Publications

Recent studies have identified oncogenic lesions in Philadelphia chromosome-positive (Ph+)  acute lymphoblastic leukemia (ALL) and ABL1 kinase mutations that confer resistance to tyrosine kinase inhibitors. We sought to determine the prevalence and clinical impact of these lesions in patients on CALGB 10001, a previously reported Phase II study of imatinib, chemotherapy, and hematopoietic cell transplant in adult Ph + ALL. Of the 58 enrolled, 22 relapsed. By direct sequencing, an ABL1 kinase mutation known to induce imatinib resistance was present at relapse in 13 of 20. Using quantitative PCR assays, the mutations were detectable at diagnosis or early during treatment in most (62%) relapsed patients. Aberrations in IKZF1, CDKN2A/B, and PAX5 were assessed in 28 samples using SNP arrays and genomic DNA sequencing. Of these, 22 (79%) had IKZF1 deletion. The combination of IKZF1 deletion and p210 BCR-ABL1 (p < 0.0001), high white blood cell count (p = 0.021), and minimal residual disease (p = 0.013) were associated with worse disease-free survival.

Although HCV is more prevalent among people with severe mental illness (SMI; e.g., schizophrenia, bipolar disorder) than in the general population (17% vs 1%), no large previous studies have examined HCV screening in this population. In this cross-sectional study, we examined administrative data for 57 170 California Medicaid enrollees with SMI to identify prevalence and predictors of HCV screening from October 2010 through September 2011. Only 4.7% (2674 of 57 170) received HCV screening, with strongest predictors being nonpsychiatric health care utilization and comorbid substance abuse.

Fifth-generation cephalosporins, ceftobiprole and ceftaroline, are promising drugs for treatment of bacterial infections from methicillin-resistant Staphylococcus aureus (MRSA). These antibiotics are able to bind native PBP2a, the penicillin-binding protein encoded by the mecA resistance determinant that mediates broad class resistance to nearly all other beta-lactam antibiotics, at clinically achievable concentrations. Mechanisms of resistance to ceftaroline based on mecA mutations have been previously described. Here we compare the genomes of 11 total parent-daughter strains of Staphylococcus aureus for which specific selection by serial passaging with ceftaroline or ceftobiprole was used to identify novel non-mecA mechanisms of resistance. All 5 ceftaroline-resistant strains, derived from 5 different parental strains, contained mutations directly upstream of the pbp4 gene (coding for the PBP4 protein), including four with the same thymidine insertion located 377 nucleotides upstream of the promoter site. In 4 of 5 independent ceftaroline-driven selections, we also isolated mutations to the same residue (Asn138) in PBP4. In addition, mutations in additional candidate genes such as ClpX endopeptidase, PP2C protein phosphatase and transcription terminator Rho, previously undescribed in the context of resistance to ceftaroline or ceftobiprole, were detected in multiple selections. These genomic findings suggest that non-mecA mechanisms, while yet to be encountered in the clinical setting, may also be important in mediating resistance to 5th-generation cephalosporins.

A key reason for the consistent gaps between evidence and practice across all areas of medicine is that there has been little attempt to identify or target factors critical for successful implementation of an evidence-based intervention. There is either no explicit implementation strategy or the strategy is based on a best guess rather than on a systematic assessment of crucial barriers and enablers. A different approach is needed to close the evidence-practice gap and thereby achieve the triple aim of improved health, improved patient experience and reduced healthcare costs. We present three fundamental principles of implementation science, which is a methodology that offers a systematic and comprehensive approach to improving healthcare practice and a series of 'how to' steps to conduct implementation science research. In an accompanying article, a scoping review of the types of implementation science research conducted in emergency medicine is reviewed, and several of the principles related to this review are discussed.

This article provides an approach to advance care planning (ACP) and goals of care communication in older adults with cardiovascular disease and multi-morbidity. The goal of ACP is to ensure that the medical care patients receive is aligned with their values and preferences. In this article, the authors outline common benefits and challenges to ACP for older adults with cardiovascular disease and multimorbidity. Recognizing that these patients experience diverse disease trajectories and receive care in multiple health care settings, the authors provide practical steps for multidisciplinary teams to integrate ACP into brief clinic encounters.