A pharmacist-managed dosing algorithm for darbepoetin alfa and iron sucrose in hemodialysis patients:A randomized, controlled trial

The attainment of target hemoglobin levels in hemodialysis patients is low. Several factors play a role, such as hyporesponsiveness to erythropoiesis-stimulating agents (ESA), but also suboptimal prescribing of ESA and iron. The goal of this study was to investigate if a pharmacist-managed dosing algorithm for darbepoetin alfa (DA) and iron sucrose improves the attainment of target hemoglobin levels. In this randomized controlled trial, 200 hemodialysis patients from a Dutch teaching hospital were included. In the intervention group (n = 100), a pharmacist monthly provided dose recommendations for DA and iron sucrose based on dosing algorithms. The control group (n = 100) received usual care. In the intervention group, the percentage per patient within the target range (PTR) for hemoglobin (target range 6.8-7.4 mmol/L) and iron status was higher than in the control group (for hemoglobin median 38.5% vs 23.1%,P = .001 and for iron status median 21.1% vs 8.3%,P = .003). The percentage of high hemoglobin levels (>8.1 mmol/L) was lower in the intervention group (median 0.0% vs 7.7%,P = .034). The weekly dose of DA was lower in the intervention group (median 34.0 vs 46.9 mcg,P = .020), whereas iron dose was higher (median 75 vs 0 mg). No difference was found for the percentage of hemoglobin levels below the target range. In conclusion, a pharmacist-managed dosing algorithm for DA and iron sucrose increased the attainment of target levels for hemoglobin and iron status, reduced the percentage of high hemoglobin levels, and was associated with a lower DA and a higher iron sucrose dose

Arginine-enriched oral nutritional supplementation in the treatment of pressure ulcers: A literature review

Abstract Purpose Pressure ulcers are a common, potentially mortal complication to disease, care and treatment for patients of all ages with mobility impairments. In addition, pressure ulcers not always heal straightforward because of multiple intrinsic factors e.g. undernutrition and extrinsic factors e.g. inadequate nutrition that may influence the healing process. The aim of this descriptive review is to investigate the treatment effect of arginine-enriched oral nutritional supplementation in pressure ulcers. Results The included studies, seven RCTs and four CTs, were published between January 2001 and October 2015, and conducted in different settings: hospital, long-term care/care homes and home care. The duration of follow-up of the studies varied from 2 weeks to complete healing and the sample size varied from 16 to 245 patients aged from 37 to 92 years and with pressure ulcer stages II, III or IV. The wound-specific oral nutritional supplementation contained 3–9 g of arginine. The main outcome measures were complete healing, time needed for complete wound closure, reduction in wound surface area, nursing time, and the number of dressings used. Ten out of eleven studies showed a beneficial effect of the arginine-enriched oral nutritional supplementation on the healing of pressure ulcers. Conclusions This review shows that there is substantial evidence supporting the positive effect of nutritional supplementation with additional protein, arginine and micronutrients to promote pressure ulcer healing. Currently, there is only one large study (N = 200) with level 1 evidence. It may be postulated that at least one extra comparable level 1 study is needed to draw firm conclusions on the importance of key nutrients in complete pressure ulcer healing

High Plasma Levels of Betaine, a Trimethylamine N-Oxide Related Metabolite, are Associated with Severity of Cirrhosis

Background and Aims: The gut microbiome-related metabolites betaine and trimethylamine N-oxide (TMAO) affect major health issues. In cirrhosis, betaine metabolism may be diminished because of impaired hepatic betaine homocysteine methyltransferase activity, whereas TMAO generation from trimethylamine may be altered because of impaired hepatic flavin monooxygenase expression. Here, we determined plasma betaine and TMAO levels in patients with end-stage liver disease and assessed their relationships with liver disease severity. Methods: Plasma betaine and TMAO concentrations were measured by nuclear magnetic resonance spectroscopy in 129 cirrhotic patients (TransplantLines cohort study; NCT03272841) and compared with levels from 4837 participants of the PREVEND cohort study. Disease severity was assessed by Child-Pugh-Turcotte (CPT) classification and Model for End-stage Liver Disease (MELD) score. Results: Plasma betaine was on average 60% higher (p < .001), whereas TMAO was not significantly lower in cirrhotic patients vs. PREVEND population (p = .44). After liver transplantation (n = 13), betaine decreased (p = .017; p = .36 vs. PREVEND population), whereas TMAO levels tended to increase (p = .085) to higher levels than in the PREVEND population (p = .003). Betaine levels were positively associated with the CPT stage and MELD score (both p < .001). The association with the MELD score remained in the fully adjusted analysis (p < .001). The association of TMAO with the MELD score did not reach significance (p = .11). Neither betaine nor TMAO levels were associated with mortality on the waiting list for liver transplantation (adjusted p = .78 and p = .44, respectively). Conclusion: Plasma betaine levels are elevated in cirrhotic patients in parallel with disease severity and decrease after liver transplantation

Profoundly Disturbed Lipoproteins in Cirrhotic Patients:Role of Lipoprotein-Z, a Hepatotoxic LDL-like Lipoprotein

Detailed information regarding lipoprotein concentrations and subfractions in cirrhotic patients before and after orthotopic liver transplantation (OLT) is lacking. Lipoprotein-Z (LP-Z) is a recently characterised abnormal, hepatotoxic free cholesterol-rich low-density lipoprotein (LDL)-like lipoprotein. We determined the lipoprotein profiles, including LP-Z, in cirrhotic patients and OLT recipients and assessed the prognostic significance of LP-Z on the OLT waiting list. We performed analyses in cirrhotic transplant candidates and non-cirrhotic OLT recipients. A population-based cohort was used as reference. The setting was a University hospital. Lipoprotein particle concentrations and subfractions were measured by nuclear magnetic resonance spectroscopy. In the cirrhotic patients (N = 130), most measures of triglyceride-rich lipoproteins (TRL), LDL, and high-density lipoproteins (HDL) were much lower compared to the OLT recipients (N = 372) and controls (N = 6027) (p &amp;lt; 0.01). In the OLT recipients, many lipoprotein variables were modestly lower, but HDL-cholesterol, triglycerides, and TRL and HDL size were greater vs. the control population. LP-Z was measurable in 40 cirrhotic patients and 3 OLT recipients (30.8% vs. 0.8%, p &amp;lt; 0.001). The cirrhotic patients with measurable LP-Z levels had profoundly lower HDL-cholesterol and particle concentrations (p &amp;lt; 0.001), and worse Child Pugh Turcotte classifications and MELD scores. The presence of LP-Z (adjusted for age, sex, and MELD score) predicted worse survival in cirrhotic patients (HR per 1 LnSD increment: 1.11, 95%CI 1.03-1.19, p = 0.003). In conclusion, cirrhotic patients have considerably lower plasma concentrations of all major lipoprotein classes with changes in lipoprotein subfraction distribution. After OLT, these lipoprotein abnormalities are in part reversed. LP-Z is associated with cirrhosis. Its presence may translate in disturbed HDL metabolism and worse survival.</p