Impact of difelikefalin on the health-related quality of life of haemodialysis patients with moderate-to-severe chronic kidney disease-associated pruritus: a single-arm intervention trial

Objective: Chronic kidney disease-associated pruritus (CKD-aP) can have a substantial negative impact on health-related quality of life (HRQoL), including an increased risk of depression, anxiety and sleep disturbance. This trial aimed to assess the impact of intravenous difelikefalin on HRQoL in haemodialysis patients with moderate-to-severe CKD-aP. Methods: Post hoc analysis of an open-label, multicentre, single-arm intervention trial assessed pruritus severity and HRQoL at baseline and at 12 weeks of difelikefalin treatment using Worst Itching Intensity Numerical Rating Scale (WI–NRS), Sleep Quality Numeric Rating Scale (SQ–NRS), 5-D itch scale, Skindex-10 scale, EQ-5D-5L with Pruritus Bolt-On (EQ-PSO). Results: A total of 222 patients received ≥ 1 dose of difelikefalin, and 197 patients completed 12 weeks of difelikefalin treatment. Clinically meaningful changes from baseline to 12 weeks were observed in all disease-specific measures: 73.7% of patients achieved a ≥ 3-point reduction in the weekly mean of 24 h WI–NRS scores and 66% of patients experienced ≥ 3-point improvements in SQ–NRS scores. Improvements were also observed in all Skindex-10 scale and 5-D itch scale domain scores. The percentage of patients reporting no problems in all EQ-PSO domains increased from 1.4 to 24.7% (p < 0.001), respectively. Patients’ generic HRQoL EQ-5D-5L mean utility and EQ-5D visual analogue scale scores increased from baseline to 12 weeks: mean changes 0.04 (p = 0.001) and 2.8 (p = 0.046), respectively. Conclusions: Patients undergoing haemodialysis with moderate-to-severe CKD-aP receiving difelikefalin reported experiencing clinically meaningful improvements in both their pruritus symptoms and itch-related QoL. ClinicalTrials.gov registration number, NCT03998163; first submitted, 7 May 2019

Cost effectiveness of difelikefalin compared to standard care for treating chronic kidney disease associated pruritus (CKD-aP) in people with kidney failure receiving haemodialysis

Background: Chronic kidney disease-associated pruritus (CKD-aP) is associated with an increased risk of depression, poor sleep and reduced health-related quality of life. Two phase III studies (KALM-1 and KALM-2) of difelikefalin showed reduced CKD-aP severity and improved itch-related health-related quality of life in patients with moderate and severe CKD-aP receiving haemodialysis for kidney failure. Objective: We aimed to estimate the cost effectiveness of difelikefalin for patients with CKD-aP receiving haemodialysis for kidney failure compared to standard care from a UK National Health Service perspective. Methods: A cohort model was developed with four health states representing levels of pruritus intensity over time, based on the KALM trials augmented with longer term CKD-aP severity data from another haemodialysis trial (SHAREHD) for standard care. Utilities were estimated from a mapping study of 5-D Itch to EQ-5D-5L in 487 patients receiving haemodialysis, costs were estimated based on resource use alongside the SHAREHD and 2018 unit costs, and inflated to 2021 costs. Costs and quality-adjusted life-years were discounted at 3.5% per annum. A de novo economic model was developed in Microsoft Excel with scenario analyses performed using a range of assumptions. Results: In the base-case analysis over a time horizon of 64 weeks, using a placeholder cost of £75 per 28-days for difelikefalin, the incremental cost-effectiveness ratio of difelikefalin compared with standard care was £19,558/quality-adjusted life-year (QALY). Scenario analyses resulted in incremental cost-effectiveness ratios that ranged from £10,154/QALY (severe only) to £16,957/QALY (5-year horizon) for difelikefalin compared to standard care. Probabilistic sensitivity analyses suggested difelikefalin has a 48.6% probability of being cost effective at a threshold of £20,000/QALY and a 57.2% probability of being cost effective at a threshold of £30,000/QALY. Conclusions: The cost effectiveness of difelikefalin in a range of scenarios could make it an important pharmacotherapy to address the high burden of disease and unmet need for treatments associated with CKD-aP in the UK

The relationship between chronic kidney disease–associated pruritus and health-related quality of life: a systematic review

Background Chronic kidney disease–associated pruritus (CKD-aP) is a common and burdensome condition for end-stage kidney disease (ESKD) patients, especially those receiving haemodialysis. High-quality evidence of the relationship between CKD-aP and health-related quality of life (HRQoL) can therefore inform clinicians and policymakers about treatment choice and reimbursement decisions. Methods A systematic literature review and narrative synthesis stratified by study design and HRQoL instrument was conducted to evaluate in adult ESKD patients receiving in-centre haemodialysis the relationship between CKD-aP and HRQoL assessed using multi dimensional generic or condition-specific preference- or non-preference-based measures. MEDLINE, Embase, Web of Science, BIOSIS Citation Index, Cochrane Library and PsycINFO from inception to March 2020 were searched, with two reviewers extracting data independently. Results Searches identified 2684 unique records, of which 20 papers relating to 18 unique studies [5 randomised controlled trials (RCTs) and 13 observational studies] were included. HRQoL was assessed using four generic and eight disease-specific measures. The impact of CKD-aP was assessed by comparison of means, linear regression and correlation. Observational studies employing comprehensively adjusted multivariable linear regression largely found associations between CKD-aP severities and HRQoL. Analyses suggest this relationship is partially mediated by the sleep disturbance caused by CKD-aP. RCTs showing improvements in CKD-aP severity were associated with clinically meaningful improvements in HRQoL. Compared with generic measures, disease-specific HRQoL instruments reported greater changes with reduced CKD-aP. Heterogeneity in study design and reporting precluded meta-analysis. Conclusions CKD-aP severity was found to be associated with a worsening of HRQoL in the majority of observational and RCT studies. Parallel improvements in CKD-aP and HRQoL with interventions may support their use (PROSPERO registration 175035)

Las epistemologías críticas en la producción de conocimiento en Ciencia Política. Un estudio desde las trayectorias de docentes-investigadores de instituciones públicas

El presente proyecto pretendió aportar al estudio del desarrollo de la Ciencia Política en Argentina en el marco de la discusión iniciada por Giovanni Sartori, quien en el año 2004 cuestionó el status epistemológico- metodológico de la disciplina, dando inicio a una fructífera reflexión en torno a sus enfoques y paradigmas. En este marco, se sistematizaron y analizaron procesos de investigación concretos que, dentro del campo disciplinar, abrevan en diversas perspectivas epistemológicas críticas. Esto se llevó adelante a través de una serie de ejes de indagación orientados a analizar dichos procesos de modo transversal: 1- el reconocimiento de la posición del sujeto cognoscente como parte de la situación de investigación, 2- las articulaciones con sujetos y saberes extra-académicos en el proceso de construcción de conocimiento, 3- los vínculos con los espacios institucionales en los que se insertan las investigaciones y 4- las prácticas investigativas, académicas y pedagógicas concretas puestas en marcha en la producción de conocimiento. Estos ejes fueron abordados desde un enfoque cualitativo que combina el análisis documental de publicaciones científicas, con el análisis de trayectorias individuales y colectivas a través de entrevistas semiestructuradas a docentes investigadores de instituciones públicas.    ARK: http://id.caicyt.gov.ar/ark:/s22504559/n86d607b

Quantitative Evidence for Revising the Definition of Primary Graft Dysfunction after Lung Transplant

RATIONALE: Primary graft dysfunction (PGD) is a form of acute lung injury that occurs after lung transplantation. The definition of PGD was standardized in 2005. Since that time, clinical practice has evolved, and this definition is increasingly used as a primary endpoint for clinical trials; therefore, validation is warranted. OBJECTIVES: We sought to determine whether refinements to the 2005 consensus definition could further improve construct validity. METHODS: Data from the Lung Transplant Outcomes Group multicenter cohort were used to compare variations on the PGD definition, including alternate oxygenation thresholds, inclusion of additional severity groups, and effects of procedure type and mechanical ventilation. Convergent and divergent validity were compared for mortality prediction and concurrent lung injury biomarker discrimination. MEASUREMENTS AND MAIN RESULTS: A total of 1,179 subjects from 10 centers were enrolled from 2007 to 2012. Median length of follow-up was 4 years (interquartile range = 2.4-5.9). No mortality differences were noted between no PGD (grade 0) and mild PGD (grade 1). Significantly better mortality discrimination was evident for all definitions using later time points (48, 72, or 48-72 hours; P < 0.001). Biomarker divergent discrimination was superior when collapsing grades 0 and 1. Additional severity grades, use of mechanical ventilation, and transplant procedure type had minimal or no effect on mortality or biomarker discrimination. CONCLUSIONS: The PGD consensus definition can be simplified by combining lower PGD grades. Construct validity of grading was present regardless of transplant procedure type or use of mechanical ventilation. Additional severity categories had minimal impact on mortality or biomarker discrimination

A Standardized Morpho-Functional Classification of the Planet’s Humipedons

It was time to take stock. We modified the humipedon classification key published in 2018 to make it easier and more practical. This morpho-functional taxonomy of the topsoil (humipedon) was only available in English; we also translated it into French and Italian. A standardized morphofunctional classification of humipedons (roughly the top 30–40 cm of soil: organic and organomineral surface horizons) would allow for a better understanding of the functioning of the soil ecosystem. This paper provides the founding principles of the classification of humipedon into humus systems and forms. With the recognition of a few diagnostic horizons, all humus systems can be determined. The humus forms that make up these humus systems are revealed by measuring the thicknesses of the diagnostic horizons. In the final part of the article, several figures represent the screenshots of a mobile phone or tablet application that allows for a fast recall of the diagnostic elements of the classification in the field. The article attempts to promote a standardized classification of humipedons for a global and shared management of soil at planet level