Older Adults Engage With Personalized Digital Coaching Programs at Rates That Exceed Those of Younger Adults.

Background: The US population is aging and has an expanding set of healthcare needs for the prevention and management of chronic conditions. Older adults contribute disproportionately to US healthcare costs, accounting for 34% of total healthcare expenditures in 2014 but only 15% of the population. Fully automated, digital health programs offer a scalable and cost-effective option to help manage chronic conditions. However, the literature on technology use suggests that older adults face barriers to the use of digital technologies that could limit their engagement with digital health programs. The objective of this study was to characterize the engagement of adults 65 years and older with a fully automated digital health platform called Lark Health and compare their engagement to that of adults aged 35-64 years. Methods: We analyzed data from 2,169 Lark platform users across four different coaching programs (diabetes prevention, diabetes care, hypertension care, and prevention) over a 12-month period. We characterized user engagement as participation in digital coaching conversations, meals logged, and device measurements. We compared engagement metrics between older and younger adults using nonparametric bivariate analyses. Main Results: Aggregate engagement across all users during the 12-month period included 1,623,178 coaching conversations, 588,436 meals logged, and 203,693 device measurements. We found that older adults were significantly more engaged with the digital platform than younger adults, evidenced by older adults participating in a larger median number of coaching conversations (514 vs. 428) and logging more meals (174 vs. 89) and device measurements (39 vs. 28) all p ≤ 0.01. Conclusions: Older adult users of a commercially available, fully digital health platform exhibited greater engagement than younger adults. These findings suggest that despite potential barriers, older adults readily adopted digital health technologies. Fully digital health programs may present a widely scalable and cost-effective alternative to traditional telehealth models that still require costly touchpoints with human care providers.

Monochromatic subdiffusive spatial frequency domain imaging provides in-situ sensitivity to intratumoral morphological heterogeneity in a murine model.

For the first time, spatially resolved quantitative metrics of light scattering recovered with sub-diffusive spatial frequency domain imaging (sd-SFDI) are shown to be sensitive to changes in intratumoral morphology and viability by direct comparison to histopathological analysis. Two freshly excised subcutaneous murine tumor cross-sections were measured with sd-SFDI, and recovered optical scatter parameter maps were co-registered to whole mount histology. Unique clustering of the optical scatter parameters µs' vs. γ (i.e. diffuse scattering vs. relative backscattering) evaluated at a single wavelength showed complete separation between regions of viable tumor, aggresive tumor with stromal growth, varying levels of necrotic tumor, and also peritumor muscle. The results suggest that with further technical development, sd-SFDI may represent a non-destructive screening tool for analysis of excised tissue or a non-invasive approach to investigate suspicious lesions without the need for exogenous labels or spectrally resolved imaging.

Comparing desferrioxamine and light fractionation enhancement of ALA-PpIX photodynamic therapy in skin cancer.

BACKGROUND: Aminolevulinic acid (ALA)-based photodynamic therapy (PDT) provides selective uptake and conversion of ALA into protoporphyrin IX (PpIX) in actinic keratosis and squamous cell carcinoma, yet large response variations in effect are common between individuals. The aim of this study was to compare pre-treatment strategies that increase the therapeutic effect, including fractionated light delivery during PDT (fPDT) and use of iron chelator desferrioxamine (DFO), separately and combined. METHODS: Optical measurements of fluorescence were used to quantify PpIX produced, and the total amount of PpIX photobleached as an implicit measure of the photodynamic dose. In addition, measurements of white light reflectance were used to quantify changes in vascular physiology throughout the PDT treatment. RESULTS: fPDT produced both a replenishment of PpIX and vascular re-oxygenation during a 2 h dark interval between the first and second PDT light fractions. The absolute photodynamic dose was increased 57% by fPDT, DFO and their combination, as compared with PDT group (from 0.7 to 1.1). Despite that light fractionation increased oedema and scab formation during the week after treatment, no significant difference in long-term survival has been observed between treatment groups. However, outcomes stratified on the basis of measured photodynamic dose showed a significant difference in long-term survival. CONCLUSIONS: The assessment of implicit photodynamic dose was a more significant predictor of efficacy for ALA-PDT skin cancer treatments than prescription of an enhanced treatment strategy, likely because of high individual variation in response between subjects.

Characterization and standardization of tissue-simulating protoporphyrin IX optical phantoms.

Optical devices for measuring protoporphryin IX (PpIX) fluorescence in tissue are routinely validated by measurements in optical phantoms. Yet there exists limited data to form a consensus on the recipe for phantoms that both mimic the optical properties found in tissue and yield a reliable and stable relationship between PpIX concentration and the fluorescence remission intensity. This study characterizes the influence of multiple phantom components on PpIX fluorescence emission intensity, using Intralipid as the scattering source, bovine whole blood as the background absorber, and Tween as a surfactant to prevent PpIX aggregation. Optical measurements showed a linear proportionality (r > 0.99) between fluorescence intensity and PpIX concentration (0.1 to 10 µg/mL) over a range of Intralipid (1 to 2%) and whole blood (0.5 to 3%) for phantoms containing low surfactant (≤ 0.1%), with fluorescence intensities and scattering and absorption properties stable for 5 h after mixing. The role of surfactant in PpIX phantoms was found to be complex, as aggregation was evident in aqueous nonturbid phantoms with no surfactant (0% Tween), and avoided in phantoms containing Intralipid as the scattering source with no additional or low amounts of added surfactant (≤ 0.1% Tween). Conversely, phantoms containing higher surfactant content (>0.1% Tween) and whole blood showed interactions that distorted the fluorescence emissions.

Spectroscopic separation of Cerenkov radiation in high-resolution radiation fiber dosimeters.

We have investigated Cerenkov radiation generated in phosphor-based optical fiber dosimeters irradiated with clinical electron beams. We fabricated two high-spatial resolution fiber-optic probes, with 200 and 400 µm core diameters, composed of terbium-based phosphor tips. A generalizable spectroscopic method was used to separate Cerenkov radiation from the transmitted signal by the fiber based on the assumption that the recorded signal is a linear superposition of two basis spectra: characteristic luminescence of the phosphor medium and Cerenkov radiation. We performed Monte Carlo simulations of the Cerenkov radiation generated in the fiber and found a strong dependence of the recorded Cerenkov radiation on the numerical aperture of the fiber at shallow phantom depths; however, beyond the depth of maximum dose that dependency is minimal. The simulation results agree with the experimental results for Cerenkov radiation generated in fibers. The spectroscopic technique used in this work can be used for development of high-spatial resolution fiber micro dosimeters and for optical characterization of various scintillating materials, such as phosphor nanoparticles, in ionizing radiation fields of high energy.

Sub-diffusive scattering parameter maps recovered using wide-field high-frequency structured light imaging.

This study investigates the hypothesis that structured light reflectance imaging with high spatial frequency patterns [Formula: see text] can be used to quantitatively map the anisotropic scattering phase function distribution [Formula: see text] in turbid media. Monte Carlo simulations were used in part to establish a semi-empirical model of demodulated reflectance ([Formula: see text]) in terms of dimensionless scattering [Formula: see text] and [Formula: see text], a metric of the first two moments of the [Formula: see text] distribution. Experiments completed in tissue-simulating phantoms showed that simultaneous analysis of [Formula: see text] spectra sampled at multiple [Formula: see text] in the frequency range [0.05-0.5] [Formula: see text] allowed accurate estimation of both [Formula: see text] in the relevant tissue range [0.4-1.8] [Formula: see text], and [Formula: see text] in the range [1.4-1.75]. Pilot measurements of a healthy volunteer exhibited [Formula: see text]-based contrast between scar tissue and surrounding normal skin, which was not as apparent in wide field diffuse imaging. These results represent the first wide-field maps to quantify sub-diffuse scattering parameters, which are sensitive to sub-microscopic tissue structures and composition, and therefore, offer potential for fast diagnostic imaging of ultrastructure on a size scale that is relevant to surgical applications.

Dual-channel red/blue fluorescence dosimetry with broadband reflectance spectroscopic correction measures protoporphyrin IX production during photodynamic therapy of actinic keratosis.

Dosimetry for aminolevulinic acid (ALA)-induced protoporphyrin IX (PpIX) photodynamic therapy of actinic keratosis was examined with an optimized fluorescence dosimeter to measure PpIX during treatment. While insufficient PpIX generation may be an indicator of incomplete response, there exists no standardized method to quantitate PpIX production at depths in the skin during clinical treatments. In this study, a spectrometer-based point probe dosimeter system was used to sample PpIX fluorescence from superficial (blue wavelength excitation) and deeper (red wavelength excitation) tissue layers. Broadband white light spectroscopy (WLS) was used to monitor aspects of vascular physiology and inform a correction of fluorescence for the background optical properties. Measurements in tissue phantoms showed accurate recovery of blood volume fraction and reduced scattering coefficient from WLS, and a linear response of PpIX fluorescence versus concentration down to 1.95 and 250 nM for blue and red excitations, respectively. A pilot clinical study of 19 patients receiving 1-h ALA incubation before treatment showed high intrinsic variance in PpIX fluorescence with a standard deviation/mean ratio of > 0.9. PpIX fluorescence was significantly higher in patients reporting higher pain levels on a visual analog scale. These pilot data suggest that patient-specific PpIX quantitation may predict outcome response.

Clinical feasibility of monitoring m-THPC mediated photodynamic therapy by means of fluorescence differential path-length spectroscopy.

The objective quantitative monitoring of light, oxygen, and photosensitizer is challenging in clinical photodynamic therapy settings. We have previously developed fluorescence differential path-length spectroscopy (FDPS), a technique that utilizes reflectance spectroscopy to monitor microvascular oxygen saturation, blood volume fraction, and vessel diameter, and fluorescence spectroscopy to monitor photosensitizer concentration. In this paper the clinical feasibility of the technique is tested on eight healthy volunteers and on three patients undergoing PDT of oral cavity cancers. Model-based analysis of the measured spectra provide quantitative tissue parameters that are corrected for background tissue absorption, autofluorescence, and the transmission of the optical system; this method allows comparison of intra- and inter-subject parameters. The FDPS correctly estimated the absence of m-THPC in volunteers and detected photobleaching in the areas receiving treatment light in patients undergoing PDT treatment. This study demonstrates the feasibility of monitoring clinical photodynamic therapy treatments using optical spectroscopy.

Integration of single-fiber reflectance spectroscopy into ultrasound-guided endoscopic lung cancer staging of mediastinal lymph nodes.

We describe the incorporation of a single-fiber reflectance spectroscopy probe into the endoscopic ultrasound fine-needle aspiration (EUS-FNA) procedure utilized for lung cancer staging. A mathematical model is developed to extract information about the physiological and morphological properties of lymph tissue from single-fiber reflectance spectra, e.g., microvascular saturation, blood volume fraction, bilirubin concentration, average vessel diameter, and Mie slope. Model analysis of data from a clinical pilot study shows that the single-fiber reflectance measurement is capable of detecting differences in the physiology between normal and metastatic lymph nodes. Moreover, the clinical data show that probe manipulation within the lymph node can perturb the in vivo environment, a concern that must be carefully considered when developing a sampling strategy. The data show the feasibility of this novel technique; however, the potential clinical utility has yet to be determined.

On morphometric measurement of oxygen diffusing capacity in middle ear gas exchange.

An accurate mathematical model of transmucosal gas exchange is prerequisite to understanding middle ear (ME) physiology. Current models require experimentally measured gas species time constants for all extant conditions as input parameters. However, studies on pulmonary gas exchange have shown that a morphometric model that incorporates more fundamental physiochemical and anatomic parameters accurately simulates transport from which the species time constants can be derived for all extant conditions. Here, we implemented a variant of that model for ME gas exchange that requires the measurement of diffusional length (tau) for the ME mucosa. That measure contributes to the mucosal diffusing capacity and reflects the resistance to gas flow between air space and capillary. Two methods for measuring tau have been proposed: linear distance between the air-mucosal boundary and capillary and the harmonic mean of all contributing pathway lengths. Oxygen diffusing capacity was calculated for different ME mucosal geometries by using the two tau measures, and the results were compared with those predicted by a detailed, two-dimensional finite element analysis. Predictive accuracy was improved by incorporating the harmonic tau measure, which captures important information regarding variations in capillary shape and distribution. However, compared with the oxygen diffusing capacity derived from the finite element analysis, both measures yielded nonlinear, positively biased estimates. The morphometric techniques underestimate diffusion length by failing to account for the curvilinear gas flow pathways predicted by the finite element model.

Barotrauma during air travel: predictions of a mathematical model.

Middle ear barotrauma during flight is a painful disorder experienced by passengers who cannot properly regulate their middle ear pressure in response to the changing cabin pressures during ascent and descent. Previous reports emphasized the important role of poor eustachian tube function in disease pathogenesis but paid little attention to other moderating factors. Here we describe a mathematical model of middle ear pressure regulation and simulate the pressure response to the changes in cabin pressure experienced over typical flights. The results document buffering mechanisms that decrease the requisite efficiency of active, muscle-assisted eustachian tube opening for disease-free flight. These include the relative difference between destination and departure elevations and the ratio of maximum tympanic membrane volume displacement to middle ear volume, where greater absolute values require lesser efficiencies for disease-free flight. Also, the specific type of functional deficit is important since ears with a completely obstructed eustachian tube can be less susceptible to barotrauma than those with a eustachian tube that passively opens but fails to dilate in response to muscle activity. These buffering systems can explain why some children and adults with poor eustachian tube function do not experience middle ear barotrauma.