Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy

Forkosh, Esther; Kenig, Ariel; Ilan, Yaron

doi:10.1002/prp2.616

Cited by 46 publications

(49 citation statements)

References 151 publications

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“…This enables the overcoming of intra-and inter-patient variability, which prevents the "single bullet for all" concept from being applicable to the majority of patients. This concept is being introduced for overcoming drug resistance in several chronic diseases (142,143,(145)(146)(147)(148)(149)(150)(151)(152)(153)(154)(155)(156). In the last step, signatures based on parameters relevant to the pathogenesis of HF, mechanisms of action, and the cardio renal axis are introduced in a personalized approach for tailoring the appropriate dosing in a continuous and consistent manner (143, 144) (Figure 2).…”

Section: Establishing a Chronotherapy And Variability-based Algorithm For Improving The Response To Effectivenss Of Diureticsmentioning

confidence: 99%

Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm

Kenig

Kolben

Asleh

et al. 2021

Front. Cardiovasc. Med.

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Heart failure is a major public health problem, which is associated with significant mortality, morbidity, and healthcare expenditures. A substantial amount of the morbidity is attributed to volume overload, for which loop diuretics are a mandatory treatment. However, the variability in response to diuretics and development of diuretic resistance adversely affect the clinical outcomes. Morevoer, there exists a marked intra- and inter-patient variability in response to diuretics that affects the clinical course and related adverse outcomes. In the present article, we review the mechanisms underlying the development of diuretic resistance. The role of the autonomic nervous system and chronobiology in the pathogenesis of congestive heart failure and response to therapy are also discussed. Establishing a novel model for overcoming diuretic resistance is presented based on a patient-tailored variability and chronotherapy-guided machine learning algorithm that comprises clinical, laboratory, and sensor-derived inputs, including inputs from pulmonary artery measurements. Inter- and intra-patient signatures of variabilities, alterations of biological clock, and autonomic nervous system responses are embedded into the algorithm; thus, it may enable a tailored dose regimen in a continuous manner that accommodates the highly dynamic complex system.

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Section: Establishing a Chronotherapy And Variability-based Algorithm For Improving The Response To Effectivenss Of Diureticsmentioning

confidence: 99%

Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm

Kenig

Kolben

Asleh

et al. 2021

Front. Cardiovasc. Med.

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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%

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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“…Their function changes over time and is unpredictable [62][63][64][65][66][67]. This dynamism is essential in both health and disease and is partly associated with the continuous need to respond and adapt to triggers to achieve new steady states [68][69][70][71][72][73][74][75].…”

Section: Entropy Variability and Randomness Characterize Biological S...mentioning

confidence: 99%

A Subject-Tailored Variability-Based Platform for Overcoming the Plateau Effect in Sports Training: A Narrative Review

Gelman

Berg

Ilan

2022

IJERPH

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The plateau effect in training is a significant obstacle for professional athletes and average subjects. It evolves from both the muscle-nerve-axis-associated performance and various cardiorespiratory parameters. Compensatory adaptation mechanisms contribute to a lack of continuous improvement with most exercise regimens. Attempts to overcome this plateau in exercise have been only partially successful, and it remains a significant unmet need in both healthy subjects and those suffering from chronic neuromuscular, cardiopulmonary, and metabolic diseases. Variability patterns characterize many biological processes, from cellular to organ levels. The present review discusses the significant obstacles in overcoming the plateau in training and establishes a platform to implement subject-tailored variability patterns to prevent and overcome this plateau in muscle and cardiorespiratory performance.

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Introducing variability in targeting the microtubules: Review of current mechanisms and future directions in colchicine therapy

Cited by 46 publications

References 151 publications

Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm

Improving Diuretic Response in Heart Failure by Implementing a Patient-Tailored Variability and Chronotherapy-Guided Algorithm

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

A Subject-Tailored Variability-Based Platform for Overcoming the Plateau Effect in Sports Training: A Narrative Review

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