Variability of Delivery of Timolol for the Treatment of Infantile Hemangiomas.

BACKGROUND/OBJECTIVES: Topical timolol maleate solution or gel-forming solution is used alone or in conjunction with oral propranolol for the treatment of infantile hemangiomas. The consistency of the amount of timolol dispensed has never been evaluated. We evaluated the variability of drug delivery between different brands and formulations of timolol solution and gel-forming solution. METHODS: Five blinded volunteers sequentially dispensed five drops from each of the eight bottles containing timolol 0.5% solution or gel-forming solution. This was repeated three times per user for each bottle. The average amount of timolol dispensed was analyzed according to brand, formulation, and user for variability. The intra- and interuser variability of dispensing both formulations of timolol was also measured. RESULTS: Our study demonstrates statistically significant differences in the amount of timolol dispensed between timolol solution and gel-forming solution, with the latter closer to manufacturer estimates. Significant differences in the amount of timolol dispensed were noted between users regardless of the formulation or brand. Variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution. Inter- and intrauser variability in the amount of timolol dispensed was greater for gel-forming solution than 0.5% solution. CONCLUSION: Statistically significant differences were noted in the amount of timolol dispensed according to formulation, brand, and user. Whether this is clinically significant is unknown given the lack of pharmacokinetic data available for timolol.

Radio-pathomic mapping model generated using annotations from five pathologists reliably distinguishes high-grade prostate cancer.

Purpose: Our study predictively maps epithelium density in magnetic resonance imaging (MRI) space while varying the ground truth labels provided by five pathologists to quantify the downstream effects of interobserver variability. Approach: Clinical imaging and postsurgical tissue from 48 recruited prospective patients were used in our study. Tissue was sliced to match the MRI orientation and whole-mount slides were stained and digitized. Data from 28 patients ( n = 33 slides) were sent to five pathologists to be annotated. Slides from the remaining 20 patients ( n = 123 slides) were annotated by one of the five pathologists. Interpathologist variability was measured using Krippendorff's alpha. Pathologist-specific radiopathomic mapping models were trained using a partial least-squares regression using MRI values to predict epithelium density, a known marker for disease severity. An analysis of variance characterized intermodel means difference in epithelium density. A consensus model was created and evaluated using a receiver operator characteristic classifying high grade versus low grade and benign, and was statistically compared to apparent diffusion coefficient (ADC). Results: Interobserver variability ranged from low to acceptable agreement (0.31 to 0.69). There was a statistically significant difference in mean predicted epithelium density values ( p < 0.001 ) between the five models. The consensus model outperformed ADC (areas under the curve = 0.80 and 0.71, respectively, p < 0.05 ). Conclusion: We demonstrate that radiopathomic maps of epithelium density are sensitive to the pathologist annotating the dataset; however, it is unclear if these differences are clinically significant. The consensus model produced the best maps, matched the performance of the best individual model, and outperformed ADC.

Gleason Probability Maps: A Radiomics Tool for Mapping Prostate Cancer Likelihood in MRI Space.

Prostate cancer is the most common noncutaneous cancer in men in the United States. The current paradigm for screening and diagnosis is imperfect, with relatively low specificity, high cost, and high morbidity. This study aims to generate new image contrasts by learning a distribution of unique image signatures associated with prostate cancer. In total, 48 patients were prospectively recruited for this institutional review board-approved study. Patients underwent multiparametric magnetic resonance imaging 2 weeks before surgery. Postsurgical tissues were annotated by a pathologist and aligned to the in vivo imaging. Radiomic profiles were generated by linearly combining 4 image contrasts (T2, apparent diffusion coefficient [ADC] 0-1000, ADC 50-2000, and dynamic contrast-enhanced) segmented using global thresholds. The distribution of radiomic profiles in high-grade cancer, low-grade cancer, and normal tissues was recorded, and the generated probability values were applied to a naive test set. The resulting Gleason probability maps were stable regardless of training cohort, functioned independent of prostate zone, and outperformed conventional clinical imaging (area under the curve [AUC] = 0.79). Extensive overlap was seen in the most common image signatures associated with high- and low-grade cancer, indicating that low- and high-grade tumors present similarly on conventional imaging.

The Impact of Teaching Prognostication at the End of Life: A Pre-Post Interventional Study.

BACKGROUND: Providing accurate and valid prognostic information significantly influences end-of-life care. Disclosing a poor prognosis can be among the most difficult of physician responsibilities, thus having appropriate knowledge during training is crucial for appropriate prognostication. OBJECTIVE: To provide internal medicine (IM) house staff with a pre- and posteducational survey to determine their ability to accurately prognosticate 5 common end-stage diseases. DESIGN: We conducted a pre- and posteducational intervention survey-based study. A preintervention survey was administered to IM postgraduate year 1 (PGY-1) and PGY-2-4 house staff. The survey consisted of case scenarios for 5 common end-stage diseases, containing 1 question on comfort level and 2 on prognostication (totaling 10 points). A 30-minute educational intervention was presented immediately after the initial survey. The same survey was readministered 4 weeks thereafter. An identical survey was administered once to palliative care faculty. RESULTS: Forty house staff completed pre- and posteducational surveys. Eight palliative care faculty completed the survey. No difference was found between all house staff pre- and postscores (mean 2.70 [1.45] vs 2.78 [1.59], P = .141). There was no significant difference between PGY-1 and PGY-2-4 pretest scores (mean 2.63 [1.71] vs 2.81 [1.42], P = .72). The PGY-2-4 posttest score was significantly greater than PGY-1 posttest score (3.38 [1.58] vs 2.38 [1.58], P = .05). Total house staff posttest score was significantly lower than gold standard palliative care faculty (mean 4.71 [1.98] vs 2.78 [1.59], P = .006). CONCLUSIONS: Our pre-post intervention survey-based study demonstrates no significant increases in all house staff scores. The PGY-2-4 postintervention scores improved significantly. We speculate the optimal time for prognostication education may be after the PGY-1 year when house staff have had sufficient exposure to common conditions.

Radio-pathomic Maps of Epithelium and Lumen Density Predict the Location of High-Grade Prostate Cancer.

PURPOSE: This study aims to combine multiparametric magnetic resonance imaging (MRI) and digitized pathology with machine learning to generate predictive maps of histologic features for prostate cancer localization. METHODS AND MATERIALS: Thirty-nine patients underwent MRI prior to prostatectomy. After surgery, tissue was sliced according to MRI orientation using patient-specific 3-dimensionally printed slicing jigs. Whole-mount sections were annotated by our pathologist and digitally contoured to differentiate the lumen and epithelium. Slides were co-registered to the T2-weighted MRI scan. A learning curve was generated to determine the number of patients required for a stable machine-learning model. Patients were randomly stratified into 2 training sets and 1 test set. Two partial least-squares regression models were trained, each capable of predicting lumen and epithelium density. Predicted density values were calculated for each patient in the test dataset, mapped into the MRI space, and compared between regions confirmed as high-grade prostate cancer. RESULTS: The learning-curve analysis showed that a stable fit was achieved with data from 10 patients. Maps indicated that regions of increased epithelium and decreased lumen density, generated from each independent model, corresponded with pathologist-annotated regions of high-grade cancer. CONCLUSIONS: We present a radio-pathomic approach to mapping prostate cancer. We find that the maps are useful for highlighting high-grade tumors. This technique may be relevant for dose-painting strategies in prostate radiation therapy.