DEVICE FOR DIAGNOSING THE EFFICACY OF VENTILATION OF A PATIENT AND METHOD FOR DETERMINING THE VENTILATORY EFFICACY OF A PATIENT

Abstract

A device for diagnosing the ventilatory efficacy of a patient under respiratory assistance, said device being intended to cooperate with a system for ventilating the patient, the device having: a bidirectional thermal mass sensor for measuring, in real time, the air flows during insufflation and during exhalation, an electronic casing connected to said sensor and configured to receive and process data relating to the air flows measured by the sensor, the electronic casing having: i. a user interface comprising a display device and data input means, ii. a data-processing center, the data-processing center functioning according to programmed algorithms for acquiring, processing and displaying the data, for analyzing the efficacy of the ventilation in real time, and for managing alarms, and iii.

means for supplying electricity.

Claims

1. A device for diagnosing a ventilatory effectiveness of a patient under a manual respiratory assistance performed by a user operating a system for ventilating the patient comprising a flexible bag or a self-inflating bag, the device including: a single use or autoclavable two-way thermal mass sensor configured to be plugged between said ventilating system and a patient interface to measure in real-time air flow rates on insufflation and on expiration; an electronic circuitry configured to receive and process data relating to the air flow rates measured by the sensor, the electronic circuitry including: a user interface comprising a display device and means for inputting data; a data processor for determining and adjusting in real-time, ideal ventilatory parameters for an optimal ventilation of said patient, and for determining and adjusting in real-time, for each ventilatory parameter, a minimum and/or maximum threshold and in case a measured value of a ventilatory parameter becomes higher than a corresponding maximum threshold and/or lower than a corresponding minimum threshold, generate an alarm and/or display on the display device a piece of information on one or more ventilatory parameters to be modified or corrections to be carried out to achieve the optimal ventilation, an electrical power supply, a disconnectable electromechanical connection to the two-way thermal mass sensor.

2. The device as claimed in claim 1, wherein the display device is a screen and the means for supplying electrical power being a battery.

3. The device as claimed in claim 1, being configured to display the inspired and expired volumes on the display device in the form of a bar graph, divided into three portions respectively indicating whether the volume is insufficient, effective or excessive.

4. The device as claimed in claim 1, wherein the sensor is single-use.

5. The device as claimed in claim 1, wherein the electronic circuitry is configured to identify in the breathing phase of the patient if he/she is in the inspiration phase or in the expiration phase or in the end-expiration phase, by analyzing the data from the sensor.

6. The device as claimed in claim 1, wherein the means for inputting data is configured to allow physical and/or physiological characteristics of the patient to be input into the electronic unit, and/or characteristics relating to the ventilation, including the type of ventilation, to the type of ventilation device and/or the type of ventilation interface to be input.

7. The device as claimed in claim 6, wherein the physical and/or physiological characteristics of the patient or physiological parameters of the patient measured by the sensor comprises at least two from the following characteristics or parameters: the size of the patient, the lung capacity of the patient, the pulmonary compliance of the patient, the pulmonary resistance of the patient, the expiratory time constant of the patient, the positive end-expiratory pressure of the patient, the concentration of CO.sub.2 in the expired air of the patient.

8. The device as claimed in claim 7, wherein the data processor is configured to, throughout the duration of the ventilatory assistance provided to the patient, in particular in each ventilation cycle, analyze said characteristics and the physiological parameters measured, in particular in each ventilation cycle, by the sensor, in order to deduce therefrom ideal ventilatory parameters for an optimal ventilation of said patient, and for each ventilatory parameter, a minimum and/or maximum threshold.

9. The device as claimed in claim 8, wherein the ventilatory parameters include at least two from the following parameters: the insufflated volume, the expired volume, the tidal volume, the leak volume, the ventilatory frequency and the insufflation pressure.

10. The device as claimed in claim 8, wherein the data processor is configured to receive ventilatory parameters measured by the sensor and to compare them to said thresholds, throughout the duration of the ventilatory assistance provided to the patient, in each ventilation cycle.

11. A ventilation system for providing respiratory assistance to a patient, including a device for diagnosing the effectiveness of the ventilation of the patient as claimed in claim 1, and a manual ventilation device chosen from the group consisting of: a flexible bag and a self-inflating bag, and a ventilation interface chosen from the group consisting of: an invasive ventilation via tracheotomy or tracheal tube, and a non-invasive ventilation via a mask, the two-way thermal mass sensor being located between the ventilation device and the ventilation interface.

12. A method for determining a ventilatory effectiveness of a patient under manual ventilation performed by a user operating a manual ventilation system for providing respiratory assistance to the patient provided with a patient interface, the system for ventilating the patient comprising a flexible bag or a self-inflating bag operated by the user, the method comprising : Measuring in real-time air flow rates on insufflation and on expiration with a diagnosing device including a single use or autoclavable two-way thermal mass sensor located between the ventilation system and the patient interface and connected via a disconnectable electro-mechanical connection to an electronic circuitry configured to receive and process data relating to the air flow rates measured by the sensor, the electronic circuitry including a user interface and a data processor, the method comprising: a) determining ideal ventilatory parameters for an optimal ventilation of said patient, and for each ventilatory parameter, a minimum and/or maximum threshold; b) measuring in real-time the ventilatory parameters of the patient; c) comparing the measured ventilatory parameters to said thresholds, respectively; d) for each ventilatory parameter, in case of value of a measured ventilatory parameter higher than a corresponding determined maximum threshold and/or lower than a corresponding determined minimum threshold, informing the user of a correction to be carried out during operation of the manual ventilating system to achieve an optimal ventilation of the patient by generating a corresponding information on the user interface.

13. The method as claimed in claim 12, wherein the ventilatory parameters include at least two from the following parameters: the insufflated volume, the expired volume, the tidal volume, the leak volume, the ventilatory frequency and the insufflation pressure.

14. The method as claimed in claim 12, wherein the inspired and expired volumes are displayed on a screen in the form of a bar graph, indicating whether the volume is insufficient, effective or excessive; the bar graph being updated in a period of less than 100 ms, and/or the insufflated volume is displayed on a screen and updated in a period of less than 100 ms.

15. A device for diagnosing a ventilatory effectiveness of a patient under manual respiratory assistance performed by a user operating manually a ventilation system comprising a flexible bag or self-inflating bag operated by the user, the device including: a two-way thermal mass sensor for measuring in real-time air flow rates on insufflation and on expiration; a heating element for heating the two-way thermal mass sensor; an electronic configured to receive and process data relating to the air flow rates measured by the sensor, the electronic unit including: a user interface comprising a display device, a data processor for analyzing said data, determining the effectiveness of the ventilation in real-time, and managing alarms; a disconnectable electromechanical connection for connecting the thermal mass sensor and heating element to the electronic circuitry and an electrical power supply.

16. The device as claimed in claim 15, wherein the heating element is controlled by the electronic circuitry to heat the sensor at a predefined temperature above 20° C.

Description

[0085] The invention will be better understood on reading the following detailed description, of a nonlimiting example of implementation thereof, and on examining the appended drawing, in which:

[0086] FIG. 1 is a schematic representation of a ventilation system according to the invention, incorporating a device for diagnosing the effectiveness of the ventilation of a patient according to the invention;

[0087] FIG. 2 schematically and partially shows, in perspective, the ventilation system of FIG. 1;

[0088] FIG. 3 schematically shows, in isolation, an example of a display of the display device of the electronic unit of the device for diagnosing the effectiveness of the ventilation of a patient of FIG. 1 or 2;

[0089] FIG. 4 schematically shows the steps of the method for ventilating a patient according to the invention;

[0090] FIGS. 5 to 7 respectively detail certain steps of the method of FIG. 4, and

[0091] FIG. 8 is a graph of the flow detected during time by the sensor of a device according to the invention when ventilating a patient.

[0092] FIG. 1 shows a manual ventilation system 1 performed by a user for providing respiratory assistance to a patient 1 including a device 10 for analyzing the ventilatory effectiveness of the patient, which will be described below.

[0093] The ventilation system 1 includes a ventilation device 11, forming in this example a self-inflating bag. The scope of the invention is not departed from if the ventilation device is different, for example consisting of a mechanical ventilator or a flexible bag inter alia.

[0094] The ventilation system 1 may be suitable for a use such as a continuous ventilation of a patient in respiratory distress, respiratory replacement for an apneic patient, spontaneous ventilation of a patient or discontinuous ventilation of a patient in cardiac arrest or another use.

[0095] The ventilation system 1 furthermore includes a ventilation interface 12 serving to connect the ventilation system 1 to the patient, consisting in the illustrated example of a non-invasive ventilation via a mask. The mask is intended to be applied to the mouth and nose of the patient. The scope of the invention is not departed from if the ventilation interface 12 consists of an invasive ventilation via tracheal tube or any other supralaryngeal device.

[0096] The ventilation system 1 further includes a one-way expiration valve 13 placed between the ventilation device 11 and the ventilation interface 12 in order to direct air originating from the ventilation device 11 toward the ventilation interface 12 and to let the air expired by the patient escape to the atmosphere.

[0097] In this example, the ventilation device 11 is equipped with a check valve 14 that opens onto open air and that allows air to flow from the atmosphere into the ventilation device 11.

[0098] The ventilation system 1 further includes a one-way insufflation valve 15 that allows the patient to be supplied with air.

[0099] The diagnostic device 10, the ventilation device 11, the ventilation interface 12, the expiration valve 13 and the insufflation valve 15 are reversibly assembled together, for example via engagement as schematically illustrated in FIG. 1, in a way known per se.

[0100] The two-way thermal mass sensor 20 is located between the ventilation device and the ventilation interface 12.

[0101] The device 10 comprises a heating element 200 for heating the two-way thermal mass sensor 20, notably at a temperature above 15° C., preferably above 20° C., as visible on FIG. 1.

[0102] The heating element 200 is integrated into the two-way thermal mass sensor 20.

[0103] The device 10 for diagnosing ventilatory effectiveness includes a two-way thermal mass sensor 20 able to measure in real-time air flow rates on insufflation and expiration and an electronic unit 21 connected to said sensor 20 by a disconnectable connection means 22 ensuring an electronic and mechanical connection. The two-way thermal mass sensor 20, also called a thermal mass flowmeter, may be single-use or autoclavable. It is intended to be plugged, as may be seen in FIGS. 1 and 2, on the one hand, between the insufflation valve 15 of the ventilation device 11 and the expiration valve 13, and, on the other hand, the ventilation interface 12. The sensor 20 makes it possible to measure the flow rates and volumes of air inspired and expired by measuring the specific heat capacity of the fluid, and by extension the amount of air passing therethrough in each ventilation cycle. The electronic unit 21 is configured to receive and process data relating to the air flow rates measured by the sensor 20.

[0104] The heating element 200 is controlled by the electronic circuitry to heat the sensor at a predefined temperature, notably above 20° C.

[0105] The heating element 200 may comprise an electrical resistor powered and controlled by the electronic unit.

[0106] In this example, to limit the water condensation in the sensor 20, the device 10 comprises a heating element for heating the sensor 20 at a temperature above 20° C. The heating element is an electrical resistor powered and controlled by the electronic unit 21.

[0107] In the illustrated example, the diagnostic device 10 does not include any other sensors, but it could include other sensors, for example a pressure sensor and/or a sensor of CO.sub.2 concentration in the air, without departing from the scope of the invention.

[0108] The electronic unit 21 of the diagnostic device 10 includes a data processor, including a hardware portion and a software portion, a control interface or user interface comprising a display device and means for inputting data, and means for supplying electrical power such as one or more batteries. The electronic unit 21 allows ventilatory curves to be interpreted and important information relating to the effectiveness of the ventilation and various warning messages to be displayed to the first responder. If the effectiveness of the ventilation is considered to be inadequate or dangerous for the patient, the diagnostic device 10 allows the main causes of this lack of effectiveness to be identified and specific warning messages to be sent to the first responder.

[0109] The electronic unit 21 includes, in this example, as may be seen in FIG. 1, a light-emitting diode 25 or LED allowing a visual alarm to be displayed and a reset button 26, and a display device 27, shown in FIG. 3, allowing various types of warnings and messages to be displayed depending on the analysis of effectiveness performed by the electronic unit 21.

[0110] The electronic unit 21 may as a variant include or consist of a tablet computer, of a laptop, of a smartphone executing a specific application, and equipped, where needs be, with a hardware interface for interfacing with the one or more sensors and other elements of the system.

[0111] Information may be exchanged between the data processor and the one or more sensors and other elements of the system via one or more wires and/or wirelessly.

[0112] The electronic unit 21 is, in this example, configured to identify the breathing phases of the patient, notably if he is in the inspiration phase Ti or in the expiration phase Te or in the end-inspiration phase Tp, by analyzing the data from the sensor 20. An example of the flow detected by the sensor 20 during ventilation is represented on FIG. 8.

[0113] The inspiration phase Ti, the expiration phase Te and the end-inspiration phase Tp are successive phases of one ventilation cycle Vc.

[0114] The electronic unit 21 incorporates specific inspiration, expiration and end-expiration triggers for the detection of the inspiration Ti, expiration Te and end-expiration Tp phases. For example, the inspiration trigger is a flow higher than 30 L/min, the expiration trigger is a flow less than −4 L/min and the end-expiration trigger is a flow higher than −1 L/min.

[0115] The triggers values are adjusted depending to the detected flows in order to avoid false detection of a breathing phase or miss a breathing phase when the flows are low.

[0116] The triggers values are determined to avoid false detection of a breathing phase in the presence of noisy signals comprising signals caused by the movements of the device and during thoracic compression, which may induce passive ventilation with a peak inspiratory airflow, for example of approximately 20 L/min.

[0117] In the example illustrated in FIG. 3, the tidal volume Vt 29, which is the volume of air reaching the lungs in each respiration, expressed in ml, is displayed on the display device 27 in each ventilatory cycle. In this example, a measured tidal volume Vt of 450 ml may be read.

[0118] The inspired and expired volumes are also displayed on the screen in the form of a bar graph 28, divided into three portions in this example, forming three zones of color 28a, 28b and 28c for respectively indicating whether the volume is insufficient (28a), effective (28b) or excessive (28c) depending on the physiological characteristics of the patient.

[0119] The bar graph 28 is, in this example, updated in a period of less than 100 ms, notably less than 50 ms, notably less than 30 ms, which allows the user to stop the application of pressure on the self-inflating bag of the ventilation device 11 at the right time.

[0120] The optimal ventilation frequencies determined by the data processor are transmitted to the first responder via a luminous and/or audio and/or tactile signal in order to inform him of the right rate to use. In the example of FIG. 3, a warning message 31 indicating that it is necessary to decrease the ventilation frequency appears.

[0121] In the example of FIG. 3, a warning message 30 indicating “leaks” appears, informing the first responder that it is necessary to decrease leaks, for example by repositioning the mask of the patient. Specifically, leaks are detected and calculated by measuring the discrepancy between the insufflated volume and the expired volume in each ventilatory cycle and/or observing a drop in the insufflation pressure simultaneously with an increase in flow rates.

[0122] Lastly, again in FIG. 3, a visual indicator 32 allows the level of charge of the one or more batteries to be viewed.

[0123] By virtue of this diagnostic device 10, information, delivered by the electronic unit 21, on the value of the main ventilatory parameters and on their conformity with respect to physiological and physical characteristics of the patient and the recommendations of ILCOR (the International Liaison Committee On Resuscitation) is, for each ventilation cycle, fed back to the first responder. Specifically, the measurement of the expired and insufflated volumes that is taken by virtue of the sensor 20 placed upstream of the ventilation interface 12 allows, after processing by the data processor of the electronic unit 21, the tidal volume, i.e. the amount of air actually being supplied to the lungs of the patient, and the leaks in each ventilation cycle to be estimated and displayed.

[0124] The measurement of flow rates also allows the detection of various phases of the ventilatory cycle by virtue of specific triggers. The latter in particular allow the end of the expiration phase of the patient to be detected in order to prevent hyperventilation of the patient, which occurs when the first responder re-insufflates the patient before the end of the expiration. When the detection of the end of the expiration phase is not possible because of excessively high expiratory leaks, it may be estimated by virtue of the measurement of the expiratory time constant of the patient.

[0125] FIGS. 4 to 7 illustrate the steps of the method for ventilating a patient using the ventilation system 1, according to the invention.

[0126] With reference to FIG. 4, the method for ventilating a patient using the ventilation system 1 includes a step 1 consisting in the first responder using the user interface, in particular the inputting means, to select or indicate a physical and/or physiological characteristic of the patient to the electronic unit 21, in particular the size of the patient. The data processor, which receives this characteristic, is then configured to automatically define the lung capacity of the patient and the right tidal volume (V.sub.t) range, i.e. a minimum threshold and a maximum threshold for the tidal volume.

[0127] In a step 2, the first responder may select or indicate a characteristic relating to the ventilation, in particular the type of ventilation, which is for example chosen from cardiopulmonary resuscitation (CPR) or ventilation alone. The data processor then automatically defines the level of filtering of the flow rate and of the trigger values used for the detection of expiratory and inspiratory phases.

[0128] In a step 3, the first responder may select another characteristic of the ventilation, for example the ventilation mode chosen from invasive or non-invasive ventilation. The data processor then automatically defines the leak-volume tolerance range i.e. a maximum leak-volume threshold.

[0129] In a step 4, the main screen of the display device 27 turns on and the main program of the data processor starts up.

[0130] In each cycle, an analysis is carried out.

[0131] In a step 5, the flow rate is measured using the sensor 20 so as to detect a pause phase 6, an inspiratory phase 7, an expiratory phase 8 and to perform a calculation phase 9. Specifically, between the pause phase 6 and inspiratory phase 7, there is a step 6bis consisting in detecting a positive flow rate generating the clock reset, this making it possible to detect that the inspiratory phase is in course. Moreover, between the inspiratory phase 7 and expiratory phase 8, in a step 7bis, a negative flow rate is detected, this making it possible to say that an expiratory phase is in course. After the expiratory phase 8, the flow rate, detected in a step 8bis, is zero, this allowing the calculation phase 9 to be triggered.

[0132] From the detection of the positive flow rate to the end of the ventilation cycle, cycle time (Tcycle) and ventilatory frequency (Fr) are measured, in a step 10.

[0133] While monitoring the ventilation cycle, and depending on the result obtained in the calculation phase 9, information is displayed and/or alarms are triggered in the form of visual and/or audio and/or tactile indicators, as will be explained below.

[0134] The detail of the method during the inspiratory phase 7 is illustrated in FIG. 5. This inspiratory phase 7 comprises the measurement of the inspiratory time T.sub.i 71. If the inspiratory time T.sub.i is longer than a preset duration, for example 4 seconds, a message 72 indicating “no expiration” is sent. It will be noted that the inspiration generally lasts between 0.5 and 2 s. Thus, if no expiration has been detected after a preset duration longer than 2 s, for example longer than 4 s after the start of the insufflation, the message 72 is displayed.

[0135] In parallel, in a step 73, the flow rate is measured, and the flow rate is integrated over the respiratory time T.sub.i, thereby allowing, in a step 74, the insufflated or inspiratory volume V.sub.i to be calculated and, in a step 75, the inspiratory volume V, to be displayed and the bar graph 28 to be raised.

[0136] In parallel, in a step 76, the insufflation pressure is measured, in a step 77, the maximum pressure P.sub.peak is measured and, in a step 78, this maximum pressure P.sub.peak is displayed.

[0137] The method in the expiratory phase 8 is detailed in FIG. 6. In the expiratory phase 8, in a step 81, the expiratory time T.sub.e is measured.

[0138] In parallel, in a step 82, the flow rate is measured, and the theoretical expiratory time TeTh is calculated. The calculation of TeTh is carried out by evaluating the expiratory time constant of the patient, which is equal to 5*R*C, where R: pulmonary resistance and C: pulmonary compliance. TeTh may also be anticipated by exponential regression of the expiratory flow-rate curve. Next, the flow rate is integrated over the expiratory time T.sub.e in order to deduce thereby the calculation of the expiratory volume Ve, in a step 84. When the ventilation mode is non-invasive, the bar graph 28 is gradually lowered over the duration TeTh, in a step 85. When the ventilation mode is invasive, the bar graph 28 is lowered in direct proportion to V.sub.e, in a step 86.

[0139] In parallel, in a step 87, the CO.sub.2 concentration is measured and the amount of CO.sub.2 expired EtCO.sub.2 displayed, for example using a measurement carried out by an optional sensor placed between the sensor 20 and the interface 12. Such a sensor is for example an NDIR (NonDispersive InfraRed) sensor allowing a measurement by infrared spectroscopy.

[0140] In parallel, in a step 88, the positive end-expiratory pressure (PEEP) is measured and displayed.

[0141] Lastly, in the calculation phase 9, as detailed in FIG. 7, the leak volume V.sub.leaks is calculated in a step 91, then the tidal volume Vt is calculated in a step 92 and the tidal volume Vt is displayed in a step 93. In a step 94, the pulmonary compliance C is calculated using the formula C=V.sub.t/(P.sub.peak−PEEP). In a step 95, the pulmonary resistance R is calculated using the formula R=T.sub.e5*C.

[0142] The pause time T.sub.p is also measured in a step 96 and, using the measurement of ventilatory frequency Fr, the size of the patient, the type of ventilation and the ventilation mode and the calculations carried out in steps 94 and 95 in particular, the lung model and the effectiveness thresholds and ventilatory parameters are defined, in a step 97, and the effectiveness of the ventilation is analyzed.

[0143] If the leak volume V.sub.leaks is higher than a maximum preset threshold, then, in a step 98, an alarm message “leaks” 30 is displayed. If the leak volume V.sub.leaks is lower than said preset maximum threshold, in a step 99, the alarm message 30 is turned off.

[0144] In parallel, if the ventilatory frequency Fr is higher than a predefined maximum threshold, then, in a step 910, a “high ventilatory frequency” or “High Fr” alarm message is displayed, but if the ventilatory frequency is lower than the preset maximum threshold then, in a step 911, the alarm message is turned off. If the ventilatory frequency Fr is lower than a preset minimum threshold, then, in a step 912, the “low ventilatory frequency” or “low Fr” alarm message is displayed, but if the ventilatory frequency Fr is higher than said preset minimum threshold, then, in a step 913, the alarm message is turned off.

[0145] In parallel, if the tidal volume Vt is higher than a preset maximum threshold, then, in a step 914, the “high tidal volume” or “High Vt” alarm message is displayed but if the tidal volume Vt is lower than this preset maximum threshold, then, in a step 915, the alarm message is turned off. If the tidal volume Vt is lower than a preset minimum threshold, then, in a step 916, the “low tidal volume” or “low Vt” alarm message is displayed. When the tidal volume Vt is higher than a preset minimum threshold then, in a step 917, the alarm message is turned off.

[0146] In a step 11 illustrated in FIG. 4, a light-emitting diode 25 of green color is turned on and an audio signal is emitted when the cycle time is longer then a constant comprised in a preset range of values, for example between 5 and 7 seconds, and the end of the expiratory phase is detected or the cycle time exceeds a preset threshold value, for example 7 seconds. This luminous and audio signal makes it possible to indicate to the first responder the right time for the insufflation. When the insufflated volume Vi reaches the right range or the start of the expiratory phase is detected, then, in a step 12, the visual indicator such as a light-emitting diode 25 of red color is turned on to warn the first responder. The right range of the insufflated volume Vi is determined in steps 1 and 97. The volume Vi is right if there are no leaks. Otherwise, the right volume is corrected depending on the leaks. The optimal cycle time is based on the pulmonary characteristics of the patient, such as his pulmonary compliance and pulmonary resistance.

[0147] The leak volume may also be expressed in percent of the insufflated volume and have a preset maximum threshold, for example comprised between about 20% and 40% of the insufflated volume. The maximum threshold of the respiratory frequency Fr is for example comprised between about 12 and 20 cycles per minute and the minimum threshold of the ventilatory frequency Fr is for example comprised between about 8 and 12 cycles per minute. As for the tidal volume Vt, the preset maximum threshold is for example comprised between about 500 ml and 700 ml and the preset minimum threshold is for example comprised between about 300 ml and 500 ml.

[0148] By virtue of the invention, the first responder may immediately have access to information on the leak volume, the ventilatory frequency Fr, the tidal volume Vt and very rapidly influence the one or more parameters to be corrected, where needs be, in order to re-establish an optimal ventilation for the patient. The iteration of the steps of the method in each ventilation cycle of the patient allows the first responder to continuously adapt to the evolution of the clinical state of the patient and to modulate the parameters indicated on the display device 27, without having in-depth knowledge of the ventilation system or respiratory physiology.

[0149] The invention is of course not limited to the example just described.

[0150] In particular, the system may be adapted to a pediatric or neonatal use and the thresholds described above may change accordingly.

[0151] Throughout the description, the expression “including a” must be understood as being synonymous with the expression “comprising at least one”.

[0152] Ranges of values are understood to be inclusive of limits unless otherwise specified.