Optimisation of protection in the medical exposure of recurrent adult patients due to computed tomography procedures: development of recurrent exposures reference levels.

OBJECTIVES: To assess the incidence (1 year) and the cumulative incidence (3 years) of the condition of patients accruing cumulative effective doses (CED) of ≥ 100 mSv and their variability among different hospitals. To establish and validate a reference level for the CED in patients with recurrent exposures (RERL) and provide a RERL value. METHODS: Data of CT exposure was collected in 9 similar hospitals. The database included 294,222 patient*years who underwent 442,278 CT exams in 3 years. The incidence proportion of patients with CED ≥ 100 mSv in a given year (I100;1) and the 3-year cumulative incidence of patients with CED ≥ 100 mSv over 3 consecutive years (I100;3) were calculated and compared among different institutions. RESULTS: I100;1 ranged from a minimum of 0.1% to a maximum of 5.1%. The percentage of recurrent patients was quite uniform among centres ranging from 23 to 38%. The I100;3 ranged from a minimum of 1.1 to 11.4%. There was a strong positive correlation between the third quartile values of yearly CED and yearly incidence (r = 0.90; R2 = 0.81; p < 0.0001). RERL value in our study was found at 34.0 mSv. CONCLUSION: The management of patients with recurrent exposures is highly variable among hospitals leading to a 50-fold variation in I100;1 and to a tenfold variation in I100;3. RERL could be established and used by taking as a RERL quantity the CED and as a RERL value the 75th percentile of the third quartiles of the distribution of the yearly CED obtained by surveying different hospitals. CLINICAL RELEVANCE STATEMENT: This is the first ever multicentre study that quantifies recurrent exposures in terms of incidence and cumulative incidence of patients with CED ≥ 100 mSv. RERL establishment and use could benefit the optimisation of radioprotection of patients with recurrent exposures. KEY POINTS: This is the first multicentre study estimating yearly incidence and 3-year cumulative incidence of patients with cumulative effective doses ≥ 100 mSv. In this study, a 50-fold inter centre variation between the maximum (5.1%) and the minimum value (0.1%) of yearly incidence of patients with cumulative effective doses ≥ 100 mSv was reported. The range of the 3-year cumulative incidence extended from 1.1 to 11.4% (a tenfold variation) The third quartile of the yearly cumulative effective doses in a centre showed a strong positive correlation with the yearly incidence of patients with cumulative effective doses ≥ 100 mSv, with a potential of being used to set reference levels for recurrent exposures.

Oxyhomologues of anandamide and related endolipids: chemoselective synthesis and biological activity.

The three amide oxyhomologues of the endolipids N-arachidonoylethanolamine (anandamide, AEA, 1a), N-oleoylethanolamine (OEA, 2a), and N-palmitoylethanolamine (PEA, 3a) have been prepared in a chemoselective way, capitalizing on the easy availability of O-[2-(triisopropylsilyoxy)ethyl]hydroxylamine (6) and the surprising complementary selectivity observed in the acylation of N-[2-(tert-butyldiphenylsilyloxy)ethyl]hydroxylamine (7) with the PPAA and the DCC/HOBT protocols. Reversal of the cannabinoid CB(1)/CB(2) receptor affinity ratio was observed for the first time in a derivative of anandamide (the O-alkyl-N-acyl hydroxylamine 1b), while the other oxyhomologues (1c and 1d) showed only marginal cannabimimetic activity. Compounds with unsaturated acyl chains generally retained vanilloid activity and showed an increased stability toward FAAH compared to their corresponding ethanolamides. Taken together, these observation show that oxyhomologation has a pronounced effect on both the pharmacodynamic and the pharmacokinetic properties of endogenous ethanolamides, suggesting a general relevance of this maneuver for the modification of amide pharmacophores.