Overcoming randomness does not rule out the importance of inherent randomness for functionality

Ilan, Yaron

doi:10.1007/s12038-019-9958-3

Cited by 32 publications

(33 citation statements)

References 111 publications

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“…Regular fixed regimens for the administration of chronic drugs may not be compatible with physiological variabilities in biology, and this can underlie the loss of response to chronic drugs [ 26 , 28 , 47 , 48 , 49 ]. However, introducing variability into therapeutic regimens can improve the response to drugs [ 26 , 27 , 28 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 ]. Dose escalations, reductions, and intermittent dosing with drug holidays exert clinical benefits while minimizing adverse effects [ 20 , 60 , 61 , 62 , 63 ].…”

Section: Second-generation Ai Systems: Focus On Improving Clinicalmentioning

confidence: 99%

“…A prospective trial of patients with inflammatory bowel disease treated with anti-TNFs showed a loss of clinical response in 36% of patients on fixed dosing, compared with only 13% in patients on variable dosing regimens [ 64 ]. Real-world data support the beneficial effects of drug holidays and dose escalation/reduction [ 24 , 28 , 29 , 49 , 50 , 54 , 55 , 56 , 57 , 65 , 66 ]. Introducing variability into biological systems may improve their overall function and correct dysfunctions that underlie diseases [ 26 , 67 ].…”

Section: Second-generation Ai Systems: Focus On Improving Clinicalmentioning

confidence: 99%

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Improving Global Healthcare and Reducing Costs Using Second-Generation Artificial Intelligence-Based Digital Pills: A Market Disruptor

Ilan

2021

IJERPH

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Background and Aims: Improving global health requires making current and future drugs more effective and affordable. While healthcare systems around the world are faced with increasing costs, branded and generic drug companies are facing the challenge of creating market differentiators. Two of the problems associated with the partial or complete loss of response to chronic medications are a lack of adherence and compensatory responses to chronic drug administration, which leads to tolerance and loss of effectiveness. Approach and Results: First-generation artificial intelligence (AI) systems do not address these needs and suffer from a low adoption rate by patients and clinicians. Second-generation AI systems are focused on a single subject and on improving patients’ clinical outcomes. The digital pill, which combines a personalized second-generation AI system with a branded or generic drug, improves the patient response to drugs by increasing adherence and overcoming the loss of response to chronic medications. By improving the effectiveness of drugs, the digital pill reduces healthcare costs and increases end-user adoption. The digital pill also provides a market differentiator for branded and generic drug companies. Conclusions: Implementing the use of a digital pill is expected to reduce healthcare costs, providing advantages for all the players in the healthcare system including patients, clinicians, healthcare authorities, insurance companies, and drug manufacturers. The described business model for the digital pill is based on distributing the savings across all stakeholders, thereby enabling improved global health.

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Section: Second-generation Ai Systems: Focus On Improving Clinicalmentioning

confidence: 99%

Section: Second-generation Ai Systems: Focus On Improving Clinicalmentioning

confidence: 99%

Improving Global Healthcare and Reducing Costs Using Second-Generation Artificial Intelligence-Based Digital Pills: A Market Disruptor

Ilan

2021

IJERPH

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“…Physiological functional systems exhibit highly irregular and complex dynamics [167] . According to nonlinear dynamics, the pathology of disease is correlated with the loss of complexity and the inability to retain the physiological state of the system 139 , 168 , 169 , 170 , 171 , 172 , 173 . Variations in the biological system, which are critical for optimal response to multiple internal and external triggers, contribute to regulated plasticity 110 , 141 , 170 , 171 .…”

Section: Enhancing the Therapy Response Based On Individual Variability Patterns To Ensure Sustainable Augmented Antiviral Responses And mentioning

confidence: 99%

A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage

Ishay¹,

Potruch²,

Schwartz³

et al. 2021

Biomedicine & Pharmacotherapy

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Coronavirus disease 2019 (COVID-19), which is a respiratory illness associated with high mortality, has been classified as a pandemic. The major obstacles for the clinicians to contain the disease are limited information availability, difficulty in disease diagnosis, predicting disease prognosis, and lack of disease monitoring tools. Additionally, the lack of valid therapies has further contributed to the difficulties in containing the pandemic. Recent studies have reported that the dysregulation of the immune system leads to an ineffective antiviral response and promotes pathological immune response, which manifests as ARDS, myocarditis, and hepatitis. In this study, a novel platform has been described for disseminating information to physicians for the diagnosis and monitoring of patients with COVID-19. An adjuvant approach using compounds that can potentiate antiviral immune response and mitigate COVID-19-induced immune-mediated target organ damage has been presented. A prolonged beneficial effect is achieved by implementing algorithm-based individualized variability measures in the treatment regimen.

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“…For the treatment of pain, randomness in dosing and time of administration are implemented to prevent tolerance to painkillers. This stage enables overcoming tolerance in a nonchronotropic and nonindividualized way (99)(100)(101)(102)(103).…”

Section: Establishing a Dynamic Algorithm Based On Individualized Variability Ans And Chronobiology For Overcoming The Compensatory Mechamentioning

confidence: 99%

Establishment of an Individualized Chronotherapy, Autonomic Nervous System, and Variability-Based Dynamic Platform for Overcoming the Loss of Response to Analgesics

2021

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Background: Control of chronic pain and mainly the partial or complete loss of response to analgesics is a major unmet need. Multiple mechanisms underline the development of tolerance to analgesics in general and specifically to opioids. The autonomic nervous system (ANS) plays a role in the development of analgesic tolerance and chronobiology. Objectives: To review the mechanisms associated with the development of nonresponsiveness to analgesics. Study Design: Literature review. Setting: The review is followed by a description of a new method for overcoming resistance and improving the response to analgesics. Methods: Conducted a detailed review of the relevant studies describing the mechanisms that underlie tolerance to pain medications, and the potential roles of the ANS and chronobiology in the development of drug resistance. Results: The autonomic balance is reflected by heart rate variability, an example of a fundamental variability that characterizes biological systems. Chronotherapy, which is based on the circadian rhythm, can improve the efficacy and reduce the toxicity of chronic medications. In this article, we present the establishment of an individualized variability- and chronobiology-based therapy for overcoming the compensatory mechanisms associated with a loss of response to analgesics. We describe the premise of implementing personalized signatures associated with the ANS, and chronobiology, as well as with the pathophysiology of pain for establishing an adaptive model that could improve the efficacy of opioids, in a highly dynamic system. Limitations: The studies presented were selected based on their relevance to the subject. Conclusions: The described variability-based system may ensure prolonged effects of analgesics while reducing the toxicity associated with increasing dosages. Key words: Painkillers, opioids, drug resistance, compensatory mechanisms

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Overcoming randomness does not rule out the importance of inherent randomness for functionality

Cited by 32 publications

References 111 publications

Improving Global Healthcare and Reducing Costs Using Second-Generation Artificial Intelligence-Based Digital Pills: A Market Disruptor

Improving Global Healthcare and Reducing Costs Using Second-Generation Artificial Intelligence-Based Digital Pills: A Market Disruptor

A digital health platform for assisting the diagnosis and monitoring of COVID-19 progression: An adjuvant approach for augmenting the antiviral response and mitigating the immune-mediated target organ damage

Establishment of an Individualized Chronotherapy, Autonomic Nervous System, and Variability-Based Dynamic Platform for Overcoming the Loss of Response to Analgesics

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