Can the Charlson Comorbidity Index be used to predict the ASA grade in patients undergoing spine surgery?

BACKGROUND: The American Society of Anaesthesiologists' Physical Status Score (ASA) is a key variable in predictor models of surgical outcome and "appropriate use criteria". However, at the time when such tools are being used in decision-making, the ASA rating is typically unknown. We evaluated whether the ASA class could be predicted statistically from Charlson Comorbidy Index (CCI) scores and simple demographic variables. METHODS: Using established algorithms, the CCI was calculated from the ICD-10 comorbidity codes of 11'523 spine surgery patients (62.3 ± 14.6y) who also had anaesthetist-assigned ASA scores. These were randomly split into training (N = 8078) and test (N = 3445) samples. A logistic regression model was built based on the training sample and used to predict ASA scores for the test sample and for temporal (N = 341) and external validation (N = 171) samples. RESULTS: In a simple model with just CCI predicting ASA, receiver operating characteristics (ROC) analysis revealed a cut-off of CCI ≥ 1 discriminated best between being ASA ≥ 3 versus < 3 (area under the curve (AUC), 0.70 ± 0.01, 95%CI,0.82-0.84). Multiple logistic regression analyses including age, sex, smoking, and BMI in addition to CCI gave better predictions of ASA (Nagelkerke's pseudo-R2 for predicting ASA class 1 to 4, 46.6%; for predicting ASA ≥ 3 vs. < 3, 37.5%). AUCs for discriminating ASA ≥ 3 versus < 3 from multiple logistic regression were 0.83 ± 0.01 (95%CI, 0.82-0.84) for the training sample and 0.82 ± 0.01 (95%CI, 0.81-0.84), 0.85 ± 0.02 (95%CI, 0.80-0.89), and 0.77 ± 0.04 (95%CI,0.69-0.84) for the test, temporal and external validation samples, respectively. Calibration was adequate in all validation samples. CONCLUSIONS: It was possible to predict ASA from CCI. In a simple model, CCI ≥ 1 best distinguished between ASA ≥ 3 and < 3. For a more precise prediction, regression algorithms were created based on CCI and simple demographic variables obtainable from patient interview. The availability of such algorithms may widen the utility of decision aids that rely on the ASA, where the latter is not readily available.

Nonpeptide tachykinin receptor antagonists. II. Pharmacological and pharmacokinetic profile of SB-222200, a central nervous system penetrant, potent and selective NK-3 receptor antagonist.

The pharmacological and pharmacokinetic profile of SB-222200 [(S)-(-)-N-(alpha-ethylbenzyl)-3-methyl-2-phenylquinoline-4-car boxami de], a human NK-3 receptor (hNK-3R) antagonist, was determined. SB-222200 inhibited (125)I-[MePhe(7)]neurokinin B (NKB) binding to Chinese hamster ovary (CHO) cell membranes stably expressing the hNK-3 receptor (CHO-hNK-3R) with a K(i) = 4.4 nM and antagonized NKB-induced Ca(2+) mobilization in HEK 293 cells stably expressing the hNK-3 receptor (HEK 293-hNK-3R) with an IC(50) = 18.4 nM. SB-222200 was selective for hNK-3 receptors compared with hNK-1 (K(i) > 100,000 nM) and hNK-2 receptors (K(i) = 250 nM). In HEK 293 cells transiently expressing murine NK-3 receptors (HEK 293-mNK-3R), SB-222200 inhibited binding of (125)I-[MePhe(7)]NKB (K(i) = 174 nM) and antagonized NKB (1 nM)-induced calcium mobilization (IC(50) = 265 nM). In mice oral administration of SB-222200 produced dose-dependent inhibition of behavioral responses induced by i.p. or intracerebral ventricular administration of the NK-3 receptor-selective agonist, senktide, with ED(50) values of approximately 5 mg/kg. SB-222200 effectively crossed the blood-brain barrier in the mouse and rat. The inhibitory effect of SB-222200 against senktide-induced behavioral responses in the mouse correlated significantly with brain, but not plasma, concentrations of the compound. Pharmacokinetic evaluation of SB-222200 in rat after oral administration (8 mg/kg) indicated sustained plasma concentrations (C(max) = about 400 ng/ml) and bioavailability of 46%. The preclinical profile of SB-222200, demonstrating high affinity, selectivity, reversibility, oral activity, and central nervous system penetration, suggests that it will be a useful tool compound to define the physiological and pathophysiological roles of NK-3 receptors, in particular in the central nervous system.

Quantitative changes in interleukin proteins following focal stroke in the rat.

The aim of the present study was to quantitate the temporal changes in protein concentration for interleukin (IL)-1alpha, IL-1beta, IL-1ra, and IL-6 from 1 h to 15 days following focal ischemia. Protein expression was evaluated by enzyme-linked immunosorbent assay utilizing newly available rat antibodies. There were no detectable basal levels of IL-1alpha, 1L-1beta, or IL-6 in the sham-operated or non-ischemic control cortex. IL-1beta (increased significantly (P<0.05) as early as 4 h and peaked at 3 to 5 days. IL-1alpha (increased significantly (P<0.05) at 3 days. IL-6 increased early and peaked at 24 h (P<0.05). IL-1ra increased significantly (P<0.05) over basal levels from 12 h to 5 days. The present study provides the first quantitative determination of interleukin protein concentrations in the rat brain following focal stroke and demonstrates that this technology is now available for mechanistic studies in neuroprotection.