Photobiomodulation Treatment with a Home-Use Device for COVID-19: A Randomized Controlled Trial for Efficacy and Safety.

Background: Photobiomodulation therapy (PBMT) using devices to deliver red and/or near-infrared light to tissues has shown promising effects in clinical settings for respiratory diseases, including potential benefits in managing symptoms associated with COVID-19. Objective: To determine if at-home self-administered PBMT for patients with COVID-19 is safe and effective. Methods: This was a randomized controlled trial (RCT) carried out at home during the COVID-19 pandemic (September 2020 to August 2021). The treatment group self-administered the Vielight RX Plus PBMT device (635 nm intranasal and 810 nm chest LEDs) and were monitored remotely. Eligible patients scored 4-7 (out of 7) for severity on the Wisconsin Upper Respiratory Symptom Survey (WURSS-44). Patients were randomized equally to Control group receiving standard-of-care (SOC) only or Treatment group receiving SOC plus PBMT. The device was used for 20 min 2X/day for 5 days and, subsequently, once daily for 30 days. The primary end-point was time-to-recovery (days) based on WURSS-44 question 1, "How sick do you feel today?". Subgroup analysis was performed, and Kaplan-Meier and Cox Proportional Hazards analysis were employed. Results: One hundred and ninety-nine eligible patients (18-65 years old) were divided into two subgroups as follows: 136 patients with 0-7 days of symptoms at baseline and 63 patients with 8-12 days of symptoms. Those with 0-7 days of symptoms at baseline recovered significantly faster with PBMT. The median for Treatment group was 18 days [95% confidence interval (CI), 13-20] versus the Control group 21 days (95% CI, 15-28), p = 0.050. The treatment:control hazard ratio was 1.495 (95% CI, 0.996-2.243), p = 0.054. Patients with symptom duration ≥7 days did not show any significant improvement. No deaths or severe adverse events (SAEs) occurred in the Treatment group, whereas there was 1 death and 3 SAEs requiring hospitalization in the Control group. Conclusions: Patients with ≤7 days of COVID-19 symptoms recovered significantly faster with PBMT compared to SOC. Beyond 7 days, PBMT showed no superiority over SOC. Trial Registration: ClinicalTrials.gov NCT04418505.

Near-Infrared Photobiomodulation of Living Cells, Tubulin, and Microtubules In Vitro.

We report the results of experimental investigations involving photobiomodulation (PBM) of living cells, tubulin, and microtubules in buffer solutions exposed to near-infrared (NIR) light emitted from an 810 nm LED with a power density of 25 mW/cm2 pulsed at a frequency of 10 Hz. In the first group of experiments, we measured changes in the alternating current (AC) ionic conductivity in the 50-100 kHz range of HeLa and U251 cancer cell lines as living cells exposed to PBM for 60 min, and an increased resistance compared to the control cells was observed. In the second group of experiments, we investigated the stability and polymerization of microtubules under exposure to PBM. The protein buffer solution used was a mixture of Britton-Robinson buffer (BRB aka PEM) and microtubule cushion buffer. Exposure of Taxol-stabilized microtubules (~2 µM tubulin) to the LED for 120 min resulted in gradual disassembly of microtubules observed in fluorescence microscopy images. These results were compared to controls where microtubules remained stable. In the third group of experiments, we performed turbidity measurements throughout the tubulin polymerization process to quantify the rate and amount of polymerization for PBM-exposed tubulin vs. unexposed tubulin samples, using tubulin resuspended to final concentrations of ~ 22.7 µM and ~ 45.5 µM in the same buffer solution as before. Compared to the unexposed control samples, absorbance measurement results demonstrated a slower rate and reduced overall amount of polymerization in the less concentrated tubulin samples exposed to PBM for 30 min with the parameters mentioned above. Paradoxically, the opposite effect was observed in the 45.5 µM tubulin samples, demonstrating a remarkable increase in the polymerization rates and total polymer mass achieved after exposure to PBM. These results on the effects of PBM on living cells, tubulin, and microtubules are novel, further validating the modulating effects of PBM and contributing to designing more effective PBM parameters. Finally, potential consequences for the use of PBM in the context of neurodegenerative diseases are discussed.

Pulsating Microbubble in a Micro-vessel and Mechanical Effect on Vessel Wall: A Simulation Study.

BACKGROUND: Microbubbles are widely used in diagnostic ultrasound applications as contrast agents. Recently, many studies have shown that microbubbles have good potential for the use in therapeutic applications such as drug and gene delivery and opening of blood- brain barrier locally and transiently. When microbubbles are located inside an elastic microvessel and activated by ultrasound, they oscillate and induce mechanical stresses on the vessel wall. However, the mechanical stresses have beneficial therapeutic effects, they may induce vessel damage if they are too high. Microstreaming-induced shear stress is one of the most important wall stresses. OBJECTIVE: The overall aim of this study is to simulate the interaction between confined bubble inside an elastic microvessel and ultrasound field and investigate the effective parameters on microstreaming-induced shear stress. MATERIAL AND METHODS: In this Simulation study, we conducted a 2D finite element simulation to study confined microbubble dynamics, also we investigated both acoustical and bubble material parameters on microbubble oscillation and wall stress. RESULTS: Based on our results, for acoustic parameters in the range of therapeutic applications, the maximum shear stress was lower than 4 kPa. Shear stress was approximately independent from shell viscosity whereas it decreased by increasing the shell stiffness. Moreover, shear stress showed an increasing trend with acoustic pressure. CONCLUSION: Beside the acoustical parameters, bubble properties have important effects on bubble behavior so that the softer and larger bubbles are more appropriate for therapeutic application as they can decrease the required frequency and acoustic pressure while inducing the same biological effects.

Artificial intelligence in outcomes research: a systematic scoping review.

Introduction: Despite the number of systematic reviews of how artificial intelligence is being used in different areas of medicine, there is no study on the scope of artificial intelligence methods used in outcomes research, the cornerstone of health technology assessment (HTA). This systematic scoping review aims to systematically capture the scope of artificial intelligence methods used in outcomes research to enhance decision-makers' knowledge and broaden perspectives for health technology assessment and adoption.Areas covered: The review identified 370 studies, consisted of artificial intelligence methods applied to adult patients who underwent any health/medical intervention and reported therapeutic, preventive, or prognostic outcomes. Artificial intelligence was mainly used for the prediction/prognosis of more frequently reported outcomes, efficacy/effectiveness, among morbidity outcomes. The predictive analysis was common in neoplastic disorders. Neural networks algorithm was predominantly found in surgical method studies, but a mixture of artificial intelligence algorithms was applied to the studies with the rest of the interventions.Expert opinion: There are certain gaps in artificial intelligence applications used in outcomes research across therapeutic areas and further considerations are needed by decision-makers before incorporating artificial intelligence usage into HTA decision-making processes.

Microbubbles and blood-brain barrier opening: a numerical study on acoustic emissions and wall stress predictions.

Focused ultrasound with microbubbles is an emerging technique for blood-brain barrier opening. Here, a comprehensive theoretical model of a bubble-fluid-vessel system has been developed which accounts for the bubble's nonspherical oscillations inside a microvessel, and its resulting acoustic emissions. Numerical simulations of unbound and confined encapsulated bubbles were performed to evaluate the effect of the vessel wall on acoustic emissions and vessel wall stresses. Using a Marmottant shell model, the normalized second harmonic to fundamental emissions first decreased as a function of pressure (>50 kPa) until reaching a minima ("transition point") at which point they increased. The transition point of unbound compared to confined bubble populations occurred at different pressures and was associated with an accompanying increase in shear and circumferential wall stresses. As the wall stresses depend on the bubble to vessel wall distance, the stresses were evaluated for bubbles with their wall at a constant distance to a flat wall. As a result, the wall stresses were bubble size and frequency dependent and the peak stress values induced by bubbles larger than resonance remained constant versus frequency at a constant mechanical index.