WO2004066182A1

WO2004066182A1 - Identification of risk of myocardial infarction

Info

Publication number: WO2004066182A1
Application number: PCT/GB2004/000130
Authority: WO
Inventors: David Wald; Yuk-Ki Wong
Original assignee: David Wald; Yuk-Ki Wong
Priority date: 2003-01-23
Filing date: 2004-01-14
Publication date: 2004-08-05
Also published as: GB2397527A; GB0301600D0

Abstract

A device for identifying if a patient is at an increased risk of myocardial infarction in the near future is arranged to detect, record and analyse the usage of a medication delivery means for delivering a dose of medication for the relief of angina, such as glyceryl trinitrate (GTN). The medication delivery means may be a spray unit which is actuatable to deliver a dose of medication or a dispensor of solid units of medication. The device detects an increase in the usage indicative of an increased risk of myocardial infarction. Such detection may be used to warn the patient to seek medical attention and for preventive treatment.

Description

Identification Of Risk Of Myocardial Infarction The present invention relates to the identification of patients at an increased risk of suffering a myocardial infarction in order to provide preventive treatment. In particular, the present invention provides a device which is capable of detecting when a patient is at such an increased risk.

It is well recognized that the majority of people who suffer a myocardial infarction (for example ST elevation myocardial infarction, non-ST elevation myocardial infarction or an acute coronary event), experience a pre-infarction syndrome of increasing symptoms of angina, usually chest pain or breathlessness, in the days and weeks preceding their myocardial infarction.

If patients can be identified during this pre-infarction syndrome, preventive measures could be provided to avert a myocardial infarction. Drug therapies such as anti- anginal medications like beta-blockers, anti-platelet agents like Ilb/IIIa inhibitors and anti-thrombotic agents like heparin, can be given and these can reduce the risk of a myocardial infarction. Revascularisation procedures such as the insertion of intra- coronary stents at the sites of coronary artery narrowings and coronary bypass procedures to by-pass such narrowings can also be undertaken before permanent heart muscle damage is sustained from complete or transient coronary artery occlusion, as occurs in a myocardial infarction. Ischaemic heart disease is the commonest cause of death in the western world and one third of all people who suffer a myocardial infarction die before reaching hospital. For those who survive a myocardial infarction (non-ST elevation type myocardial infarction in particular), the widely adopted clinical strategy is to investigate patients with coronary angiography within days after their myocardial infarction and provide coronary revascularisation treatments whenever possible, as studies have shown that an early coronary revascularisation approach rather than delayed or no revascularisation is the preferable strategy to avoid recurrent acute coronary events. It would be desirable to develop strategies that identify people at an earlier stage, before they suffer a myocardial infarction so that effective preventive measures can be delivered. Such preventive measures decrease the chances of death or permanent heart muscle damage.

According to the present invention, there is provided a device for identifying if a patient is at an increased risk of a myocardial infarction, the device comprising: a sensor arranged to detect delivery of a dose of medication for the relief of angina; a memory arranged to record the delivery of the medication detected by the sensor, over time; and analysis means arranged to analyse the delivery of the medication recorded in said memory according to a predetermined algorithm to detect an increase in the delivery of the medication indicative of an increased risk of myocardial infarction.

Here described is a device for monitoring and analysing changes in the delivery of a medication for the relief of angina. The preferred medication to which the present invention may be applied is glyceryl trinitrate (GTN), but the invention is equally applicable to any other medication for the relief of angina. The invention records data relating to the delivery of medication and performs analysis on this data to enable the identification of patients who are at increased risk of myocardial infarction occurring in the near future, typically within days or weeks. This provides a window of opportunity for preventive treatment. It enables the identification of patients likely to suffer various types of myocardial infarction, for example ST-elevation myocardial infarction, non-ST elevation myocardial infarction, non Q wave myocardial infarction, Q wave myocardial infarction, subendocardial myocardial infarction, acute coronary event or acute coronary syndrome. People who have clinical manifestations of ischaemic heart disease, for example a diagnosis of angina or a previous myocardial infarction, are usually prescribed a medication for the relief of angina such as glyceryl trinitrate (GTN) in a form in which doses of GTN may be self-administered. Commonly the GTN is provided in a small hand-held aerosol spray unit that patients keep with them. The spray unit is actuatable to deliver a dose of GTN as a spray. Alternatively, the GTN is often provided as sub- lingual tablets. Both forms of GTN allow self-administration under the tongue when the patient experiences symptoms of angina. GTN is a molecule which increases coronary artery blood flow and therefore oxygen delivery to heart muscle, through a mechanism involving coronary artery vasodilatation. A dose of GTN usually relieves symptoms of angina within minutes.

Corresponding to the increase in symptoms of angina leading up to a myocardial infarction, it is recognized that a person's GTN requirement may also increase. The problem is that this increase in GTN use can be insidious. Most patients fail to recognise the significance of an increase in symptoms of angina, or the corresponding increase in GTN use, despite advice given to patients to take such symptoms seriously and consult a doctor. Most people first seek medical attention after they suffer a myocardial infarction and so miss the opportunity for preventive action. Even if doctors are consulted, the doctors themselves may overlook the prognostic significance of an increase in GTN use and fail to take appropriate preventive action.

The present invention overcomes this problem by providing a device which automatically monitors the delivery of the medication for relief of angina. Thus the usage of the medication is used as a surrogate marker of coronary artery stability. By detecting an increase in the usage indicative of an increased risk of myocardial infarction, the device can be used to identify a high risk group.

Thus the device in accordance with the present invention detects a prognostically important change in symptoms and is therefore an attractive medical tool. The device assists both patient and doctor in appropriately interpreting this change in symptoms, identifying a group of patients at high risk of a myocardial infarction and providing a window of opportunity to intervene with preventive medical and revascularisation therapies. At present such treatments are focussed largely on those who have suffered and survived a myocardial infarction. The proposed device would enable a strategy of delivering treatment at an earlier stage, before death or permanent cardiac muscle damage has occurred.

Medication dispensers employing an electronic record of medication delivery have been proposed in the past. For example: US-A-5,363,842 describes an inhalation device for use in delivering inhalable medication. The device collects data relating to the patients' inhalation technique for analysis to allow patients to alter their inhalation technique for improving the delivery of the medication to their lungs; WO-99/35588 describes a method for managing the administration of medicines and in particular monitoring patient compliance with a prescribed treatment requirement. The method relies on input of patient data to a central computer workstation which calculates and transmits dosage data to a dispensing device via a conrinunications link. WO 01/24690 describes an electronic medication delivery and data management system with wireless communication capability for calculating the optimum amount of medication to dispense. However such proposals have not included identification of patients who are at increased risk of myocardial infarction.

In the hereinafter described embodiments of the present invention, the medication delivery means is either a spray unit or a dispensor of solid units of medication. In the case of the spray unit, it may be an aerosol actuatable to deliver the dose of medication as a spray. The device includes a holding arrangement for holding the spray unit. The sensor is arranged to detect delivery of a dose of medication by detecting actuation of the spray unit.

In the case of a dispensor of discrete solid units, such as a tablet, capsule or lozenge the medication delivery means may take the form of a mechanism which is actuatable to deliver one or more solid units constituting a dose of the medication. In this case, the sensor would be arranged to detect actuation of the mechanism.

The present invention is equally applicable to any other form of medication delivery means which delivers a dose of medication for the relief of angina.

Preferably, the device further comprises a warning means arranged to output a warning when said analysis means detects an increase in the delivery of the medication indicative of an increased risk of myocardial infarction.

The warning thus acts as a prompt for the user to consult a doctor. The warning may be a visible warning on a display or an audible warning from a transducer. A variety of different algorithms may be used to detect an increase in delivery of the medication indicative of an increased risk of myocardial infarction. For example, the algorithm may detect when the rate of delivery exceeds a predetermined threshold. Alternatively, the algorithm may detect when the rate of delivery exceeds a background rate by a predetermined absolute amount or by a predetermined proportion. Different algorithms may be used for different categories of patient. For example, for low- frequency users it is preferable to use an algorithm which detects when the rate of delivery exceeds a predeteπnined threshold, whereas for high-frequency users it is preferable to use an algorithm which detects when the rate of delivery exceeds a background rate by a predetermined amount. More complicated algorithms may take into account other factors such as the time of day of delivery of the medication or the amount of movement of the device in the period leading up to delivery of the medication. To achieve this the memory means is arranged to record the time of day or the amount of movement as detected by a movement detector, respectively. Preferably, the analysis means comprises a microprocessor having a program which, on execution, implements the predetermined algorithm.

This allows the algorithm to be changed easily, for example for different categories of patients.

Preferably, the device further comprises a display arranged to display the delivery of the medication recorded in the memory. Alternatively, or in addition the device may include a terminal for outputting the delivery of the medication recorded by said memory from the device to an external device, such as a printer or a computer. This provides a doctor with objective information on the clinical control of angina. This is useful for informing clinical decisions. Primarily, the recorded delivery of the medication is useful for selecting a preventive treatment when a patient presents themself after the device has detected an increase in the delivery of the medication indicative of an increased risk of myocardial infarction. However, the recorded delivery of the medication is also of use to a doctor in the long term treatment of patients who, whilst not at high risk of a myocardial infarction in the near future, have nonetheless experienced a gradual deterioration in their angina control. The objective information on how the frequency of delivery of the medication has changed, for example over a period of weeks to months, enables doctors to alter treatment approaches aimed at improving symptoms of angina.

To allow better understanding, there will now be given a description of embodiments of the present invention given by way of non-limitative example with reference to the accompanying drawings, in which:

Fig. 1 is a perspective view of a first device; Fig. 2 is an exploded, perspective view of the holding arrangement of the device of Fig. 1;

Fig. 3 is a perspective view of the assembled holding arrangement of Fig. 2;

Fig. 4 is a perspective view of the device of Fig. 1 with panels removed to show the electronic circuitry; Fig. 5 is an enlarged, partial view of the device of Fig. 1 illustrating the sensor arrangement in exploded view;

Fig. 6 is a perspective view of a second device; and

Fig. 7 is a perspective view of the spray unit of the second device;

Fig. 8 is a perspective view of a third device; Fig. 9 is an exploded perspective and view of the third device, showing a cartridge in cross-section;

Fig. 10 is a perspective detailed view of the dispensing mechanism of the third device; Fig. 11 is a cross-sectional view of the dispensing mechanism of the third device showing its relation to the electronic circuitry of the device.

Three devices which embody the present invention will be described. The first device illustrated in Figs. 1 to 5 is designed to hold and be used with existing aerosol spray units of different sizes. The second device illustrated in Fig. 6 and 7 is integrated with an aerosol spray unit. The third device illustrated in Figs. 8 to 11 is designed to dispense solid units (for example tablets, capsules or lozenges) of medication.

Both aerosol devices are arranged to hold an aerosol spray unit containing GTN or another medication for the rapid relief of angina. The aerosol spray units are in themselves of conventional design. They comprise a cylindrical container containing medication under pressure. At one end, the container has an actuator which is actuated by manual depression to deliver a metered dose of GTN, usually lOOμg to 400 g. The actuator is fitted with a cap. Depression of the cap actuates the actuator. The cap has a flow path and nozzle for directing the dose of GTN delivered under pressure from the container as a spray. Existing GTN spray units are available in various sizes, differing principally with respect to the diameter and height of the cylindrical container. This variation is relatively small, usually within a few centimetres.

The first device is illustrated in Fig. 1 and comprises a chamber 1 for accommodating a spray unit 43 of the type described above. The spray unit 43 comprises a cylindrical container 44 and a cap 45. Protruding from the upper end of the device adjacent to the open end of the chamber 1 is a depressor 2 which engages the cap of a spray unit 43 held in the chamber 1 to actuate the spray unit 43. The device has a compartment 3 arranged on one side of chamber 1 to accommodate electronic circuitry. The device has a lid 4 which fits over the depressor 2 to close the chamber 1 and protect the spray unit 43 from contamination and accidental actuation. The device, including the chamber 1, depressor 2, compartment 3 and lid 4, may be made from any suitable material, for example metal and/or plastic.

The chamber 1 is arranged with the following elements which act as a holding arrangement for holding the spray unit 43 in the chamber 1, and are illustrated in Fig. 2 which is an exploded view and in Fig. 3 which is a view of the holding arrangement assembled in the chamber 1. In both Figs. 2 and 3, the various components are illustrated as though transparent to allow the internal construction and arrangement to be seen. The chamber 1 comprises a cylindrical wall 5. To the inner cylindrical surface of the cylindrical wall 5 are mounted four resilient strips 6, although any number could in fact be used. The resilient strips 6 are biassed inwardly to engage the cylindrical surface of the container 44 of the spray unit 43 accommodated in the chamber 1. The resilient strips 6 are deflectable outwardly to accommodate spray units 43 of different sizes. The cylindrical wall 5 is provided, towards its lower end, with a pair of spiral grooves 7 formed on the inner surface of the cylindrical wall 5. The spiral grooves 7 are symmetrical so that the corresponding points on both spiral grooves 7 are diametrically opposite each other. The chamber 1 further comprises an inner cylinder 8, shorter than the cylindrical wall 5. The inner cylinder 8 fits tightly within the lower end of the outer cylinder 5, overlapping the spiral grooves 7. The inner cylinder 8 has two vertical slits 10 which are diametrically opposite each other. The inner cylinder 8 has a base 9 which closes the lower end of the chamber 1 and is of larger diameter so that it does not fit within the cylindrical wall 5. The inner cylinder 8 may be rotated within the cylindrical wall 5 by turning the base 9. The final component of the holding arrangement is a platform 11 in the form of a circular disk provided inside the inner cylinder 8. The platform 11 engages the end of the spray unit 43 accommodated in the chamber 1. The platform 11 has two protrusions 12 arranged diametrically opposite each other around the circumference of the platform 11. The protrusions 12 fit through the vertical slits 10 in the inner cylinder 8 into the spiral grooves 7 formed in the outer cylinder 5. Consequently, rotation of the base 9 relative to the cylindrical wall 5 rotates the platform 11. In addition, the spiral grooves 8 and the protrusions 12 act cooperatively as a cam and as a cam follower, respectively, so that rotation of the platform 11 moves the platform 11 axially along the cylindrical wall 5. Thus, by manually framing the base 9, the platform 11 may be raised or lowered to engage spray units 43 of different lengths and hold them against the depressor 2 so that depression of the depressor 2 causes actuation of the held spray unit 43.

The electronic circuitry of the device contained in the compartment 3 will now be described.

As shown in Fig. 4, the compartment 3 has a first panel 13 which is removable to allow the user to change a battery 14 which acts as a power source for the electronic circuitry. The compartment 3 has a second panel 15 which covers the remainder of the electronic circuitry. The second panel 15 is not removed in normal use, but is shown removed in Fig. 4 for illustration.

The electronic circuitry is mounted on a circuit board 16 on which the electronic components are mounted and connected together.

The circuitry includes an IC chip 40 in wliich there are integrated the following components: a microprocessor for controlling operation of the device; a non- volatile read-only memory for storing a control program for execution by the microprocessor; a non- volatile re- writable memory for storing a record of delivery of the medication from the spray unit 43 over time; RAM used by the microprocessor; and an internal clock.

The two memories may be constituted by different regions of the same memory element, for example an EPROM. Any suitable architecture for the IC chip 40 may be used. As an alternative, it would be possible to provide the various components of the IC chip 40 in separate IC chips.

The microprocessor running the control program controls operation of all the electronic circuitry, including the recording of delivery of the medication and analysis of the recorded delivery according to a predetermined algorithm, as will be described in more detail below.

The electronic circuitry fVαrther includes a motion detector 46 for detecting and measuring motion and a temperature sensor 47 for measuring temperature.

The electronic circuitry further includes an output terminal 17, for outputting data to an external device, for example a printer or an external computer, typically a PC. The output terminal 17 may be a Universal Serial Bus port.

The circuitry further includes a transducer 41 for outputting an audible sound and a light emitting diode 19 which acts as a display element. In use, the transducer 41 and the LED 19 are used for outputting an audible warning and a visible warning, respectively.

The circuitry also includes an electronic display 18, preferably a liquid crystal display, used to display a plurality of information to the user, for example the current time and date; the remaining power of the battery 14; a timer that is activated each time a dose is delivered; and information about the delivery of the medication from the spray unit 43 recorded in the memory.

The circuit board 16 also mounts buttons 20, 21 to allow the user to control the electronic circuitry. To prevent accidental operation, the buttons 20, 21 are set flush with the outer surface of the panel 15.

Lastly, the electronic circuitry includes a micro-switch 27 which acts as a sensor to detect actuation of a spray unit 43 held in the chamber 1.

The arrangement of the depressor 2 will now be described with reference to Fig. 5. The depressor 2 comprises a rod 22 slidably mounted in a guiding cylinder 23 fixed on one end of the compartment 3 containing the electronic circuitry.

The upper end of the rod 22 protrudes from the guiding cylinder 23 and has fixed thereto a hollow cap 24 having a wider diameter than the guiding cylinder 23 to fit around the top of the guiding cylinder 23. Attached to the hollow cap 24 is a plate 25 which engages the cap 45 of the spray unit 43.

The rod 22 extends through the guiding cylinder into the compartment 3 where -lithe lower end of the rod 22 is connected to a spring 26 which is coiled around the rod 22 and couples the rod 22 to the compartment 3. The lower end of the rod is positioned above the micro-switch 27 but biassed away from the micro-switch 27 by the spring 26. On depression of the depressor 2 to actuate the spray unit 43, the rod 22 is moved against the action of the spring 26 to activate the micro-switch 27. After depression of the depressor 2, the spring 26 returns the rod 22 to its original position.

The spring also allows rotation of the rod 22 which allows the plate 25 to be swung out of the way when the spray unit 43 is being inserted into, or removed from, the chamber 1. The operation of the electronic circuitry under the control of the control program iTirining in the microprocessor will now be described.

Activation of the micro-switch 27 causes an electrical signal to be sent to the microprocessor. On receipt of such an electrical signal, the microprocessor stores the time and date derived using the clock installed in the memory. In this way, the time and date of each actuation of the spray unit 43 is recorded in the memory, thereby creating a record of the delivery of the medication from the spray unit 43 over time. In some cases, patients use plural doses, one immediately after the other. To accommodate this, actuations occurring within a minimum period, for example ten seconds, after a previous actuation are ignored. The microprocessor subsequently analyses the delivery of the medication recorded in the memory. The control program implements a predetermined algorithm which causes the microprocessor to detect an increase in the delivery of the medication indicative of an increased risk of myocardial infarction. Suitable algorithms will be described in more detail below. On detecting such an increase in the delivery of the medication indicative of an increased risk of myocardial infarction, the microprocessor causes either one or both of the transducer 41 and the LED 19 to output a warning to the user. This warning signifies that the user should consult a doctor to consider the possibility of preventative treatment. The microprocessor also records the time and date of each warning in the memory.

The microprocessor also causes display on the display 18 of a timer to allow the user to monitor how long their symptoms persist following use of the spray unit 43.

Lastly, the microprocessor causes information about the recorded delivery of the medication to be displayed on the display 18, for example by displaying the number of times that the medication has been delivered over a given period, for example daily, weekly or monthly. The control program also allows the recorded delivery of the medication to be output to the output terminal 17.

The algorithm used to detect an increased risk of myocardial infarction will now be described. In general, any algorithm which identifies a clinically important increase may be used. There is considerable flexibility in the precise choice of the algorithm. For example, it may be desirable to vary the point at which a warning is given.

The preferred algorithm is as follows.

For the purposes of defining the algorithm, patients are divided into three broad categories with respect to GTN usage, namely:

1. Non-users: Patients who rarely suffer symptoms of angina and so rarely, if ever, use their spray unit.

2. Routine Users: Patients who use their spray unit to alleviate symptoms of angina or to prevent its development during anticipated effort (prophylactic use). The frequency of use varies widely between users. Low frequency routine users administer approximately 1 to 3 doses per month, moderate frequency routine users administer approximately 1 to 6 doses per week and high frequency routine users administer approximately 1 to 3 doses per day.

3. Extreme users: Patients who rely heavily on their GTN pump either out of habit or because of intractable angina for which no effective treatment remains.

Most patients with clinical manifestations of coronary heart disease are in groups 1 and 2 while those in group 3 represent a minority of patients.

To determine the user category, the device may operate initially in a calibration mode during which the recorded delivery of the medication is used to determine a background rate of delivery. The calibration mode is maintained for a calibration period when the patient first acquires the device. This calibration period may be of any length, typically in the range from two weeks to three or four months. If a myocardial infarction occurs within the calibration period then the device is reset and recalibrated.

The preferred algorithm causes a warning to be issued when the delivery of the medication exceeds a threshold. Three types of threshold are specified, namely:

1. Absolute use threshold

A first type of threshold is an absolute rate of delivery threshold. The warning is output when the usage over a predetermined period, ie the rate of delivery, exceeds a predetermined threshold. The predetermined period and/or the predetermined threshold may be of any suitable value and may be different for different categories of user. The absolute rate of delivery threshold applies mainly to non-users and low, moderate and high frequency routine users. For patients who are non-users or who use their spray unit less than once a day, the hourly and daily rates of use are small, so it is preferable to use an absolute rate of delivery alarm threshold rather than trying to refer to a particular increase in the rate of usage.

Examples of possible threshold values are as follows.

For non-users and low and medium frequency routine users, the predetermined thresholds could be more than 5 doses over a 24-hour period or more than 1 dose per day over 5 consecutive days. If either of these two thresholds are reached the warning is output.

For high frequency users, the corresponding thresholds could be more than 7 doses over a 24 hour period and more than 4 doses per day for 5 days. The threshold might range from 2 to 10 doses over a 24-hour period and between

1 to 10 doses per day over a 3 to 14 day period.

2. Increased rate threshold

A second type of threshold is an increased rate of delivery threshold. The warning is output when the usage over a predetermined period , ie the rate of delivery, exceeds the background rate by a predetennined amount, preferably a proportional amount although an absolute amount is also possible. The predetermined period and/or the predetermined amount may be of any suitable value and may be different for different categories of user. The increased rate of delivery threshold applies mainly to extreme frequency users. For high frequency users and extreme users, the hourly and daily rates of use are high and so it is preferable to specify alarm thresholds when the rate of delivery exceeds the background rate by a predetermined amount. Examples of possible threshold values are as follows. The threshold could be 5 times the usual hourly rate of delivery when averaged over a four hour period or 1.5 times the usual daily rate over a 5 day period. If either of these two thresholds were reached the warning is output.

The threshold might range from 2 to 8 times the usual hourly rate when averaged over 2 to 12 hours or 1.5 to 2 times the daily rate over 3 to 7 consecutive days. 3. Over-ride threshold

A third type of threshold, the 'over-ride' threshold applies to all users. The warning is output when the delivery exceeds any one of a number of predetermined thresholds that signify that the patients is likely to be suffering an acute myocardial infarction at the time. An examples of a possible threshold values is that the alarm activates if the number of doses exceeds 5 per hour with a range of 4 to 10 doses per hour.

The particular thresholds specified above may be changed, for example as a consequence of variations in an individual's usage.

Various modifications may be made to increase the sensitivity of the algorithms in identifying patients at high risk of a myocardial infarction, for example as follows. Angina is more likely to be prognostically significant if it occurs at rest rather than during exertion. An optional feature is the motion detector 46 provided with the objective of improving the sensitivity of the alarm thresholds. The motion detector 46 detects whether there has been any significant exertion in a predetermined period prior to delivery of the medication. The movement detected by the motion detector is recorded in the memory of the IC chip 40. The algorithm uses the recorded amount of movement. For example, if actuation occurs while the device is at rest, then the dose would be considered equivalent to a specified multiple (for example 1.25 to 3 times) of the dose used after exertion. In this way, the above thresholds can still be applied.

A further modification of the invention would be to incorporate a geographic positioning system (GPS) with the objective of improving the sensitivity of the alarm thresholds. The GPS would allow the assessment of distance travelled in a predetermined period prior to the use of GTN and whether that distance was along the flat or up or down a gradient. The output of the GPS could be used in a similar manner to the output of the motion detector.

Angina is more likely to be prognostically significant if it occurs at night and in the early morning compared with that occurring during the day. A modification of the device would consider that a GTN dose delivered between 23 :00 and 09:00 as being equivalent to a multiple (for example 1.25 to 3 times) of the dose used at all other times. In this way, the above thresholds can still be applied.

Angina is likely to be less prognostically significant if it occurs at the extremes of temperature. An optional feature of the device is the temperature sensor 47 provided with the objective of improving the sensitivity of the alann thresholds. The temperature sensor 47 measures the current temperature. The algorithm uses the current temperature measured by the temperature sensor. For example, if activation occurs at an extreme of temperature the dose would be considered equivalent to a specified proportion (for example 3/4 to Vz) of the dose under standard conditions. In this way the above thresholds can still be applied.

The device can also be used to detect a gradual deterioration of angina control. The device can calculate the average daily, weekly and monthly GTN delivery for any preceding time period and display this information on an LCD screen. An alarm will not activate but clinicians and patients will have a visual guide which enables one period of time to be compared with another with a view to guiding decision making regarding changes in treatment strategy.

The second device will now be described with reference to Fig. 6 and 7. Much of the second device, including many components and the electronic circuitry and control process are identical to the first device. Therefore, for the common components, the same reference numerals will be used and a description thereof will not be repeated.

The second device is integrated with a spray unit 28, having an actuator 31, the spray unit 28 being of a known type as described above. The second device is designed to fit a particular spray unit 28 of a particular, known height and width. Accordingly, the holding arrangement of the second device consists solely of the chamber 1 and second device does not include the additional components of the holding arrangement of the first device (for example the resilient strip 6 and moveable platform 11). Instead, the spray unit 28 fits directly in the chamber 1 with a tight fit between the inner cylindrical surface of the chamber 1 and the container 35 of the spray unit 28.

Similarly, the chamber 1 is closed at the lower end by a base (not shown) at a fixed position chosen with regard to the height of the spray unit 28 to hold the spray unit 28 at the desired position axially along the chamber 1.

By avoiding the requirement to accommodate spray units of different sizes, the second device may be smaller and more compact.

The second device has a single depressor 29 in which is integrated the cap portion 32 of the spray unit 28 and components equivalent to the depressor 2 in the first device. The cap portion 32 of the depressor 29 is the same as the normal cap of a known spray unit. In particular, the cap portion 32 is arranged to fit directly onto the actuator 31 of the spray unit 28 and includes an internal flow path 33 for directing a dose of medication delivered as a spray out of a nozzle 34. Integrated with the cap portion 32, the depressor 29 has a switch activator 30 which protrudes from the rear surface of the cap portion 32 and engages the micro-switch 27. Thus, on depression of the cap portion 32, the switch activator 30 activates the micro-switch 27.

The electronic circuitry of the second device is identical to that of the first device. Thus in operation, the second device records and analyses the delivery of the medication from the spray unit 28 in the same manner as the first device, as described above.

The third device will now be described with reference to Figs. 8 to 11. Much of the electronic circuitry and control process of the third device are identical to the first device. Therefore, for the common components, the same reference numerals will be used and a description thereof will not be repeated. Fig. 8 shows a perspective view of the assembled third device.

The arrangement of the various components of the third device will now be described with reference to Fig 9. The third device comprises an outer container 48 and a chamber housing the electronic circuitry 49. These components are illustrated as though transparent to allow the internal construction and arrangement to be seen. The container 48 accommodates a snap-fit cartridge 50 which is shown in cross section to illustrate its internal arrangement. The cartridge 50 comprises an upper compartment 51 which contains the solid units of medication. The floor of the upper compartment 51 is funnel shaped to direct units of medication down towards a lower compartment 52 which houses the medication dispensing mechanism. The arrangement of the medication dispensing mechanism is shown in an exploded form in Fig. 10. The dispensing mechanism comprises an actuator 53 which activates the device when manually depressed. The actuator 53 is connected to a ramp 54. The ramp 54 channels solid units of medication down from the upper compartment of the medication cartridge 51 into a chamber 55 which is sized to accommodate one unit of medication at a time. Chamber 55 does not have a floor and is positioned over the solid floor of compartment 52. When the actuator is depressed it moves the dispensing mechanism horizontally forward pushing the solid unit of medication in chamber 55 over an opening 56 in the floor of compartment 52, thereby dispensing a single unit of medication. Chamber 55 is connected to two resilient strips 57 which return the dispensing mechanism to its starting position. Chamber 55 is then automatically refilled with another unit of medication.

Fig. 11 illustrates how manual depression of the actuator activates the electronic circuitry in chamber 49. The actuator 53 comprises a rod 58 mounted on its upper surface. The rod 58 protrudes through a rectangular opening 59 in the floor of compartment 49. When the actuator is depressed rod 61 slides forward and activates a micro-switch 60 within compartment 49. Activation of the micro-switch causes an electrical signal to be sent to the microprocessor in the same manner as described for the first device. Thus in operation, the third device records and analyses the delivery of the medication from the cartridge 50 in the same manner as the first device, as described above.

The device, including the outer case 48, the cartridge 50, the chamber housing the electronic circuitry 49, the dispensing mechanism and actuator 53 may be made from any suitable material, for example metal, plastic or glass.

While the form of the third device is preferred, a dispensor of solid units of medication may alternatively be of the type commonly known for delivering individual sweets or pellets of artificial sweetener for a hot drink from a container, which are straightforward, known mechanisms. While the invention has been described and illustrated with reference to certain particular embodiments thereof, those skilled in the art will appreciate that various changes and modifications can be made therein without departing from the scope of the invention.

Claims

1. A device for identifying if a patient is at an increased risk of a myocardial infarction, the device comprising: a sensor arranged to detect delivery of a dose of medication for the relief of angina by said medication delivery means; a memory arranged to record the delivery of the medication detected by the sensor, over time; and analysis means arranged to analyse the delivery of the medication recorded in said memory according to a predetermined algorithm to detect an increase in the delivery of the medication indicative of an increased risk of myocardial infarction.

2. A device according to claim 1, further comprising said medication delivery means for delivering a dose of medication for the relief of angina;

3. A device according to claim 2, wherein said medication delivery means comprises a spray unit which is actuatable to deliver the dose of medication as a spray, the device including a holding arrangement for holding the spray unit.

4. A device according to claim 2, wherein said medication delivery means comprises a mechanism actuatable to deliver one or more solid units of medication as said dose. ^•

5. A device for identifying if a patient is at an increased risk of a myocardial infarction, the device comprising: a holding arrangement for holding a spray unit which is actuatable to deliver, as a spray, a dose of medication for the relief of angina; a sensor arranged to detect delivery of a dose of medication from of a spray unit held by said holding arrangement; a memory arranged to record the delivery of the medication detected by the sensor, over time; and analysis means arranged to analyse the delivery of the medication recorded in said memory according to a predetermined algorithm to detect an increase in the delivery of the medication indicative of an increased risk of myocardial infarction.

6. A device according to any one of the preceding claims, wherein the device further comprises a warning means arranged to output a warning when said analysis means detects an increase in the delivery of the medication indicative of an increased risk of myocardial infarction.

7. A device according to claim 6, wherein the warning means includes a display element for outputting a visible warning.

8. A device according to claim 6 or 7, wherein the warning means includes a transducer for outputting an audible warning.

9. A device according to any one of the preceding claims, wherein the predetermined algorithm detects when the rate of delivery of the medication exceeds a predetermined threshold as an increase indicative of an increased risk of myocardial infarction.

10. A device according to any one of claims 1 to 8, wherein the predetermined algorithm detects when the rated delivery of the medication exceeds a background rate by a predetermined amount as an increase indicative of an increased risk of myocardial infarction.

11. A device according to claim 10, wherein the predetermined algorithm detects when the rate of delivery of the medication exceeds a background rate by a predetermined absolute amount as an increase indicative of an increased risk of myocardial infarction.

!

12. A device according to claim 10, wherein the predetermined algorithm detects when the rate of delivery of the medication exceeds a background rate by a predetermined proportional amount as an increase indicative of an increased risk of myocardial infarction.

13. A device according to any one of claims 10 to 12, wherein the analysis means is arranged to determine the background rate during a calibration period.

14. A device according to any one of the preceding claims, wherein the memory means is arranged to record the time of day of delivery of the medication, and the predetermined algorithm uses the recorded time of day.

15. A device according to any one of the preceding claims, wherein the device further comprises a movement detector for detecting movement of the device, the memory is arranged to record the amount of movement of the device in a period leading up to delivery of the medication, and the predetermined algorithm uses the recorded amount of movement.

16. A device according to any one of the preceding claims, wherein the device further comprises a temperature sensor for measuring temperature and the predetermined algorithm uses the temperature measured by the temperature sensor at the time the medication is delivered.

17. A device according to any one of the preceding claims, wherein the analysis means comprises a microprocessor having a program which, on execution, implements the predetermined algorithm.

18. A device according to any one of the preceding claims, wherein the device further comprises a display arranged to display the delivery of the medication recorded in the memory.

19. A device according to any one of the preceding claims, wherein the device includes a terminal for outputting the delivery of the medication recorded by said memory from the device to an external device.

20. A device according to any one of the preceding claims, wherein the device further comprises a display arranged to display the time since the last delivery of the medication detected by the sensor.

21. A device according to any one of the preceding claims when appendant to claim 3 or 5, wherein the holding arrangement is adaptable to hold spray units of different sizes.

22. A device according to any one of the preceding claims when appendant to claim 3 or 5, wherein said medication for the relief of angina is glyceryl trinitrate.

23. A device according to any one of the preceding claims when appendant to claim 3 or 5, wherein said spray unit is an aerosol spray unit.

24. A device according to any one of the preceding claims when appendant to claim 3 or 5, having a said spray unit held in the holding arrangement.

25. A device according to claim 23, wherein the holding arrangement is integrated with the spray unit.

26. A device for identifying if a patient is at an increased risk of a myocardial infarction constructed and arranged to operate substantially as hereinbefore described.

27. Use of a device according to any one of the preceding claims to identify if a patient is at an increased risk of myocardial infarction.

28. A method of using a device according to any one of the preceding claims to identify if a patient is at an increased risk of myocardial infarction.

29. A method of identifying if a patient is at an increased risk of a forthcoming myocardial infarction by analysing the usage of a medication for the relief of angina by the patient to detect a clinically significant increase in the usage indicative of an increased risk of myocardial infarction.

30. A method according to claim 28, wherein said step of analysing the usage is performed by a device having a record of the usage stored therein.

31. A method according to claim 29, further comprising using the device to monitor the usage and store the record of the usage.

32. A method of identifying if a patient is at an increased risk of a forthcoming myocardial infarction substantially as hereinbefore described.