Challenges and Regulatory Considerations in the Acoustic Measurement of High‐Frequency (>20 MHz) Ultrasound

This article examines the challenges associated with making acoustic output measurements at high ultrasound frequencies (>20 MHz) in the context of regulatory considerations contained in the US Food and Drug Administration industry guidance document for diagnostic ultrasound devices. Error sources in the acoustic measurement, including hydrophone calibration and spatial averaging, nonlinear distortion, and mechanical alignment, are evaluated, and the limitations of currently available acoustic measurement instruments are discussed. An uncertainty analysis of acoustic intensity and power measurements is presented, and an example uncertainty calculation is done on a hypothetical 30‐MHz high‐frequency ultrasound system. This analysis concludes that the estimated measurement uncertainty of the acoustic intensity is +73%/?86%, and the uncertainty in the mechanical index is +37%/?43%. These values exceed the respective levels in the Food and Drug Administration guidance document of 30% and 15%, respectively, which are more representative of the measurement uncertainty associated with characterizing lower‐frequency ultrasound systems. Recommendations made for minimizing the measurement uncertainty include implementing a mechanical positioning system that has sufficient repeatability and precision, reconstructing the time‐pressure waveform via deconvolution using the hydrophone frequency response, and correcting for hydrophone spatial averaging.     

The Role of Graduate Medical Education in Global Health: Proceedings From the 2013 Academic Emergency Medicine Consensus Conference

The past 40 years have seen expanded development of emergency medicine (EM) postgraduate residency training programs worldwide. An important part of this educational experience is the ability of resident trainees to participate in experiences abroad. However, little is known about how these experiences shape trainees and the populations they serve. During the 2013 Academic Emergency Medicine consensus conference, a group of educators met to define and outline current trends in graduate medical education (GME) emergency care research. The authors discuss future research questions bridging the gap of GME and global health.     

MAPPED study design: A 6 month randomised controlled study to evaluate the effect of dutasteride on prostate cancer volume using magnetic resonance imaging

ObjectiveTo evaluate the percentage change in volume of prostate cancer, as assessed by T2-weighted MRI, following exposure to dutasteride (Avodart) 0.5 mg daily for six months.Patients and methodsMRI in Primary Prostate cancer after Exposure to Dutasteride (MAPPED) is a double-blind, placebo-controlled trial, supported by GlaxoSmithKline (GSK). Men with prostate cancer suitable for active surveillance (low-intermediate risk prostate cancer on biopsy), and a visible lesion on T2-weighted MRI of at least 0.2 cc, were eligible for consideration. Forty-two men were randomised to 6 months of daily dutasteride 0.5 mg or placebo. Multi-parametric MRI (mpMRI) scans were performed at baseline, 3 and 6 months. The percentage changes in cancer volume over time will be compared between the dutasteride and placebo groups. Planned analyses will examine the association between tumour volume and characteristics (perfusion and contrast washout) as seen on mpMRI, HistoScan ultrasound and biopsy histopathology in both groups.DiscussionMAPPED is the first randomised controlled trial to use mpMRI to look at the effect of dutasteride on the volume of prostate cancer. If dutasteride is shown to reduce the volume of prostate cancer, it might be considered as an adjunct for men on active surveillance. Analysis of the placebo arm will allow us to comment on the short-term natural variability of the MR appearance in men who are not receiving any treatment.ConclusionMAPPED will evaluate the short-term effect of dutasteride on prostate cancer volume, as assessed by mpMRI, in men undergoing active surveillance for low or intermediate risk prostate cancer. The study completed recruitment in January 2012.     

Fosamprenavir or atazanavir once daily boosted with ritonavir 100 mg, plus tenofovir/emtricitabine, for the initial treatment of HIV infection: 48-week results of ALERT

Background

Newer antiretroviral (ARV) agents have improved pharmacokinetics, potency, and tolerability and have enabled the design of regimens with improved virologic outcomes. Successful antiretroviral therapy is dependent on patient adherence. In previous research, we validated a subset of items from the ACTG adherence battery as prognostic of virologic suppression at 6 months and correlated with adherence estimates from the Medication Event Monitoring System (MEMS). The objective of the current study was to validate the longitudinal use of the Owen Clinic adherence index in analyses of time to initial virologic suppression and maintenance of suppression.

Results

278 patients (naïve n = 168, experienced n = 110) met inclusion criteria. Median [range] time on the first regimen during the study period was 286 (30 – 1221) days. 217 patients (78%) achieved an undetectable plasma viral load (pVL) at median 63 days. 8.3% (18/217) of patients experienced viral rebound (pVL > 400) after initial suppression. Adherence scores varied from 0 – 25 (mean 1.06, median 0). The lowest detectable adherence score cut point using this instrument was ≥ 5 for both initial suppression and maintenance of suppression. In the final Cox model of time to first undetectable pVL, controlling for prior treatment experience and baseline viral load, the adjusted hazard ratio for time updated adherence score was 0.36_{score ≥ 5} (95% CI: 0.19–0.69) [reference: <5]. In the final generalized estimating equations (GEE) logistic regression model the adjusted odds ratio for time-updated adherence score was 0.17_{score ≥ 5} (0.05–0.66) [reference: <5].

Conclusion

A brief, longitudinally administered self report adherence instrument predicted both initial virologic suppression and maintenance of suppression in patients using contemporary ARV regimens. The survey can be used for identification of sub-optimal adherence with subsequent appropriate intervention.     

Case Report: Delayed Subclavian Vein Injury Secondary to Clavicular Malunion

Background

Fractures of the clavicle are extremely common, representing 2.6–12% of all fractures and 35–44% of all shoulder girdle injuries; 69–82% of these fractures occur in the middle third of the clavicle. Vascular injuries relating to clavicle fracture are usually due to extreme force applied to the clavicle in an acute setting. No other reports of delayed subclavian vein laceration were found on literature search.

Objectives

We present this case to increase awareness among emergency physicians of the potential delayed presentation of this rare condition.

Case Report

A 21-year-old man presented to the Emergency Department with acute swelling of the base of the neck after carrying a heavy load on his left shoulder the night before. He had been recovering from a clavicle fracture for 2 months. Malunion of his left midshaft clavicle fracture led to subclavian vein injury and formation of a large hematoma secondary to reinjury that occurred at work the night before presentation. Computed tomography revealed a 9-cm hematoma at the fracture site. The patient was found to have a subclavian vein injury without evidence of arterial injury or nervous system involvement. The patient was admitted for observation and subsequently discharged without need for surgical intervention.

Conclusion

Subclavian vein laceration is a rare complication of clavicle fracture. Patient education at discharge after conservative management is important due to the risk of vascular complications from malunion and reinjury.     

The physiology of incretins

The discovery of incretins-glucagon-like peptide (GLP)-1 and glucose-dependent insulinotrop peptide (GIP)-, clarification of their physiological properties as well as therapeutic application of incretin-based blood glucose lowering drugs opened new perspectives in the medical management of type 2 diabetes. New results of basic research investigations led to revaluation of the role of GIP in metabolic processes and a more established use of GLP-1 action. The article overviews the most relevant data of production and effects of incretins, as well as future possibilities of their therapeutic use.     

Testing the language of German cerebral palsy patients with right hemispheric language organization after early left hemispheric damage

Language functions are generally represented in the left cerebral hemisphere. After early (prenatally acquired or perinatally acquired) left hemispheric brain damage language functions may be salvaged by reorganization into the right hemisphere. This is different from brain lesions acquired in adulthood which normally lead to aphasia. Right hemispheric reorganized language (RL) is not associated with obvious language deficits. In this pilot study we compared a group of German-speaking patients with left hemispheric brain damage and RL with a group of matched healthy controls. The novel combination of reliable language lateralization as assessed by neuroimaging (functional magnetic resonance imaging) and specific linguistic tasks revealed significant differences between patients with RL and healthy controls in both language comprehension and production. Our results provide evidence for the hypothesis that RL is significantly different from normal left hemispheric language. This knowledge can be used to improve counselling of parents and to develop specific therapeutic approaches.