Anti-Xa-activiteit van therapeutisch nadroparine bij verminderde nierfunctie en behandeling conform richtlijn Nederlandse federatie voor nefrologie:vergelijking met standaarddosis bij normale nierfunctie.

Anti-Xa activity of therapeutic nadroparin in patients with renal impairment treated according to the Dutch Federation of Nephrology guideline: comparison with standard dosing in patients with normal renal function OBJECTIVE To determine equivalence of the mean anti-Xa activity (aXa) in patients with eGFR < 60 mL/min treated with a reduced therapeutic dose of nadroparin using the dosage guideline of the Dutch Federation of Nephrology (NfN) and patients with eGFR > 60 mL/min receiving a standard therapeutic dose of nadroparin. DESIGN Prospective, observational, multicentre, cohort study. METHODS In three general teaching hospitals, patients were included between July 2014 and April 2016 if they met inclusion criteria: age > 18 years, therapeutic dose of nadroparin, subcutaneous administration for at least three days and written informed consent. Exclusion criteria were: dialysis, participation in another study and use of anti-Xa inhibitors other than nadroparin or four-factor prothrombin complex concentrate within seven days before the start or during the study. After at least three adjusted doses on the third day of therapy a blood sample was drawn four hours after administration of nadroparin (therapeutic range: 0.6-1.0 IU/mL). RESULTS 97 patients with eGFR < 60 mL/min and 100 patients with eGFR > 60 mL/min were included. The mean aXa was 0.63 IU/mL respectively 0.62 IU/mL (P for equivalence = 0.015). In the group with renal impairment 52%, 12% respectively 37% of the patients achieved sub-, supra- and therapeutic aXa, compared with 47%, 7% respectively 46% in the group with normal renal function (P = 0.30). CONCLUSION This study shows that in patients with renal impairment a dosage reduction of therapeutic nadroparin using the dosage guideline of the NfN results in aXa that is equivalent with standard dose treatment in patients with normal renal function

A limited sampling schedule to estimate individual pharmacokinetics of pemetrexed in patients with varying renal functions

PURPOSE: Pemetrexed is a widely used cytostatic agent with an established exposure-response relationship. Although dosing is based on body surface area (BSA), large interindividual variability in pemetrexed plasma concentrations is observed. Therapeutic drug monitoring (TDM) can be a feasible strategy to reduce variability in specific cases leading to potentially optimized pemetrexed treatment. The aim of this study was to develop a limited sampling schedule (LSS) for the assessment of pemetrexed pharmacokinetics. METHODS: Based on two real-life datasets, several limited sampling designs were evaluated on predicting clearance, using NONMEM, based on mean prediction error (MPE %) and normalized root mean squared error (NRMSE %). The predefined criteria for an acceptable LSS were: a maximum of four sampling time points within 8 h with an MPE and NRMSE </= 20%. RESULTS: For an accurate estimation of clearance, only four samples in a convenient window of 8 h were required for accurate and precise prediction (MPE and NRMSE of 3.6% and 5.7% for dataset 1 and of 15.5% and 16.5% for dataset 2). A single sample at t = 24 h performed also within the criteria with MPE and NRMSE of 5.8% and 8.7% for dataset 1 and of 11.5% and 16.4% for dataset 2. Bias increased when patients had lower creatinine clearance. CONCLUSIONS: We presented two limited sampling designs for estimation of pemetrexed pharmacokinetics. Either one can be used based on preference and feasibility

Correlates of fear of hypoglycemia among patients with type 1 and 2 diabetes mellitus in outpatient hospitals in Zambia

Background: Severe hypoglycemia is a burdensome complication of diabetes mellitus that can induce fear of hypoglycemia and contribute to suboptimal glycemic control. The challenge is to achieve and maintain adequate glycemic control while avoiding episodes of severe hypoglycemia. The purpose of the study was to determine how common fear of hypoglycemia was in Zambian out-patients with diabetes and also to explore correlates of fear of hypoglycemia. Methods: One hundred fifty-seven individuals with types 1 and 2 diabetes participated in the study. Fear of Hypoglycemia Scale, Diabetes Self-Care Inventory, Problem Areas in Diabetes, and the Major Depression Inventory were completed. Multiple linear regression models were computed to assess the association between fear of hypoglycemia and psychological factors. Results: About 19% [16.3% type 1 and 12.6% type 2] of individuals with diabetes based on item endorsement expressed fear of hypoglycemia especially among individuals with type 1 diabetes. After controlling for demographic variables, diabetes self-care (ß = 0.24, p \u3c 0.05), and diabetes specific distress (ß = 0.41, p \u3c 0.001) were associated with fear of hypoglycemia. Conclusion: Fear of hypoglycemia was common and was positively associated with diabetes specific emotional distress and diabetes self-care. Interventions to avert fear of hypoglycemia are needed while optimizing glycemic control through managing diabetes care and emotion distress in individuals with diabetes

Exploration of the perceptions, barriers and drivers of pharmacogenomics practice among hospital pharmacists in Adelaide, South Australia

There is little literature regarding the barriers to the uptake of pharmacogenomics (PG) in pharmacy practice, especially with respect to Australia. To date, pharmacists have seldom been engaged in discussions of these issues. This study aimed to obtain an in-depth understanding of these barriers by interviewing pharmacists in Adelaide, South Australia. Ethics approved semistructured interviews were carried out with 21 public hospital pharmacists. Analysis of the data identified themes including: confidence to engage in PG, clinician acceptance of a pharmacist PG role, and the importance of timely and relevant PG education. Interviewees thought that pharmacists could have a greater participation in PG in the future, but they questioned whether this would be possible at the moment given, among other factors, existing time and work constraintsMM Dias, HM Ward, MJ Sorich, and RA McKinno