A Review of Continuous Quality Improvement Processes at Ten Medical Schools.

The Liaison Committee on Medical Education now expects all allopathic medical schools to develop and adhere to a documentable continuous quality improvement (CQI) process. Medical schools must consider how to establish a defensible process that monitors compliance with accreditation standards between site visits. The purpose of this descriptive study is to detail how ten schools in the Association of American Medical Colleges' (AAMC) Southern Group on Educational Affairs (SGEA) CQI Special Interest Group (SIG) are tackling practical issues of CQI development including establishing a CQI office, designating faculty and staff, charging a CQI committee, choosing software for data management, if schools are choosing formalized CQI models, and other considerations. The information presented is not meant to certify that any way is the correct way to manage CQI, but simply present some schools' models. Future research should include defining commonalities of CQI models as well as seeking differences. Furthermore, what are components of CQI models that may affect accreditation compliance negatively? Are there "worst practices" to avoid? What LCME elements are most commonly identified for CQI, and what are the successes and struggles for addressing those elements? What are identifiable challenges relating to use of standard spreadsheet software and engaging information technology for support? How can students be more engaged and involved in the CQI process? Finally, how do these major shifts to a formalized CQI process impact the educational experience?

Epigenetic analysis of neurocognitive development at 1 year of age in a community-based pregnancy cohort.

Multiple studies show that molecular genetic changes and epigenetic modifications affect the risk of cognitive disability or impairment. However, the role of epigenetic variation in cognitive development of neurotypical young children remains largely unknown. Using data from a prospective, community-based study of mother-infant pairs, we investigated the association of DNA methylation patterns in neonatal umbilical cord blood with cognitive and language development at 1 year of age. No CpG loci achieved genome-wide significance, although a small number of weakly suggestive associations with Bayley-III Receptive Communication scales were noted. While umbilical cord blood is a convenient resource for genetic analyses of birth outcomes, our results do not provide conclusive evidence that its use for DNA methylation profiling yields epigenetic markers that are directly related to postnatal neurocognitive outcomes at 1 year of age.

Comparison between southern blots and qPCR analysis of leukocyte telomere length in the health ABC study.

Only a few studies, primarily limited to small samples, have examined the relationship between leukocyte telomere length (LTL) data generated by Southern blots, expressed in kilobases, versus quantitative PCR data, expressed in the telomere product/a single gene product (T/S). In the present study, we compared LTL data generated by the two methods in 681 elderly participants (50% African Americans, 50% of European origin, 49.2% women, mean age 73.7±2.9 years) in the Health Aging and Body Composition Study. The correlation between the data generated by the two methods was modest (R (2) = .27). Both methods captured the age effect on LTL and the longer LTL in women than in men. However, only the Southern blot method showed a significantly longer LTL in African Americans than in European decent individuals, which might be attributed to the larger measurement error of the quantitative PCR-based method than the Southern blots.

Naturally occurring dominant resistance mutations to hepatitis C virus protease and polymerase inhibitors in treatment-naïve patients.

UNLABELLED: Resistance mutations to hepatitis C virus (HCV) nonstructural protein 3 (NS3) protease inhibitors in <1% of the viral quasispecies may still allow >1000-fold viral load reductions upon treatment, consistent with their reported reduced replicative fitness in vitro. Recently, however, an R155K protease mutation was reported as the dominant quasispecies in a treatment-naïve individual, raising concerns about possible full drug resistance. To investigate the prevalence of dominant resistance mutations against specifically targeted antiviral therapy for HCV (STAT-C) in the population, we analyzed HCV genome sequences from 507 treatment-naïve patients infected with HCV genotype 1 from the United States, Germany, and Switzerland. Phylogenetic sequence analysis and viral load data were used to identify the possible spread of replication-competent, drug-resistant viral strains in the population and to infer the consequences of these mutations upon viral replication in vivo. Mutations described to confer resistance to the protease inhibitors Telaprevir, BILN2061, ITMN-191, SCH6 and Boceprevir; the NS5B polymerase inhibitor AG-021541; and to the NS4A antagonist ACH-806 were observed mostly as sporadic, unrelated cases, at frequencies between 0.3% and 2.8% in the population, including two patients with possible multidrug resistance. Collectively, however, 8.6% of the patients infected with genotype 1a and 1.4% of those infected with genotype 1b carried at least one dominant resistance mutation. Viral loads were high in the majority of these patients, suggesting that drug-resistant viral strains might achieve replication levels comparable to nonresistant viruses in vivo. CONCLUSION: Naturally occurring dominant STAT-C resistance mutations are common in treatment-naïve patients infected with HCV genotype 1. Their influence on treatment outcome should further be characterized to evaluate possible benefits of drug resistance testing for individual tailoring of drug combinations when treatment options are limited due to previous nonresponse to peginterferon and ribavirin.

Preliminary findings: 25(OH)D levels and PTH are indicators of rapid bone accrual in pubertal children.

OBJECTIVE: The objective of this study was to evaluate the role of serum levels of 25(OH)D and PTH on the accumulation of whole body bone mass in a cohort of children. METHODS: This was a longitudinal study (1.98 +/- 0.07 y) of sixty-nine children (89% Caucasian, 44% male) enrolled in a calcium supplementation trial. Bone area, bone mineral content (BMC) and density (BMD) of the whole body and radius were assessed using a QDR 2000 (Hologic, Inc) dual energy x-ray absorptiometer. Serum PTH and 25(OH)D were measured using radioimmunoassays. RESULTS: Vitamin D stores were inversely related gain in bone area (p < 0.002), BMC (p < 0.002) BMD (p < 0.027), as well as to PTH levels (p < 0.0001). Compared to those with adequate vitamin D stores (>34 ng/ml), those who had consistently low vitamin D stores (18 ng/ml) had a 8% larger gain in bone area (p < 0.05); 11% in BMC (p < 0.05) and no differences in gain in BMD; after adjusting for baseline bone measurements, race, gender, season measured, Tanner stage, and calcium intake. CONCLUSIONS: High normal PTH with low-normal 25(OH)D stores and moderate to high calcium intake may be beneficial to accruing larger bone size and BMC during puberty.

Hepatitis C hypervariable region 1: association of reduced selection pressure in african americans with treatment failure.

In a prospective therapeutic trial, features of the hepatitis C quasispecies were investigated as possible markers of therapeutic response. Individuals chronically infected with hepatitis C genotype 1 received antiviral therapy consisting of alpha-interferon plus ribavirin. The study targeted the most rapidly evolving segment of the viral genome, hypervariable region 1 within the envelope-2 gene. Among individuals failing to clear virus in response to therapy, significant differences were observed between quasispecies of African-American and Caucasian subjects. While distance measures for synonymous substitutions were similar between racial subgroups, measures of distance at the amino acid level (nonsynonymous substitutions) varied significantly. Taken together, the observed patterns of variability corresponded to reduced host selection pressure against hypervariable region 1 in African-American nonresponders. Reduced selection pressure was present at baseline and persisted through treatment and follow-up, suggesting population stratification of host factors that influence selection pressure on hepatitis C virus.