BACKGROUND The use of radioactive microspheres (RM) for the measurement of regional myocardial blood flow (RMBF) is limited and inaccessible to many investigators due to radiation safety concerns and radioactive waste disposal problems. Therefore, a new method for the measurement of RMBF using colored microspheres (CM) was developed. METHODS AND RESULTS Polystyrene spheres (diameter, 15 +/- 0.1 [SD] micron; density, 1.09 g/ml) were dyed with one of five colors. With the injection of CM into the left atrium or into a coronary perfusion line, RMBF and its distribution can be determined. CM are extracted from the myocardium and blood by digestion with potassium hydroxide and subsequent microfiltration. The dyes are then recovered from the CM within a defined volume of a solvent, and their concentrations are determined by spectrophotometry. The separation of composite absorbance spectra by spectrophotometry with the CM technique was as good as the separation of energy spectra by a gamma-counter using the RM technique. Leaching of dye from the CM was less than 0.1% during a 2-month period in vitro. Significant leaching of dye from the microspheres also did not occur during 8 hours in the blood and myocardium of four anesthetized dogs in vivo. For further validation of this method, pairs of CM and RM (15.5 +/- 0.1 [SD] microns) were simultaneously injected under five different RMBF conditions (range, 0-10 ml/[min.g]) into the left anterior descending coronary artery of four anesthetized pigs, with coronary inflow as a flow reference, or into the left atrium of four anesthetized dogs using aortic blood withdrawal as a reference. The relation between RMBF determined by CM and RM was CM = 0.01 + 1.00.RM (r = 0.98, n = 1,080 data points) in the pigs, and CM = -0.19 + 0.92.RM (r = 0.97, n = 1,813 data points) in the dogs. CONCLUSIONS Measurement of RMBF with CM yields values very similar to those of RM. Their use is less expensive and avoids all the disadvantages related to radioactivity, thus offering an alternative method for as many as five RMBF measurements in a single experiment.

Subsequent interventions should incorporate lessons learned from this first randomized controlled trial of a multi-modal longitudinal tobacco treatment curriculum in multiple U.S. medical schools. NIH Trial Registry Number: NCT01905618.

INTRODUCTION Physician-delivered tobacco treatment using the 5As is clinically recommended, yet its use has been limited. Lack of adequate training and confidence to provide tobacco treatment are cited as leading reasons for limited 5A use. Tobacco dependence treatment training while in medical school is recommended, but is minimally provided. The MSQuit trial (Medical Students helping patients Quit tobacco) aims to determine if a multi-modal and theoretically-guided tobacco educational intervention will improve tobacco dependence treatment skills (i.e. 5As) among medical students. METHODS/DESIGN 10 U.S. medical schools were pair-matched and randomized in a group-randomized controlled trial to evaluate whether a multi-modal educational (MME) intervention compared to traditional education (TE) will improve observed tobacco treatment skills. MME is primarily composed of TE approaches (i.e. didactics) plus a 1st year web-based course and preceptor-facilitated training during a 3rd year clerkship rotation. The primary outcome measure is an objective score on an Objective Structured Clinical Examination (OSCE) tobacco-counseling smoking case among 3rd year medical students from schools who implemented the MME or TE. DISCUSSION MSQuit is the first randomized to evaluate whether a tobacco treatment educational intervention implemented during medical school will improve medical students’ tobacco treatment skills. We hypothesize that the MME intervention will better prepare students in tobacco dependence treatment as measured by the OSCE. If a comprehensive tobacco treatment educational learning approach is effective, while also feasible and acceptable to implement, then medical schools may substantially influence skill development and use of the 5As among future physicians.

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