Objective.To develop system-level performance measures for evaluating the care of patients with inflammatory arthritis (IA), including rheumatoid arthritis (RA), psoriatic arthritis, ankylosing spondylitis, and juvenile idiopathic arthritis.Methods.This study involved several methodological phases. Over multiple rounds, various participants were asked to help define a set of candidate measurement themes. A systematic search was conducted of existing guidelines and measures. A set of 6 performance measures was defined and presented to 50 people, including patients with IA, rheumatologists, allied health professionals, and researchers using a 3-round, online, modified Delphi process. Participants rated the validity, feasibility, relevance, and likelihood of use of the measures. Measures with median ratings ≥ 7 for validity and relevance were included in the final set.Results.Six performance measures were developed evaluating the following aspects of care, with each measure being applied separately for each type of IA except where specified: waiting times for rheumatology consultation for patients with new onset IA, percentage of patients with IA seen by a rheumatologist, percentage of patients with IA seen in yearly followup by a rheumatologist, percentage of patients with RA treated with a disease-modifying antirheumatic drug (DMARD), time to DMARD therapy in RA, and number of rheumatologists per capita.Conclusion.The first set of system-level performance measures for IA care in Canada has been developed with broad input. The measures focus on timely access to care and initiation of appropriate treatment for patients with IA, and are likely to be of interest to other arthritis care systems internationally.
Abstract-Volume regulatory ClϪ channels are key regulators of ischemic preconditioning (IPC). Because Cl Ϫ efflux must be balanced by an efflux of cations to maintain cell membrane electroneutrality during volume regulation, we hypothesize that I K1 channels may play a role in IPC. We subjected cultured cardiomyocytes to 60-minute simulated ischemia (SI) followed by 60-minute of simulated reperfusion (SR) and assessed percent cell death using trypan blue staining. Ischemic preconditioning (10-minute SI/10-minute SR) significantly (PϽ0.0001) reduced the percent cell death in nontransfected cardiomyocytes [IPC CM 18.0Ϯ2.1% versus control (C CM ) 48.3Ϯ1.0%]. IPC protection was not altered by overexpression of the reporter gene (enhanced green fluorescent protein, EGFP). However, overexpression of dominant-negative Kir2.1 or Kir2.2 genes using adenoviruses (AdEGFPKir2.1DN or AdEGFPKir2.2DN) encoding the reporter gene EGFP prevented IPC protection [both IPC CM ϩAdEGFPKir2.1DN 45.8Ϯ2.3% (meanϮSEM) and IPC CM ϩAdEGFPKir2.2DN 47.9Ϯ1.4% versus IPC CM ; PϽ0.0001] in cultured cardiomyocytes (nϭ8 hearts). Transfection of cardiomyocytes with AdEGFPKir2.1DN or AdEGFPKir2.2DN did not affect cell death in control (nonpreconditioned) cardiomyocytes (both C CM ϩ AdEGFPKir2.1DN 45.8Ϯ0.7% and C CM ϩAdEGFPKir2.2DN 46.2Ϯ1.3% versus C CM ; not statistically significant). Similar effects were observed in both cultured (nϭ5 hearts) and freshly isolated (nϭ4 hearts) ventricular cardiomyocytes after I K1 blockade with 20 mol/L BaCl 2 plus 1 mol/L nifedipine (to prevent Ba 2ϩ uptake). Nifedipine alone neither protected against ischemic injury nor blocked IPC protection. Our findings establish that I K1 channels play an important role in IPC protection. Key Words: ischemic preconditioning Ⅲ cardiomyocytes Ⅲ ischemia Ⅲ potassium channels Ⅲ gene transfer I schemic preconditioning (IPC) is a strong native protective mechanism that limits the amount of necrosis during a subsequent prolonged ischemia and reperfusion period. 1 Although much is known about the cell membrane receptors and intracellular pathways involved in IPC, 2-5 very little is known about the end effector(s) of IPC. Finding the end effector(s) of IPC is important to guide the development of new specific therapeutic approaches to protect the ischemic myocardium.Our recent results in cardiomyocytes established that blockade of Cl Ϫ channels inhibits cell volume regulation following hypoosmotic stress (regulatory volume decrease, RVD), 6,7 which results in loss of protection against necrosis induced by both ischemic 8 and pharmacological preconditioning. 6 Because accumulation of metabolic by-products is responsible for increasing the intracellular osmotic load in ischemia and thereby increasing water uptake in cardiomyocytes, and because IPC only produces a small reduction in the estimated osmotic load in ischemic cardiomyocytes, 7 we hypothesized that enhanced cell volume regulation as a result of Cl Ϫ channel activation plays a significant role in the protection induced by IP...
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