Large-scale multi-ethnic cohorts offer unprecedented opportunities to elucidate the genetic factors influencing complex traits related to health and disease among minority populations. At the same time, the genetic diversity in these cohorts presents new challenges for analysis and interpretation. We consider the utility of race and/or ethnicity categories in genome-wide association studies (GWASs) of multi-ethnic cohorts. We demonstrate that race/ethnicity information enhances the ability to understand population-specific genetic architecture. To address the practical issue that self-identified racial/ethnic information may be incomplete, we propose a machine learning algorithm that produces a surrogate variable, termed HARE. We use height as a model trait to demonstrate the utility of HARE and ethnicity-specific GWASs.

In this proof-of-concept study, we demonstrated application of the PheWAS using large EHR biobanks to inform drug effects. The findings of an association of the IL6R SNP with reduced risk for aortic aneurysms correspond with the newest indication for IL6R blockade, giant cell arteritis, of which a major complication is aortic aneurysm.

We describe a method for measuring high-density lipoprotein cholesterol. MgCl2 and dextran sulfate are used to precipitate all low-density and very-low-density lipoproteins. The supernate contains only high-density lipoproteins, the cholesterol concentration of which is estimated by an enzymic method, with a discrete analyzer (Abbott Bichromatic Analyzer). Concentration and instrument response are linearly related to 50 mg/liter. The precision of the method is excellent in the range of clinical interest (100 to 1000 mg of cholesterol per liter). The precision and efficiency of the precipitation are shown at various concentrations of high-density lipoprotein cholesterol. The method was compared to that of two laboratories in the Cooperative Lipoprotein Phenotyping Study group by testing a number of split samples, and agreement was good.

Contaminated blood cultures may cause results to be misinterpreted, create unnecessary work for the laboratory, and increase costs. Disinfection of the venipuncture site is considered to be necessary for preventing contamination, although there is little information about the effectiveness of using different disinfection materials. The use of 70% isopropyl pads and povidone iodine saturated swabs (conventional method) was compared with the use of a 70% isopropyl/10% acetone scrub and povidone iodine dispenser (PREP method) for skin disinfection. Blood culture "kits" were prepared--bags containing collection tubes, instructions, and either conventional or PREP materials and were distributed randomly. The contents were concealed by a cover to prevent the user from selecting a specific type of decontamination kit. The kits were identified in the laboratory by color-coded labels on the collection tubes. Among 1,546 specimens evaluated, the contamination rate observed with conventional disinfection was significantly higher (4.6%; N = 763) than with PREP materials (2.2%; N = 783, P = 0.011) and was equivalent to the preceding 6-month contamination rate (4.7%). The lower contamination rate may be associated with greater effectiveness of a scrub or isopropyl/acetone solution, or both. Decontamination materials may have a significant impact on reducing blood culture contaminants from skin flora.

Prostate-specific antigen (PSA) is a sensitive and specific serum marker for monitoring disease activity in men with prostatic carcinoma. Despite reports of elevation of levels of this analyte in men with benign prostatic hyperplasia, no information is available correlating the serum levels with the actual prostatic abnormalities in men having prostatectomy for presumed benign disease. In the present investigation, the authors compared preoperative serum PSA levels with prostate disease in 81 men with bladder outlet obstruction. Five pathologic groups were found: incidental high-grade carcinoma (n = 3), low-grade carcinoma (n = 11), acute inflammation (n = 16) with or without chronic inflammation, Prostatic intraepithelial neoplasia (PIN) (n = 25), and benign hyperplasia (n = 26). Serum PSA levels were significantly elevated in both low- and high-grade carcinoma, acute inflammation, and PIN when compared with the patients with benign hyperplasia with and without chronic inflammation. Within the four groups with elevated levels, use of PSA levels could separate only the high-grade cancer patients who were subsequently shown to have metastatic disease. Only one patient with simple hyperplasia had PSA levels in the abnormal range.

Rapid laboratory methods provide optimal support for active surveillance efforts to screen for methicillinresistant Staphylococcus aureus (MRSA). Most laboratories struggle to determine the optimal use of resources, considering options to balance cost, speed, and diagnostic accuracy. To assess the performance of common methods, the first comparison of MRSASelect agar (MS) and CHROMagar MRSA (CA), with and without broth enrichment followed by a 24-h subculture to MS, was performed. Results were compared to those of the Xpert MRSA assay. For direct culture methods, the agreement between MS and CA was 98.8%. At 18 h, direct MS identified 93% of all positive samples from direct culture and 84% of those identified by the Xpert MRSA. For Trypticase soy broth-enriched MS culture, incubated overnight and then subcultured for an additional 24 h, the agreement with Xpert MRSA was 96%. The agreement between direct MS and Xpert MRSA was 100% when semiquantitative culture revealed a bacterial density of 2؉ or greater; however, discrepancies between culture and Xpert MRSA arose for MRSA bacterial densities of 1؉ or less, indicating low density as a common cause of false-negative culture results. Since 1؉ or less was established as the most common MRSA carrier state, broth enrichment or PCR may be critical for the identification of all MRSA carriers who may be reservoirs for transmission. In this active-surveillance convenience sample, the use of broth enrichment followed by subculture to MS offered a low-cost but sensitive method for MRSA screening, with performance similar to that of Xpert MRSA PCR.The spread of methicillin-resistant Staphylococcus aureus (MRSA) is a major concern in healthcare settings because human "carriers" can spread MRSA to others, resulting in increased morbidity, mortality, and costs (13,14,17). One strategy to help prevent and control MRSA infections is the use of active surveillance cultures to screen patients for nasal carriage of MRSA, a practice coupled with appropriate barrier precautions for colonized or infected patients. Active surveillance programs are growing in number in the United States (10,20,23,24), despite differences in opinions about the practice and reported gaps in the literature (19). Therefore, clinical microbiology laboratories must respond to provide support for active surveillance screening methods.There is continued debate about the practicality and cost benefit of different MRSA detection methods. Typically, agar culture or PCR methods are used (4); however, additional workload and costs cause laboratories to struggle with resource allocation issues, which often depend on the interplay between assay accuracy, turnaround time, cost per test, and workforce availability. While PCR results can be available in as little as 2 h and are known to provide excellent sensitivity and specificity for MRSA screening (4, 25, 28), PCR methods are more costly than culture methods (6). Alternately, selective and differential chromogenic agars have gained popularity because of lower cost and...

We identified Campylobacter jejuni infections in four patients infected with the human immunodeficiency virus (HIV); three had persistent and severe C. jejuni infections. Multiple isolates obtained from each patient had the same biochemical and serotypic characteristics, indicating recurrent infection rather than reinfection with unrelated strains. Serum antibody responses to C. jejuni group antigens by enzyme-linked immunosorbent assay were markedly impaired in the three patients with persistent infection compared with forty-two immunocompetent C. jejuni-infected controls and with the HIV-infected patient who readily cleared the organism. One patient was bacteremic; his blood isolate was killed by normal serum but was resistant to his own serum, whereas a simultaneous stool isolate of a different serotype was sensitive. Failure of two patients to eradicate the organism and long-term administration of erythromycin therapy led to the in-vivo development of resistance to this antibiotic, which is most frequently used to treat C. jejuni infections.

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