WO2014008342A1

WO2014008342A1 - Patient analyte information display

Info

Publication number: WO2014008342A1
Application number: PCT/US2013/049226
Authority: WO
Inventors: John Michael Dobbles; Yaron Keidar; Michael Higgins
Original assignee: Edwards Lifesciences Corporation
Priority date: 2012-07-03
Filing date: 2013-07-03
Publication date: 2014-01-09

Abstract

A patient analyte information display system is disclosed. Embodiments of the invention provide for real time, persistent graphical monitoring of a patient analyte, in a historical context. A monitoring system stores and displays numerical values over time for an analyte such as blood glucose, where each value is determined based on sensor input. In some embodiments, these values can be compared to a stored limit or stored limits, which may define an acceptable range for the analyte. A graphical attribute of the display device can be set in accordance with how the numerical values compare to a the set limits in order to notify caregivers when the analyte level deviates from the acceptable range. The capability to statistically analyze analyte values over time can also be provided to enhance the display and/or project future analyte levels.

Description

PATIENT ANALYTE INFORMATION DISPLAY

BACKGROUND

[0001] Devices for measuring various physiological parameters of a patient have been a standard part of medical care for many years. The vital signs of some patients typically are measured on a substantially continuous basis to enable physicians, nurses, and other healthcare providers to detect sudden changes in a patient' s condition. Patient monitors are typically employed to display a variety of physiological patient data to physicians and other healthcare providers. Such patient data facilitates diagnosis of abnormalities or the patient's current condition.

[0002] In some circumstances, a hospital subject is continuously monitored or repeatedly tested for changes in some blood analyte levels, such as for diagnosing, monitoring and/or prognosticating a subject's medical status. In some circumstances, blood samples are collected at regular intervals, and sent to a laboratory analysis. For example, of importance for health care providers with some patients is accurate information representing the blood glucose levels of the subject, especially in a surgical or intensive care setting. In some circumstances, a bedside analyte monitor can used to monitor the levels of the analyte and the current numerical value can be displayed.

SUMMARY

[0003] Embodiments of the present invention provide for real time, persistent monitoring of a patient analyte, in a historical context. Such monitoring can provide caregivers with the ability to monitor the responsiveness of individual patients to various forms of treatment. A caregiver can use enhanced information to devise therapies, for example, in the case of blood glucose monitoring, various techniques and rates of delivering insulin. Statistical techniques can also be used to display numerical analyte values over time as a smooth curve, making it easier to spot historical tendencies and possible future trends. In some embodiments, the capability to predict future analyte levels is also provided.

[0004] Embodiments of the invention can be implemented by a processor controlled patient monitoring system. In some embodiments readings are obtained from a sensor through a sensor interface. Numerical values for the patient analyte are calculated over time, and these historical numerical values, based on a corresponding reading from the sensor, are stored in a memory. For each recent sensor reading, a numerical value for a patient analyte is determined. An indication of both the historical numerical values, if any, and the most recent numerical value for the patient analyte is graphically and persistently displayed on a display device.

[0005] In some embodiments, the recent numerical value, at least some of the historical numerical values or both are compared to at least one stored limit. A graphical attribute of the display device can be set in accordance with how the numerical values compare to the stored limit. In some embodiments, the setting of the graphical attribute includes filling an area between the numerical values or the continuous smooth curve representing the numerical values and the limit value. This information can again be persistently and graphically displayed. An area of the curve over or under an appropriate limit can be highlighted on many other ways, for example with color, made to flash, etc. In some embodiments, the at least one stored limit is actually a low-level limit and a high level limit. In some embodiments either or both of these can be set or negated by user input. For example, if the patient analyte is blood glucose, a low-level limit for the blood glucose level, and a high level limit for the blood glucose level can be set so that whenever readings deviate from the acceptable range, a graphical notification appears on the display device. Setting these levels by user input can consist of simply enabling or disabling the effect or can include adjusting the actual numerical limits. A system can be designed to provide audio notifications as well of or instead of graphical notifications, and either of these could be provided remotely as well.

[0006] In some embodiments, a continuous, smooth curve is calculated and displayed as the indication of both historical numerical values and the recent numerical value for the patient analyte. This curve can be displayed by itself, or together with graphical, persistent indications of discrete numerical values. The limit and/or limits as described above can be applied to the continuous smooth curve. In some embodiments, one or more predicted numerical values for the patient analyte can be calculated and extrapolated based on at least some of the historical numerical values and the most recent numerical value for the patient analyte. The limit and/or limits as already described can also be applied to extrapolated values. The extrapolated values can be displayed as a continuation of a continuous, smooth curve, as discrete values, or as both. In some embodiments, the display can include a graphical indication of a therapeutic infusion rate, for example of insulin in the case of blood glucose monitoring.

[0007] Embodiments of the invention can be implemented on a computer system, instruction execution platform, or a workstation with appropriate input and output capabilities. Embodiments of the invention may also be implemented on a patient monitoring system including a display device and a processor operatively connected to the display device and connected with a memory. The memory may be used to store historical numerical values for the patient analyte as well as non-transitory computer program code which, when executed, causes the processor to carry out all or a portion of the process of an embodiment of the invention. Such a system may also include an input/output (I/O) interface to connect sensors, pumps and the like, a network interface, and may include a graphics engine either on-chip with the principal microprocessor or controller, or in a dedicated graphics processor. This hardware along with a sensor interface and any other input and output components form at least some of the means to carry out the various process elements of embodiments of the invention.

BRIEF DESCRIPTION OF THE DRAWINGS

[0008] FIG. 1 is an illustration of a typical operating environment for example embodiments of the present invention.

[0009] FIG. 2 is a block diagram of a system according to example embodiments of the invention.

[0010] FIG. 3 and FIG. 4 present screenshots of a screen of the display device that is part of the system of FIG. 2. Such screens may be produced by embodiments of the invention.

[0011] FIG. 5 is a flowchart illustrating a process that can be carried out with example embodiments of the invention. [0012] FIG. 6, FIG. 7 and FIG. 8 are additional screenshots of a screen of the display device of the system of FIG. 2. These screens may be produced by additional embodiments of the invention.

[0013] FIG. 9 is a flowchart illustrating a process that can be carried out with additional example embodiments of the invention.

[0014] FIGs. 10A, 10B, IOC and 10D illustrate a screenshot and how a displayed chart might change over time in an embodiment of the invention that combined the electronic display of analyte values with the electronic display of dosing information according to some embodiments of the invention.

DETAILED DESCRIPTION OF EXAMPLE EMBODIMENTS

[0015] The following detailed description teaches specific example embodiments of the invention. Other embodiments do not depart from the scope of the present invention. The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. As used herein, the singular forms "a", "an" and "the" are intended to include the plural forms as well, unless the context clearly indicates otherwise. It will be further understood that the terms "includes" and/or

"including" when used herein, specify the presence of stated features, integers, steps, operations, elements, and/or components, but do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and/or groups thereof. [0016] Unless otherwise defined, all terms (including technical and scientific terms) used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs. It will be further understood that terms used herein should be interpreted as having a meaning that is consistent with their meaning in the context of this specification and the relevant art and will not be interpreted in an idealized or overly formal sense unless expressly so defined herein. Unless otherwise expressly stated, comparative, quantitative terms such as "less" and "greater", are intended to encompass the concept of equality. As an example, "less" can mean not only "less" in the strictest mathematical sense, but also, "less than or equal to."

[0017] As will be appreciated by one of skill in the art, the present invention may be embodied as a method, device, article, system, computer program product, or a combination of the foregoing. Any suitable computer usable or computer readable medium may be utilized for a computer program product including non-transitory computer program code to implement all or part of an embodiment of the invention. The computer usable or computer readable medium may be, for example but not limited to, a tangible electronic, magnetic, optical, electromagnetic, or semiconductor system, apparatus or device. More specific examples (a non-exhaustive list) of the computer readable medium would include the following: a portable computer diskette, a hard disk, a random access memory (RAM), a read-only memory (ROM), an erasable programmable read-only memory (EPROM or Flash memory), a portable compact disc read-only memory (CD-ROM), or an optical storage device. The computer usable or computer readable medium may be one or more fixed disk drives or flash drives deployed in instruction execution platforms, such as servers or workstations, forming a "cloud" or network. [0018] Computer program code for carrying out operations of the present invention or for assisting in the carrying out of a method according to an example embodiment of the invention may be written in an object oriented, scripted or unscripted programming language such as Java, Perl, Smalltalk, C++ or the like. However, the computer program code for carrying out operations of the present invention may also be written in

conventional procedural programming languages, such as the "C" programming language or similar programming languages.

[0019] Computer program instructions may be provided to a processor of an instruction execution platform such as a general purpose computer, special purpose computer, server, workstation or other programmable data processing apparatus to produce a machine, such that the instructions, which execute via the processor of the computer or other

programmable data processing apparatus, create means for implementing the functions/acts necessary to carry out an embodiment of the invention.

[0020] A processor used to implement an embodiment of the invention may be a general purpose digital signal processor, such as those commercially available from Texas

Instruments, Inc., Analog Devices, Inc., or Freescale Semiconductor, Inc. It may also be a general purpose processor such as those typically provided for either workstation or embedded use by companies such as Advanced Micro Devices, Inc. or Intel Corporation. It could as well be a field programmable gate array (FPGA) as are available from Xilinx, Inc., Altera Corporation, or other vendors. The processor could also be a fully custom gate array or application specific integrated circuit (ASIC). Any combination of such processing elements may also be referred to as a processor, microprocessor, controller, or central processing unit (CPU). In some embodiments, firmware, software, or microcode can be stored in a non-transitory form on or in a tangible medium that is associated with the processor. Such a medium may be a memory integrated into the processor, or may be a memory chip that is addressed by the processor to perform various functions. Such firmware, software or microcode is executable by the processor and when executed, causes the processor to perform its display control and calculation functions. Such firmware or software could also be stored in or on a tangible medium such as an optical disk or traditional removable or fixed magnetic medium such as a disk drive used to load the firmware or software into a monitoring system according to embodiments of the present invention.

[0021] The term "analyte" as used herein relates to a substance or chemical constituent in a biological sample (e.g., bodily fluids, including, blood, serum, plasma, interstitial fluid, cerebral spinal fluid, lymph fluid, ocular fluid, saliva, oral fluid, urine, excretions, or exudates. Analytes can include naturally occurring substances, artificial substances, metabolites, and/or reaction products. The analyte for measurement by the sensor, devices, and methods is inclusive of glucose. Any other physiological analyte or metabolite can be substituted or combined with the measurement of glucose. The term "subject" as used herein relates to mammals, inclusive of warm-blooded animals (domesticated and non- domesticated animals), and humans.

[0022] The term "calibration" as used herein refers to one or more process of determining the relationship between sensor data and a corresponding reference data. A continuous analyte sensor can be initially calibrated, calibration can be updated or recalibrated over time (whether or not if changes in the relationship between the sensor data and reference data occur), for example, due to changes in disconnection/reconnection, sensitivity, baseline, analyte transport, metabolism, and the like. The sensed values produced by a calibrated sensor can be referred to as "calibrated values."

[0023] The phrases "operatively connected" and "operably connected" as used herein relate to one or more components linked to one or more other components, such that a function is enabled. The terms can refer to a mechanical connection, an electrical connection, or any connection that allows transmission of signals between the components. For example, one or more electrodes can be used to detect the amount of analyte in a sample and to convert that information into a signal; the signal can then be transmitted to a circuit. In such an example, the electrode is "operably connected" to the electronic circuitry. The terms include wired and wireless connections, and situations where there is are or may be intervening components.

[0024] The term "sensor" as used herein relates to a device, component, or region of a device capable of detecting and/or quantifying and/or qualifying an analyte in the intravascular and/or subcutaneous space of a subject. The phrase "sensor system" as used herein relates to a device, or combination of devices operating at least in part in a cooperative manner, that is inclusive of the sensor. In preferred aspects, sensor relates to a device, component, or region of a device capable of detecting and/or quantifying and/or qualifying an analyte in the intravascular and/or subcutaneous space in vivo.

[0025] FIG. 1 depicts an operating environment and a system that incorporates aspects of embodiment of the invention described in this document. In this example, analyte information display system 10 is configured to monitor blood glucose levels in a subject. The subject in this case is a hospitalized medical patient. The system is built around a monitor and control unit 12, which comprises programmed processor to control the functioning of the system, and a display device including a visible panel configured to communicate information regarding the system and its functions, as well as the condition of the patient, to a user of the system. The display panel may also serve as a touch screen interface through which a user can enter information and commands for controlling the system's operations.

[0026] In FIG. 1, an access point 14 provides access for the system to the patient's body. The access point may provide an entry site for a catheter placed in the vein or another vessel in the vasculature of the patient, access to interstitial fluid located under the patient's skin, or to any other sight through which access can be provided to fluids or materials bearing glucose or otherwise providing a reliable indicator of blood glucose levels or corresponding information relevant to the subject. FIG. 1 illustrates a configuration in which an intravascular catheter is disposed inside a vein of the patient, and through which blood can be drawn over an electronic sensor to measure directly glucose levels in the patient's blood. The sensor in this configuration can be a glucose oxidase sensor configured to produce a current or voltage proportional to the patient's blood glucose level. It cannot be

overemphasized that this arrangement is an example. Other mechanisms can be used to monitor blood glucose, and a system according to embodiments of the invention can be devised to measure other analytes. Some sensor systems that can be used with

embodiments of the invention are described in U.S. Patent Publication No. 2007/0027385, the entire disclosure of which is incorporated herein by reference. [0027] Still referring to FIG. 1, the system further includes a supply of infusion fluid 16, housed inside an infusion vessel 32, and in fluid communication with the sensor and the access point 14 through a fluid line 22 between the infusion bag and the access point. A fluid pump 20 controls the flow of fluids back and forth through the fluid line between the access point and the fluid bag. Under control of the pump, blood may be drawn from the patient's vein over the sensor. At other times, infusion fluid may be used in the sensor system by being directed from the bag to flow over and rinse the sensor. The infusion fluid may also at times be infused into the patient. The infusion fluid may comprise normal medical saline solution. The infusion fluid may further comprise glucose at a known concentration, which may be directed over the sensor from time-to-time in order to calibrate the sensor by reading the resultant current or voltage from the sensor at times when the known-concentration glucose solution in the infusion bag is being directed over and in contact with the sensor. The system 10 further includes an insulin supply controller 18 configured to supply insulin in a controlled fashion through an insulin supply line 19 to the fluid line 22 and from there into the body of the patient. The elements of system 10 are mounted on and supported by a wheeled, movable stand 34, so that the system can be moved as needed with the patient. It should be noted that the term "system" may be used herein to refer to the entire arrangement of electronic elements and connection cables described above. However, the term system may also be used to refer only to the monitor and control unit including installed software and/or firmware that together direct and execute the functions described herein.

[0028] Continuing to refer to FIG. 1, a signal line 36 provides electrical communication between the sensor near the access point 14 and the monitor and control unit 12. Electrical communication is similarly provided between the monitor and control unit and the fluid pump 20 through a first data and control cable 38, and similarly between the monitor and control unit and the insulin supply controller 18 through a second data and control cable 39. The system 10 pictured in FIG. 1 is thus a "closed-loop" system configured both to monitor the patient's blood glucose level and to control that level by administering doses of insulin, all as determined and controlled by software and circuitry of the monitor and control unit 12. The visual display and touch-screen control of the monitor and control unit communicate information to a user of the system. The user may further input commands to the system through that same visual display and touch-screen control. It should be noted that the graphical display features and functions described herein can also be used in a so- called "open-loop" system to great advantage. An open loop system is one where an appropriate medication, in this case insulin, is administered manually by medical personnel in response to indications presented by the display panel of a monitor and control unit like the monitor and control unit 12.

[0029] FIG. 2 is an enlarged view, schematically illustrating detail of the monitor and control unit 12 of FIG. 1. The insulin supply portions of FIG. 1 are omitted. The system includes I/O interface 202, which may in turn include an appropriate connector, and circuitry to monitor signals from the sensor system. This circuitry may include analog-to- digital converters, encoders, decoders, and the like. I/O interface 202 is coupled to a central processing unit (CPU) 204, which controls the operation of the entire system. The I/O interface receives sensor signals and may also send signals to control the supply of insulin to the subject with some embodiments of the invention. CPU 204 is further operatively connected to memory 206. Memory 206 stores all of the information needed for the system to operate. Such information may be stored in a temporary fashion, or may be stored more permanently. This memory may include a single, or multiple types of memory. For example, a portion of the memory connected with CPU 204 may be "flash" memory which stores information semi-permanently for use by the system. In either event memory 206 of FIG. 2 in this example embodiment includes computer program code 208 which, when executed by CPU 204, causes the system to carry out the various processes to graphically display information according to example embodiments of the invention. Memory 206 also stores data 210, which in example embodiments includes historical numerical values for the analyte being measured, for example, blood glucose.

[0030] Still referring to FIG. 2, monitoring and control unit 12 may also include a network interface 213. This network interface can allow the system to be connected to a wired or wireless network to allow monitoring on a remote display (not shown). For example, the remote display could duplicate, or be used in place of the local display panel. Network interface 213 could also be simply used to trigger an alarm at a nurse's station or on a mobile device. In the embodiment of FIG. 2, a local display device, 217, is connected with CPU 204 via a graphics engine 224. The local display device may be an LCD panel, plasma panel, or any other type of display component and accompanying circuitry to interface the display device to graphics engine 224. Graphics engine 224 may be on its own chip, or in some embodiments it may be on the same chip as CPU 204. Note that display device 217 may include user input functionality, for example an optical or capacitive touchscreen over the display screen. In such a case, monitoring control unit 12 may include additional circuitry to process such input. Alternatively, such circuitry may be included in the display device itself, the graphics engine, or the CPU 204. [0031] FIG. 3 illustrates one possible configuration of at least a part of the display screen of the display device in the monitor and control unit 12. This configuration includes a graphical display of an electronic chart 300 displayed on the screen of the unit. This chart displays multiple points, each said point indicating a measured numerical value for the blood glucose level of a patient, indicated in milligrams of glucose per deciliter of blood (mg/di) and charted on the vertical axis 302 of the electronic chart. Each said point is positioned along the horizontal axis 304 of the electronic to indicate a time at which that measurement was taken. The most recent numerical value is indicated by point 306, which is all the way to the viewer's right, as is the convention with time-based graphs. The user of the system is thus provided with a convenient and easily understandable indication of the patient's current blood glucose level as well as historical numeral values that provide historical context indicating how that level has changed over time. This information is graphically and persistently displayed on an electronic screen as shown in these examples.

[0032] It should be noted that a "persistent" display of historical numerical values in this example includes values going back as much as 12 hours in time. Historical context over such time periods can be important in some clinical settings with some analytes. Thus the memory in a system according to embodiments of the invention may include non- volatile flash memory for such readings in addition to firmware, so that this historical data is retained in the event of power outages or so-called, "brownouts." A chart displayed by a system like that described herein may display data going back about 1 hour or greater, 4 hours or greater, 8 hours or greater, 12 hours or greater, 24 hours or greater, 36 hours or greater, or as much as about 72 hours. [0033] A displayed chart of the type illustrated in FIG. 3 might be enhanced in various ways to make it more useful in providing better care and superior control over the patient's blood glucose level. FIG. 4 illustrates one such potential enhancement. FIG. 4 shows the same data points as FIG. 3 on the same horizontal and vertical axis. FIG. 4 illustrates a displayed chart 400 in which high and low blood glucose level limits have been established in the system and shown on the display screen. More specifically, this screen indicates by line 402 a high level limit of 120 mg/di, and by line 404 a low level limit of 80 mg/dl. These limits may be either inherent and coded to be unchanging in the system, or they might be set by the user as desired and appropriate for a particular patient under certain conditions, as determined and controlled by the user. One of skill in the art will understand that there is currently no very uniform consensus as to the most appropriate ranges within which blood glucose levels should be controlled in hospital operating room or intensive care settings. Optimal high and low limits may thus best be left to the preference and expertise of individual users, and may further deviate considerable from the limits shown in this illustration. Nevertheless, the 80-120 mg/di range illustrated in FIG. 4 is believed to provide a plausible illustration sufficient to illustrate the principles of this feature for the purposes of this disclosure.

[0034] Still referring to FIG. 4, the blood glucose level measurement history depicted in FIG. 4 includes a considerable period of time during which the patient's blood glucose level, as measured by the system, was well above the 120 mg/dl high limit illustrated on the screen. This time can be highlighted by a graphical attribute that the display device in the system is capable to exhibiting under program control, after the CPU has determined that the limit has been exceeded by comparing numerical values of the blood glucose level to the relevant stored limit. For example, this time can be illustrated on the screen display with cross-hatching, a different color, or some other means for "filling" the area 407 between the measured blood glucose level for individual measurements and the baseline "floor" at the 120 mg/dl limit. The area of this hatched, shaded, or differently colored region thus provides a visual indication of the deviation of the measured blood glucose level greater than the high level limit, integrated over the time the blood glucose level spent over that limit. Similar highlighting can be provided for a level less than the low level limit.

[0035] It is currently believed that adverse consequences to the patient of high blood glucose levels may be proportional or at least correspond or correlate with both (a) the degree to which the blood glucose levels have exceeded some critical threshold, and (b) the time over which that excess persisted. An enhanced display such as that shown in FIG. 4 thus can provide a user of the system with a conveniently readable and understandable visual indication of the severity of a deviation above a permissible limit, in the form of a clearly delineated and indicated area, the size of which would correspond at least to some reasonable approximation to the severity of the consequences of such a deviation.

[0036] The system may be further enhanced where the CPU calculates and the system displays to the user a numerical value corresponding to the area between the blood glucose level measurements and the established permissible limit. Such a numerical value would have the units of mg*sec/dl for example, and that value could then be shown, e.g., on the display and superimposed inside the shaded or otherwise differentiated display area. The deviation-time value could also be shown elsewhere on the display or otherwise provided to the system's user. Similar displayed areas and calculated deviation-time integral values could be provided in situations where the measured blood glucose levels had gone beyond the 80 mg/dl low limit established in the system. Blood glucose levels lower than a threshold value may have adverse consequences of their own, and the severity of those consequences may depend in a similar way on not only the extent to which the patient's blood glucose had deviated below the acceptable limit, but also by the time spent at a given level under that permissible limit.

[0037] FIG. 5 is a flowchart illustrating the details of a process for generating a display like those shown in FIG. 3 and FIG. 4. Like most flowcharts, FIG. 5 illustrates process 500 as a series of process or sub-process blocks. At block 502, the process begins. Block 502 may correspond to the initiation of monitoring of a patient by switching on or resetting the monitor and control unit. At block 504, the system obtains readings from the sensor, calculates, and stores numerical values for the patient analyte, for example blood glucose, over time. In the case of blood glucose, each of these values may be referred to as an estimated glucose value (EGV) since it is calculated based on an electronic property read from the sensor. Block 506 represents the determining and storing of the most recent numerical value based on the most recent sensor reading. At block 508, the recent numerical value and historical numerical values for the patient analyte are graphically and persistently displayed as has been previously described. Block 510 includes curve fitting an extrapolation of predicted numerical values. These processes are statistical in nature and will be further discussed with respect to FIG. 6, FIG. 7, FIG. 8 and FIG. 9. Block 510 is optional, as are many of the other process blocks and/or specifics recited within the blocks. At block 511, information about insulin dosing can be determined and displayed if the monitor and control unit can be and is connected to the insulin supply controller to obtain this information.

[0038] Still referring to FIG. 5, at block 512 numerical values for the patient analyte are compared to numerical limits. Numerical limit settings 514 serve as an input to this portion of process 500. The recent numerical value and/or at least some of the historical numerical values are compared to at least one stored limit. As previously discussed, these limit settings can be hardcoded, or can be supplied via user input. If an extrapolated numerical value exists from the process of block 510, this value can be compared to a stored limit or limits as well. At block 516, a graphical attribute on the display device of the system is set, updated, or adjusted in accordance with the comparison to indicate a value over a limit, under a limit, or outside an acceptable range as the case may be. At block 518, a determination is continuously made as to whether the system is still active. For example, whether the system has been switched off, or the sensor has been disconnected because the subject is no longer being monitored. If so, processing continues. Otherwise, processing ends at block 520.

[0039] FIG. 6 illustrates another potential enhancement for chart-style displays of multiple blood glucose measurement levels taken over time. In displayed chart 600 of FIG. 6, a continuous smoothed curve 602 has been calculated and overlaid over the multiple discrete data points that indicate the actual blood glucose measurements. Such a curve could be constructed in any of numerous ways known to those of skill in the art. For example, a curve could be calculated by the CPU in the monitor and control unit using a least squares fit with either vertical or perpendicular offset. An appropriate curve fitting technique would help to smooth the indicated values in comparison to the actual measured data, which might provide a more useful sense of actual changes in the patient's blood glucose level, by reducing random variations or "noise" that arise naturally from the limitations of precision in the actual physical measurements. It should be noted that block 510 of FIG. 5, which is further illustrated in FIG. 9, to be discussed below, includes the sub- process of displaying the smooth curve, whereas block 508 includes the display of discrete sampled values. In some embodiments it may be desirable to only display the smoothed curve, in which case block 508 of FIG. 5 may not be executed, and the discrete points would not be shown in a display screen like that pictured in FIG. 6. These options may be configurable by a user of the system.

[0040] Such a curve-fitting technique as shown in FIG. 6 can be combined, moreover, with an area indication and display like that described above in with respect to FIG. 4. FIG. 7 illustrates such a combination by presenting display 700, in which a mathematical curve has been fit to and overlaid over individual data points reflecting actual measurements, with the area between that curve and a 120 mg/dl acceptable lower limit threshold then displayed as a shaded region. That displayed area would then be indicative of the time spent above the limit and the severity of that deviation, but with the display based on the smoothed curve rather than the somewhat noisy discrete points of the actual measurements. Once again, a numerical value indicative of the size of the shaded area between the smoothed curve and the acceptable limit might be calculated and displayed, either overlaid on the region of interest in the chart itself, or shown elsewhere on the display or otherwise communicated to the system's user. An area of deviation above the permissible limit based on the smoothed curve rather than the actual data points might more clearly indicate the actual changes in the patient's blood glucose level, and therefore to be more clinically relevant and helpful to the user in devising appropriate insulin dosing to best correct the patient's hyperglycemic condition.

[0041] FIG. 8 illustrates another embodiment of an electronic blood glucose level chart 800, this one combining a smooth curve-fitting operation with an extrapolation reflecting a prediction of future analyte levels. In particular, a smooth curve 804 has been computed and overlaid in part as before onto a discrete series of points 806 representing actual measured blood glucose values. The actual measured values end at a time around 15:00 near the middle of the chart. After that time, the smooth curve is continued over a series of crosses 807 displayed to indicate future anticipated numerical values for the analyte, which are predicted and displayed based on the smoothed curve that had been fit to the measured values. The crosses 807 illustrated in FIG. 8 would serve to alert the user that these are not actual measured data, but rather predictions of the patient's future condition. Some systems according to example embodiments of the present invention could be expected to show different parts of a chart like that displayed in FIG. 8 or any of the other figures herein - actual measurements, smoothed curve values, predicted values, etc. using different colors so that the system's user could very readily distinguish between them.

[0042] FIG. 8 further illustrates display by the system of predicted values including an extrapolation of how long it would be expected to take for the patient's blood glucose level to return to below the acceptable 120 mg/dl upper limit. That time value - the time to return to within the permissible bound— could also be calculated and displayed as a numerical value, whether displayed directly on the chart, elsewhere on the system screen, or otherwise provided to the user.

[0043] The same type of extrapolation, in which a future patient analyte numerical value is predicted based on a trend projected from a smoothed curve, could be used in the case of blood glucose to determine a time at which a patient would be expected to enter a hypoglycemic condition. This might be based, for example, on the time at which the smoothed curve would cross a lower acceptable limit preprogrammed into the monitor and control unit or entered by the device's user, and representing the lower bound of an acceptable range, i.e., the upper bound of an unacceptably low value of blood glucose representing the hypoglycemic condition. These methods for determining and displaying indications of a patient's analyte levels over time may form bases for improved assessment of the patient's condition or improved methods for treating relevant conditions. Various statistical techniques can be used to calculate extrapolated numerical values of the analyte. Examples include least square estimation, linear regression, and geometric regression.

[0044] FIG. 9 is a flowchart illustrating sub-process 510 from FIG. 5 in further detail. At block 902 the sub-process begins. At block 904, one or more predicted, future, numerical values for the patient analyte are statistically calculated from past values. Like many processes of both FIG. 5 and FIG. 9, block 904 is an optional operation. At block 906, a continuous smooth curve for display is calculated taking into account the most recent numerical value for the blood glucose level or whatever analyte is being monitored. At block 908, the display is updated with the continuous smooth curve. If predicted values are being displayed, they can be highlighted in the screen. The sub-process ends at block 910 where processing returns to the flowchart of FIG. 5.

[0045] FIG. 10 illustrates a displayed electronic chart in an embodiment of the invention where therapeutic dosing information is displayed along with analyte values. In this example embodiment, the analyte values are estimated glucose values and insulin is being administered to the patient. Such a display could be useful in either an open-loop or closed- loop system. In an open loop system, the insulin protocol is adjusted by medical personnel. Through a connection with an insulin supply controller for an insulin pump, the dosing is continuously recorded in memory so that a current dose as well as historical dosing is displayed. In a closed-loop system, insulin protocol decisioning is accomplished in an automated fashion by a processor, and the current status and history is displayed on a display device along with the EGV history for the subject. Even in an open-loop system, the firmware for the system could calculate and recommend an adjustment to the insulin infusion rate. In such situation, the EGV for the patient is not likely to change very fast, to that this information can be useful even if it is only observed every hour or so. A caregiver can look at a monitor, see the last change visually, which would be either a change in the EGV and/or the insulin infusion rate. The system may then recommend the next insulin infusion rate level on the screen. The system could programmatically update the recommended level every few minutes. The user interface for the system could be provided with a soft key or similar screen element on the monitor to activate the new insulin infusion protocol and a user can modify the protocol from the recommended dose as needed. [0046] FIG. 10A illustrates a displayed electronic chart 1000 with glucose values on vertical axis 1002 and time on horizontal axis 1004. Glucose values 1006 are displayed as previously described and the chart includes limit lines as previously described. Curve 1008 is a graphical portrayal of historical insulin infusion rates in units per hour. Line 1010 is the rate currently recommended by the system. In this particular example, the rate was 3.5 units per hour at the start of the current treatment and changed over time to 6 and 5 units per hour, respectively.

[0047] FIG. 10B is the same display shown at a later time. The recommended insulin infusion rate in this case changed to 5.5 units per hour and it was adjusted to that rate. In FIG. IOC, the system has begun recommending a new infusion rate of 3.5 units per hour just before an elapsed time of 7 hours. In FIG. 10D, the infusion rate has been adjusted in accordance with the system recommendation. The accuracy of the system can, to an extent be automatically maintained by using a "quality value" for any discrete EGV. Previous, even non-displayed values can be weighted and displayed to further recommend to the user a modification or adjustment to existing insulin protocol.

[0048] To appreciate illustrative examples of the use of embodiments of the invention in blood glucose monitoring, consider that with an embodiment of the invention, deviations from acceptable limits can be frequently recorded and reported as a number of events, with corresponding blood glucose values above or below some acceptable range. More continuous blood glucose monitoring allows calculations of areas under curves representing blood glucose values above or below acceptable limits, integrated over times spent in those unacceptable regions, as described above. Such area values, combining as they do the severity of out-of-permissible-range events with durations of occurrence of such deviations, should be more useful to physicians and other caregivers in assessing the severity of patients' conditions, and devising optimal therapies for controlling and counteracting those conditions.

[0049] As another example, visual display of an area representing a time spent by a patient in a hypoglycemic condition, or a slope of a smoothed curve representing the patient's measured blood glucose, might indicate to the caregiver that a given patient would be unusually prone to hypoglycemia under a usual course of therapy. The caregiver might then choose to be more conservative with insulin therapy in the case of that individual patient, for example.

[0050] Patient tendencies including the responsiveness of individual patients to various forms of treatment - as evidenced by enhanced recording, calculation and display of blood glucose levels as described above could be used in other ways to direct the delivery of blood glucose control therapies. A caregiver could use such enhanced information, for example, to devise different therapies combining IV-delivered and subcutaneously-delivered insulin, the former being relatively quick too act but also relatively short-lived, the latter acting more gradually but in general being more persistent in the patient's body.

[0051] Such information could also be used in selecting between or combining more recently available varieties of fast-acting and slow-acting (or "basal") types of insulin. Enhancing the level of detail available to the caregiver (through the provision of continuous or near-continuous, historical sampled data), along with enhancing the forms in which such data are provided to the caregiver through the various display and reporting methods described should allow the caregiver to improve the delivery of appropriate therapies to individual patients, and to better assess the responses of those patients to those therapies.

[0052] As previously mentioned, these schemes for calculation, estimation, and display of patient blood glucose levels may find use either in more conventional "open-loop" blood glucose measurement systems, in which blood glucose levels are displayed and treatment decisions and therapy made and performed by the caregiver, in newer "closed-loop" blood glucose control systems, in which blood glucose levels are calculated and therapies delivered automatically based on algorithms built into the systems, or in hybrid systems that combine various aspects of open and closed-loop systems.

[0053] References cited herein, including but not limited to published and unpublished applications, patents, and literature references, are incorporated herein by reference in their entirety and are hereby made a part of this specification. To the extent publications and patents or patent applications incorporated by reference contradict the disclosure contained in the specification; the present specification supersedes and/or takes precedence over any such contradictory material of the incorporated reference.

[0054] All numbers expressing quantities of ingredients, reaction conditions, and so forth used in the specification are to be understood as being modified in all instances by the term "about." Accordingly, unless indicated to the contrary, the numerical parameters set forth herein are approximations that may vary depending upon the desired properties sought to be obtained. At the very least, and not as an attempt to limit the application of the doctrine of equivalents to the scope of any claims in any application claiming priority to the present application, each numerical parameter should be construed in light of the number of significant digits and ordinary rounding approaches.

[0055] Although specific embodiments have been illustrated and described herein, those of ordinary skill in the art appreciate that any arrangement which is calculated to achieve the same purpose may be substituted for the specific embodiments shown and that the invention has other applications in other environments. This application is intended to cover any adaptations or variations of the present invention. The following claims are in no way intended to limit the scope of the invention to the specific embodiments described herein.

Claims

WHAT IS CLAIMED IS:

1. A method of displaying patient analyte information, the method comprising: calculating, by a processor, historical numerical values for a patient analyte over time, each numerical value based on and corresponding to a reading from a sensor;

determining, by a processor, for a most recent sensor reading, a recent numerical value for the patient analyte; and

graphically and persistently displaying, by the processor on a display device, an indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte.

2. The method of claim 1 further comprising:

comparing by the processor, at least one of the recent numerical value and at least some of the historical numerical values to at least one stored limit; and

setting by the processor, a graphical attribute of the display device in accordance with the comparing to the at least one stored limit.

3. The method of claim 2 wherein the patient analyte comprises blood glucose.

4. The method of claim 3 further comprising displaying an insulin infusion rate.

5. The method of claim 3 wherein the at least one stored limit comprises a low level limit and a high level limit, and at least one of which can be set by user input.

6. The method of claim 1 further comprising calculating and displaying a continuous smooth curve as the indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte.

7. The method of claim 6 further comprising:

8. The method of claim 7 wherein the setting by the processor of the graphical attribute further comprises filling an area between the continuous smooth curve and the at least one stored limit.

9. The method of claim 7 wherein the patient analyte comprises blood glucose.

10. The method of claim 9 wherein the at least one stored limit comprises a low level limit and a high level limit, and at least one of which is set by user input.

11. The method of claim 1 further comprising: extrapolating by the processor at least one predicted numerical value based on at least some of the historical numerical values and the recent numerical value for the patient analyte; and

graphically and persistently displaying, by the processor on a display device, the at least one predicted numerical value for the patient analyte.

12. The method of claim 11 further comprising:

comparing by the processor, at least one of the recent numerical value, at least some of the historical numerical values and the at least one predicted numerical value to at least one stored limit; and

13. The method of claim 12 wherein the patient analyte comprises blood glucose.

14. The method of claim 13 wherein the at least one stored limit comprises a low level limit and a high level limit, and at least one of which is set by user input.

15. The method of claim 14 further comprising calculating and displaying a continuous smooth curve as the indication of the historical numerical values, if any, the recent numerical value and the at least one predicted numerical value for the patient analyte.

16. A system for displaying patient analyte information, the system comprising: a display device;

a processor operably connected to the display device; and

a memory operably connected with the processor to store historical numerical values for a patient analyte over time, the memory also operable to store computer program code which, when executed, causes the processor to determine, for a most recent sensor reading, a recent numerical value for the patient analyte, and graphically and persistently present, on the display device, an indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte.

17. The system of claim 16 wherein the patient analyte comprises blood glucose.

18. The system of claim 17 wherein the computer program code cause the processor to display an insulin infusion rate.

19. The system of claim 17 wherein the memory is further operable to store at least one limit and the computer program code, when executed further causes the processor to set a graphical attribute of the display device in accordance with a comparison of at least one of the recent numerical value and at least some of the historical numerical values to the at least one limit.

20. The system of claim 17 wherein the indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte comprises a continuous smooth curve taking into account the recent numerical value.

21. The system of claim 20 wherein the setting of the graphical attribute of the display further comprises filling an area between the continuous smooth curve and the at least one limit.

22. The system of claim 17 wherein the computer program code, when executed, further causes the processor to extrapolate at least one predicted numerical value based on at least some of the historical numerical values and the recent numerical value and to graphically and persistently present the at least one predicted numerical value for the patient analyte.

23. The system of claim 22 wherein the memory is further operable to store at least one limit and the computer program code, when executed further causes the processor to set a graphical attribute of the display device in accordance with at least one of the recent numerical value, at least some of the historical numerical values and the at least one predicted numerical value as compared to the at least one stored limit.

24. The system of claim 22 wherein the indication of the historical numerical values, if any, the recent numerical value and the at least one predicted numerical value for the patient analyte comprises a continuous smooth curve taking into account the historical numerical values, if any, the recent numerical value and the at least one predicted numerical value.

25. Apparatus comprising:

means for storing historical numerical values for a patient analyte over time, each numerical value based on and corresponding to a reading from a sensor;

means for calculating, for a most recent sensor reading, a recent numerical value for the patient analyte; and

means for graphically and persistently displaying an indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte.

26. The apparatus of claim 25 further comprising:

means for comparing at least one of the recent numerical value and at least some of the historical numerical values to at least one stored limit; and

means for setting a graphical attribute of the display device in accordance with the comparing to the at least one stored limit.

27. The apparatus of claim 26 further comprising means for calculating and displaying a continuous smooth curve as the indication of both the historical numerical values, if any, and the recent numerical value for the patient analyte.

28. The apparatus of claim 25 further comprising: means for extrapolating at least one predicted numerical value based on at least some of the historical numerical values and the recent numerical value for the patient analyte; and

means for graphically and persistently displaying the at least one predicted numerical value for the patient analyte.

29. The apparatus of claim 28 further comprising:

means for comparing at least one of the recent numerical value, at least some of the historical numerical values and the at least one predicted numerical value to at least one stored limit; and

30. The apparatus of claim 29 further comprising means for calculating and displaying a continuous smooth curve as the indication of the historical numerical values, if any, the recent numerical value and the at least one predicted numerical value for the patient analyte.

31. The apparatus of claim 25 further comprising means for display a therapeutic infusion rate.