Validating TrueAllele® Interpretation of DNA Mixtures Containing up to Ten Unknown Contributors.

Most DNA evidence is a mixture of two or more people. Cybergenetics TrueAllele® system uses Bayesian computing to separate genotypes from mixture data and compare genotypes to calculate likelihood ratio (LR) match statistics. This validation study examined the reliability of TrueAllele computing on laboratory-generated DNA mixtures containing up to ten unknown contributors. Using log(LR) match information, the study measured sensitivity, specificity, and reproducibility. These reliability metrics were assessed under different conditions, including varying the number of assumed contributors, statistical sampling duration, and setting known genotypes. The main determiner of match information and variability was how much DNA a person contributed to a mixture. Observed contributor number based on data peaks gave better results than the number known from experimental design. The study found that TrueAllele is a reliable method for analyzing DNA mixtures containing up to ten unknown contributors.

Knowledge and Practice Discordance in Treating Urinary Tract Infections.

BACKGROUND AND OBJECTIVES: Urinary tract infections (UTIs) are a common condition in women. Guidelines have been published on the diagnosis and management of such infections with the twin goals of improved patient safety and avoiding unnecessary health care costs. In this study we evaluated both physicians' knowledge of these guidelines, and whether that knowledge translates to their clinical practice. METHODS: We performed a retrospective chart review of UTI management before and after an educational intervention in a family medicine residency. Two control sites were also included. We also assessed physicians' knowledge of current UTI management guidelines using an anonymous quiz. RESULTS: At the intervention site, guideline adherence improved following the educational session. Inappropriate culture use decreased from 88% to 68% (P<.005) while first-line antibiotic use increased from 68% to 92% (P<.005). No such benefits were seen at the control sites. The control and intervention site providers did not differ in knowledge of antibiotic choice on the quiz (86% and 88% correct respectively, P=.85), but all control providers felt routine cultures were appropriate, whereas only 38% of the intervention providers did (P<.05). CONCLUSIONS: A simple educational intervention made an impact on the management of UTI. Our results also highlighted that knowledge and practice are not always aligned.

Variation in high-priority drug-drug interaction alerts across institutions and electronic health records.

Objective: The United States Office of the National Coordinator for Health Information Technology sponsored the development of a "high-priority" list of drug-drug interactions (DDIs) to be used for clinical decision support. We assessed current adoption of this list and current alerting practice for these DDIs with regard to alert implementation (presence or absence of an alert) and display (alert appearance as interruptive or passive). Materials and methods: We conducted evaluations of electronic health records (EHRs) at a convenience sample of health care organizations across the United States using a standardized testing protocol with simulated orders. Results: Evaluations of 19 systems were conducted at 13 sites using 14 different EHRs. Across systems, 69% of the high-priority DDI pairs produced alerts. Implementation and display of the DDI alerts tested varied between systems, even when the same EHR vendor was used. Across the drug pairs evaluated, implementation and display of DDI alerts differed, ranging from 27% (4/15) to 93% (14/15) implementation. Discussion: Currently, there is no standard of care covering which DDI alerts to implement or how to display them to providers. Opportunities to improve DDI alerting include using differential displays based on DDI severity, establishing improved lists of clinically significant DDIs, and thoroughly reviewing organizational implementation decisions regarding DDIs. Conclusion: DDI alerting is clinically important but not standardized. There is significant room for improvement and standardization around evidence-based DDIs.

Herpes virus genome, the pressure is on.

Herpes simplex virus type 1 (HSV-1) packages its micrometers-long double-stranded DNA genome into a nanometer-scale protein shell, termed the capsid. Upon confinement within the capsid, neighboring DNA strands experience repulsive electrostatic and hydration forces as well as bending stress associated with the tight curvature required of packaged DNA. By osmotically suppressing DNA release from HSV-1 capsids, we provide the first experimental evidence of a high internal pressure of tens of atmospheres within a eukaryotic human virus, resulting from the confined genome. Furthermore, the ejection is progressively suppressed by increasing external osmotic pressures, which reveals that internal pressure is capable of powering ejection of the entire genome from the viral capsid. Despite billions of years of evolution separating eukaryotic viruses and bacteriophages, pressure-driven DNA ejection has been conserved. This suggests it is a key mechanism for viral infection and thus presents a new target for antiviral therapies.

The effect of topical arnica on muscle pain.

BACKGROUND: The herb Arnica montana, in topical formulations, has been reputed to decrease bruising and muscle pain. This claim has been inadequately and incompletely addressed. OBJECTIVE: To determine whether topical A. montana cream could decrease subjective leg pain following calf raises. Secondary outcomes were effects on ankle range of motion and muscle tenderness. METHODS: A randomized, double-blind, placebo-controlled trial was conducted in 53 subjects. Active range of motion was measured in both ankles, and then a series of calf-raises were completed according to a standardized protocol. Each participant received 2 tubes of cream, 1 with active arnica and 1 with placebo. The creams were applied to the lower legs immediately after the exercise, and again at 24 and 48 hours postexercise according to the "RIGHT" or "LEFT" labels. At 48 hours postexercise, subjects had their ankle range of motion and muscle tenderness measured. Subjects used the analog scale to rate pain in each leg at baseline, 24 hours, 48 hours, and 72 hours. RESULTS: No significant differences in pain scores were seen before exercise (arnica: 0.07 vs placebo: 0.09, p = 0.32). Pain scores on legs treated with arnica were higher than scores on those receiving placebo 24 hours after exercise (3.04 vs 2.36, respectively; p < 0.005). Pain scores on day 3 (arnica: 3.44 vs placebo: 3.20, p = 0.66) and day 4 (arnica: 2.36 vs placebo: 2.31, p = 0.62) were not significantly different. There was no difference in muscle tenderness (arnica: 1.05 vs placebo: 1.05, p = 1.0). Ankle range of motion did not differ significantly on either day 1 (arnica: 64.70 degrees vs placebo: 66.15, p = 0.352 or day 3 (arnica: 63.32 degrees vs placebo: 65.94, p = 0.058). CONCLUSIONS: Rather than decreasing leg pain, arnica was found to increase leg pain 24 hours after eccentric calf exercises. This effect did not extend to the 48-hour measurement.

Controlling hypertension in patients with diabetes.

Hypertension and diabetes mellitus are common diseases in the United States. Patients with diabetes have a much higher rate of hypertension than would be expected in the general population. Regardless of the antihypertensive agent used, a reduction in blood pressure helps to prevent diabetic complications. Barring contraindications, angiotensin-converting enzyme inhibitors are considered first-line therapy in patients with diabetes and hypertension because of their well-established renal protective effects. Calcium channel blockers, low-dose diuretics, beta blockers, and alpha blockers have also been studied in this group. Most diabetic patients with hypertension require combination therapy to achieve optimal blood pressure goals.