Improvements in clinical signs of Parkinson’s disease using photobiomodulation: A prospective proof-of-concept study

Liebert, Ann; Bicknell, Brian; Laakso, E-Liisa; Heller, Gillian Z.; Jalilitabaei, Parastoo; Tilley, Sharon; Mitrofanis, John; Kiat, Hosen

doi:10.1101/2021.05.26.21257833

Cited by 7 publications

(11 citation statements)

References 84 publications

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“…Of the 74 selected reports in the definition branch, 15 were randomized controlled trials (RCTs) (25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39), two were not randomized controlled trials (40,41), three were studies nested in RCTs (42)(43)(44), seven were retrospective reanalysis or discussions of RCTs (23,24,(45)(46)(47)(48)(49), three were pilot studies prior to an RCT (50)(51)(52), and one was an RCT protocol (53). Further, there were 18 observational studies (54-71), 18 pre-post intervention studies or audits (21,22,(72)(73)(74)(75)(76)(77)(78)(79)(80)(81)(82)(83)(84)(85)(86)…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Of the 15 purposely selected reports in primary care, outpatient clinics, or healthy subjects in the meta-analysis branch, the appraisal of the HE was based on a retrospective cohort pre-post intervention analysis in one study (72), in three studies on a post-hoc comparison of the RCT population to a non-RCT population (24,30,94), in three studies on the comparison of study parameters between enrollment and randomization in an RCT (28,43,51), in two studies on the comparison of persons consenting vs. not consenting to participate in a study (45,67), in two studies on the followup of study populations exposed to repeated measurements Frontiers in Medicine 04 frontiersin.org (77, 95), and in four studies comparing a population being aware of exposure to observation or assessment to a population who were not aware (33,64,83,96). The main binary outcomes that were inputted in the tables of the review manager to compute an effect size and standard error were sleeping time (28), anti-malarial drug prescriptions (33), time up and go measure (51), self-reported alcohol consumption (96), pain intensity (43), and subjective shared decision-making (95) in the RCTs or RCT feasibility studies. It was an antibiotic selection in a quasi-experimental RCT (30).…”

Section: Study Characteristicsmentioning

confidence: 99%

“…In the meta-analysis branch, one study had a low risk of bias (28), seven a moderate risk (24,30,33,43,45,94,96), and seven a high risk (51,64,67,72,77,83,95).…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

“…It happens because values are observed with random error, that is a non-systematic variation in the observed values around a true mean (103). When patients are enrolled into a trial based on a deviating value of the main outcome and randomized a couple of weeks or months later, it can happen at randomization that the deviation of the main outcome is considerably reduced (26,28,43,51). It is then difficult to differentiate the part of the HE and the one of the RTM.…”

Section: Figurementioning

confidence: 99%

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Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis

et al. 2022

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In 2015, we conducted a randomized controlled trial (RCT) in primary care to evaluate if posters and pamphlets dispensed in general practice waiting rooms enhanced vaccination uptake for seasonal influenza. Unexpectedly, vaccination uptake rose in both arms of the RCT whereas public health data indicated a decrease. We wondered if the design of the trial had led to a Hawthorne effect (HE). Searching the literature, we noticed that the definition of the HE was unclear if stated. Our objectives were to refine a definition of the HE for primary care, to evaluate its size, and to draw consequences for primary care research. We designed a Preferred Reporting Items for Systematic reviews and Meta-Analyses review and meta-analysis between January 2012 and March 2022. We included original reports defining the HE and reports measuring it without setting limitations. Definitions of the HE were collected and summarized. Main published outcomes were extracted and measures were analyzed to evaluate odds ratios (ORs) in primary care. The search led to 180 records, reduced on review to 74 for definition and 15 for quantification. Our definition of HE is “an aware or unconscious complex behavior change in a study environment, related to the complex interaction of four biases affecting the study subjects and investigators: selection bias, commitment and congruence bias, conformity and social desirability bias and observation and measurement bias.” Its size varies in time and depends on the education and professional position of the investigators and subjects, the study environment, and the outcome. There are overlap areas between the HE, placebo effect, and regression to the mean. In binary outcomes, the overall OR of the HE computed in primary care was 1.41 (95% CI: [1.13; 1.75]; I2 = 97%), but the significance of the HE disappears in well-designed studies. We conclude that the HE results from a complex system of interacting phenomena and appears to some degree in all experimental research, but its size can considerably be reduced by refining study designs.

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Section: Study Characteristicsmentioning

confidence: 99%

Section: Study Characteristicsmentioning

confidence: 99%

“…In the meta-analysis branch, one study had a low risk of bias (28), seven a moderate risk (24,30,33,43,45,94,96), and seven a high risk (51,64,67,72,77,83,95).…”

Section: Risk Of Bias Within Studiesmentioning

confidence: 99%

Section: Figurementioning

confidence: 99%

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Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis

et al. 2022

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“…A review of PBM as a therapy for Alzheimer's disease is provided in dos Santos Cardoso et al ( 26 ). In a recent proof-of-concept study, significant improvements in clinical signs of Parkinson's disease after treatment with NIR PBM have been found ( 27 ). The effect of NIR PBM on brain activity (resting and evoked) in humans using MRI has also been investigated ( 28 ).…”

Section: Introductionmentioning

confidence: 99%

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

Staelens

Gregorio

Kalra

et al. 2022

Front. Med. Technol.

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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.

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Photobiomodulation for modulation of neuropathic pain and improvement of scar tissue

Santiago¹,

Gomes²,

Ozsarfati³

et al. 2022

Scars, Burns & Healing

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Background This case-report explores the effects of photobiomodulation therapy (PBMT) on the healing of scar tissue. The patient was a 32-year old female two years post cholecystectomy resulting in a 15 cm linear scar that was causing severe pain. Methods Treatment was initiated using the BIOFLEX® therapist device which consists of LED arrays and laser probes of a specific wavelength, power and frequency applied directly on the skin overlying the scar. The frequency and duration of treatment was every other day for six weeks in a clinic setting, followed by three times a week for two months at home. Then the patient continued to use the BIOFLEX® therapist home device on an as-needed basis. Findings The final result of this patient's treatment was significant flattening and decreased redness of her scar. Her self-reported pain decreased to a 6/10. At the one year follow up, the patient reported that she stopped taking her opioids, antidepressant and sleeping pills and that her pain decreased to a 4/10. At the last review her pain score was 1/10; and she had returned to work and took Tylenol (acetaminophen) occasionally for breakthrough pain. Conclusions We attribute the patient's improvement in scar appearance and pain symptoms to PBMT. Since pain is often associated with depressed mood and sleep disturbances, it cannot be determined whether PBMT was the direct or indirect cause of this patient's improved mood. For future studies, we propose the use of control subjects with similar scars treated with sham treatment compared to those who will receive the PBMT and observed for the same duration of time and compare the overall results. Lay Summary Dermatological applications, especially wound healing; are accepted indications for photobiomodulation therapy (PBMT). The expansion into other clinical applications, particularly neurological ones show potential benefit. We present a case of a patient with a hypertrophic scar associated with severe neuropathic pain and concurrent depression, all of which improved directly or indirectly with PBMT. Although the original focus of treatment was dermatological the improvement in pain plus the discontinuation of therapy (opioids, antidepressants and benzodiazepines) were considered to be due to the PBMT.

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Improvements in clinical signs of Parkinson’s disease using photobiomodulation: A prospective proof-of-concept study

Cited by 7 publications

References 84 publications

Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis

Defining and evaluating the Hawthorne effect in primary care, a systematic review and meta-analysis

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

Photobiomodulation for modulation of neuropathic pain and improvement of scar tissue

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