BackgroundThe gold standard for cobalamin deficiency treatment is administration of cobalamin by intramuscular injection. The injection is painful and inconvenient, particularly for elderly persons. Cobalamin might also be administered intranasally. Previous studies do not provide insight into the pharmacokinetics of intranasal cobalamin administration in comparison with cobalamin injection.AimTo quantify the pharmacokinetics of intranasally and intramuscularly administered cobalamin to determine if intranasal administration might be an alternative for intramuscular administration.MethodsTen inpatients and outpatients of a geriatrics unit were recruited and randomly assigned to receive a single dose of 1000 μg cobalamin administered either by intranasal spray or intramuscular injection (5 per group). Inclusion criteria were written informed consent, age >65 years, and a cobalamin serum concentration <200 pmol/L. Total cobalamin serum concentrations were determined 10 times within 48 hours after administration. The differences in Cmax, Tmax, and AUC0–48 h per administration route were statistically compared using ANOVA.ResultsThe average Cmax was 1 nmol/L after intranasal and 38.5 nmol/L after intramuscular administration. The average Tmax for intranasal and intramuscular administration was 42 minutes versus 342 minutes, respectively, and the AUC0–48 h was 1.3 µmol/L/min versus 45.4 µmol/L/min, respectively. These values also differed significantly (P<0.05). The estimated bioavailability of the intranasal administration was 2%.ConclusionsThe pharmacokinetics of intranasal and intramuscular cobalamin administration in elderly, cobalamin-deficient patients differ significantly. However, the estimated 2% bioavailability of cobalamin after intranasal administration makes intranasal cobalamin administration a potentially interesting administration route for elderly patients. Netherlands Trial Registry identifier: NTR 3005.

Background: Anticholinergic acting drugs have been associated with delirium in older patients.Objective: To examine the association between the anticholinergic burden (ACB) and the duration and severity of delirium in older hip-surgery patients with or without haloperidol prophylaxis.Methods: Older patients with a postoperative delirium following hip surgery from a randomized controlled trial investigating the effects of haloperidol prophylaxis on delirium incidence were included in this study. The ACB was quantified using two different tools, the Anticholinergic Drug Scale and an Expert Panel. Using linear regression, the association between the ACB and delirium was analyzed.Results: Overall delirium duration and severity were not significantly associated with the ACB. Also, no statistically significant differences were found in delirium duration or severity between the placebo and haloperidol treatment groups for the ACB groups.The protective effect of haloperidol on delirium duration and severity however tended to be present in patients with no or a low ACB but not or to a lesser extent in patients with an intermediate to high ACB. Conclusions:The ACB was not significantly associated with delirium duration or severity. Haloperidol prophylaxis tended to shorten delirium duration and decrease delirium severity in patients with no or a low ACB. To further explore the influence of anticholinergic acting drugs on delirium duration and severity and the effect of concomitant haloperidol use, additional research with a higher haloperidol dose, a larger study population, and ACB quantification taking drug exposure into account is warranted.

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The development of a positive donor-crossmatch after transplantation is usually seen as a bad prognostic sign with regard to graft survival. Since a number of positive post-transplant-crossmatches with the original donor in the absence of graft rejection was noticed in our center, we started a systematic investigation of donor-crossmatches after transplantation.