Workplace-Based Assessment of Internal Medicine Resident Diagnostic Accuracy.

BACKGROUND: Making an accurate diagnosis is a core skill residents must develop. Assessments of this skill and decisions to grant residents clinical independence often are based on global impressions. A workplace-based assessment of diagnostic accuracy could be a useful part of a competency-based assessment program and could inform decisions about granting residents independence. INNOVATION: We developed a method for measuring diagnostic accuracy that was integrated into the workflow of internal medicine residents and attending physicians. METHODS: Four senior medical residents and 6 attending physicians working in the internal medicine clinical teaching unit of a tertiary hospital participated in this study. To determine their diagnostic accuracy, residents documented a leading diagnosis for each patient they evaluated in the emergency department. After reviewing each case with the resident and after examining the patient, the resident's attending physician documented the diagnosis. Discharge diagnosis was determined by retrospective chart review to allow determination of resident and attending physician diagnostic accuracy. Data were collected for 240 consecutive patients referred for a medicine consultation. RESULTS: Resident diagnostic accuracy was 66% (95% CI 60-72), whereas attending physician accuracy was significantly higher at 79% (95% CI 74-84, P < .001). By logistic regression, the accuracy of the attending physician was found to be influenced by the accuracy of the resident. Participants felt this process motivated them to improve their clinical reasoning. CONCLUSIONS: Measuring resident diagnostic accuracy provides information that could be used in a competency-based assessment program to provide feedback and motivation to stimulate performance improvement.

Cytotoxic activities of nucleoside and nucleobase analog drugs in malignant mesothelioma: characterization of a novel nucleobase transport activity.

This study was designed to evaluate the cytotoxic activity of several nucleoside and nucleobase analog drugs as possible new agents for treatment of malignant mesothelioma and to identify factors responsible for the clinical variation of nucleoside analog drug response in chemotherapy of mesothelioma. Three human mesothelioma cell lines (MSTO-211H, H2452 and H2052) were tested for gemcitabine sensitivity and nucleoside transport activity. MSTO-211H, H2452 and H2052 exhibited differences in sensitivity to gemcitabine, nucleoside transport rates and hENT1 site densities. In H2052 cells, gemcitabine, 5-fluoro-2'-deoxyuridine, clofarabine and cladribine were most active with IC(50) values of 46, 43, 240 and 490 nM, respectively, whereas 5-fluorouracil was the least cytotoxic drug tested. In H2052 cells, the combination of gemcitabine and fludarabine or cladribine resulted in synergistic cytotoxic response. In nucleobase transport studies, hypoxanthine and 6-mercaptopurine but not 5-fluorouracil was transported into H2052 cells by a novel purine-specific, sodium-independent nucleobase transport activity. In summary differences in nucleoside analog drug transport activities are likely to contribute to the observed clinical variation in nucleoside analog response in patients and for the first time a correlation between nucleobase drug sensitivities and transport activities was shown. A novel combination of gemcitabine and fludarabine or cladribine had synergistic cytotoxic activity against the least sensitive mesothelioma cell line. These drug combinations merit further evaluation as effective therapeutic regimens in patients with aggressive mesothelioma.

New haplotypes in the Bedlington terrier indicate complexity in copper toxicosis.

Copper toxicosis (CT) is an autosomal recessive disorder common in Bedlington terriers. Previously, the CT locus was mapped to canine Chromosome (Chr) 10q26 through linkage to marker C04107. Diagnosis, traditionally based on liver biopsy, has recently shifted to interpretation of the C04107 microsatellite alleles where allele 2 segregates with the disease with 90-95% accuracy. Recently, CT has been attributed to a deletion of exon 2 in the MURR1 gene. We also identified a deletion of exon 2 of MURR1 in our collection of 2-2 homozygous affected terriers. However, our collection also included affected 1-1 homozygotes and 1-2 heterozygotes, and these dogs did not have the homozygous deletion. In addition to C04107, we analyzed an adjacent microsatellite (C04107B), and two novel SNPs, all within intron 1 of MURR1, and sequenced all exons and their intronic boundaries. Pedigree analysis indicates that there are two typical haplotypes, one normal and one affected, maintaining complete linkage disequilibrium between C04107 allele 2 and the deletion in most pedigrees. Most importantly, we identified a recombinant haplotype present in a North American pedigree, where allele 2 is not linked with the deletion, and a fourth haplotype containing a splice site variant. Although the splice site alteration appears to be a normal variant, it is present in two affected dogs, which do not carry homozygous deletions of MURR1.