Patent Publication Number: US-2012029372-A1

Title: Drug Delivery Methods and Systems

Description:
TECHNICAL FIELD 
     This disclosure relates to drug delivery methods and systems, for example, methods and systems that include a determination of whether a cardiac condition is normal or abnormal, so that a drug may be administered in accordance with that determination. 
     BACKGROUND 
     Many people have an abnormal heart condition. One example of abnormal heart conditions is an arrhythmia where the heart beats irregularly. An arrhythmia can be a bradycardia where the heart beats abnormally slow or a tachyarrhythmia where the heart beats abnormally fast. Various different devices and systems are available to detect and address abnormal heart conditions. For example, cardiac stimulation devices may provide electrical therapy to address a detected arrhythmia. In another example, a physician may evaluate a patient&#39;s condition, and prescribe drug therapy to address an abnormal condition that the physician determines to be present. In the case of a determined arrhythmia, for example, an antiarrihythmic drug such as Ibutilide may be prescribed to prevent or reduce a patient&#39;s arrhythmia. An improvement in the patient&#39;s arrihythmic condition may result that a dosage prescribed by a physician becomes unnecessarily strong. 
     Another example of an arrhythmia condition is atrial fibrillation (AF). AF may be a chronic condition in some patients, or may be non-chronic, in the case of atrial flutter or generally paroxysmal AF. During AF, blood is not pumped effectively from the atria, so it may pool there and clot. If a whole or partial blood clot leaves the heart and becomes lodged in an artery in the brain, a stroke results. Current statistics show that approximately fifteen percent of strokes occur in people with AF. 
     Anticoagulants such as Warfarin and Heparin thin the blood, making it less prone to clotting. Therefore, these drugs are used to help reduce the risk of stroke in people with AF. Long-term use of Warfarin in patients with AF and other stroke risk factors has been shown to reduce stroke by sixty-eight percent. However, while Warfarin is effective against embolic stroke, its chronic use may have serious side effects which may include potential bleeding problems and ulcers. 
     SUMMARY 
     In one general aspect, a method of regulating drug administration to a patient includes administering a drug at an initial dosage level to a patient via a drug delivery unit. The method also includes monitoring a cardiac signal using a cardiac monitoring unit. The method further includes reducing to a reduced dosage level that is lower than the initial dosage level when the monitored cardiac signal indicates a healthy cardiac sinus rhythm is present for at least a predetermined amount of time. 
     In various implementations, the method may include one or more of the following features. The method may include administering the drug that may be accomplished by the patient or by a drug delivery system that may be external to the patient or implanted in the patient. The cardiac monitoring unit may be implanted in the patient and may monitor various cardiac signals including an electrocardiogram signal, a blood flow signal, and a blood pressure signal. The drug delivered may include an anticoagulant drug or an antiarrhythmic drug. The initial dosage level may be determined by a physician. The reduced dosage level may be a predetermined minimum level for patient safety that may be selected by a physician. 
     The method may also include factoring in the ability of blood to properly clot before reducing to the reduced dosage level. The ability of blood to properly clot may be represented by a lab-measured, device-measured or patient-measured International Normalization Ratio (INR), and a desired INR level may be determined by the amount of time that the patient is in a healthy sinus rhythm. 
     The method may further include resuming the drug administration or increasing the drug dosage when the monitored cardiac signal indicates the absence of a healthy cardiac sinus rhythm for at least a predetermined period of time. The amount of drug dosage increase may be determined by the amount of time the patient is in a healthy sinus rhythm. In some implementations, the dosage increase does not exceed the initial dosage level. 
     The method may also include tracking the amount of the drug that has been administered to the patient and providing an alert when the amount of the drug administered reaches a predetermined maximum dosage amount. In some implementations, the drug delivery unit and the cardiac monitoring unit are contained within a single housing. In some implementations, the drug delivery unit is contained within a first housing, and the cardiac monitoring unit is contained within a second housing different from the first housing. 
     In another general aspect, a patient monitoring and notification system includes a cardiac monitoring system having a cardiac condition sensor and a processing unit adapted to receive cardiac signals sensed over a time period by the cardiac condition sensor; determine from the received cardiac signals a time measure indicating a duration of the time period that a cardiac condition is normal; and generate, from the determined duration of the normal cardiac condition, prescriptive information relevant to an on-going therapy being administered to the patient. The system also includes a user notification device adapted to receive the prescriptive information from the cardiac monitoring system, and provide a user output adapted to inform the user as to how the therapy should be administered. 
     In various implementations, the patient monitoring and notification system may include one or more of the following features. The cardiac monitoring system may be an implantable subcutaneous ECG monitoring system having a first telemetry component to wirelessly transmit information indicative of the determined cardiac condition of normal or abnormal. The notification device may be a component of external equipment having a second telemetry component to receive the wirelessly transmitted information indicative of the determined cardiac condition. The cardiac monitoring system may process a monitored subcutaneous system to evaluate sinus rhythm, and determines a cardiac condition to be normal if a healthy sinus rhythm has been present for a predetermined amount of time. The determination of the cardiac condition being normal or abnormal may involve use of a ratio of an amount of time during which healthy sinus rhythm is present compared to overall time. 
     In still another general aspect, a drug infusion system includes a cardiac monitoring unit adapted to sense, from a subject, cardiac signals from which a sinus rhythm condition is evidenced if present. The system also includes a drug delivery unit adapted to contain and deliver to the patient an anticoagulant drug. The system further includes a processing and control unit adapted to receive the sensed cardiac signals, perform an assessment of sinus rhythm, and control delivery of the anticoagulant drug by the drug delivery unit based on the assessment of sinus rhythm. 
     In various implementations, the system may include one or more of the following features. The processing and control unit may be programmable to provide an initial drug dosage level at which the anticoagulant drug is delivered to the patient. The processing and control unit may be adapted to cease delivery of the anticoagulant drug if the processing and control unit determines that the subject is in healthy sinus rhythm for a predetermined amount of time. The processing and control unit may also be adapted to reduce the dosage level at which the anticoagulant drug is delivered if the processing and control unit assesses that a condition exists indicative of a reduced risk of blood clotting from atrial fibrillation. The cardiac monitoring unit may include a cardiac electrical activity sensor or a hemodynamic sensor. 
     In yet another general aspect, a method for providing anticoagulant therapy to a patient having an atrial fibrillation condition includes controlling, at a programmed initial dosage level, infusion of an anticoagulant drug from a drug delivery unit to a subject. The method also includes monitoring cardiac signals of the subject, and determining from the monitored cardiac signals if there is present an improved condition indicative of a reduced risk of blood clotting in the subject from atrial fibrillation. The method further includes if the improved condition is determined to be present, controlling the infusion of the anticoagulant drug from the drug delivery unit at a reduced dosage level that is lower than the initial dosage level. 
     In various implementations, the method may include one or more of the following features. The method may include receiving an input providing the programmed initial dosage level. The reduced dosage level may be substantially zero if it is determined that the atrial fibrillation condition has ceased to exist in the subject. The sensed cardiac signals may include electrical signals indicative of cardiac activity or hemodynamic signals indicative of cardiac activity. 
     The details of one or more implementations are set forth in the accompanying drawings and the description below. Other features, objects, and advantages will be apparent from the description and drawings, and from the claims. 
    
    
     
       DESCRIPTION OF DRAWINGS 
         FIG. 1  is a block diagram of an exemplary drug delivery system; 
         FIGS. 2A-2C  are diagrams that illustrate a variety of different ways that the drug delivery system of  FIG. 1  could be implemented; 
         FIG. 2D  is a diagram illustrating a patient monitoring system that provides a notification of a patient cardiac condition. 
         FIGS. 3A and 3B  are flow charts illustrating exemplary methods for regulating drug administration to a patient with abnormal cardiac condition using the drug delivery system shown in  FIGS. 2A-2D ; and 
         FIG. 4  is a flow chart illustrating an exemplary method of continued drug administration after implementing the method shown in  FIG. 3A . 
         FIG. 5  is a block diagram of various components that may be used in a device to implement the methods described herein or portions thereof. 
     
    
    
     Like reference symbols in the various drawings indicate like elements. 
     DETAILED DESCRIPTION 
     Generally, this document describes systems and methods that include a determination of whether a cardiac condition is normal or abnormal, so that, for example, a drug may be administered in accordance with that determination. In one implementation, shown for example in  FIGS. 1 ,  2 A- 2 C and  3 A, a controllable drug delivery unit (for example, a wearable or implantable drug infusion pump) is used, and is controlled in accordance with a determination made as to whether a cardiac condition is normal or abnormal. For example, in a case where it is detected that a cardiac condition is no longer abnormal (i.e., the condition is normal), then the drug delivery device may be controlled to reduce, or perhaps entirely suspend, delivery of the drug. In another implementation, shown for example in  FIGS. 2D and 3B , a patient monitoring device monitors and makes a determination as to a duration that a cardiac condition is normal, and provides an output indicative of the determination. In this case, a patient may alter a drug therapy in accordance with the determination of normal or abnormal that is made by the monitoring device. 
     Referring first to  FIG. 1 , there is shown a general block diagram of a drug delivery system  100 . The drug delivery system  100 , generally, includes a cardiac monitoring unit  110  that is adapted to monitor cardiac signals, a drug delivery unit  120  that is adapted to deliver a drug using a pump for example, and a processing and control unit  130  that is adapted to receive and assess monitored cardiac signals and control drug delivery. 
     Generally, in operation, the drug delivery system  100  may be programmed to perform as follows. Initially, the processing and control unit  130  may be programmed, for example using programming equipment (not shown), to control the drug delivery unit  120  to infuse a drug at an initial dosage level. The cardiac monitoring unit  110  of the system  100  monitors cardiac signals of a subject, for example, an electrocardiogram (ECG) signal. That monitored information may be used by the system  100  to alter the dosage level after the initial programming. In particular, for example, the system  100  may determine that the cardiac activity of the subject is sufficiently satisfactory to reduce the dosage level of the drug being infused. The processing and control unit  130  may be programmed to analyze the monitored signals, and to employ an algorithm that determines when to reduce the dosage level, and by how much. This feature may be useful, for example, in situations where there may be negative consequences to applying a drug when not necessary or in too large of dosage levels. More generally even, it is preferable not to provide a patient a drug unnecessarily. 
     One example in which the drug delivery system  100  may be particularly useful is in the administration of anticoagulation therapy to a patient with AF. In this example, the processing and control unit  130  may be user programmable to provide an initial dosage level at which an anticoagulant is delivered to the patient by the drug delivery unit  120 . Representative examples of anticoagulants include Biotinylated Idraparinux, Heparin, Warfarin, Clopidogrel, and Dipyridamole. The cardiac monitoring unit  110  senses cardiac signals of the patient that may indicate whether an AF condition is present in the patient. Examples of such cardiac signals include ECG and blood pressure or flow. The processing and control unit  130  executes a stored algorithm (i.e., computer program with executable instructions) to receive the sensed cardiac signals and assess the patient&#39;s AF condition, and to reduce the dosage level at which the anticoagulant is delivered to the patient or even suspend the delivery of the anticoagulant when the assessment shows the risk of blood clotting from AF is reduced or the patient appears to no longer have an AF condition. This ability to reduce anticoagulant delivery after initial dosage may be a significant improvement on traditional anticoagulation therapies where constant dosage levels may otherwise be carried out for an entire period of time between visits to a physician. During these intervals, the patient&#39;s condition may improve, either permanently or for periods of time, and it may be a benefit to reduce the dosage levels when this occurs. 
     Regarding more details of the basic components of the drug delivery system  100 , the cardiac monitoring unit  110  may be any suitable device that is capable of monitoring cardiac signals of a subject. As an example of a cardiac monitoring unit  110  that monitors cardiac electrical activity, the unit  110  may be a sensor that senses an ECG signal and may employ a lead system to do that. The monitoring unit  110  may be an external unit that monitors a skin or surface ECG signal, or may be fully implantable. The lead system includes electrodes that may be provided, for example, on a surface of the unit  110  (e.g., for an implantable unit to monitor a subcutaneous ECG signal), or may extend from the unit  110 . The electrical activity may be, for example, a subcutaneous ECG signal, or in an embodiment where the lead system extends into and has electrodes that are positioned within the heart, the electrical activity being monitored may be a cardiac electrogram, also referred to as an Egram or EGM. 
     Additionally or alternatively to sensing cardiac electrical activity, the cardiac monitoring unit  110  may include a pressure sensor to measure blood pressure or flow. An example of such a pressure sensor is a pressure sensor device that comprises a fluid-filled pressure transmission catheter that transmits a pressure force exerted on a distal tip of the catheter through a pressure transmitting fluid contained within a lumen of the catheter and to a pressure transducer positioned at a proximal end of the pressure transmission catheter. Such a device may be used to measure pressure at a location where the tip of the pressure transmission catheter is positioned, which may be, for example, within a blood vessel of a patient. Other representative examples of catheter-based, blood pressure or flow sensors include Millar catheters and Swann-Ganz catheters. Non-catheter-based pressure sensors may also be used. 
     The drug delivery unit  120  of the drug delivery system  100  can be any suitable device that is controlled by a control unit and is capable of delivering a drug to a patient. For example, the drug delivery unit  120  can be a drug pump with a reservoir through which the drug is delivered. The drug delivery unit  120  may be an externally worn device, for example clipped to a belt and having an attached infusion set for delivering a drug internally into the patient. Alternatively, the drug delivery unit  120  may be a fully implantable device. 
     The processing and control unit  130  of the drug delivery system  100  comprises processing circuitry that executes an algorithm to control the receipt of the monitored cardiac signals and the analysis of the signals to determine whether the dosage level of drug infusion should be altered. As one example, the control unit  130  may process the monitored cardiac signals to determine if a healthy cardiac sinus rhythm is present for at least a predetermined period of time, in which case, the dosage level may be reduced, and the control unit  130  may calculate when to reduce the dosage level, and by how much. In addition, for example, the control unit  130  may also, subsequent to causing the dosage level to be reduced, determine that newly monitored cardiac signals show abnormal cardiac activity has returned, and as a result may increase the dosage level, for example, to the level initially programmed, or for example, to a level that is somewhere between the initially programmed level and a present, lower dosage level. 
     Sinus rhythm is the normal rhythm of the heart originated in the sinoatrial node. Sinus rhythm can be measured by ECG. A healthy sinus rhythm with ECG including normal sinus rhythm, sinus bradycardia and sinus tachycardia is typically characterized by regular rhythm, rate between 40 and 160 beats per minute where rate changes are gradual, P-waves that are upright and have a consistent morphology and precede each QRS complex, PR interval that is from 0.12 to 0.20 seconds, QRS duration that is 0.1 seconds or less, consistent QRS morphology, and the like. Sinus rhythm can also be measured by blood pressure or flow. A healthy sinus rhythm with blood pressure or flow is typically characterized by regular rhythm, consistent amplitude and morphology for a given rate, gradual rate changes, and the like. 
     In addition to analyzing the monitored cardiac signals, the processing and control unit  130  also controls the operation of the drug delivery unit  120 . For example, the processing and control unit  130  can instruct the drug delivery unit  120  to dispense to a patient a drug at an initial dosage level that is determined by a physician to treat the patient&#39;s abnormal cardiac condition. The processing and control unit  130  can also command the drug delivery unit  120  to reduce the drug dosage level, or stop the drug administration entirely, when the unit  130  determines that the monitored cardiac signals indicate a healthy cardiac sinus rhythm for at least a predetermined period of time. 
       FIGS. 2A-2D  illustrate a variety of different ways that the drug delivery system  100  of  FIG. 1  could be implemented.  FIG. 2A  illustrates a drug delivery system  200  where the cardiac monitoring unit  210 , the drug delivery unit  220  and the processing and control unit  230  are all contained within a single housing  260 . The system  200  also includes an external programming device  240  that communicates, for example wirelessly, with the processing and control unit  230 . As shown in  FIG. 2A , the housing  205  can be implanted in the body of a patient  202  or worn by the patient  202 , and in particular implanted subcutaneously or worn in a pectoral region of the patient&#39;s body  202 . Alternatively, the housing  205  can be implanted subcutaneously or worn in an abdominal region of the patient&#39;s body  200  with the sensing electrodes (not shown) of the monitoring unit  210  placed in the heart. Such positioning is useful, for example, to enable the monitoring unit  210  to monitor, for example, an electrocardiogram (ECG) signal of the body&#39;s heart. In other embodiments, however, the monitoring unit  210  may monitor blood pressure or flow. Communication links (not shown) such as bus links allow signal transmissions between the processing and control unit  230  and the cardiac monitoring unit  210  and the drug delivery unit  220 . The external programming device  240  can be any suitable device where a user (e.g., patient or physician) can input various commands to program the processing and control unit  230 . 
       FIG. 2B  illustrates a drug delivery system  200  where the cardiac monitoring unit  210  and the processing component  230 A of the processing and control unit  230  are contained within one housing  262  while the drug delivery unit  220  and the control component  230 B of the processing and control unit  230  are contained within a different housing  264 . The system  200  also includes an external programming device  240  that communicates, for example wirelessly, with the processing component  230 A of the unit  230 . As shown in  FIG. 2B , both housings  262 ,  264  can be implanted in the body of a patient  202  or worn by the patient  202 , and in particular the housing  262  implanted subcutaneously or worn in a pectoral region of the patient&#39;s body  202  and the housing  264  implanted subcutaneously or worn in an abdominal region of the patient&#39;s body  202 . Communication links (not shown) such as bus links allow signal transmission between the processing component  230 A of the unit  230  and the cardiac monitoring unit  210  and between the control component  230 B of the unit  230  and the drug delivery unit  220 . A telemetry link such as a wireless data transmission link allows communication between the processing component  230 A and the control component  230 B of the unit  230 . 
       FIG. 2C  illustrates a drug delivery system  200  where the cardiac monitoring unit  210  is contained within one housing  266  while the drug delivery unit  220  and the processing and control unit  230  are contained within a different housing  268 . The system  200  also includes an external programming device  240  that communicates, for example wirelessly, with the processing and control unit  230 . As shown in  FIG. 2C , both housings  266 ,  268  can be implanted in the body of a patient  202  or worn by the patient  202 , and in particular the housing  266  implanted subcutaneously or worn in a pectoral region of the patient&#39;s body  202  and the housing  268  implanted subcutaneously or worn in an abdominal region of the patient&#39;s body  202 . A communication link (not shown) such as a bus link allows signal transmission between the processing and control unit  230  and the drug delivery unit  220 . A telemetry link such as a wireless data transmission link allows communication between the processing and control unit  230  and the cardiac monitoring unit  210 . 
       FIG. 2D  illustrates a patient monitoring and notification system  280  where the cardiac monitoring unit  210  and a processing component  230 A are contained within one housing  269 . The patient monitoring and notification system  280  also includes an external programming device  240  that communicates, for example wirelessly, with the processing component  230 A. The system  280  further includes a cardiac condition notifying device  245 . The notifying device  245  can be any suitable device that is capable of providing notice to a patient or physician or caregiver about the status of the patient&#39;s cardiac condition (e.g., whether the cardiac condition is normal or abnormal). For example, the notifying device  245  may be an indicator that is wearable by a patient or a patient bedside monitor that a physician or caregiver checks regularly. The drug delivery unit  220  can be a drug patch that can be adhered, for example, to an arm of a patient  202 . As shown in  FIG. 2D , the housing  269  can be implanted in the body of a patient  202  or worn by the patient  202 , and in particular implanted subcutaneously or worn in a pectoral region of the patient body  202 . The processing component  230 A communicates with the notifying device  245  via a telemetry link such as a wireless data transmission link. If the processing component  230 A determines that the patient&#39;s cardiac condition is sufficiently satisfactory to reduce the drug dosage level, the component  230 A sends a message to the notifying device  245 , reminding the patient who wears the notifying device  240  or a physician or caregiver who receives the message to remove the previously attached drug patch or to replace the previously attached drug patch with a new patch that has a lower drug dosage level or a new drug with less pharmaceutical effect. 
       FIGS. 3A and 3B  are flow charts illustrating exemplary methods  300 A,  300 B that include a determination of whether a cardiac condition is normal or abnormal. The method  300 A shown in  FIG. 3A  may be performed, for example, by the systems  200  shown in FIGS.  1  and  2 - 2 C, and the method  300 B shown in  FIG. 3B  may be performed, for example, by the system  280  shown in  FIG. 2D . 
     Referring first to  FIG. 3A , at step  305 , the processing and control unit  230  of the system  200  instructs the drug delivery unit  220  of the system  280  to infuse to a patient with abnormal cardiac condition a drug at an initial programmed dosage level that is determined by a physician to treat the patient&#39;s abnormal cardiac condition. In one implementation, the drug administered includes an antiarrhythmic drug. Representative example of antiarrhythmic drugs include Digoxin, Amiodarone, Dronedarone, Sotalol and Ibutilide. In another implementation, the drug administered includes an anticoagulant drug. Representative examples of anticoagulant drugs include Biotinylated Idraparinux, Heparin, Warfarin, Clopidogrel, and Dipyridamole. In one implementation, the drug is delivered subcutaneously. In another implementation, the drug is delivered intravenously. In still another implementation, the drug is delivered orally. 
     At step  310 , the cardiac monitoring unit  210  of the system  200  monitors cardiac signals of the patient including the ECG, blood pressure or flow, or the like. In one implementation, the monitoring unit  210  monitors the ECG. In another implementation, the monitoring unit  210  monitors the blood pressure or flow. In still another implementation, the monitoring unit  210  monitors both the ECG and the blood pressure or flow. 
     At step  315 , the processing and control unit  230  executes a stored algorithm to receive the monitored cardiac signals from the cardiac monitoring unit  210  and analyze the signals to assess whether the patient&#39;s cardiac condition has become normal. In one implementation, the monitoring unit  210  transmits the monitored cardiac signals to the processing and control unit  230  via a communication link such as a bus link. In another implementation, the monitoring unit  210  transmits the monitored cardiac signals to the processing and control unit  230  via a telemetry link  260  such as a wireless data transmission link. 
     If at step  315  the processing and control unit  230  determines that the patient&#39;s cardiac condition has been normal for at least a predetermined period of time, the unit  230  at step  320  reduces the drug delivery dosage to an appropriate level that may be determined by a physician and at step  325  commands the drug delivery unit  220  to dispense the dosage at the reduced dosage level. If at step  315  the processing and control unit  230  determines that the patient&#39;s cardiac condition is still abnormal, steps  305 - 325  are repeated until the unit  230  determines that the patient&#39;s cardiac condition has been normal for at least a predetermined period of time. 
     In one implementation where an anticoagulant drug is administered to treat a patient with an AF condition, the processing and control unit  230  may decrease the initial anticoagulant drug dosage level to a proper lower dosage level that may be prescribed by a physician when the unit  230  detects a condition that indicates a reduced risk of blood clotting from AF. The tendency of blood to clot can be represented by international normalized ratio (INR) which measures the time it takes for blood to clot and compares the time measured to an average normal time. An INR test can be performed in a laboratory or near a patient such as at the patient&#39;s home. The higher the INR, the longer it takes blood to clot. In healthy people, the INR is about 1.0. For AF patients on anticoagulants, the INR typically should be between 2.0 and 3.0. The risk of blood clotting from a patient&#39;s AF condition may thus be considered to be reduced if the patient has been taking an anticoagulant such as Warfarin and maintaining  2  to  3  INR for at least a predetermined period of time. 
     In another implementation where an anticoagulant drug is administered to treat a patient with an AF condition, the processing and control unit  230  may suspend the anticoagulant drug administration entirely when the unit  230  detects that the patient&#39;s AF condition has ceased to exist. A patient&#39;s AF condition may have ceased to exist if the patient has exhibited a healthy cardiac sinus rhythm for at least a predetermined period of time. A healthy sinus rhythm with ECG including normal sinus rhythm, sinus bradycardia and sinus tachycardia is typically characterized by regular rhythm, rate between 40 and 160 BPM where rate changes are gradual, P-waves that are upright and have a consistent morphology and precede each QRS complex, PR interval that is from 0.12 to 0.20 seconds, QRS duration that is 0.1 seconds or less, consistent QRS morphology, and the like. A healthy sinus rhythm with blood pressure or flow is typically characterized by regular rhythm, consistent amplitude and morphology for a given rate, gradual rate changes, and the like. 
     In one implementation, the drug delivery unit  220  can measure the amount of the drug that has been delivered to the patient. If the amount delivered reaches or exceeds a predetermined maximum amount, the drug delivery unit  220  provides an alert to the patient or a physician/caregiver to stop the drug administration. In another implementation, the drug delivery unit  220  can measure the amount of the drug that remains in its drug reservoir. If the remaining drug amount is below a predetermined level, the drug delivery unit  220  informs the patient or a physician/caregiver to refill the drug reservoir. 
     Referring to  FIG. 3B , at step  350 , the cardiac monitoring unit  210  of the system  200  monitors cardiac signals of the patient including the ECG, blood pressure or flow, or the like. At step  355 , the processing and control unit  230  of the system  200  analyzes the monitored cardiac signals to determine whether the patient&#39;s cardiac condition is normal or abnormal. A patient has a normal cardiac condition if the patient exhibits a healthy cardiac sinus rhythm for at least a predetermined period of time. At step  360 , the cardiac condition notifying device  245  of the system  200  produces a message to the patient or a physician/caregiver, indicating whether the patient&#39;s cardiac condition was determined to be normal or abnormal. Based on this notification message, the patient or physician/caregiver at step  365  can administer an appropriate drug dosage accordingly. In one implementation, the patient or physician/caregiver can remove a previously attached drug patch or to replace the previously attached drug patch with a new patch that has a lower drug dosage level or a new drug with less pharmaceutical effect. 
       FIG. 4  is a flow chart illustrating an exemplary method  400  of continued drug administration after implementing the method  300 A of  FIG. 3A . At step  410 , the processing and control unit  230  assesses whether the patient is still in a healthy sinus rhythm condition for at least a predetermined period of time at the current drug dosage level. If so, the unit  230  at step  420  calculates a new reduced dosage level at which the drug should be delivered. At step  422 , the unit  230  determines whether the calculated reduced dosage level has already reached or gone below a predetermined minimum dosage level that may be selected by a physician. If so, the unit  230  at step  424  sets the drug dosage to the predetermined minimum level and then at step  440  signals the drug delivery unit  220  to dispense the drug at the minimum dosage level. In one implementation, the predetermined minimum dosage level is a dosage level below which the patient with AF may suffer strokes as a result of an under-administration of an anticoagulant drug. In another implementation, the predetermined minimum dosage level is substantially zero. 
     If at step  422  the processing and control unit  230  determines that the reduced drug dosage level that is calculated at step  420  is still above the predetermined minimum level, the unit  230  at step  426  decreases the drug dosage to the level calculated at step  420  and then at step  440  instructs the drug delivery unit  220  to infuse the drug at the calculated reduced dosage level. 
     If at step  410  the processing and control unit  230  detects that the patient&#39;s cardiac condition is no longer normal, the unit  230  at step  430  calculates a new increased dosage level at which the drug should be delivered to remedy the patient&#39;s recurring abnormal cardiac condition. At step  432 , the unit  230  determines whether the increased dosage level that is calculated at step  430  has already reached or exceeded the initial dosage level that may be programmed by a physician. If so, the unit  230  at step  434  sets the drug dosage to the initial programmed level and then at step  440  commands the drug delivery unit  220  to deliver the drug at the initial dosage level. Otherwise, the unit  230  increases the drug dosage to the level calculated at step  430  and then at step  440  signals the unit  220  to dispense the drug at the calculated increased dosage level. 
       FIG. 5  is a block diagram illustrating various components that may be incorporated into a device  500  to perform the previously described methods. In some implementations, the device  500  can implement any of the methods described herein, or any portion of the methods. In some cases, the device  500  can cooperate with one or more other devices (whether implanted or external) to implement the methods discussed herein. The device  500  may include a cardiac monitoring unit  510 , a drug delivery unit  520 , a processing and control unit  530 , and a cardiac condition notifying unit. The processing and control unit  530  includes a processor  532 , a memory  534 , a storage device  536 , and a communication link  538 . Each of the components  532 ,  534 ,  536 , and  538  are interconnected using bus links. 
     The cardiac monitoring unit  510  is capable of sensing a patient&#39;s cardiac signals over a predetermined number of heartbeats or for a predetermined time interval and transmitting the sensed signals to the processing and control unit  530  for further processing. For example, the unit  510  can sense and transmit an ECG signal, or a hemodynamic signal. In some implementations, the unit  510  may sense and transmit multiple cardiac signals, such as both an electrical signal and a hemodynamic signal, either or both of which may be analyzed independently or cooperatively to determine cardiac conditions. 
     In some implementations, the monitoring unit  510  includes one or more leads (not shown), which may be configured for positioning inside or outside of a patient&#39;s heart. The one or more leads can include one or more electrodes that can sense cardiac signals. In some implementations, the one or more leads are intracardiac leads; in some implementations, the one or more leads are configured for subcutaneous positioning within a patient; in some implementations, at least one intracardiac lead and at least one subcutaneous lead are included. In some implementations, the one or more leads may be replaced or supplemented with one or more sensors or ports configured to sense a hemodynamic signal. Some implementations may include one or more catheters that may facilitate hemodynamic measurements at a distance from the device. For example, a pressure transmission catheter may be used to sense a body pressure and refer the pressure to a pressure transducer, which may be housed within the body of the monitoring unit  510  or in a separate housing, in which case the pressure information may be communicated to the monitoring unit by wired or wireless communication link. Various combinations of leads and electrodes are possible. As one example, the monitoring unit  510  may include a single lead with a single electrode, and may include a second electrode on the housing of the unit  510 . As another example, a lead may include two or more electrodes, or the housing may include two or more electrodes. Leadless implantable devices are also contemplated, where an exterior surface or the device includes electrodes and/or sensor(s) to make the measurements discussed herein. 
     In some implementations, the monitoring unit  510  includes a transceiver (not shown). The transceiver may include a transmitter and a receiver, and may communicate wirelessly with an external (or implanted) device, such as the processing and control unit  530 , using an antenna. In some implementations, the transceiver can be configured to receive command signals. For example, the receiver can receive a command that instructs the monitoring unit  510  to record a cardiac signal. In other implementations, the transceiver can receive a command signal indicating that the monitoring unit  510  should record and transmit a cardiac signal on a specified periodic basis, such as hourly, daily, or weekly. In other implementations, the transceiver can receive a command signal that instructs the monitoring unit  510  to measure a cardiac signal and transmit the signal without storing it within the unit  510 , including continuous measurement and transmit in some implementations. 
     The drug delivery unit  520  is capable of delivering a drug to a patient under the control of the processing and control unit  530 . In some implementations, the drug delivery unit  520  is a drug pump with a reservoir through which the drug is delivered. The drug delivery unit  520  may be an externally worn device, for example clipped to a belt and having an attached infusion set for delivering a drug internally into the patient. Alternatively, the drug delivery unit  120  may be a fully implantable device. In some implementations, the drug delivery unit  520  delivers the drug subcutaneously. In some implementations, the drug delivery unit  520  delivers the drug intravenously. 
     In one implementation, the processing and control unit  530  is capable of receiving the cardiac signals measured by the monitoring unit  520 , assessing the monitored signals to determine whether a patient&#39;s cardiac condition is normal or abnormal, and controlling the drug dosage delivered by the drug delivery unit  520  in accordance with that determination. The processor  532  of the processing and control unit  530  is capable of receiving and processing instructions stored in the memory  534  of the unit  530  to perform the methods disclosed herein or portions thereof. The processor  532  can be any suitable processors for the execution of instructions including both general and special purpose microprocessors, and sole processor or multiple processors. The processor  532  can execute instructions to cause the unit  530  to receive the monitored cardiac signal from the monitoring unit  510  via the communication link  538  of the unit  530 . The processor  532  can also execute instructions to cause the unit  530  to process the received cardiac signals to assess whether a patient&#39;s cardiac condition is normal or abnormal. The processor  532  can further execute instructions to cause the unit  530  to send via the communication link  538  a control signal to the drug delivery unit  520 . Based on the assessment, the signal can instruct the unit  520  to reduce the dosage administered or stop the drug administration completely if the patient&#39;s cardiac condition is normal, or to increase the drug dosage level or resume drug delivery if the patient&#39;s cardiac condition is abnormal. In some implementations, processor  532  and the memory  534  may be implemented in a programmable device, such as a programmable logical device (PLD, e.g. an FPGA) or application specific integrated circuit (ASIC). 
     In another implementation, the processing and control unit  530  is capable of receiving the cardiac signals that the monitoring unit  520  has sensed over a time period, determining from the received signals a time measure that indicates a duration of the time period that a cardiac condition is normal, and generating from the determined time measure prescriptive information that is relevant to a therapy being administered to a patient. The processor  532  of the unit  530  can execute instructions to cause the unit  530  to receive the cardiac signals that the monitoring unit  520  has measured over a time period via the communication link  538  of the unit  530 . The processor  532  can also execute instructions to cause the unit  530  to process the received cardiac signals to determine the duration of the time period that a cardiac condition is normal. The processor  532  can further execute instructions to cause the unit  530  to generate based on the determined duration prescriptive information that is relevant to an on-going patient therapy and send via the communication link  538  the prescriptive information to the cardiac condition notifying unit  545 . Based on the information received, the unit  545  can provide a user output to inform the user as how the therapy should be administered. The cardiac condition monitoring unit The notifying device  245  can be any suitable device that is capable of providing notice to a patient or physician or caregiver about the status of the patient&#39;s cardiac condition (e.g., whether the cardiac condition is normal or abnormal). For example, the notifying device  245  may be an indicator that is wearable by a patient or a patient bedside monitor that a physician or caregiver checks regularly. 
     The memory  534  can be any suitable memory that is capable of storing information. For example, the memory  534  can be a read-only memory or a random access memory or both. The communication link  538  can be any suitable link that is capable of transmitting signal data. In some implementations, the communication link  538  includes a telemetry component that can transmit or receive data wirelessly over an antenna. In some implementations, the communication link  538  includes a bus link that provides interconnectivity between the processing and control unit  530  and the monitoring unit  510  and the drug delivery unit  520 . The storage device  536  of the unit  530  can be any suitable storage device that is capable of providing mass storage such data files. For example, the storage device  534  can be a computer-readable medium such a hard disk device or an optical disk device. 
     A number of embodiments of the invention have been described. Nevertheless, it will be understood that various modifications may be made without departing from the spirit and scope of the invention. Accordingly, other embodiments are within the scope of the following claims.