Measurement of quality of recovery using the QoR-40: a quantitative systematic review.

BACKGROUND: Several rating scales have been developed to measure quality of recovery after surgery and anaesthesia, but the most extensively used is the QoR-40, a 40-item questionnaire that provides a global score and subscores across five dimensions: patient support, comfort, emotions, physical independence, and pain. It has been evaluated in a variety of settings, but its overall psychometric properties (validity, reliability, ease of use, and interpretation) and clinical utility are uncertain. METHODS: We undertook a quantitative systematic review of studies evaluating psychometric properties of the QoR-40. Data were combined in meta-analyses using random effects models. This resulted in a total sample of 3459 patients from 17 studies originating in nine countries. RESULTS: We confirmed content, construct, and convergent [pooled r=0.58, 95% confidence interval (CI): 0.51-0.65] validity. Reliability was confirmed by excellent intraclass correlation (pooled α=0.91, 95% CI: 0.88-0.93), test-retest reliability (pooled r=0.90, 95% CI: 0.86-0.92), and inter-rater reliability (intraclass correlation=0.86). The clinical utility of the QoR-40 instrument was supported by high patient recruitment into evaluation studies (97%), and an excellent completion and return rate (97%). The mean time to complete the QoR-40 was 5.1 (95% CI: 4.4-5.7) min. CONCLUSIONS: The QoR-40 is a widely used and extensively validated measure of quality of recovery. The QoR-40 is a suitable measure of postoperative quality of recovery in a range of clinical and research situations.

A survey of anaesthetists' understanding of Australian mandatory reporting laws.

Australian mandatory reporting laws for healthcare practitioners were introduced nationally in July 2010. We distributed an online survey to specialist anaesthetists and anaesthesia trainees in our institution with the aim of assessing anaesthetists' awareness, understanding and interpretation of the new laws. One hundred and three completed responses were received (response rate 67%). The majority of respondents were aware of their professional (85%) and legal (68%) reporting obligations. Respondents were most likely to report conduct relating to alcohol intoxication or sexual misconduct (75%) and least likely to report a colleague with an impairment that may be placing the public at risk of harm (12%). Consultant anaesthetists were more likely than trainees to report students (P=0.002), junior colleagues (P=0.01) and senior colleagues (P=0.03). Some anaesthetists believed the laws would deter them from seeking medical help themselves if they were impaired (39%). Mandatory reporting laws aim to improve patient safety while being fair to doctors who are reported and protecting those who report. Our survey indicates that there are differences among anaesthetists about the type of conduct they would report and their perception of the consequences of making a report.

Two mathematical programming models of cheese manufacture.

The standardization problem faced by cheese makers is formulated as a nonlinear programming problem using the assumptions of the Van Slyke cheese yield formula. The objective function of the model is to minimize the net cost of producing a given quantity of cheese subject to a set of production constraints. An approximation of the standardization problem formulated as a linear programming problem is also presented. Two different approaches to finding a solution are provided. The model is implemented in Microsoft Excel and solved with the standard add-in solver available in that program. An example is provided to contrast the difference between the nonlinear programming and its linear approximation, and a second example is used to illustrate the yield implications of ultrafiltered milk protein products in Cheddar cheese production. Additionally, a method for pricing inputs using the sensitivity analysis generated by the solver is demonstrated.

Neodymium neutron cross section measurements.

Neutron capture and transmission measurements were performed by the time-of-flight technique at the Rensselaer Polytechnic Institute LINAC using metallic neodymium samples. The capture measurements were made at the 25-m-long flight station with a 16-segment NaI(Tl) multiplicity detector, and the transmission measurements were performed at 15 and 25 m flight stations with a 6Li glass scintillation detector. After the data were collected and reduced, resonance parameters were determined by simultaneously fitting the transmission and capture data with the multilevel R-matrix Bayesian code SAMMY. The resonance parameters for all naturally occurring neodymium isotopes lie within the energy range of 1.0-500 eV. The resulting resonance parameters were used to calculate the capture resonance integral with this energy region and were compared to calculations obtained when using the resonance parameters from ENDF-B/VI. The RPI parameters gave a resonance integral value of 32 +/- 0.5 b that is approximately 7% lower than that obtained with the ENDF-B/VI parameters. The current measurements significantly reduce the statistical uncertainties on the resonance parameters when compared with previously published parameters.

Micellar electrokinetic chromatography of tri aza aromatic ligand compounds of iron (II): influence of bile salt type on enantiomeric separation.

Micellar electrokinetic chromatography is used with a variety of bile salt micelles to separate the enantiomers of bis(8-((pyridine-2-methylene)amino)quinoline)iron(II) hexafluorophosphate, Fe(PMAQ)2(PF6)2; bis(8-((pyridine-2-methylene)amino)lepidine iron(II) hexafluorophosphate, Fe(PMAL)2(PF6)2; and bis(1-(2-pyridinyl)ethylidine)-8-aminoquinoline iron(II) hexafluorophosphate, Fe(PEAQ)2(PF6)2. The influence of ten different bile salts on the resolution of each pair of enantiomers is investigated. Significant changes in resolution are seen depending upon the bile salt used. The dihydroxy bile salts are superior to the trihydroxy bile salts in terms of resolution, and the taurine or glycine conjugated bile salts yield better results than the unconjugated bile salts. Resolution for most enantiomers is maximized in a buffer solution containing 10-15% acetone and employing either taurochenodeoxycholic or glycochenodeoxycholic acid as the bile salt. Evidence for the separation of the corresponding Fe(III) complexes is presented.

Differential effects of alpha-adrenoceptor agonists on human retinal microvessel diameter.

The effects of locally administered brimonidine, clonidine, and p-aminoclonidine on microvessel caliber were compared in human retinal tissues grafted into the hamster cheek pouch. Clonidine and p-aminoclonidine, but not brimonidine, potently constricted human retinal microvessels over a broad concentration range. All three agonists elicited significant vasoconstriction in naive hamster cheek pouch microvasculature. The alpha2-adrenoceptor antagonist, rauwolscine, inhibited p-aminoclonidine-induced constriction in naive hamster cheek pouch microvessels, but not p-aminoclonidine-induced effects in retinal grafts. Selective alpha1-adrenoceptor agonists evoked vasoconstriction in retinal grafts only at relatively high concentrations. These differential effects on the retinal microvasculature could not be readily explained solely on the basis of alpha1- or alpha2-adrenoceptor involvement. Clonidine, p-aminoclonidine and brimonidine are also imidazoline derivatives that interact with putative non-adrenergic imidazoline-sensitive binding sites, the so-called I1-imidazoline binding site subtype implicated by some investigators in mediation of peripheral vasoconstriction. As with p-aminoclonidine, the potent vasoconstriction in human retinal microvasculature elicited by moxonidine, an alpha-adrenergic agonist that has also been reported to exhibit selectivity for putative I1-imidazoline binding sites, was not inhibited by the selective alpha-adrenoceptor antagonist, rauwolscine, nor by idazoxan, an antagonist characterized as having substantial activity at putative I2-imidazoline binding sites. These data suggest the possible involvement of an unconventional non-adrenergic imidazoline-sensitive pathway in regulation of microvascular responses in the inner retina, and that drug activity mediated via such an imidazoline-sensitive component could potentially evoke deleterious effects in the retinal microvasculature.

Spinal epidural hematoma associated with tissue plasminogen activator treatment of acute myocardial infarction.

We report a case of tissue plasminogen activator-associated spinal epidural hematoma in a patient who underwent treatment for myocardial infarction. Diagnostic magnetic resonance imaging was used within 24 hr of coronary artery stent implantation. We review the literature on thrombolytic-associated epidural spinal hematoma and discuss its management. Cathet. Cardiovasc. Intervent. 48:390-396, 1999.

Synthesis and evaluation of 2-(arylamino)imidazoles as alpha 2-adrenergic agonists.

A series of 2-(arylamino)imidazoles was synthesized and evaluated for activity at alpha 1- and alpha 2-adrenoceptors. This class of agents has been shown to have potent and selective agonist activity at the alpha 2-adrenoceptors. The most potent member of this class, 2-[(5-methyl-1,4-benzodioxan-6yl)amino]imidazole, proved efficacious for the reduction of intraocular pressure upon topical administration and for the reduction of blood pressure upon intravenous administration. During the course of our studies, we developed a new reagent that allowed rapid assembly of the target compounds. This reagent, N-(2,2-diethoxyethyl)carbodiimide, was convenient to prepare and was stable under low-temperature storage conditions.

In-vivo activity and enzymatic hydrolysis of novel prostaglandin F2 alpha prodrugs in ocular tissues.

Enzymatic hydrolysis and in-vivo ocular studies were performed on a novel series of prostaglandin F2 alpha (PGF2 alpha) pivaloyl ester prodrugs to assess their therapeutic potential. These novel PGF2 prodrugs were esterified at the 9-, 11-, and 15-OH positions. Their enzymatic hydrolysis rates were compared to PGF2 alpha 1-isopropyl ester in dog, monkey, and human ocular tissues. Intraocular pressure (IOP) studies were performed in monkeys and dogs, and ocular surface hyperemia was monitored in dogs. PGF2 alpha 9-monopivaloyl ester was not enzymatically hydrolysed in dog and human ocular tissues. PGF2 alpha 11- and 15-monopivaloyl esters and PGF2 alpha 11,15-dipivaloyl ester were converted to PGF2 alpha by all ocular tissues at a substantially slower rate than PGF2 alpha l-isopropyl ester. Despite their slow enzymatic hydrolysis rates, the ocular hypotensive activity of PGF2 alpha mono and dipivaloyl esters, where positions 11- and 15- were functionalized, closely approached the activity achieved with PGF2 alpha l-isopropyl ester. The degree of ocular surface hyperemia associated with PGF2 alpha 11-pivaloyl ester and PGF2 alpha 11,15-dipivaloyl ester was less than that associated with equivalent doses of PGF2 alpha l-isopropyl ester. It appears that rapid enzymatic hydrolysis rates are not necessary to obtain efficacious ocular hypotensive PGF2 alpha ester prodrugs. Slow enzymatic hydrolysis rates may assist in reducing the degree of ocular surface hyperemia. A further contributory factor in this regard could be the approximately ten-fold favorable difference in enzymatic hydrolysis rates between iris-ciliary body and conjunctival tissue for these novel pivaloyl esters of PGF2 alpha. These factors appear to translate into an improved therapeutic index for separating ocular hypotensive and ocular surface hyperemic effects.

Synthesis and evaluation of 2-[(5-methylbenz-1-ox-4-azin-6-yl)imino]imidazoline, a potent, peripherally acting alpha 2 adrenoceptor agonist.

We have synthesized 2-[(5-methylbenz-1-ox-4-azin-6-yl)imidazoline, 3, a potent, peripherally acting alpha 2 adrenoceptor agonist. The agent is conveniently prepared in five steps from 2-amino-m-cresol. The agent has demonstrated good selectivity for alpha 2 adrenoceptors in binding and functional studies. When applied topically to eyes, the agent is efficacious for the reduction of intraocular pressure. The agent does not penetrate the blood-brain barrier and, as a consequence, does not lower blood pressure or induce sedation when administered topically or intravenously. We have determined the pKa and log P in water versus both octanol and dodecane of 3 and a set of related agents. The best physical parameter to explain its lack of central nervous system penetration appears to be log P measured in octanol versus water.

Molecular characterization and ocular hypotensive properties of the prostanoid EP2 receptor.

The cloning of the genes that encode for prostaglandin (PG) receptors has resolved much of the complexity and controversy in this area by confirming the classification proposed by Coleman, et al. Two issues that remained unresolved were (1) the inability of the EP2 agonist butaprost to interact with the cloned putative EP2 receptor and (2) molecular biological confirmation of a fourth PGE2-sensitive receptor, which was pharmacologically designated EP4. In order to provide clarification, we attempted to clone further PGE2-sensitive receptors. By using a cDNA probe that encodes for the human EP3A receptor, a cDNA clone that encoded for a novel PGE2-sensitive receptor was obtained by screening a human placenta library. This cDNA clone was transfected into COS-7 cells for pharmacological studies. The cDNA clone obtained from human placenta had only about 30% amino acid identity with cDNAs for other PG receptors, including those that encode for the previously proposed murine and human EP2 receptors. Radioligand binding studies on the novel EP receptor expressed in COS-7 cells revealed that selective EP2 agonists such as butaprost, AH 13205, AY 23626 and 19(R)-OH PGE2 all competed with 3H-PGE2 for its binding sites, whereas selective agonists for other PG receptor subtypes had minimal or no effect. This receptor was coupled to adenylate cyclase and EP2 agonists caused dose-related increases in cAMP. It appears that the cDNA described herein encodes for the pharmacologically defined EP2 receptor. Ocular studies revealed that AH 13205 decreased intraocular pressure in normal and ocular hypertensive monkeys by a mechanism that does not appear to involve inhibition of aqueous humor secretion.

Studies on the ocular hypotensive effects of prostaglandin F2 alpha ester prodrugs and receptor selective prostaglandin analogs.

The use of natural prostaglandins (PG), such as PGD2, PGE2, PGF2 alpha, and PGI2, for treating glaucoma is limited by their ocular side effects. One approach to achieve the required separation of ocular hypotensive activity from side effects is to employ ester prodrugs. From a novel series of 11- and 15-mono and 11,15-diacyl esters of PGF2 alpha we identified prodrugs where PGF2 alpha formation rates in the iris-ciliary body exceeded those in the conjunctiva, sclera, and corneal endothelium. Compared to PGF2 alpha-1-isopropyl ester the ocular tissue hydrolysis rates of the 11-monopivaloyl, the 11,15-dipivaloyl ester and the 1,11-lactone were up to 1000 fold less. Despite this large disparity in hydrolysis rates, the pivaloyl esters and the 1,11-lactone were potent ocular hypotensives in our animal models. In studying prostaglandin analogs, we found that a diverse variety of prostanoid receptor selective agonists lowered intraocular pressure in dogs and/or monkeys. These included DP-, EP1-, EP2-, EP3-, and FP-receptor selective compounds. These findings were surprising and prompted us to re-examine the receptor selectivity of these agonists by radioligand binding studies. Using radiolabelled PGE2, 17-phenyl PGF2 alpha, and sulprostone we were able to confirm the selectivity of the agonists currently used for receptor characterization directly by radioligand binding competition studies. It appears that multiple prostanoid receptor subtypes may be involved in regulating intraocular pressure.

Chiral stationary phase designed for beta-blockers.

A chiral stationary phase (CSP) derived from an N-3,5-dinitrobenzoyl-alpha-amino phosphonate was prepared for the direct separation of the enantiomers of underivatized beta-blockers. Structure-chromatographic activity relationships for beta-blockers and closely related analogues are reported for this CSP and are found to be consistent with the model used to design this CSP. The effect of temperature on the chromatographic behavior of beta-blocker enantiomers is unusual. A reduction in temperature reduces the retention of the less retained enantiomer and increases the retention of the more retained enantiomer without appreciable band broadening.

Clinical and angiographic results of balloon-expandable intracoronary stents in right coronary artery stenoses.

Balloon-expandable stents were placed successfully in 35 (95%) of 37 patients whose right coronary artery lesion was believed to have a poor short- or long-term prognosis with conventional balloon angioplasty because of prior restenosis or adverse lesion morphology. Quantitative angiography showed a reduction in stenosis diameter from 83 +/- 14% to 42 +/- 14% after conventional balloon dilation, with a further reduction to -3 +/- 12% after stent placement (p less than 0.001). There were no acute stent thromboses, but one patient (with two stents and unstented distal disease) developed subacute thrombosis on day 8 after self-discontinuation of warfarin and was treated with thrombolytic therapy and redilation. Follow-up angiography was performed at 4 to 6 months in 25 patients, demonstrating restenosis (83 +/- 13%) in 4 (57%) of 7 patients with multiple stents, but only 3 (17%) of 18 patients with a single stent (p less than 0.05). Six of the seven in-stent restenotic lesions were subtotal (80 +/- 12%) and were subjected to repeat conventional balloon angioplasty (postdilation stenosis 13 +/- 21%). The 18 patients without restenosis had a maximal in-stent diameter stenosis of 29 +/- 15%, corresponding to a maximal focal neointimal thickness of 0.68 +/- 0.26 mm within the stented segment. These preliminary results suggest that the Schatz-Palmaz stent may be a useful adjunctive device in the performance of coronary angioplasty.

Ocular inhibitory effects of the dopamine DA2 agonist (Ha-118) in cats and rabbits.

1. Topical administration of the dopamine (DA2) receptor agonist, Ha-118, produced unilateral ocular hypotension and miosis in normal cats. 2. The ocular hypotensive and mitotic effects of Ha-118 were not observed in surgically sympathectomized cats indicating that an intact sympathetic pathway is necessary to demonstrate activity. 3. Ha-118 caused dose-dependent suppression of contractions of the cat nictitating membrane (CNM) elicited by electrical stimulation of the pre- and postganglionic sympathetic nerve trunks but not by exogenously administered noradrenaline suggesting that Ha-118 affected prejunctional but not ganglionic or postjunctional receptors. 4. Sulpiride antagonized Ha-118-induced inhibition of neuronally mediated contractions in the CNM suggesting an interaction at DA2 receptors. 5. Topical administration of Ha-118 inhibited the rise in intraocular pressure induced by oral water loading in rabbits. 6. Topical pretreatment with metoclopramide, a DA2 antagonist, inhibited the ocular antihypertensive effect of Ha-118 in rabbits. 7. These studies demonstrate that Ha-118 decreased intraocular pressure (IOP) and pupil diameter (PD) in the cat and that this activity can be correlated with suppression of peripheral sympathetic tone in the CNM.

Prejunctional adrenoceptor activity of N-0437: a relatively selective DA2 dopamine receptor agonist.

Prejunctional adrenoceptor activity of N-0437, 2[N-n-propyl-N-2-(thienylethyl-amino)-5-hydroxytetralin], was investigated by means of the cat nictitating membrane (CNM) preparation. Intra-arterial (i.a.) administration of N-0437 produced a dose-related inhibition (ED50 = 14 micrograms) of the CNM contractions elicited by electrical stimulation of pre- and postganglionic sympathetic nerves of the superior cervical ganglion. Pretreatment with domperidone i.a., a relatively selective DA2 receptor antagonist, markedly attenuated the CNM response to racemic N-0437 (ED50 = 6.7 x 10(2) micrograms). However, pretreatment with rauwolscine i.a., a relatively selective alpha 2-receptor antagonist, did not alter the CNM responses to racemic N-0437. Evaluation of the (R)-(+) and (S)-(-) enantiomers showed that only the (S)-(-) enantiomer was active in suppressing the contractions in the CNM preparation. These results demonstrate that N-0437 is a potent agonist for prejunctional DA2 dopamine receptors on peripheral sympathetic nerves in the CNM and that these peripheral DA2 receptors appear to be enantioselective.

Prostaglandin F2 alpha effects on intraocular pressure negatively correlate with FP-receptor stimulation.

According to the current working classification for prostanoid receptors, the prostaglandin F2 alpha-sensitive receptor (FP-receptor) may be identified by comparing the rank order of activity of prostaglandin F2 alpha (PGF2 alpha) and its analogues. In order to further understand the pharmacology of PGF2 alpha-induced ocular hypotension, the intraocular pressure response to PGF2 alpha and selected analogues was compared with their rank order of activity in typical FP-receptor preparations such as contraction of the cat iris sphincter and affinity for corporal luteal membrane binding sites. The rank order of potency for decreasing intraocular pressure was as follows: PGF2 alpha greater than PGF1 alpha greater than 16-phenoxytetranor PGF2 alpha greater than 17-phenyltrinor PGF2 alpha = fluprostenol (inactive). For cat iris sphincter contraction, the rank order of potency appears to be fluprostenol = 17-phenyltrinor PGF2 alpha greater than 16-phenoxytetranor PGF2 alpha = PGF2 alpha greater than PGF1 alpha. The rank order of potency for PGF2 alpha analogues in decreasing intraocular pressure appears to negatively correlate with the rank order for cat iris sphincter contraction and literature values for corporal luteal membrane binding. It is concluded that the ocular hypotensive effect of PGF2 alpha is not mediated by the FP-receptor.

Community programs to enhance in-school anti-tobacco efforts.

This article presents theoretical bases for the development of community-wide anti-tobacco programs to reinforce school-based programs, discusses the problems involved in translating these theoretical bases into practice, and suggests means for minimizing those problems. Spiral of silence theory, diffusion theory, and expectancy value theory are covered. Special attention is given to the importance of a community program based in and "belonging" to the community, the need for high visibility, maximum participation by community individuals and organizations, mechanisms for program self-perpetuation, and explicit and visible ties to school-based anti-tobacco programs.

Prevalence and predictors of smokeless tobacco use: Iowa's program against smoking.

Data from surveys of adolescents were analyzed so that we could determine the prevalence of smokeless tobacco use and identify and compare the concurrent correlates of its use and cigarette smoking. Panel data from seventh through eleventh and eighth through twelfth graders between 1980 and 1984 and cross-sectional data from seventh graders in 1980 and 1985 suggest that boys are more likely to use SLT than are girls and that the boys' use has increased with age and over time. Concurrent correlates of seventh-grade boys' and girls' SLT use and cigarette smoking were identified with discriminant analyses. Predictors of smokeless tobacco use were compared with those of weekly smoking for boys and girls separately. Predictors of use by boys were also compared with those by girls. Trying alcohol and the other form of tobacco were the only predictors that related to the use of either form by boys and girls. Differences among other predictors were noted and their implications for prevention are discussed.

LY141865: a relatively selective DA2 agonist with complex ocular activity.

LY141865 (LY), an ergoline derivative, was investigated for ocular effects in rabbits and monkeys. LY lowered intraocular pressure (IOP) bilaterally in monkeys and rabbits, prevented the bilateral rise in IOP caused by oral waterloading in rabbits and slowed the rate of IOP recovery bilaterally in rabbits. The ocular hypotensive activity of LY in rabbits was inhibited by sympathectomy and pretreatment with sulpiride. Since LY has cardiovascular effects that are centrally mediated, ocular responses may also be mediated, in part, by an action in the CNS.