ACCF/AHA/ASE/ASNC/HFSA/HRS/SCAI/SCCT/SCMR/STS 2013 multimodality appropriate use criteria for the detection and risk assessment of stable ischemic heart disease: a report of the American College of Cardiology Foundation Appropriate Use Criteria Task Force, American Heart Association, American Society of Echocardiography, American Society of Nuclear Cardiology, Heart Failure Society of America, Heart Rhythm Society, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Cardiovascular Magnetic Resonance, and Society of Thoracic Surgeons.

The American College of Cardiology Foundation along with key specialty and subspecialty societies, conducted an appropriate use review of common clinical presentations for stable ischemic heart disease (SIHD) to consider use of stress testing and anatomic diagnostic procedures. This document reflects an updating of the prior Appropriate Use Criteria (AUC) published for radionuclide imaging (RNI), stress echocardiography (Echo), calcium scoring, coronary computed tomography angiography (CCTA), stress cardiac magnetic resonance (CMR), and invasive coronary angiography for SIHD. This is in keeping with the commitment to revise and refine the AUC on a frequent basis. A major innovation in this document is the rating of tests side by side for the same indication. The side-by-side rating removes any concerns about differences in indication or interpretation stemming from prior use of separate documents for each test. However, the ratings were explicitly not competitive rankings due to the limited availability of comparative evidence, patient variability, and range of capabilities available in any given local setting. The indications for this review are limited to the detection and risk assessment of SIHD and were drawn from common applications or anticipated uses, as well as from current clinical practice guidelines. Eighty clinical scenarios were developed by a writing committee and scored by a separate rating panel on a scale of 1-9, to designate Appropriate, May Be Appropriate, or Rarely Appropriate use following a modified Delphi process following the recently updated AUC development methodology. The use of some modalities of testing in the initial evaluation of patients with symptoms representing ischemic equivalents, newly diagnosed heart failure, arrhythmias, and syncope was generally found to be Appropriate or May Be Appropriate, except in cases where low pre-test probability or low risk limited the benefit of most testing except exercise electrocardiogram (ECG). Testing for the evaluation of new or worsening symptoms following a prior test or procedure was found to be Appropriate. In addition, testing was found to be Appropriate or May Be Appropriate for patients within 90 days of an abnormal or uncertain prior result. Pre-operative testing was rated Appropriate or May Be Appropriate only for patients who had poor functional capacity and were undergoing vascular or intermediate risk surgery with 1 or more clinical risk factors or an organ transplant. The exercise ECG was suggested as an Appropriate test for cardiac rehabilitation clearance or for exercise prescription purposes. Testing in asymptomatic patients was generally found to be Rarely Appropriate, except for calcium scoring and exercise testing in intermediate and high-risk individuals and either stress or anatomic imaging in higher-risk individuals, which were all rated as May Be Appropriate. All modalities of follow-up testing after a prior test or percutaneous coronary intervention (PCI) within 2 years and within 5 years after coronary artery bypass graft (CABG) in the absence of new symptoms were rated Rarely Appropriate. Pre-operative testing for patients with good functional capacity, prior normal testing within 1 year, or prior to low-risk surgery also were found to be Rarely Appropriate. Imaging for an exercise prescription or prior to the initiation of cardiac rehabilitation was Rarely Appropriate except for cardiac rehabilitation clearance for heart failure patients.

Ethical considerations in CT angiography.

The rapid development and clinical deployment of CT angiography raises several important issues, including assurance of professional competence and technical quality, self-referral, the relative role of radiologists and cardiologists, appropriateness and proper indications, the detection and disposition of unexpected or incidental findings and the concern for the rapidly increasing costs of health care and imaging. These questions are properly addressed within the framework of medical ethics, including principles of beneficence, autonomy and justice.

Causes of DNA single-strand breaks during reduction of chromate by glutathione in vitro and in cells.

Carcinogenic chromates induce DNA single-strand breaks (SSB) that are detectable by conventional alkali-based assays. However, the extent of direct breakage has been uncertain because excision repair and hydrolysis of Cr-DNA adducts at alkaline pH also generate SSB. We examined mechanisms of SSB production during chromate reduction by glutathione (GSH) and assessed the significance of these lesions in cells using genetic approaches. Cr(VI) reduction was biphasic and the formation of SSB occurred exclusively during the slow reaction phase. Catalase or iron chelators completely blocked DNA breakage, as did the use of GSH purified by a modified Chelex procedure. Thus, the direct intermediates of GSH-chromate reactions were unable to cause SSB unless activated by H2O2. SSB repair-deficient XRCC1(-/-) and proficient XRCC1+ EM9 cells had identical survival at doses causing up to 60% clonogenic death and accumulation of 1 mM Cr(VI). However, XRCC1(-/-) cells displayed higher lethality in the more toxic range and the depletion of GSH made them hypersensitive even to moderate doses. Elevation of cellular catalase or GSH levels eliminated survival differences between XRCC1(-/-) and XRCC1+ cells. In summary, formation of toxic SSB in cells occurs at relatively high chromate doses, requires H2O2, and is suppressed by high GSH concentrations.

Lower mutagenicity but higher stability of Cr-DNA adducts formed during gradual chromate activation with ascorbate.

Recent epidemiological and risk assessment studies have found a very high risk of lung cancer among chromium(VI)-exposed workers even at permissible levels of exposure. However, mechanistic views on the key genotoxic role of transient Cr(V) intermediates were more consistent with the threshold or highly non-linear (heavy dose) models of genetic damage by intracellular Cr(VI). In this work, we examined the production of mutagenic DNA lesions during metabolism of Cr(VI) by its dominant reducer ascorbate (vitamin C) under conditions promoting increased yield of transient Cr forms. We found that slow reductive activation of Cr(VI) by limited concentrations of ascorbate resulted in a greater yield of DCFH-oxidizing Cr intermediates but these species were unable to cause DNA strand breaks. Cr(VI)-ascorbate reactions generated a high number of Cr-DNA adducts that were responsible for all mutagenic responses detected in Cr(VI)-treated pSP189 shuttle plasmids following their replication in human cells. Mutagenicity of DNA damage resulting from the reactions with increased stability of Cr intermediates was approximately four times lower relative to the conditions lacking detectable Cr(V) formation. Unlike other reactions, slow reduction of Cr(VI) with ascorbate produced Cr-DNA adducts that were more resistant to dissociation by chelators, suggesting multicoordinate binding of Cr(III) to DNA. Overall, our findings do not support the possibility that increased Cr(V) formation at depleted ascorbate levels modeling heavy dose exposures causes higher levels of mutagenic DNA damage.

ACCF/ASNC appropriateness criteria for single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI): a report of the American College of Cardiology Foundation Quality Strategic Directions Committee Appropriateness Criteria Working Group and the American Society of Nuclear Cardiology endorsed by the American Heart Association.

Under the auspices of the American College of Cardiology Foundation (ACCF) and the American Society of Nuclear Cardiology (ASNC), an appropriateness review was conducted for radionuclide cardiovascular imaging (RNI), specifically gated single-photon emission computed tomography myocardial perfusion imaging (SPECT MPI). The review assessed the risks and benefits of the imaging test for several indications or clinical scenarios and scored them based on a scale of 1 to 9, where the upper range (7 to 9) implies that the test is generally acceptable and is a reasonable approach, and the lower range (1 to 3) implies that the test is generally not acceptable and is not a reasonable approach. The mid range (4 to 6) implies that the test may be generally acceptable and may be a reasonable approach for the indication. The indications for this review were primarily drawn from existing clinical practice guidelines and modified based on discussion by the ACCF Appropriateness Criteria Working Group and the Technical Panel members who rated the indications. The method for this review was based on the RAND/UCLA approach for evaluating appropriateness, which blends scientific evidence and practice experience. A modified Delphi technique was used to obtain first- and second-round ratings of 52 clinical indications. The ratings were done by a Technical Panel with diverse membership, including nuclear cardiologists, referring physicians (including an echocardiographer), health services researchers, and a payer (chief medical officer). These results are expected to have a significant impact on physician decision making and performance, reimbursement policy, and future research directions. Periodic assessment and updating of criteria will be undertaken as needed.

Differentiation of DNA reactive and non-reactive genotoxic mechanisms using gene expression profile analysis.

Genotoxic stress triggers a variety of biological responses including the transcriptional activation of genes regulating DNA repair, cell survival and cell death. Here, we investigated whether gene expression profiles can differentiate between DNA reactive and DNA non-reactive mechanisms of genotoxicity. We analyzed gene expression profiles and micronucleus levels in L5178Y cells treated with cisplatin and sodium chloride. The assessment of cisplatin genotoxicity (up to six-fold increase in the number of micronuclei) and gene expression profile (increased expression of genotoxic stress-associated genes) was in agreement with cisplatin mode of action as a DNA adduct-forming agent. The gene expression profile analysis of cisplatin-treated cells identified a number of genes with robust up regulation of mRNA expression including genes associated with DNA damage (i.e. members of GADD45 family), early response (i.e. cFOS), and heat shock protein (i.e. HSP40 homologue). The gene expression changes correlated well with DNA damage as measured by DNA-protein crosslinks and platinum-DNA binding. To differentiate the genotoxic stress-associated expression profile of cisplatin from a general toxic stress, we have compared the gene expression profile of cisplatin-treated cells to cells treated with sodium chloride, which causes osmotic shock and cell lysis. Although the sodium chloride treatment caused a two-fold induction of micronuclei, the gene expression profile at equitoxic concentrations was remarkably distinct from the profile observed with cisplatin. The profile of sodium chloride featured a complete lack of expression changes in genes associated with DNA damage and repair. In summary, the gene expression profiles clearly distinguished between DNA reactive and non-reactive genotoxic mechanisms of cisplatin and sodium chloride. Our results suggest the potential utility of gene expression profile analysis for elucidating mechanism of action of genotoxic agents.

Assessing practice-based learning and improvement.

BACKGROUND: Practice-based learning and improvement (PBLI) is 1 of 6 general competencies expected of physicians who graduate from an accredited residency education program in the United States and is an anticipated requirement for those who wish to maintain certification by the member boards of the American Board of Medical Specialties. This article describes methods used to assess PBLI. SUMMARY: Six electronic databases were searched using several search terms pertaining to PBLI. The review indicated that 4 assessment methods have been used to assess some or all steps of PBLI: portfolios, projects, patient record and chart review, and performance ratings. Each method is described, examples of application are provided, and validity, reliability, and feasibility characteristics are discussed. CONCLUSION: Portfolios may be the most useful approach to assess residents' PBLI abilities. Active participation in peer-driven performance improvement initiatives may be a valuable approach to confirm practicing physician involvement in PBLI.