illnesses.

Systematic Review of Per Person Violence Costs.

INTRODUCTION: Data on the long-term and comprehensive cost of violence are essential for informed decision making regarding the future benefits of resources directed toward violence prevention. This review aimed to summarize original per-person estimates of the attributable cost of interpersonal violence to support public health economic research and decision making. METHODS: In 2023, English-language peer-reviewed journal articles published in 2000-2022 with a focus on high-income countries reporting original per-person average cost of violence estimates were identified using index terms in multiple databases. Study contents, including violence type (e.g., adverse childhood experiences), timeline and payer cost perspective (e.g., hospitalization event-only healthcare payer cost), and associated per-person cost estimates, were summarized. Costs were in 2022 U.S. dollars. RESULTS: Per-person cost estimates related to adverse childhood experiences, community violence, sexual violence, intimate partner violence, homicide, firearm violence, youth violence, workplace violence, and bullying from 73 studies (majority focusing on the U.S.) were summarized. For example, among 23 studies with a focus on adverse childhood experiences, monetary estimates ranged from $390 for adverse childhood experience-related annual healthcare out-of-pocket costs per U.S. adult with ≥3 adverse childhood experiences to $20.2 million for the lifetime societal economic burden of a U.S. child maltreatment fatality. CONCLUSIONS: This review provides a descriptive summary of available per-person cost of violence estimates. Results can help public health professionals to describe the economic burden of violence, identify the best available estimate for a particular public health question, and address data gaps. Ultimately, understanding the long-term and comprehensive cost of violence is necessary to anticipate the economic benefits of prevention.

Temperature-dependent electron mobility in InAs nanowires.

Effective electron mobilities are obtained by transport measurements on InAs nanowire field-effect transistors at temperatures ranging from 10 to 200 K. The mobility increases with temperatures below ∼30-50 K, and then decreases with temperatures above 50 K, consistent with other reports. The magnitude and temperature dependence of the observed mobility can be explained by Coulomb scattering from ionized surface states at typical densities. The behaviour above 50 K is ascribed to the thermally activated increase in the number of scatterers, although nanoscale confinement also plays a role as higher radial subbands are populated, leading to interband scattering and a shift of the carrier distribution closer to the surface. Scattering rate calculations using finite-element simulations of the nanowire transistor confirm that these mechanisms are able to explain the data.

Toward highly effective loading of DNA in hydrogels for high-density and long-term information storage.

Digital information, when converted into a DNA sequence, provides dense, stable, energy-efficient, and sustainable data storage. The most stable method for encapsulating DNA has been in an inorganic matrix of silica, iron oxide, or both, but are limited by low DNA uptake and complex recovery techniques. This study investigated a rationally designed thermally responsive functionally graded (TRFG) hydrogel as a simple and cost-effective method for storing DNA. The TRFG hydrogel shows high DNA uptake, long-term protection, and reusability due to nondestructive DNA extraction. The high loading capacity was achieved by directly absorbing DNA from the solution, which is then retained because of its interaction with a hyperbranched cationic polymer loaded into a negatively charged hydrogel matrix used as a support and because of its thermoresponsive nature, which allows DNA concentration within the hydrogel through multiple swelling/deswelling cycles. We were able to achieve a high DNA data density of 7.0 × 109 gigabytes per gram using a hydrogel-based system.

Bone Density, Geometry, Structure and Strength Estimates in Adolescent and Young Adult Women with Atypical Anorexia Nervosa versus Typical Anorexia Nervosa and Normal-Weight Healthy Controls.

Our objective was to characterize bone outcomes in adolescent and young adult women with atypical anorexia nervosa (AAN) compared to typical AN and normal-weight healthy controls (HC) based on DSM-5 criteria. Four hundred thirty-two participants (141 AN, 131 AAN and 160 HC), ages 12-21 years, underwent dual-energy X-ray absorptiometry for areal BMD, and a subset had high-resolution peripheral quantitative CT assessment of the distal radius and tibia for volumetric BMD (vBMD), bone geometry and microarchitecture, and microfinite element analysis for estimated strength. The groups did not differ for age, pubertal stage, menarcheal age or physical activity. BMI and bone outcomes overall were intermediate in AAN compared with AN and HC. This applied to spine, total hip and femoral neck BMD measures and many distal tibial measures. However, the mean whole-body less head BMD Z-score did not differ between AAN and AN, and it was lower in both vs. HC. Similarly, many distal radius measures did not differ between AAN vs. AN or HC but were lower in AN than HC. Lower BMI, lean mass and bone age, older menarcheal age and longer illness duration correlated with greater impairment of bone outcomes. These data indicate that individuals with AAN overall have bone outcomes that are intermediate between AN and HC.