Pharmacy-Based Tuberculosis Skin Testing (TST): Approaches to Legal Authority

The Mantoux Tuberculin Skin Test (TST) is the standard method for detecting latent tuberculosis and has been provided by pharmacists since at least 2006. In the largest published study of pharmacy-based TST involving 578 patients, the most common reason for obtaining the test were employment or school requirements.Pharmacists have demonstrated high rates of follow-up for the reading of the test, reported to be 92.8% to 94.4%. The biggest barrier to pharmacy-based TST is that a prescription is required for the two tuberculosis (TB) purified protein derivative products available on the market in the United States. States have adopted three strategies to enable pharmacy-based TST prescribing: 1) collaborative practice agreements; 2) statewide protocols; and 3) independent prescribing. These three approaches are reviewed, with a focus on the New Mexico statewide protocol and the recent statutory authority in Idaho that grants pharmacists independent prescriptive authority for TST. States may consider pursuing more autonomous models of TST prescribing given the safety and track record of this service at pharmacies.   Type: Commentar

Excavations at the Bluff Creek Sites: 41MK10 and 41MK27, McColloch County, Texas

From late 1978 through early 1979, Ann M. Irwin of the Texas Department of Transportation (TxDOT) supervised excavations of two prehistoric archeological sites, 41MK10 and 41MK27, that were to be affected by construction along FM 765 in McCulloch County, Texas. The sites are located on Bluff Creek in the northern part of McCulloch County. Analyses of sites 41MK10 and 41MK27 and their cultural materials were conducted by TxDOT personnel in 1979, and an initial draft form of the report was prepared by Irwin in the early 1980s. TxDOT subsequently contracted SWCA, Inc. Environmental Consultants in 1999 to complete the report of the results of archeological investigations at 41MK10 and 41MK27 and to prepare the artifacts and records for curation. Site 41MK27 contained a small burned rock midden, Feature I. This midden was approximately 8 to 10 m in diameter, and 50 cm thick, and annular in form. A single internal feature (Feature IA), a rock-lined pit or hearth, was located in the approximate center and bottom of the midden. Lying between the midden and Bluff Creek were a series of small hearths, of which eight were excavated and designated as Features III through X. These small hearths, most of which had been at least somewhat disturbed, appeared to have been simple structures composed of one or more layers of rock. Many of the individual rocks appear to have been fire-fractured in place. No true basin-shaped hearths were observed. Associated with these hearths were an accompanying scatter of living debris in the form of flint and burned rock and significant quantities of freshwater mussel shell. Although the individual specimens are relatively small, the quantities recovered suggest that they served as a source of food. Radiocarbon data suggest that the site was intermittently occupied from the Late Archaic through the Late Prehistoric. The midden apparently dates to the Late Prehistoric, although the Transitional Archaic period may have been the period of most intense occupation at the site. Site 41MK10 was smaller than 41MK27 and not as intensively investigated. Two small burned rock features were excavated. The site was at least visited in the Late Archaic times, as is evidenced by the presence of a Castroville point, and in the Transitional Archaic, indicated by the recovery of two Ensor projectile points. It is likely, though by no means firmly established, that these dart point types are in fact associated with the use of the features

An aggregating U-Test for a genetic association study of quantitative traits

We propose a novel aggregating U-test for gene-based association analysis. The method considers both rare and common variants. It adaptively searches for potential disease-susceptibility rare variants and collapses them into a single “supervariant.” A forward U-test is then used to assess the joint association of the supervariant and other common variants with quantitative traits. Using 200 simulated replicates from the Genetic Analysis Workshop 17 mini-exome data, we compare the performance of the proposed method with that of a commonly used approach, QuTie. We find that our method has an equivalent or greater power than QuTie to detect nine genes that influence the quantitative trait Q1. This new approach provides a powerful tool for detecting both common and rare variants associated with quantitative traits

Evaluating methods for the analysis of rare variants in sequence data

A number of rare variant statistical methods have been proposed for analysis of the impending wave of next-generation sequencing data. To date, there are few direct comparisons of these methods on real sequence data. Furthermore, there is a strong need for practical advice on the proper analytic strategies for rare variant analysis. We compare four recently proposed rare variant methods (combined multivariate and collapsing, weighted sum, proportion regression, and cumulative minor allele test) on simulated phenotype and next-generation sequencing data as part of Genetic Analysis Workshop 17. Overall, we find that all analyzed methods have serious practical limitations on identifying causal genes. Specifically, no method has more than a 5% true discovery rate (percentage of truly causal genes among all those identified as significantly associated with the phenotype). Further exploration shows that all methods suffer from inflated false-positive error rates (chance that a noncausal gene will be identified as associated with the phenotype) because of population stratification and gametic phase disequilibrium between noncausal SNPs and causal SNPs. Furthermore, observed true-positive rates (chance that a truly causal gene will be identified as significantly associated with the phenotype) for each of the four methods was very low (<19%). The combination of larger than anticipated false-positive rates, low true-positive rates, and only about 1% of all genes being causal yields poor discriminatory ability for all four methods. Gametic phase disequilibrium and population stratification are important areas for further research in the analysis of rare variant data

Using the posterior distribution of deviance to measure evidence of association for rare susceptibility variants

Aitkin recently proposed an integrated Bayesian/likelihood approach that he claims is general and simple. We have applied this method, which does not rely on informative prior probabilities or large-sample results, to investigate the evidence of association between disease and the 16 variants in the KDR gene provided by Genetic Analysis Workshop 17. Based on the likelihood of logistic regression models and considering noninformative uniform prior probabilities on the coefficients of the explanatory variables, we used a random walk Metropolis algorithm to simulate the distributions of deviance and deviance difference. The distribution of probability values and the distribution of the proportions of positive deviance differences showed different locations, but the direction of the shift depended on the genetic factor. For the variant with the highest minor allele frequency and for any rare variant, standard logistic regression showed a higher power than the novel approach. For the two variants with the strongest effects on Q1 under a type I error rate of 1%, the integrated approach showed a higher power than standard logistic regression. The advantages and limitations of the integrated Bayesian/likelihood approach should be investigated using additional regions and considering alternative regression models and collapsing methods