The methods yielded different absolute values but the agreement for binary classification was good. An altered pituitary secretome in autumn that affects apparent [ACTH] values is likely. The Summary is available in Spanish - see Supporting information.
AIMSAn algorithm based on the CYP3A5 genotype to predict tacrolimus clearance to inform the optimal initial dose was derived using data from the DeKAF study (Passey et al. Br J Clin Pharmacol 2011; 72: 948-57) but was not tested in an independent cohort of patients. Our aim was to test whether the DeKAF dosing algorithm could predict estimated tacrolimus clearance in renal transplant recipients at our centre.
METHODSPredicted tacrolimus clearance based on the DeKAF algorithm was compared with dose-normalized trough whole-blood concentrations (estimated clearance) on day 7 after transplantation in a single-centre cohort of 255 renal transplant recipients.
RESULTSThere was a weak correlation (r = 0.431) between clearance based on dose-normalized trough whole-blood concentrations and DeKAF algorithm-predicted clearance. The means of the tacrolimus clearance predicted by the DeKAF algorithm and the estimated tacrolimus clearance based on the dose-normalized trough blood concentrations were plotted against the differences in the clearance as a Bland-Altman plot. Logarithmic transformation was performed owing to the increased difference in tacrolimus clearance as the mean clearance increased. There was a highly significant systematic error (P < 0.0005) characterized by a sloped regression line [gradient, 0.88 (95% confidence interval, 0.75-1.01)] on the Bland-Altman plot.
CONCLUSIONSThe DeKAF algorithm was unable to predict the estimated tacrolimus clearance accurately based on real tacrolimus doses and blood concentrations in our cohort of patients. Other genes are known to influence the clearance of tacrolimus, and a polygenic algorithm may be more predictive than those based on a single genotype.
Background: A reduction in the Egg Reappearance Period (ERP) has been
suggested to be an early indication of emerging anthelmintic resistance
in strongyles. Objective:To measure the strongyle ERP following
moxidectin treatment of horses in the southeast of England. Study
Design: Prospective study. Methods: Horses with a faecal egg count (FEC)
of > 400 strongyle eggs per gram (EPG) in a routine
screening sample were enrolled into the study. Moxidectin (400 mcg/kg)
was administered per os and FEC tests repeated every 2 weeks for 16
weeks. Results: Forty-eight horses completed the study. The mean EPG
prior to treatment was 1047 (range 375 – 2137 EPG). In all but two
horses, FEC was 0 EPG 2 weeks after moxidectin administration. In the
remaining two, the FECs were 12.5 EPG (97.8-98.3% reductions compared
to pre-treatment FEC). At 4 weeks post-treatment, 6 horses had positive
FECs (96.6-99.2% reductions). At 6 weeks, 11 horses had positive FECs
(83.8% reduction in one horse; >90% reduction in 10). At
8 weeks, 21 horses exhibited positive FECs (<90% reduction in
2). At 10 weeks, 27 horses had positive FECs (<90% in 6). At
12 weeks, 31 horses had positive FECs (<90% reduction in 11).
At 14 weeks, 34 horses had positive FECs (<90% reduction in
13). At 16 weeks, 38 horses had positive FECs (<90% reduction
in 17). Limitations: Weights of some horses were estimated using weigh
tapes rather than a weighbridge. Dosing of the horses with moxidectin
was carried out by owners. Conclusions: The results indicated acceptable
efficacy of moxidectin at 14 days after treatment; however, the ERP
pattern measured across the group suggest that this anthelmintic has a
considerably shorter suppressive effect on strongyle egg shedding than
measured when it was first introduced ( >13 weeks and up to
24 weeks).
BackgroundA reduction in the egg reappearance period (ERP) has been suggested to be an early indication of emerging anthelmintic resistance in strongyles.ObjectiveTo measure the strongyle ERP following moxidectin treatment of horses in the southeast of England.Study designProspective study.MethodsHorses with a faecal egg count (FEC) of ≥400 strongyle eggs per gram (EPG) in a routine screening sample were enrolled into the study. Moxidectin (400 μg/kg) was administered per os and FEC tests repeated every 2 weeks for 16 weeks.ResultsForty‐eight horses completed the study. The mean EPG prior to treatment was 1047 (range 375–2137 EPG). In all but two horses, FEC was 0 EPG 2 weeks after moxidectin administration. In the remaining two, the FECs were each 12.5 EPG (97.8%–98.3% reductions compared to pre‐treatment FEC). At 4 weeks post‐treatment, 6 horses had positive FECs (96.6%–99.2% reductions). At 6 weeks, 11 horses had positive FECs (83.8% reduction in one horse; >90% reduction in 10). At 8 weeks, 21 horses exhibited positive FECs (<90% reduction in 2). At 10 weeks, 27 horses had positive FECs (<90% in 6). At 12 weeks, 31 horses had positive FECs (<90% reduction in 11). At 14 weeks, 34 horses had positive FECs (<90% reduction in 13). At 16 weeks, 38 horses had positive FECs (<90% reduction in 17).Main limitationsWeights of some horses were estimated using weigh tapes rather than a weighbridge. Dosing of the horses with moxidectin was carried out by owners.ConclusionsThe results indicated acceptable efficacy of moxidectin at 14 days after treatment; however, the ERP pattern measured across the group suggests that this anthelmintic has a considerably shorter suppressive effect on strongyle egg shedding than measured when it was first introduced (12–16 weeks).
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