Development of an international standard set of value-based outcome measures for patients with chronic kidney disease : a report of the International Consortium for Health Outcomes Measurement (ICHOM) CKD working group

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care

Loss of the BMP Antagonist, SMOC-1, Causes Ophthalmo-Acromelic (Waardenburg Anophthalmia) Syndrome in Humans and Mice

Ophthalmo-acromelic syndrome (OAS), also known as Waardenburg Anophthalmia syndrome, is defined by the combination of eye malformations, most commonly bilateral anophthalmia, with post-axial oligosyndactyly. Homozygosity mapping and subsequent targeted mutation analysis of a locus on 14q24.2 identified homozygous mutations in SMOC1 (SPARC-related modular calcium binding 1) in eight unrelated families. Four of these mutations are nonsense, two frame-shift, and two missense. The missense mutations are both in the second Thyroglobulin Type-1 (Tg1) domain of the protein. The orthologous gene in the mouse, Smoc1, shows site- and stage-specific expression during eye, limb, craniofacial, and somite development. We also report a targeted pre-conditional gene-trap mutation of Smoc1 (Smoc1tm1a) that reduces mRNA to ∼10% of wild-type levels. This gene-trap results in highly penetrant hindlimb post-axial oligosyndactyly in homozygous mutant animals (Smoc1tm1a/tm1a). Eye malformations, most commonly coloboma, and cleft palate occur in a significant proportion of Smoc1tm1a/tm1a embryos and pups. Thus partial loss of Smoc-1 results in a convincing phenocopy of the human disease. SMOC-1 is one of the two mammalian paralogs of Drosophila Pentagone, an inhibitor of decapentaplegic. The orthologous gene in Xenopus laevis, Smoc-1, also functions as a Bone Morphogenic Protein (BMP) antagonist in early embryogenesis. Loss of BMP antagonism during mammalian development provides a plausible explanation for both the limb and eye phenotype in humans and mice

Development of an International Standard Set of Value-Based Outcome Measures for Patients With Chronic Kidney Disease

Value-based health care is increasingly promoted as a strategy for improving care quality by benchmarking outcomes that matter to patients relative to the cost of obtaining those outcomes. To support the shift toward value-based health care in chronic kidney disease (CKD), the International Consortium for Health Outcomes Measurement (ICHOM) assembled an international working group of health professionals and patient representatives to develop a standardized minimum set of patient-centered outcomes targeted for clinical use. The considered outcomes and patient-reported outcome measures were generated from systematic literature reviews. Feedback was sought from patients and health professionals. Patients with very high-risk CKD (stages G3a/A3 and G3b/A2-G5, including dialysis, kidney transplantation, and conservative care) were selected as the target population. Using an online modified Delphi process, outcomes important to all patients were selected, such as survival and hospitalization, and to treatment-specific subgroups, such as vascular access survival and kidney allograft survival. Patient-reported outcome measures were included to capture domains of health-related quality of life, which were rated as the most important outcomes by patients. Demographic and clinical variables were identified to be used as case-mix adjusters. Use of these consensus recommendations could enable institutions to monitor, compare, and improve the quality of their CKD care

Chronic Kidney Disease:Exploring Value-Based Healthcare as a Potential Viable Solution

International audienceIncreasing healthcare expenditures have triggered a trend from volume to value by linking patient outcome to costs. This concept first described as value-based healthcare (VBHC) by Michael Porter is especially applicable for chronic conditions. This article aims to explore the applicability of the VBHC framework to the chronic kidney disease (CKD) care area.Methods: The 4 dimensions of VBHC (measure value; set and communicate value benchmarking; coordinate care; payment to reward value-add) were explored for the CKD care area. Available data was reviewed focusing on CKD initiatives in Europe to assess to what extent each of the 4 dimensions of VBHC have been applied in practice.Results: Translating VBHC into value-based renal care (VBRC) seems to be initiated to a limited extent in European health systems. In most cases not all dimensions of VBHC have been utilized in the renal care initiatives.Conclusion: The translation of VBHC into VBRC is possible and even desirable if an optimal treatment pathway for CKD patients could be achieved. This would require an organizational change in health system set up and should include a strategy focusing on full care responsibility. The patient outcome perspective and health economic analysis need to be the centre of attention

Kinetic of lactic acid formation in kefir

This bachelor thesis deals with the kinetic production of lactic acid and consumption of lactose in the kefir fermentation from one type of milk under the same conditions. The theoretical part contains information on kefir and kefir grains, lactose intolerance, antimicrobial properties and high-performance liquid chromatography. The experimental part describes the methods and procedures used in the manufacture of kefir itself, the determination of lactic acid and lactose. Kefir samples were tested at precise time intervals for lactose, lactic acid and lactobacilli. The data was graphically evaluated and commented. The results of this work may be beneficial for consumers with lactose maldigestion and for consumers searching for qualite source of lactobacilli for enhancing their gut microflora

An international observational study suggests that artificial intelligence for clinical decision support optimizes anemia management in hemodialysis patients

International audienceManaging anemia in hemodialysis patients can be challenging because of competing therapeutic targets and individual variability. Because therapy recommendations provided by a decision support system can benefit both patients and doctors, we evaluated the impact of an artificial intelligence decision support system, the Anemia Control Model (ACM), on anemia outcomes. Based on patient profiles, the ACM was built to recommend suitable erythropoietic-stimulating agent doses. Our retrospective study consisted of a 12-month control phase (standard anemia care), followed by a 12-month observation phase (ACM-guided care) encompassing 752 patients undergoing hemodialysis therapy in 3 NephroCare clinics located in separate countries. The percentage of hemoglobin values on target, the median darbepoetin dose, and individual hemoglobin fluctuation (estimated from the intrapatient hemoglobin standard deviation) were deemed primary outcomes. In the observation phase, median darbepoetin consumption significantly decreased from 0.63 to 0.46 μg/kg/month, whereas on-target hemoglobin values significantly increased from 70.6% to 76.6%, reaching 83.2% when the ACM suggestions were implemented. Moreover, ACM introduction led to a significant decrease in hemoglobin fluctuation (intrapatient standard deviation decreased from 0.95 g/dl to 0.83 g/dl). Thus, ACM support helped improve anemia outcomes of hemodialysis patients, minimizing erythropoietic-stimulating agent use with the potential to reduce the cost of treatment

Synthesis, Antiplasmodial, and Antileukemia Activity of Dihydroartemisinin–HDAC Inhibitor Hybrids as Multitarget Drugs

Artemisinin-based combination therapies (ACTs) are the gold standard for the treatment of malaria, but the efficacy is threatened by the development of parasite resistance. Histone deacetylase inhibitors (HDACis) are an emerging new class of potential antiplasmodial drugs. In this work, we present the design, synthesis, and biological evaluation of a mini library of dihydroartemisinin–HDACi hybrid molecules. The screening of the hybrid molecules for their activity against selected human HDAC isoforms, asexual blood stage P. falciparum parasites, and a panel of leukemia cell lines delivered important structure–activity relationships. All synthesized compounds demonstrated potent activity against the 3D7 and Dd2 line of P. falciparum with IC50 values in the single-digit nanomolar range. Furthermore, the hybrid (α)-7c displayed improved activity against artemisinin-resistant parasites compared to dihydroartemisinin. The screening of the compounds against five cell lines from different leukemia entities revealed that all hydroxamate-based hybrids (7a–e) and the ortho-aminoanilide 8 exceeded the antiproliferative activity of dihydroartemisinin in four out of five cell lines. Taken together, this series of hybrid molecules represents an excellent starting point toward the development of antimalarial and antileukemia drug leads