阅读说明：本技术 使用光疗以增强药物有效性的昼夜节律协动 (Circadian rhythm co-activation using phototherapy to enhance drug effectiveness ) 是由 拉里·佩德森 于 2018-09-27 设计创作，主要内容包括：昼夜节律协动平台能使用药物昼夜概况,该药物昼夜概况包括药物与昼夜节律扰乱的对映并能将这种昼夜节律扰乱转变为光疗的施用以适应这种扰乱。昼夜节律协动平台能指定如何使用光疗来协动患者的昼夜节律以补偿或预期药物的副作用,并针对患者的昼夜节律来优化药物计划表以使副作用最小化并增加药物效果。昼夜节律协动平台也能收集关于药物对昼夜节律的效果的信息并与患者,医疗提供者,以及与光疗关联的其他供应者进行互动。(The circadian rhythm coordination platform can employ a drug circadian profile that includes an enantiomer of the drug with circadian rhythm disruptions and can convert such circadian rhythm disruptions into administration of phototherapy to accommodate such disruptions. The circadian rhythm coordination platform can specify how light therapy is used to coordinate a patient's circadian rhythm to compensate for or anticipate side effects of a drug, and to optimize a drug schedule for the patient's circadian rhythm to minimize side effects and increase drug efficacy. The circadian rhythm coordination platform also enables information to be gathered about the effect of drugs on circadian rhythms and to interact with patients, healthcare providers, and other providers associated with phototherapy.)

1. A method in a circadian rhythm coordination platform, the method comprising: obtaining a representation of one or more medications for a patient;

obtaining one or more circadian profiles for the one or more drugs, wherein each circadian profile maps at least one of the one or more drugs with one or more expected circadian variation;

before the circadian rhythm condition for the patient is fulfilled:

determining a current circadian rhythm of the patient;

determining a pre-treatment circadian rhythm adjustment based on the one or more circadian profiles and the patient's current circadian rhythm;

converting the pre-treatment circadian rhythm adjustment into a pre-treatment phototherapy regime; and

causing a representation of the pre-treatment phototherapy regime to be communicated via a device associated with a patient; and

after the circadian conditions for the patient are satisfied:

determining a circadian rhythm adjustment during the treatment based on the one or more circadian profiles and an expected circadian rhythm of the patient;

converting the circadian rhythm adjustment during treatment to a phototherapy regime during treatment; and

causing a representation of a phototherapy regime over the course of treatment to be communicated via a device associated with the patient.

2. The method of claim 1, wherein,

at least one of the one or more circadian profiles defines a pre-treatment circadian rhythm that specifies what the patient should be prior to commencement of the associated medication; and

the pre-treatment circadian rhythm adjustment is a difference between a patient's current circadian rhythm and a pre-treatment circadian rhythm.

3. The method of claim 1, wherein,

the patient's expected circadian rhythm is the patient's measured circadian rhythm; and

the circadian rhythm adjustment during the treatment is based on a difference between a normal circadian rhythm and a measured circadian rhythm of the patient; and the method further comprises:

determining a post-treatment circadian rhythm adjustment based on a difference between a second expected circadian rhythm and the normal circadian rhythm of the patient;

converting the post-treatment circadian rhythm adjustment into a post-treatment light therapy regimen; and

causing a representation of the post-treatment light therapy regimen to be communicated via a device associated with a patient.

4. The method of claim 1, wherein the circadian rhythm adjustment during treatment is determined as follows:

calculating an uncompensated circadian rhythm that would be generated imposing an expected circadian variation on an expected circadian rhythm of the patient; and

the difference between the uncompensated circadian rhythm and the normal circadian rhythm is determined.

5. The method of claim 1, wherein,

the circadian rhythm adjustment during treatment is a circadian rhythm adjustment during a first treatment, the circadian rhythm adjustment during the first treatment being determined based on a first circadian variation determined in one or more circadian profiles for a first phase in a course of treatment of the one or more drugs; and

the method further comprises the following steps:

determining a circadian rhythm adjustment during a second treatment based on a second circadian change determined in the one or more circadian profiles for a second phase of the course of therapy of the one or more drugs;

converting the circadian rhythm adjustment during the second treatment session to a phototherapy regime during the second treatment session; and

causing a representation of the phototherapy regime in the second therapy session to be communicated via a device associated with the patient.

6. The method of claim 1, wherein the pre-treatment circadian adjustment or the circadian adjustment during treatment is determined based on a modifier for at least one of the one or more expected circadian changes, wherein the modifier specifies one expected circadian change based on the age of the patient.

7. The method of claim 1, wherein the circadian rhythm condition comprises determining that an updated current circadian rhythm of the patient is within a threshold amount of a pre-treatment circadian rhythm, wherein the pre-treatment circadian rhythm is based on the one or more circadian profiles.

8. The method of claim, wherein the circadian rhythm condition comprises determining that the patient has completed the pre-treatment phototherapy regime.

9. A computer-readable storage medium storing instructions that, when executed by a computing system, cause the computing system to perform operations in a circadian rhythm coordination platform, the operations comprising:

obtaining a representation of one or more medications for a patient;

obtaining one or more circadian profiles for the one or more drugs, wherein each circadian profile maps at least one of the one or more drugs with one or more expected circadian rhythm variations;

determining one or more circadian rhythms of the patient;

determining circadian rhythm adjustments over one or more treatment sessions based on the one or more circadian profiles and one or more circadian rhythms of the patient;

converting the circadian rhythm adjustment during the one or more treatments into a phototherapy regime during the one or more treatments; and

causing a representation of each of the phototherapy regimes of the one or more therapy sessions to be communicated via a device associated with the patient.

10. The computer-readable storage medium of claim 9, wherein the operations further comprise, prior to determining circadian rhythm adjustments during the one or more treatments:

determining a pre-treatment circadian rhythm modulation based on the one or more circadian rhythms and a normal circadian rhythm of the patient; and

converting the pre-treatment circadian rhythm adjustment into a pre-treatment phototherapy regime.

11. The computer-readable storage medium of claim 9, wherein the operations further comprise determining a medication administration schedule for the one or more medications represented, wherein the one or more medications are expected to be most effective, and wherein the medication administration schedule is based on:

the determined one or more circadian rhythms of the patient; and

a drug circadian effect level specified in the one or more circadian profiles, wherein the drug circadian effect level defines a point in the patient's circadian rhythm at which the one or more drugs have been determined to be most effective.

12. The computer-readable storage medium of claim 9, wherein at least one of the circadian adjustments in the one or more treatment sessions is determined as follows:

calculating an uncompensated circadian rhythm that would be generated imposing an expected circadian variation on an expected circadian rhythm of the patient; and

the difference between the uncompensated circadian rhythm and the normal circadian rhythm is determined.

13. The computer readable storage medium of claim 9, wherein the circadian adjustment in the one or more treatment sessions is determined based on a modifier for at least one of the one or more expected circadian changes, wherein the modifier specifies one expected circadian change based on patient age.

14. The computer-readable storage medium of claim 9, wherein the representation of the one or more medications for the patient is obtained through an interface with a healthcare provider of the patient.

15. A system, comprising:

one or more processors;

a memory; and

a circadian rhythm coordination platform that, when executed by the one or more processors, causes the system to:

obtaining a representation of one or more medications for a patient;

obtaining one or more circadian profiles for one or more drugs, wherein each circadian profile maps at least one of the one or more drugs with one or more circadian rhythm disruptions;

determining a circadian rhythm adjustment during treatment based on the one or more circadian profiles and an expected circadian rhythm of the patient;

converting the circadian rhythm modulation during treatment to an in-treatment phototherapy regime; and

causing a representation of a phototherapy regime over the course of treatment to be communicated via a device associated with the patient.

16. The system of claim 15, wherein,

execution of the circadian rhythm coordination platform further causes the system to obtain, for a patient, a representation of a sleep or non-sleep related biometric feature or activity; and

the patient's expected circadian rhythm is based on a mapping of the representation to the patient's circadian rhythm.

17. The system of claim 16, wherein the circadian rhythm adjustment during treatment is determined as follows:

calculating an uncompensated circadian rhythm that would be generated imposing an expected circadian variation on an expected circadian rhythm of the patient; and

the difference between the uncompensated circadian rhythm and the normal circadian rhythm is determined.

18. A computer memory storing a data structure for a circadian rhythm coordination platform, the data structure comprising:

determination of one or more drugs; and

one or more enantiomers of the one or more drugs corresponding to one or more expected changes in the patient's circadian rhythm,

wherein the one or more enantiomers are based on observation of changes in circadian rhythm in the patient while the patient is taking the one or more drugs, and

wherein the data structure is used for the circadian rhythm coordination platform to determine a light therapy regime to counteract side effects of the one or more drugs.

19. The computer memory of claim 18, further comprising one or more modifiers each specifying an adjustment to an expected change in a patient's circadian rhythm for a particular context, the context comprising one or more of:

the amount of the one or more drugs prescribed;

drug administration schedule:

interaction of one or more drugs with other drugs;

the age of the patient; or

Any combination thereof.

20. The computer memory of claim 18, wherein the one or more enantiomers includes a first enantiomer for a first stage in a regimen and a second enantiomer for a second stage in the regimen specifying a different expected change in circadian rhythm for the patient from the first enantiomer.

Technical Field

The present disclosure relates to techniques for optimizing a patient's circadian rhythm (circadian rhythm) by reducing drug side effects and enhancing drug effectiveness through phototherapy. More particularly, the present disclosure relates to using phototherapy to orchestrate a patient's circadian rhythm, determining various aspects of such phototherapy personalized for both the patient and the medication, and related techniques for interacting with the patient and a variety of providers (interventions) related to the orchestration.

Background

Many serious health problems afflict the various levels of society today, largely due to the fundamental disruption (intervention) of our modern lifestyle to our daily circadian rhythm (our internal "body clock").

There are many environmental cues (cue) used to regulate the human clock, but the two strongest external cues are exposure to "light" in the morning (especially light in the blue part of the visible spectrum, i.e. the peak wavelength of sunlight), and "dark" in the night (i.e. no light, especially in the blue part of the spectrum).

Unlike our ancestors who spend time outdoors mainly during the day and sleep in a completely dark environment at night, most people today spend time indoors with limited exposure to sunlight, especially the first 1-2 hours after waking up, and at night are typically exposed to bright light from a range of electronic devices (televisions, computers, tablets, smartphones, etc.) that emit light in the blue part of the spectrum. Without the predictable and consistent environmental cues of light at the first time of waking up every morning and complete darkness at night, the human clock becomes chaotic and "out of sync" with the congenital "day/night-light/dark" convention that humans evolve in response to millions of years of time.

This circadian disturbance causes severe disruption to many different Health critical rhythms in the human body, including the wake/sleep cycle, digestion, metabolism, immune system, blood pressure, core body temperature, and cell division, etc. all of these cycles and systems are controlled by the main "body clock" located in the suprachiasmatic nucleus ("SCN") in the brain (SCN in turn communicates with "secondary clocks" located in multiple organs, and as recently demonstrated, this communication continues up to the cellular level.) each cell within the body contains its own "circadian clock" which responds to the main clock in SCN, much like musicians responding and following the guidance of the conductor in the symphonlogy consortium.) these widely spread circadian rhythms are currently thought to cause or at least contribute to the prevalence of many diseases in society including cancer, cardiovascular disease, obesity, circadian sleep disorders, and depression etc. viesh nmugam et al's "cancer, metabolic syndrome and increased risk of cardiovascular disease" can be found by Journal of Health/2013. Journal 863. the Global perturbation of Health related questions can be found by Journal of Health/2013.

This circadian disturbance impairs the body's ability to effectively and efficiently utilize the beneficial effects of melatonin peak secretion at "night", i.e. the restorative activity that occurs in vivo at night with a well-coordinated circadian rhythm, and further allows the body's immune system to function optimally against conditions ranging from less severe infections to more severe diseases.

Melatonin is commonly referred to as "sleep hormone" -but it has been well documented that it has more important functions: it acts as a "garbage collector" for the body, entering every night every cell in the body to remove "free radicals" (precursors to cancer and other diseases). All repair work that occurs in humans-up to the cellular level and this "free radical" repair-occurs while the individual is sleeping. More specifically, this internal repair work occurs only when the individual's melatonin continues uninterrupted at its maximum peak level for at least four hours (i.e., referred to as "restorative sleep"). It is during this "restorative" sleep that melatonin secreted by the pineal gland of the brain reaches its highest level in the bloodstream.

The individual has a well-coordinated or "optimal" circadian rhythm and a healthy "normal" wake/sleep "light/dark" cycle and therefore often experiences the required melatonin peak level and "restorative" sleep every night, which is done regularly and continuously, and the individual's body is and usually is capable of self-repair. In the opposite case, for individuals with disturbed circadian rhythms, the repair work does not occur regularly every night and the individual's physical repair capacity is impaired. This asynchronous body clock in turn can severely impair an individual's ability to maximally utilize the administered drugs for combating disease.

The effectiveness of drugs and other treatments, such as radiation in human clinical trials, is limited in many disease states, including many cancers, i.e., the results of the study indicate that the drug or treatment is only marginally effective compared to placebo ("control"). Many of these drugs and treatments also cause a wide range of side effects, some of which can be dangerous and even life threatening. In some cases, the side effects are severe enough to allow the patient the option to discontinue therapy rather than continue to suffer from the side effects.

Discontinuing drug therapy prior to completion of the entire prescribed (prescribed) course of therapy will at least stop any beneficial effects of the drug, rendering its efficacy less than expected or desirable. For some patients, such as patients with life-threatening diseases, premature cessation of treatment can have fatal consequences.

The most commonly reported serious (> 75%) side effect for cancer patients is fatigue associated with cancer ("CRF"). Unlike general tiredness, CRF does not disappear after sleep or rest or after treatment discontinuation-for some patients it lasts five years after treatment. CRF is difficult to alleviate, malignant and disconcerting, commonly referred to as "permanent time difference". CRF can theoretically be caused by the cancer itself or more likely by a severe disruption of the patient's internal body clock triggered by the administered drug and/or therapy. CRF has previously been demonstrated to be therapeutically resistant, and all forms of drug and behavioral intervention have failed to achieve significant patient remission.

Chronotherapy (chronotherapy) is an emerging field of research on adjusting the timing of drug administration to improve effectiveness and reduce the effects of side effects. Researchers have now demonstrated positive results in animal studies and small human clinical trials, but performance in clinical practice remains largely impractical. Currently, most patients obtain general or vague recommendations about timing of medications from the drug manufacturer or prescribing physician, such as "twice daily"; "take with food"; or "taken before sleep". Some drugs, particularly drugs administered in a clinical setting, such as chemotherapeutic drugs, include recommendations for timing, such as "administered at the same time every 24 hours or 7 days". However, these proposals are primarily directed to maintaining a constant therapeutic level of drug in the patient over time. Little attention has been paid by the manufacturer, physician, or patient himself to the patient's circadian rhythm state before, during, or after the treatment period of administration of the drug or treatment.

Known phototherapy devices (e.g., L itemook EDGE by L itemook, go L ITE B L U by Koninklijke Philips n.v. corporation, and Happy L ight L cent by Verilux corporation) can shift the user's circadian rhythm forward or backward by exposing the user's eyes to the light output of the device with peak intensity in the blue range of the visible spectrum.

More recently, devices worn on the wrist or other parts of the body, or alternatively devices mounted to beds referred to as "sleep trackers" or "activity trackers", are able to accurately monitor and record various biometric (biometrics) and activities of the wearer, such as the length of sleep (including specific sleep stages, e.g., REM), sleep onset, sleep end, heart rate, body temperature, etc., as well as the time of activity for the body-mounted device, non-nighttime sleep, etc.