Surgery checklist implementation to reduce clinical risk in the pediatric operating room.

AIM: The aim of this prospective cohort study was to conduct a proactive analysis of procedural errors as revealed after implementation of a surgical safety checklist in the pediatric operating room of the Maggiore della Carità University Hospital, Novara. A further aim was to determine the effect the checklist had on the reduction, prevention, and protection against clinical risk in this setting. METHODS: A "Checklist for Patient Safety in the Pediatric Operating Room" was derived from documentation in the international literature and implemented in June 2011. All data were collected by a single observer. RESULTS: In all, 61 checklists were compiled. Analysis revealed 189 errors (absolute frequency), with the highest error incidence (59.78%) recorded for the sign-out phase (percentage cumulative frequency). Two categories of events were distinguished (surgical and orthopedic) and compared. The absolute frequency of near-miss events (n=168) and adverse events (n=21) was then broken down into the five phases of checklist compilation. The percentage cumulative frequency of near-miss was 88.89% and that of adverse events was 11.11%. CONCLUSION: Safety checklist implementation led to reduction, prevention and protection against adverse events with patient injury in 88.89% of cases. The error incidence in this pediatric operating room was lower than the average rates published in the literature.

New CCK antagonists derived from the amino acid residues of the CCK-8 fragment.

The synthesis of lipophylic derivatives of the amino acid residues of the CCK-8 fragment is described. According to "in vitro" binding studies and functional test, nearly all the compounds behaves as CCK-antagonists; moreover some compounds are able to interact differentially with CCK-A and CCK-B receptor subtype. In particular, compounds 2c, 2g, and 2h possess a high affinity for the CCK-A receptor subtype coupled with a low affinity for the CCK-B subtype. This results in an interesting selectivity profile. However, the same compounds are not able to antagonize the effects exerted by CCK-itself, when tested in "in vivo" assays.

Synthesis and biological evaluation of new antimuscarinic compounds with amidine basic centers. A useful bioisosteric replacement of classical cationic heads.

Amidines (guanidine, formamidine, and acetamidine) were introduced as substitutes for the cationic heads present in atropine, scopolamine, and corresponding quaternary derivatives. Amidine systems are intermediate in structure between tertiary amines and quaternary compounds, at least as regards ionization and electronic properties, but differ from the latter in shape (planar not tetrahedral). They have additional binding opportunities on account of their hydrogen-bond-forming capacity. The effect of the introduction of these cationic heads on the affinity for different muscarinic acetyl choline receptor (m-AcChR) subtypes was investigated in vitro, in binding displacement studies, and in functional tests on isolated organs. All new compounds (3a,b-5a,b) showed high affinity for the m-AcChR considered, comparable or slightly inferior to that of the parent drugs (1a-e). The new amidine derivatives proved effective as spasmolytic agents, with little tendency to cause central effects. However, no separation was achieved of spasmolytic and other untoward effects, like inhibition of salivation. Thus, amidine moieties are effective bioisosteric substitutes for conventional cationic heads present in antimuscarinic agents. Their unusual physical-chemical properties make them useful tools when modulation of pharmacokinetic or pharmacodynamic effects is required.

(Imidazolylphenyl)formamidines. A structurally novel class of potent histamine H2 receptor antagonists.

Structure-activity considerations of N alpha-guanylhistamine, the first compound found with detectable H2-antagonist activity, led to the synthesis of a series of conformationally rigid guanylhistamine analogues, namely, (imidazolylphenyl)guanidines, imidazolylbenzamidines, and (imidazolylphenyl)formamidines. It was found that in the guanidine and benzamidine classes, the meta-substituted derivatives (3, 4, 7, and 8) possessed H2-antagonist activity, whereas in the class of formamidines, only the para-substituted derivative 10 was found active. A subsequent increase in the size of the substituent at the formamidino group of 10 led to compounds (15-20) of high H2-antagonist affinity, which was related to the gastric antisecretory effect. Members of this structurally novel class of H2 antagonists were 20- to 50-fold more potent than cimetidine both "in vitro" and "in vivo". Structure-activity relationships are discussed in terms of ionization properties, partitioning behavior, conformational aspects of the selected compound 17, and of possible modes of interaction with the histamine H2 receptor. It was found that the formamidine moiety was an important structural feature and that H2-antagonist activity requires correct steric and electronic properties. Compound 17 (DA 4577), owing to its pharmacological profile and demonstrated safety in animals, was selected to be clinically investigated.

Synthesis and analgetic-antiinflammatory activity of 3,5-pyrazolidinediones bearing small-ring cycloalkyl groups.

Six 1,2-diphenyl-3,5-pyrazolidinediones substituted in the 4-position with small-ring cycloalkyl groups were prepared and tested for analgetic-antiinflammatory activity. Three of the synthesized compounds exerted an analgetic-antiinflammatory activity quantitatively superior to that of phenylbutazone used as a reference standard. In particular, one of the compounds (VI) proved twice as potent as phenylbutazone while possessing the same ulcerogenic effect.

Synthesis and analgesic activity of N-substituted 6,7-benzomorphans.

Some new N-substituted 6,7-benzomorphans were prepared and tested for analgetic activity. The compounds (I) and (II), which proved the most active in a preliminary screening, were submitted to a more detailed investigation, and their ED50 was determined in mice by the phenylquinone, hot-plate and tail-pinch tests. Studies of acute toxicity and physical dependence capacity were also performed.