Validity and reliability of an objective structured assessment tool for performance of ultrasound-guided regional anaesthesia.

BACKGROUND: We examined the validity and reliability of the previously developed criterion-referenced assessment checklist (AC) and global rating scale (GRS) to assess performance in ultrasound-guided regional anaesthesia (UGRA). METHODS: Twenty-one anaesthetists' single, real-time UGRA procedures (total: 21 blocks) were assessed using a 22-item AC and a 9-item GRS scored on 3-point and 5-point Likert scales, respectively. We used one-way analysis of variance to compare the assessment scores between three groups (Group 1: ≤30 blocks in the preceding year; Group 2: 31-100; and Group 3: >100). The concurrent validity was evaluated using Pearson's correlation (r). We calculated Type A intra-class correlation coefficient using an absolute-agreement definition in two-way random effects model, and inter-rater reliability using an absolute agreement between raters. The inter-item consistency was assessed by Cronbach's α. RESULTS: The greater UGRA experience in the preceding year was associated with better AC [F (2, 18) 12.01; P<0.001] and GRS [F (2, 18) 7.44; P=0.004] scores. There was a strong correlation between the mean AC and GRS scores [r=0.73 (P<0.001)], and a strong inter-item consistency for AC (α=0.94) and GRS (α=0.83). The intra-class correlation coefficient (95% confidence interval) and inter-rater reliability (95% confidence interval) for AC were 0.96 (0.95-0.96) and 0.91 (0.88-0.95), respectively, and 0.93 (0.90-0.94) and 0.80 (0.74-0.86) for GRS. CONCLUSIONS: Both assessments differentiated between individuals who had performed fewer (≤30) and many (>100) blocks in the preceding year, supporting construct validity. It also established concurrent validity and overall reliability. We recommend that both tools can be used in UGRA assessment.

ß-Blockers have differential effects on the murine asthma phenotype.

BACKGROUND AND PURPOSE: Our previous studies have shown the ß2 -adrenoceptor and its endogenous ligand, adrenaline, are required for development of the asthma phenotype in murine asthma models. Chronic administration of some, but not other, ß-blockers attenuated the asthma phenotype and led us to hypothesize that biased signalling was the basis of their differential effects, experimentally and clinically. EXPERIMENTAL APPROACH: We used mice with no detectable systemic adrenaline (PNMT(-/-) ) and wild-type (WT) mice to study the effects of four ß-blockers, alprenolol, carvedilol, propranolol and nadolol, in an ovalbumin sensitization and challenge (Ova S/C) murine model of asthma. The parameters measured were inflammatory cell infiltration, mucous metaplasia and airway hyperresponsiveness. To interpret the pharmacological action of these ligands quantitatively, we conducted computer simulations of three-state models of receptor activation. KEY RESULTS: Ova S/C PNMT(-/-) mice do not develop an asthma phenotype. Here, we showed that administration of alprenolol, carvedilol or propranolol in the absence of interference from adrenaline using Ova S/C PNMT(-/-) mice resulted in the development of an asthma phenotype, whereas nadolol had no effect. Ova S/C WT mice did develop an asthma phenotype, and administration of alprenolol, propranolol and carvedilol had no effect on the asthma phenotype. However, nadolol prevented development of the asthma phenotype in Ova S/C WT mice. Computer simulations of these four ligands were consistent with the isolated three-state receptor model. CONCLUSION AND IMPLICATIONS: ß-Blockers have different effects on the murine asthma phenotype that correlate with reported differences in activation or inhibition of downstream ß2 -adrenoceptor signalling pathways.

Enkephalinase inhibitors: potential agents for the management of pain.

Management of acute and chronic pain has always been a key area of clinical research. Enkephalinase inhibitors (EIs) seem to be promising as therapeutic agents having antinociceptive action. They additionally possess anticraving, antidiarrhoeal and antidepressant actions. The antinociceptive action of EIs has been reported for over a decade however, their therapeutic potential is yet to be effectively explored. EIs may be broadly classified as endogenous and those that are obtained synthetically. Endogenous EIs include peptides like spinorphin and opiorphin. And compounds like RB 101, RB 120, RB 3007 constitute the synthetically obtained EIs. Endogenous and synthetic inhibitors enkephalin degrading enzymes have been studied in vivo using standard animal models. The potential EI targets appear to be APN (Aminopeptidase N), NEP (Neutral endopeptidase), DPP-III (Dipeptidyl peptidase). EIs possess the advantage that they lack the opioid side effects. This article reviews the mechanisms by which EIs act and elucidates the pathways involved.