Patent Publication Number: US-2023158298-A1

Title: Systems and methods for controlling blood pressure

Description:
INCORPORATION BY REFERENCE TO ANY PRIORITY DOCUMENTS 
     This application is a continuation of U.S. Pat. Application No. 17/706,528, filed on Mar. 28, 2022, which is a continuation of U.S. Pat. Application No. 16/288,605, filed on Feb. 28, 2019, now Pat. No. 11,357,981, which claims the benefit of priority to U.S. Provisional Application No. 62/637,100, filed on Mar. 1, 2018, and U.S. Provisional Application No. 62/674,832, filed on May 22, 2018, all of which are herein incorporated by reference in their entirety for all purposes. Priority is claimed pursuant to 35 U.S.C. § 120 and 35 U.S.C. § 119. 
    
    
     BACKGROUND OF THE INVENTION 
     Embodiments of the present invention relate to systems and methods for controlling blood pressure in living subjects. 
     SUMMARY OF THE INVENTION 
     In a first embodiment of the present disclosure, a system for controlling blood pressure includes a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a first limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the first limb of the subject, and an energy application module carried by the wearable interface and configured to apply energy of two or more types to the first limb of the subj ect. 
     In another embodiment of the present disclosure, a system for controlling blood pressure includes a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the limb of the subject, wherein the sensing module includes at least one sensor for determining a flow characteristic, and an energy application module carried by the wearable interface and configured to apply energy to the limb of the subject. 
     In yet another embodiment of the present disclosure, a method for controlling blood pressure of a subject includes providing a system for controlling blood pressure including a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a first limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the first limb of the subject, and an energy application module carried by the wearable interface and configured to apply energy of two or more types to the first limb of the subject, placing the system on an arm of a patient, measuring blood pressure with the system, and applying energy with the system to a median nerve of the subject. 
     In still another embodiment of the present disclosure, a method for controlling blood pressure of a subject includes providing a system for controlling blood pressure including a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a first limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the first limb of the subject, and an energy application module carried by the wearable interface and configured to apply energy of two or more types to the first limb of the subject, placing the system on an arm of a patient, measuring blood pressure with the system, and applying energy with the system to a radial nerve of the subject. 
     In yet another embodiment of the present disclosure, a method for controlling blood pressure of a subject includes providing a system for controlling blood pressure including a wearable interface having an internal contact surface, the wearable interface configured to at least partially encircle a first portion of a first limb of a subject, a sensing module carried by the wearable interface and configured to determine at least a change in blood pressure of the first limb of the subject, and an energy application module carried by the wearable interface and configured to apply energy of two or more types to the first limb of the subject, placing the system on an arm of a patient, measuring blood pressure with the system, and applying energy with the system to a ulnar nerve of the subject. 
    
    
     
       BRIEF DESCRIPTION OF THE DRAWINGS 
         FIG.  1    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
         FIG.  2    is a perspective view of the wearable blood pressure control system of  FIG.  1    in a fastened, unexpanded condition. 
         FIG.  3    is a perspective view of the wearable blood pressure control system of  FIG.  1    in a fastened, partially expanded condition. 
         FIG.  4    is a perspective view of the wearable blood pressure control system of  FIG.  1    in a fastened, substantially expanded condition. 
         FIG.  5    is a perspective view of the wearable blood pressure control system of  FIG.  1    in use on the wrist of a user. 
         FIG.  6    is a perspective view of the wearable blood pressure control system of  FIG.  1    during the measurement of blood pressure. 
         FIG.  7    is a perspective view of the wearable blood pressure control system of  FIG.  1    during activation in response to a detected change in blood pressure. 
         FIG.  8    is a cross-section of the wearable blood pressure control system of  FIG.  1    in use on the wrist of a user. 
         FIG.  9    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
         FIG.  10    is a plan view of a user interface of the wearable blood pressure control system of  FIG.  9   . 
         FIG.  11    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
         FIG.  12    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
         FIG.  13    is a perspective view of the wearable blood pressure control system of  FIG.  12    in a decoupled state. 
         FIG.  14    is a flow chart describing a method for controlling blood pressure in a subj ect. 
         FIG.  15    is a perspective view of a wearable blood pressure control system in use on the wrist of a user, according to an embodiment of the present disclosure. 
         FIG.  16    is an exploded view of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  17    is a further exploded view of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  18    is a bottom view of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  19    is a perspective cut-away view of a sensing module of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  20 A  is a first exploded view of a pump and bladder assembly of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  20 B  is a second exploded view of a pump and bladder assembly of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  21    is a plan view of a user interface of the wearable blood pressure control system of  FIG.  15   . 
         FIG.  22    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
         FIG.  23    is a bottom view of the wearable blood pressure control system of  FIG.  22   . 
         FIG.  24    is an active element array of the wearable blood pressure control system of  FIGS.  22  and  23   , according to an embodiment of the present disclosure. 
         FIG.  25    is a perspective view of the active element array of  FIG.  24    in use on the wrist of a user. 
         FIG.  26    is an active element array of the wearable blood pressure control system of  FIGS.  22  and  23   , according to an embodiment of the present disclosure. 
         FIG.  27    is a perspective view of the active element array of  FIG.  26    in use on the wrist of a user. 
         FIG.  28    is a cross-sectional view of the wearable blood control system of  FIG.  22   , taken through line 28-28. 
         FIG.  29    is a perspective view of a wearable blood pressure control system, according to an embodiment of the present disclosure. 
     
    
    
     DETAILED DESCRIPTION OF THE ILLUSTRATED EMBODIMENTS 
     Hypertension (high blood pressure) affects a large section of the world’s population, with estimates of between 16% to 37% of the population affected. Hypertension can be persistent or transient, but in either case, is a significant factor which commonly increases morbidity and mortality, both on its own and in conjunction with other maladies. Hypertension is thought to be a factor in about 18% of deaths worldwide. Hypertension is of concern in all parts of the world, among most population subgroups. The lowering of mean blood pressure by a small amount (e.g., about 5 mm Hg or more), can significantly reduce stroke or other cardiovascular events. 
     A simple, wearable device that can sense increases in blood pressure, and in response, deliver blood pressure lowering therapy is described herein, according to several embodiments.  FIG.  1    illustrates a wearable blood pressure control system  10  configured for placement on the wrist of a patient. The wearable blood pressure control system  10  comprises a housing  12  and a band  14  coupled to an underside  16  of the housing  12 . The wearable blood pressure control system  10  is shown in  FIG.  1    in an unfastened condition. The band  14  is secured to the underside  16  of the housing  12  by epoxy or adhesive  18 . In other embodiments, the band  14  may be secured by fasteners, sewing, fusing, or may slide through slits or elongate spaces in the housing  12 . The band  14  is configured to wrap around the wrist of a user/patient and secure to itself by use of a hook and loop (Velcro®-type) system  20 . The loop surface  20   a  on an interior of a portion of the band  14  secures to the hook surface  20   b  on an exterior portion of the band  14 . The band may be provided in a number of different sizes to optimize placement on a particularly-sized patient (e.g., small, medium, large or pediatric, adult). An inflatable cuff  22  extends around a circumferential path  24  encircling an interior  26  of the band  14 . In some embodiments, the band  14  may be configured to be worn like a watch or a bracelet, and may be configured to partially or fully encircle a limb (e.g., arm) at a portion (e.g., wrist). The hook and loop system  20  may be replaced in alternative embodiments by a button closure, a snap closure, an adhesive closure, or a magnetic closure. 
       FIG.  2    illustrates the wearable blood pressure control system  10  in a fastened condition, with the loop surface  20   a  secured to the hook surface  20   b . No arm of a user is shown in  FIGS.  2 - 4    in order to better show the activity of the inflatable cuff  22 . A sensor  28  is carried on an interior face  30  of the band  14 , and is configured to sense one or more cardiovascular parameter, such as heart rate, heart rate variability, electrocardiogram (ECG), including any measured arrythmias, or blood pressure. In some embodiments, the sensor  28  may comprise a pulse wave sensor. The pulse wave sensor may comprise CMOS (complementary metal-oxide-semiconductor) technology. In some embodiments, the sensor  28  may comprise an ultrasound transducer. The ultrasound transducer may comprise two or more piezoelectric elements. The ultrasound transducer may be configured to be operated as a Doppler transducer. In alternative embodiments, the sensor  28  may comprise one or more optical sensor for performing photoplethysmography (PPG). A controller  32  within the housing  12  is configured to receive signals from the sensor  28 . The controller  32  may comprise a microcontroller. The controller  32  may be coupled to a transceiver  34 , configured to communicate wirelessly to a cellular phone, smart phone, or other personal communication device, including a chip implanted in a user’s body, or carried on a portion of the user’s body or clothing. The data monitoring, and data analysis, are thus capable of being performed remotely. The controller  32  can be configured to analyze data from the sensor  28  to determine the presence of conditions including bradycardia, tachycardia, atrial arrythmia such as atrial fibrillation or atrial flutter, or ventricular arrythmia such as ventricular tachycardia. The identification of any of these phenomena may be based on real time analysis of heart rate, heart rate variability, or ECG amplitude. The sensor  28  may be capable of sensing more than one cardiovascular parameter. For example, the sensor  28  may be configured to sense blood pressure and heart rate, or blood pressure and heart rate variability, or may be configured to obtain an electrocardiogram and measure blood pressure. In some embodiments, the sensor  28  may comprise two or more sensors. In some embodiments, the two or more sensor may comprise a first sensor for measuring a first cardiovascular parameter, and a second sensor for measuring a second cardiovascular parameter, different from the first cardiovascular parameter. 
     Changes in heart rate variability, for example a reduction in heart rate variability, have been shown to have some predictive capability of mortality after myocardial infarction. A more continual or even continuous measurement of blood pressure using the sensor  28  allows an awareness of how the heart responds to the changing environment during each day. Rather than focusing on simple lowering average (e.g., mean) blood pressure values, there may be more protection against heart disease by achieving hour-to-hour, day-to-day controlled blood pressure values over time. These data may be used to help physicians make more informed decisions relating to the treatment of hypertension, and overall treatment of the heart. The wearable blood pressure control system  10  is configured to monitor blood pressure throughout the day at different activities (eating, drinking, dieting, fasting, exercising, sleeping, walking, standing). Data obtained by the sensor  28  may be used intelligently to apply treatment based on specific or custom patient needs, and may be guided by saved information related to optimum times to apply the therapy. 
     The inflatable cuff  22  may be operated as a sphygmomanometer cuff, configured to determine blood pressure of the user. The transceiver  34  may comprise a wifi antenna. An actuator  36 , coupled to the controller  32  is configured to receive signals from the controller  32  to cause the inflatable cuff  22  to expand. The actuator  36  may comprise a pneumatic pump configured to increase air pressure within the inflatable cuff  22 . The inflatable cuff  22  is shown in  FIG.  2    in a substantially unexpanded condition. The inflatable cuff  22  in  FIG.  3    is shown in a partially expanded condition. The inflatable cuff  22  in  FIG.  4    is shown in a substantially expanded condition. The inflatable cuff  22  may also be expanded by the controller  32  via the actuator  36  in order to apply a therapeutic compression on the wrist of the patient. In a first embodiment, the sensor  28  is configured to sense blood pressure, and the inflatable cuff  22  is configured to apply therapeutic compression. In a second embodiment, the sensor  28  is configured to sense at least one parameter related to blood pressure, and the inflatable cuff  22  is configured to sense at least one parameter related to blood pressure, and to also apply therapeutic compression. In a third embodiment, the inflatable cuff  22  is configured to sense blood pressure and to apply therapeutic compression, and the sensor  28  is configured to sense one or more cardiovascular parameter other than blood pressure. In a fourth embodiment, the sensor  28  is configured to sense at least one parameter related to blood pressure, the inflatable cuff  22  is configured to sense at least one parameter related to blood pressure, and some other element (not shown) is configured to apply a therapy for reducing blood pressure. 
     In  FIG.  5   , the wearable blood pressure control system  10  is in use, in place on the wrist  38  of the arm  40  of a user  42 . The band  14  may be secured immediately adjacent the hand  44  of the user  42 , or may be attached around the wrist  38  (or other portion of the arm  40 ) a distance d away from the hand  44 , for example 0.5 cm, 1 cm, 2 cm, 5 cm, 10 cm, or 15 cm, or any distance between 0 cm and 15 cm. 
     Turning to  FIG.  8   , wearable blood pressure control system  10  is shown coupled to an arm  40  of the user  42 . Anatomical elements such as the radius  49 , ulna  51 , radial artery  45  and ulnar artery  47  are shown in relation to the band  14  and housing  12 . The positioning of the wearable blood pressure control system  10  in relation to the arm  40  in  FIG.  8    is one of many possible choices. The wearable blood pressure control system  10  may be oriented differently (e.g., circumferentially/rotationally and/or longitudinally/axially) if a different juxtaposition between the sensor  28  and one or more of the arteries  45 ,  47  or between the inflatable cuff  22  and one or more of the arteries  45 ,  47  is desired. An interior  53  of the inflatable cuff  22  is inflated by air pressurized by the actuator  36 , which is free to enter into the housing  12  (or exit out of the housing  12 ) via a vent hole  55 . The air is forced by the actuator  36  into the inflatable cuff  22  through an access conduit  57  having a valve  59 . The valve  59  is configured to maintain air pressure in the interior  53  of the inflatable cuff  22 . The actuator  36  and/or valve  59  are also configured to allow air to exit through the valve  59  when it is desired to lower the air pressure inside the interior  53  of the inflatable cuff  22 . 
     In  FIG.  6   , the sensor  28 , in use, senses the blood pressure  46  of the user  42 . The blood pressure  46  may be measured continuously or in a series of samples. The blood pressure  46  may be treated as a systolic pressure over a diastolic pressure, or may be treated as a mean arterial pressure (MAP). The sensor  28  outputs a signal  48  proportional to the blood pressure  46  that is received by the controller  32 . In  FIG.  7   , the controller  32  commands the actuator  36  to expand the inflatable cuff  22 . In embodiments wherein the inflatable cuff  22  is configured to be used as a sphygmomanometer cuff, the controller  32  controls the inflation of the inflatable cuff  22  by the actuator  36  so that the interior  53  ( FIG.  8   ) is pressurized to a starting pressure P s  that is above the expected maximum systolic arterial pressure. The controller  32  then commands the actuator  36  and/or valve  59  to allow the release of air from the interior  53  at a particular rate, so that the pressure of the interior  53  is reduced over a time period T to a pressure P f  that is below expected minimum arterial diastolic pressure. The oscillometric sensing (e.g., by the sensor  28 ) of the occlusion and subsequent opening up of one or more arteries can also be used to determine the actual systolic and diastolic pressures, and the pressurization and depressurization of the inflatable cuff  22  can be controlled by these data (e.g., via the controller  32 ). 
     In embodiments wherein the inflatable cuff  22  is configured to be used as a therapeutic compression element, the controller  32  controls the inflation of the inflatable cuff  22   by the actuator  36  so that the interior  53  is pressurized to a desired treatment inflation pressure P t . The therapeutic compression imparted on the arm  40  by the inflatable cuff  22  can be directed to apply stresses to the median nerve  43  ( FIG.  8   ). Stimulation of the median nerve by application of energy, such as compression, can help lower blood pressure, via a known neural pathway, which may include the central nervous system (CNS). In some cases, the reduction in blood pressure may be achieved via down-regulation of sympathetic outflow. In some embodiments, the inflatable cuff  22  may be configured to be used both as a sphygmomanometer cuff and as a therapeutic compression element. 
       FIG.  9    illustrates a wearable blood pressure control system  100  configured for placement on the wrist of a patient. The wearable blood pressure control system  100  comprises a housing  102  and a band  104  coupled to an underside  105  of the housing  102 . The wearable blood pressure control system  100  is shown in  FIG.  9    in a fastened condition, though without the arm  40  visible, in order to better show features of the wearable blood pressure control system  100 . A loop  106  is secured to a first portion  108  of the band  104  and a series of rubber wedges  110  are carried by a second portion  112  of the band  104 . To attach the wearable blood pressure control system  100  to the user’s wrist  38 , the user  42  (or a person aiding the user  42 ) slips first end  114  of the band  104  through an opening  116  of the loop  106  and, while applying traction on the first end  114 , pulls one or more of the wedges  110  through the opening  116  of the loop  106 , until the band  104  is at a comfortable tightness around the user’s wrist  38 . A flat edge  118  of one of the wedges  110   a , abuts an edge  120  of the loop  106 , locking it in place. To remove the band  104 , the band  104  is forced in the opposite direction, temporarily (elastically) deforming the wedges  110  as they are pulled through the opening  116  in the loop  106  (or deforming the loop  106 ) and/or temporarily (elastically) deforming the loop  106 . Alternatively, a hook and loop system  20 , like that of the wearable blood pressure control system  10  of  FIG.  1    may be used. The wearable blood pressure control system  100  also includes a user interface  101  on a visible surface  103  of the housing  102 . 
     The wearable blood pressure control system  100  includes a cuff  122  extending circumferentially within the band  104  between a second end  124  of the band  104  and the first portion  108 . The cuff  122  is secured to the band  104  along a first edge  126  and a second edge  128 , each running circumferentially around an internal periphery of the band  104 . The cuff  122  may be secured to the band  104  at the first and second edges  126 ,  128  by adhesive, epoxy, or hotmelt, or may be sewn, stapled, or secured with other fastening means. The cuff  122 , as named, represents an outer layer, though it is an inner portion of a circle when attached. As shown in  FIG.  9   , the cuff  122  is configured to have an interior space  130  that is inflatable. 
     The cuff  122  carries a pair of sensing elements  132 ,  134  and a pair of vibration elements  136 ,  138 . The vibration elements  136 ,  138  may comprise piezoelectric crystals, and may comprise quartz, artificial quartz, or PZT (lead zirconate titanate) ceramics. The vibration elements  136 ,  138  may be configured to vibrate at ultrasound frequencies of between about 20 kHz and about 1 MHz, or between about 20 kHz and about 700 kHz, or between about 20 kHz and about 500 kHz, or between about 25 kHz and about 500 kHz, or between about 30 kHz and about 200 kHz, or between about 100 kHz and about 300 kHz. Frequencies between about 20 kHz and about 700 kHz can be very effective at stimulating nerves, such as the median nerve  43  in the arm  40 , or the radial nerve or ulnar nerve. Ultrasound can serve to stimulate several physiological processes that can aid the reduction of blood pressure. Ultrasound energy application is capable of dilating blood vessels, such as arteries, and can thus improve blood perfusion. Via sensory feedback, the brain is signaled, in turn, to modify other physiological functions, to further reduce blood pressure. Thus, the vibration elements  136 ,  138 , when constructed of an appropriate material and having an appropriate thickness to vibrate at one or more frequencies in the 20-700 kHz range, may be configured to stimulate the median nerve  43  via vibration. The applied vibration to the median nerve  43  will be sensed in the brain of the user  42 , which lowers blood pressure accordingly as part of a physiological feedback loop. The brain is thus “tricked” into playing a more involved interventional role. In some embodiments, one vibration element  136  may be configured to vibrate within a lower frequency range (e.g., 20 kHz to 100 kHz) while the other vibration element  138  may be configured to vibrate at a higher (ultrasound) frequency range (e.g., 100 kHz to 700 kHz), in order to induce multiple types of effect. In other embodiments two or more vibration elements  136 ,  138  may be configured to vibrate within a lower frequency range while two or more additional vibration elements  136 ,  138  may be configured to vibrate within a higher frequency range. In some embodiments, one or more vibration elements  136 ,  138  may be configured to vibrate at multiple frequencies, for example a fundamental frequency (or first harmonic) and a second harmonic. The first harmonic, for example, in a particular embodiment may be 150 kHz and the second harmonic may be 300 kHz. In other embodiments, a third harmonic, or even fourth, fifth, or higher harmonics may be used, as described by the harmonic series. One particular treatment protocol may comprise a first period of activation of the vibration elements  136 ,  138  which is initiated immediately after the sensing elements  132 ,  134  detect a change (e.g., increase) in blood pressure. This first period of activation may be followed by pressurization of the cuff  122 . In relation to the wearable blood pressure control system  10  of  FIGS.  1 - 8   , a further embodiment may add the vibration elements  136 ,  138 . A particular treatment protocol associated with this alternative embodiment may comprise a first period of activation of the vibration elements  136 ,  138  which is initiated immediately after the sensor  28  detects a change (e.g., increase) in blood pressure. This first period of activation may be followed by an increase in pressurization of the inflatable cuff  22 . Though the median nerve  43  is often the target, in other cases, the effect may be focused, or shared, on the radial nerve or the ulnar nerve. 
     Returning to  FIG.  9   , in some embodiments, the sensing elements  132 ,  134  and vibration elements  136 ,  138  may be replaced by multi-purpose elements which are configured to perform both the sensing function of the sensing elements  132 ,  134  and the energy application function of the vibration elements  136 ,  138 . 
     One or more of the sensing elements  132 ,  134  or vibration elements  136 ,  138  may be carried on an outer surface  140  of the cuff  122 , or may be carried on an inner surface  142  of the cuff  122 , or a combination thereof. The cuff  122  is configured to maintain the sensing elements  132 ,  134  and vibration elements  136 ,  138  in proximity to the wrist  38  of the user  42  (or other portion of any limb upon which the band  104  has been attached). It may be desired to cover the wrist  38  with an acoustic coupling gel, or other acoustic coupling media, for optimal acoustic coupling between skin of the user  42  and the sensing elements  132 ,  134  or vibration elements  136 ,  138 . The sensing elements  132 ,  134  and vibration elements  136 ,  138  can be secured to the outer surface  140  and/or inner surface  142  of the cuff  122  by an epoxy or adhesive  144  that has appropriate transition acoustic impedance properties. The wearable blood pressure control system  100  also includes a controller  151  and a connection port  191 , which will be described in greater detail in subsequent embodiments herein. 
       FIG.  10    illustrates the user interface  101  which includes a power switch  109  configured for turning the wearable blood pressure control system  100  on or off. The user interface  101  may comprise a touch screen, and may utilize capacitive or resistive touch sensitivity. Alternatively, mechanical or membrane buttons/switches may be utilized. A first control  111  having a first button  113  and a second button  115  is configured for manually adjusting the vibration mode. In other words, the vibration elements  136 ,  138  may be manually set (for example, to low (intensity) vibration, medium vibration, or high vibration) using the first and/or second buttons  113 ,  115 . One of the buttons  113 ,  115  may increase the intensity of vibration, while the other button  113 ,  115  may decrease the intensity of vibration. Alternatively, an application (App)  153  on a mobile phone or device  155  may be configured (via software or firmware) to receive one or more signals  157  from the sensing elements  132 ,  134 , and to automatically adjust the vibration mode, either turning it on or off, or adjusting it between low, medium, and high vibration. The vibration mode in some embodiments may be automatically adjustable, via servo control or other methods, such that the vibration elements  136 ,  138  are caused to activate in a manner which is proportional to or matches in some way the reduction or increase in amplitude, intensity and/or prevalence of blood pressure changes. For example, the vibration elements  136 ,  138  may be configured to operate at a derived function of the blood pressure increase that is measured or calculated by the sensing elements  132 ,  134  (or by the cuff  122  if used as a sphygmomanometer cuff). 
     A second control  117  having a first button  119  and a second button  121  is configured for manually adjusting the compression mode. The inflation of the interior space  130  of the cuff  122  may be manually set (for example, to low inflation, medium inflation, or high inflation) using the first and/or second buttons  119 ,  121 . One of the buttons  119 ,  121  may increase the pressure or injected volume of inflation, while the other button  119 ,  121  may decrease the pressure or injected volume of inflation. Alternatively, the controller  151  within the housing  102  and/or the App  153  may be configured (via software or firmware) to receive one or more signals from the sensing elements  132 ,  134 , and to automatically adjust the compression mode, either turning it on or off, or adjusting it between low, medium, and high compression. 
       FIG.  11    illustrates a wearable blood pressure control system  250  that is similar to the wearable blood pressure control system  100  of  FIG.  9   , but additionally comprises stimulation electrodes  252 ,  254 ,  256  carried on the outer surface  140  of the cuff  122 . The user interface  101  and/or App  153  may be configured to adjust or program a controller  251  such that signals received from the one or more signals from the sensing elements  132 ,  134  cause current to run through wires or traces  258 ,  260 ,  262  electrically coupled to the electrodes  252 ,  254 ,  256 , thus applying one or more potentials (voltages) across two or more of the electrodes. A current may be applied using voltage control. A current may also be applied using current control. The applied current is capable of activating nerves, such as the median nerve  43 , for example, to provide an additional input to the brain of the patient. The user interface  101  ( FIG.  10   ) may include a third mode that is an electrical stimulation mode, also capable of being adjusted manually, or with feedback from the sensing elements  132 ,  134 . Any combination of two or three (or more) modes may be possible, or in some embodiments, only a single mode. The electrodes  252 ,  254 ,  256  may be configured such that the one or more applied potentials are directed to the median nerve  43  to thereby stimulate it in order to alter or induce the brain’s control or modification of blood pressure. In alternative embodiments, the electrodes  252 ,  254 ,  256  may be configured to sense physiological signals related to changes in blood pressure or other cardiovascular parameters. 
     The controller  251  may be configured or programmable to be configured, via hardware, firmware, or software, such that any one or more of the inflation of the cuff  122 , activation of the electrodes  252 ,  254 ,  256 , or activation of the vibration elements  136 ,  138  is applied with a particular range of set parameters or set parameter ranges, thus serving as a programmable pulse generator. For example, in certain embodiments, the voltage, current, frequency, or pulse width of the activation of the electrodes  252 ,  254 ,  256  may be controlled within the following ranges. Current: 0.1 mA to 200 mA, or 0.1 mA to 50 mA; frequency/rate of application: 0.1 mA to 200 mA, or 1 Hz to 5,000 Hz, or 1 Hz to 1,000 Hz, or 1 Hz to 200 Hz; pulse width: 0.01 microsecond (µs) to 1000 microseconds (µs), or 1 microsecond (µs) to 1000 microseconds (µs), or 0.01 microsecond (µs) to 5 microseconds (µs). The controller  251  may fire the electrodes in a continuous mode, or in random mode comprising one or more bursts. The on-time of the bursts and the off-time of the bursts may each be independently controlled. A particular program or algorithm may be used to vary the on-times and off-times. In alternative embodiments, the controller  251  may be configured or programmable to be configured, via hardware, firmware, or software, such that any one or more of the inflation of the cuff  122 , activation of the electrodes  252 ,  254 ,  256 , or activation of the vibration elements  136 ,  138  is applied in an at least partially random or pseudo-random manner. The human body is adaptable, and many physiological systems tend to adjust to therapeutic treatments, sometimes in a manner that, to the body, appears helpful, when in fact it is antagonistic to the purposes or effects of treatment. Nervous systems are able to continually change by processes such as synaptic adaptation. Adding in random changes to the way the therapeutic elements (cuff  122 ; vibration elements  136 ,  138 ; electrodes  252 ,  254 ,  256 ) are applied can serve as a way of getting ahead of or “tricking” the body’s adaptation schemes that may otherwise actually prove antagonistic to efforts to control blood pressure. Parameters that may be adjusted, randomly, or non-randomly, by the controller  251  include: time of application of energy (mechanical, electrical, etc.), length of interval of time between application of energy, number of repetitions of application of energy, particular operational frequency of a non-static mode of energy (e.g., applying ultrasound at varying pulse rates), amplitude of the applied energy, timing of particular combinations of more than one element of a particular type of energy, or of two or more different types of energy. Any of these parameters can be increased or decreased. The controller  251  may be configured to allow the user/patient to control some or all of these parameter adjustments, for example, via the user interface  101  and/or App  153 . In addition, in some embodiments, there may be security levels to control how much the user can control: a first level for a user and a second level for a prescribing physician. In some embodiments, the existence of controls available to the physician that are not available to the user may assure a certain amount of randomness in the treatment. This may even be necessary in some cases, for example, for particular patients that do not want to be surprised with a compression, electrode firing, or vibration event. The security levels may include encryption and/or password control. The “smart” nature of the wearable blood pressure control system  250 , or any of the other systems described in the embodiments herein, allows it to be managed by primary care physicians, ad thus, not requiring a specialist. Also, because the device requires no surgery or invasive procedure, only a single healthcare person/location need be involved with the patient’s care. 
       FIG.  12    illustrates a wearable blood pressure control system  300  having multi-mode energy delivery therapy including both vibration and electrical stimulation. The wearable blood pressure control system  300  is similar to the wearable blood pressure control system  100  of  FIG.  9   , but does not include compression, and does comprise stimulation electrodes  302 ,  304 ,  306  carried on the limb-facing surface  308  of the band  310 . The band  310  has a first end  330  and a second end  332  and is removably attached to a removable/replaceable housing  336 . A loop  334  is secured to the band  310 , and has an opening width W 1 . An insertion section  340  of the band  310  has a thickness W 2  that is less than opening width W 1 . The normal wall  338  of the band  310  has a thickness W 3  that is slightly greater than the opening width W 1 , thus creating a friction fit, which renders wedges  110  or hook/loop  20   a / 20   b  unnecessary. In use, a user inserts the insertion section  340  into the loop  334  and pulls the band  310  from the first end  330  until adjusted to an acceptable amount on the limb of the wearer. The friction between the normal wall  338  and the loop  334  maintains the band  310  secure. The user interface  312  and/or App  153  may be configured to adjust or program the controller  314  such that signals sent by the controller in response to one or more signals from the sensing elements  316 ,  318  cause current to run through wires or traces  320 ,  322 ,  324  electrically coupled to the electrodes  302 ,  304 ,  306 , thus applying one or more potentials (voltages) across two or more of the electrodes. A current may be applied using voltage control. A current may also be applied using current control. The applied current is capable of activating nerves, such as the median nerve  43 , for example, to provide an additional input to the brain, which can aid the lowering of blood pressure. The user interface  312  includes a vibration mode  311  and a stimulation mode  313  (via electrode(s)), which are each capable of being adjusted manually, or automatically with feedback from the sensing elements  316 ,  318 . Any combination of the two modes may be possible, such that a mixed signal may be created. The mixed signal may include a cycle having a first period of only one of vibration or stimulation and a second period of the other of vibration or stimulation. The mixed signal may also include at least one period of simultaneous vibration and stimulation. The electrodes  302 ,  304 ,  306  may be configured such that the one or more applied potentials are directed to the median nerve  43  to thereby stimulate it in order to alter or induce the brain’s control or modification of blood pressure (e.g., lowering blood pressure). In alternative embodiments, the electrodes  302 ,  304 ,  306  may be configured to sense physiological signals related to changes in blood pressure or other cardiovascular parameters. The combination of vibration and electrical stimulation working in synchrony can delivery a tailored, optimal result, and can be further informed by the measurement of cardiovascular parameters such as continuous blood pressure, heart rate, heart rate variability, or ECG, including the detection of particular heart arrythmias. 
     The controller  314  may be configured or programmable to be configured, via hardware, firmware, or software, such that any one or more of the activation of the electrodes  302 ,  304 ,  306  or activation of the vibration elements  326 ,  328  is applied with a particular range of set parameters or set parameter ranges, thus serving as a programmable pulse generator. For example, in certain embodiments, the voltage, current, frequency, or pulse width of the activation of the electrodes  302 ,  304 ,  306  may be controlled within the following ranges. Current: 0.1 mA to 200 mA, or 0.1 mA to 50 mA; frequency/rate of application: 0.01 Hz to 50 kHz, or 1 Hz to 5,000 Hz, or 1 Hz to 1,000 Hz, or 1 Hz to 200 Hz; pulse width: 1 microsecond (µs) to 1000 milliseconds (µs), or 1 microsecond (µs) to 1000 microseconds (µs), or 0.01 millisecond (ms) to 5 milliseconds (ms). The controller  314  may fire the electrodes in a continuous mode, or in random mode comprising one or more bursts. The activation may comprise a particular initiation time (start time), a particular end time (stop time), and/or a particular duration. The period of activation of the electrodes  302 ,  304 ,  306  may include one or more of the following patterns: a biphasic sine wave, a multiphasic wave, a monophasic sine wave, a biphasic pulsatile sine wave, a biphasic rectangular wave, a monophasic square wave, a monophasic pulsatile rectangular wave, a biphasic spiked wave, a monophasic spiked wave, and a monophasic pulsatile spiked wave. The one-time of the bursts and the off-time of the bursts may each be independently controlled. A particular program or algorithm may be used to vary the on-times and off-times. In alternative embodiments, the controller  314  may be configured or programmable to be configured, via hardware, firmware, or software, such that any one or more of the activation of the electrodes  302 ,  304 ,  306  or activation of the vibration elements  326 ,  328  is applied in an at least partially random or pseudo-random manner, as described in relation for the embodiment of  FIG.  11   . Any one of the electrodes  302 ,  304 ,  306  may serve as a patient return electrode, thus making unnecessary an additional skin-placed return electrode patch. Thus, the simple coupling of the band  310  on the limb of the wearer/user allows the wearer/user to immediately begin using the wearable blood pressure control system  300 . 
     Multiple touch points are provided by the electrodes  302 ,  304 ,  306  and vibration elements  326 ,  328 , which are located at different clock locations around the limb-facing surface  308  of the band  310 , thus allowing for a high success rate, as an optimal anatomical location for effective therapy is more likely to be identified and treated. The controller  314  may be configured to allow the user/patient to control some or all of these parameter adjustments, for example, via the user interface  312  and/or App  153 . In addition, in some embodiments, there may be security levels to control how much the user can control: a first level for a user and a second level for a prescribing physician. In some embodiments, the existence of controls available to the physician that are not available to the user may assure a certain amount of randomness in the treatment. This may even be necessary in some cases, for example, for particular patients that do not want to be surprised with an electrode firing, or vibration event. The security levels may include encryption and/or password control. A connection port  191  may be used to temporarily or permanently attach a USB cable, USB drive, or other cables or drives, for transferring information, charging internal batteries, or supplying power to any internal components. Many of the components described in the wearable blood pressure control system  300  have relatively low power requirements, thus being amenable to a chargeable battery system. The connection port  191  may also be used to attached a wireless antenna, if needed, whether or not there is internal wireless capability within the wearable blood pressure control system  300 . The communication can allow the wearable blood pressure control system  300  to be controlled by an application on a mobile device, such as a mobile telephone/smartphone. Data monitoring and analysis can also be done remotely at one or more sites. 
     The wearable blood pressure control system  300  may include adaptive capabilities. For example, the controller  314  may be programmable, or pre-programmed, to provide a particular therapy plan, such as a morning application of energy, a mid-day application of energy, and an evening application of energy. However, by analyzing changes in one or more cardiovascular parameters measured by the sensing elements  316 ,  318 , the controller  314  may be configured to change the therapy plan to optimize patient response. For example, the change may include a larger amplitude and/or longer duration of the application of vibrational energy and a smaller amplitude and/or shorter duration of the application of electrical stimulation energy. Or, in other cases, the change may include a larger amplitude and/or longer duration of the application of electrical stimulation energy and a smaller amplitude and/or shorter duration of the application of vibrational energy. An energy modulation algorithm may be applied, to allow the wearable blood pressure control system  300  to learn to better deliver custom neuromodulation management to each wearer, which may correspond to each patient’s blood pressure or other cardiovascular parameter. The wearable blood pressure control system  300  is thus able to learn from the physiology and treatment effect of each patient for a personalized and optimized treatment. Each individual energy modality (application of electrical stimulation or application of vibration) can be optimized, and the combination of more than one energy modality can also be optimized. Beat-to-beat intervals used in the calculation of heart rate or heart rate variability may be derived from ECG data or from blood pressure data. In some embodiments, an RR interval (from successive R points in the QRS complex of the ECG) is used. RR Intervals are sometimes called NN intervals when referring to an RR interval in a normal beat of the heart, or more particularly, beats of the heart not including beats not originating in the sinoatrial node. In some embodiments, time-domain methods may be used for beat-related calculations. In other embodiments, geometric methods may be used for beat-related calculations. In other embodiments, frequency domain methods may be used for beat-related calculations. 
     In  FIG.  13   , the housing  336  has been removed from the band  310 . The housing  336  is removeable from and reattachable to the band  310  for multiple reasons. The housing  336  may include one or more rechargeable batteries which can be recharged by attachment of a power cable to the connection port  191 , or to another port, connected to the batteries. The batteries may be rechargeable by wired or by wireless methods, including inductively-coupled charging. A wireless charging unit  345  may also be used to charge the batteries. In alternative embodiments, one or more of the batteries may be a primary cell, configured to be used and discarded (or recycled). The housing  336  is secured to the band  310  via two magnets  346 ,  348  which are configured to attract magnets  350 ,  352  carried on a surface  344  of the band  310 . In the embodiment of  FIG.  13   , magnet  348  has an externally-facing positive pole which is configured to magnetically engage with magnet  350 , which has an externally-facing negative pole. Magnet  346  has an externally-facing negative pole which is configured to magnetically engage with magnet  352 , which has an externally-facing positive pole. The magnets may comprise rare earth magnets, such as neodymium-iron-boron or samarium cobalt. The neodymium-iron-boron magnets may be chosen from a grade of N30 or higher, or N33 or higher, or N35 or higher, or N38 or higher, or N40 or higher, or N42 or higher, or N45 or higher, or N48 or higher, or N50 or higher. In some embodiments, the neodymium-iron-boron magnets may have a grade between N30 and N52, or between N33 and N50 or between N35 and N48. In some embodiments one of the two magnets in each attractive pair may be replaced by a magnetic material such as iron, or 400-series stainless steel, which can be attracted by a pole of the opposing magnet. 
     Electrical connection may be achieved by conductive projections  354  carried on the band  310  and which are configured to conductively engage with conductive depressions  356  carried on the bottom surface  342  of the housing  336 . The conductive depressions  356  are electrically connected to the various electrical components of the housing  336 , which may include the user interface  312 , the controller  314 , and the connection port  191 . The conductive projections  354  are electrically connected to the traces  320 ,  322 ,  324  and stimulation electrodes  302 ,  304 ,  306 , the vibration elements  326 ,  328 , and the sensing elements  316 ,  318  ( FIG.  12   ). Thus, when the housing  336  is attached to the band  310  via the attraction of the magnets  346 ,  348 ,  350 ,  352 , the conductive projections  354  are electrically coupled to the conductive depressions  356 . The user interface  312 , the controller  314 , and the connection port  191  are thereby electrically interlinked with the traces  320 ,  322 ,  324  and stimulation electrodes  302 ,  304 ,  306 , the vibration elements  326 ,  328 , and the sensing elements  316 ,  318 . A user may choose to remove the housing  336  from the band  310  for other reasons than recharging. For example, a first housing  336  may be replaced by a second housing  336 , if the first housing  336  is damaged or ceases to function. The housing  336  may be removed to present to a medical facility, which may upload or download information or software revisions, or for maintenance or repair. The conductive projections  354  and the conductive depressions  356  are shown in  FIG.  13    between the magnets  350 ,  352  or magnets  346 ,  348 , respectively, but in other embodiments, the conductive projections  354  and/or the conductive depressions  356  may be located laterally from the magnets  350 ,  352  and/or magnets  346 ,  348 . In some embodiments, the conductive projections  354  and conductive depressions  356  may each be replaced by a series of conductive terminals that each have both projections and depressions, or by a series of terminals that have a substantially planar array of conductive terminals (neither projections nor depressions). 
     In alternative embodiments, the magnets  346 ,  348 ,  350 ,  352  may be substituted by other connections, such as snaps, hooks-and-loops (Velcro®), sliding engagements, or adhesive strips. 
     A method for controlling blood pressure in a subject is described in relation to  FIG.  14   . In a first step  360  a wearable blood pressure control system  10 ,  100 ,  250 ,  300  is provided. In a second step  362 , the wearable blood pressure control system  10 ,  100 ,  250 ,  300  is placed on an arm of the subject. The wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be placed in proximity to the median nerve  43 . In some cases, the wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be placed on the right arm in proximity to the right median nerve. In some cases, the wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be placed on the left arm in proximity to the left median nerve. In some cases, a first wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be placed on the right arm in proximity to the right median nerve and a second wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be placed on the left arm in proximity to the left median nerve. 
     In a third step  364 , the wearable blood pressure control system  10 ,  100 ,  250 ,  300  measures blood pressure of the subject. The blood pressure may in some cases be measured via a sphygmomanometer cuff, and in other cases, the blood pressure may be measured by a blood pressure sensor. In some cases, a sensor and a sphygmomanometer cuff may work in conjunction with each other to measure blood pressure. The blood pressure measured may be presented or analyzed as a systolic pressure over a diastolic pressure, or in other cases may be presented or analyzed as a mean arterial pressure (MAP). In a fourth step  366 , if the blood pressure is determined to be elevated, or high, or hypertensive, or above a predetermined threshold, the wearable blood pressure control system  10 ,  100 ,  250 ,  300  applies energy to the median nerve of the arm on which the wearable blood pressure control system  10 ,  100 ,  250 ,  300  is worn. The energy applied may comprise compressive stresses (pressure), or electrical stimulation, or vibratory stimulation, ultrasonic stimulation, or heat application, or heat removal (cooling), or magnetic exposure, or electromagnetic exposure, or sonic stimulation, or other mechanical energy application. In some cases, the application of energy to the median nerve may have duration of between about five minutes and about one hour, or between about ten minutes and about 45 minutes, or between about 15 minutes and about 35 minutes, or between about 20 minutes and about 30 minutes, between about one minute and ten minutes, or between about five minutes and about ten minutes. The combination of energy application modalities (e.g., vibration and electrical stimulation) can be effective in significantly reducing the time required to reduce blood pressure in the patient. Once the increase blood pressure is sensed, a combination of energy application modalities can lower the blood pressure in less than about fifteen minutes, or less than about ten minutes, which is significantly faster than traditional single energy modalities. 
     The wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be configured or configured to be programmable so that step  364  (and step  366  if determined by the system to be appropriate) occur at particular periods in the day while the subject wears the wearable blood pressure control system  10 ,  100 ,  250 ,  300 . For example, the step(s) may be applied a) when the subject wakes up or gets out of bed, b) at a particular time in the morning (e.g., after eating), c) at a particular time in the middle of the day (e.g., immediately before lunch, during lunch, or immediately after lunch), prior to going to bed or at some other time in the evening. The wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be configured or configurable to perform step  364  one, two, three, or more times per day. The wearable blood pressure control system  10 ,  100 ,  250 ,  300  may be configured or configurable to perform step  366  one, two, three, or more times per day. 
       FIG.  15    illustrates a wearable blood pressure control system  400  having multi-mode energy delivery therapy including both vibration and electrical stimulation. The wearable blood pressure control system  400  includes features of the wearable blood pressure control system  250  of  FIG.  11   , the wearable blood pressure control system  300  of  FIG.  12   , and the wearable blood pressure control system  100  of  FIG.  9   , as well as having other distinct features. A housing  402  is connected to a first band  404  by any of the manners described herein. The first band  404 , having a first end  401  and a second end  403 , includes an adjustable internal surface  406  which is configured to be inflated to allow the first band  404  to fit onto a wide range of limb sizes (e.g., arm circumference, wrist circumference, etc.). The first band  404  may be secured to itself by a hook and loop system or any of the other modalities described herein in relation to the other embodiments. A second band  408  is carried in parallel with the first band  404  and is configured to place a sensing module and/or an energy application module in proximity to the limb. The sensing module can be configured to measure one or more cardiovascular parameters, including blood pressure, electrocardiographic data, heart rate or, heart rate variability from the limb. The energy application module may be configured to delivery two or more types of energy to the limb, such as vibrational energy or electrical stimulation energy. A user interface  410  having a display  412  and controls  414  is carried on top of the housing  402 . 
     The first band  404 , shown in detail in  FIG.  16   , comprises an inflatable bladder  416  which is sealed within an upper band  418  and a lower band  420 . The bladder  416  may comprise a relatively high strength, flexible material such as polyurethane or polyethylene terephthalate (PET). The bladder  416  may comprise an upper sheet  405  and a lower sheet  407 , sealed around a perimeter seal  409 . The upper band  418  and the lower band  420  may comprise a fabric, such as woven polyamide (nylon). The perimeter  422  of the upper band  418  is sealed to the perimeter  424  of the lower band  420 , such that when an interior cavity  426  of the bladder  416  is inflated with air, the lower band  420  is forced away in a radial direction from the upper band  418 , except at circumferential seams  428 ,  430  ( FIG.  15   ). Thus, a contact surface  432  of the lower band  420  serves as the adjustable internal surface  406 , configured to contact the skin of a limb of a user. The perimeters  422 ,  424  may be sealed to each other with hot melt adhesive, thermal bonding, or epoxies or adhesives. The bladder  416  includes an inlet port  434  for entry of inflation fluid (e.g., air) and an outlet port  436  for exit of the inflation fluid. Each of the ports  434 ,  436  has an external diameter  438 , an inner diameter  440 , and tapered snap wings  442 ,  444 , as shown in  FIG.  17   . Returning to  FIG.  16   , the ports  434 ,  436  extend through holes  446 ,  448  of the upper band  418 , respectively, such that they are accessible for attachment to a main housing  450  of the housing  402 . The bladder  416  is trapped (e.g., sandwiched) between the upper band  418  and the lower band  420  without being bonded at the bonding region  454 . Thus, the bladder is not over constrained in relation to the upper band  418  or the lower band  420 , and the outer surfaces of the bladder  416  are able to slide along the inner surfaces of the upper band  418  and lower band  420  as the bladder  416  is inflated. In an alternative embodiment, the bladder  416  includes an upper face  452  having a bonding region  454 , at least around its periphery  458  or a portion of its periphery  458 , that is bonded to an underside  456  of the upper band  418 . The bonding region  454  may be sealed to the underside  456  of the upper band  418  by hot melt adhesive, thermal bonding, or epoxies or adhesives. 
     An attachment pin  460  has a distal end  462  that is attached into a hole  466  in a first end  470  of the second band  408  and an increased diameter proximal end  464  configured for removably snapping into one of a series of holes  468  in a second end  472  of the second band  408 . The second band  408  is secured to the first band  404  along a lateral edge  474 , as shown in  FIG.  18   , such that when the first band  404  and second band  408  are secured around a limb, a series of active elements  476  are coupled in proximity to the skin of the limb. The securement of the second band  408  to the first band  404  may be by stitching, welding, overmolding, or thermal bonding. Returning to  FIG.  16   , the active elements  476  comprise four ceramic piezoelectric discs  478  (478a-d) and four electrodes  480  ( 480   a - d ). The piezoelectric discs  478  may be fully molded within the second band  408 . The second band  408  may comprise a material that acoustically couples to the piezoelectric crystals of the piezoelectric discs  478 , for example, a silicone elastomer. The electrodes  480  are exposed at a contact surface  482  of the second band  408 , as shown in  FIG.  18   , such that they may directly contact the skin of the user when the second band  408  is secured to the limb of the user. An acoustic coupling gel may be used on the contact surface  482  and on the electrodes  480 , to maximize the coupling to the skin of the subject. Turning to  FIG.  19   , the second band  404  is shown transparently, such that the active elements  476  are visible in their embedded array. Each piezoelectric disc  478   a - d  has an electrically conductive layer  484  that may be sputtered or applied by other forms of deposition. A first conductor wire  486  and second conductor wire  488  are soldered to the electrically conductive layer  484  at first bare ends  490 ,  492 . The conductor wires  486 ,  488  may include outer insulative jackets  494 ,  496  along most of their lengths. Second bare ends  498 ,  499  of the conductor wires  486 ,  488  are configured for electrically coupling to electronic components within the housing  402 . Each electrode  480   a - d  is soldered to a bare end  497  of a conductor wire  495  having an insulative jacket  493 . A second bare end  491  is configured for electrically coupling to electronic components within the housing  402 . The lateral edge  474  of the second band  408  includes a plurality of snaps  489  configured for snapping and securing the insulative jackets  493 ,  494 ,  496  of the conductor wires  495 ,  486 ,  488 , to hold the conductor wires  495 ,  486 ,  488  in place in relation to the second band  408  and the first band  404 , thus holding them in place and providing strain relief. 
     Returning to  FIG.  16   , the main housing  450  includes a main circuit board  487  and a liquid crystal display (LCD)  485 , covered by a glass cover  483 . These components are enclosed within the main housing  450  by a cover  481 , which is secured to the main housing by screws  479 . The user interface  410  is adhered to the cover  481  by a shaped adhesive layer  477 . Actuatable buttons  475 ,  473 ,  471  coupled to the main circuit board  487  are accessible via touch buttons  469 ,  467 ,  465  of the user interface  410 , and via cutaways  463 ,  461  in the cover  481  and the adhesive layer  477 , respectively.  FIG.  17    shows the tactile switches  459 ,  457 ,  455  that are actuated by pressing the actuatable buttons  475 ,  473 ,  471 , respectively. In alternative embodiments, the user interface may include capacitive touch sensitivity or resistive touch sensitivity. A diaphragm pump  453  is carried on an auxiliary circuit board  451 , configured for controlling blood pressure measurements. The pump  453  may comprise a piezoelectric-actuated micropump. A spacer  449  is configured to separate the auxiliary circuit board  451  from the main circuit board  487  for space or cooling concerns, but the main circuit board  487  is electrically coupled to the auxiliary circuit board  451 . Either of the circuit boards  451 ,  487  may be fabricated by printing or other mass fabrication techniques. Power is provided to the electronic components by a battery  447 , also contained within the housing  402 . In some embodiments, the battery comprises a rechargeable battery. In some embodiment, the battery comprises a lithium ion 3.7 Volt rechargeable battery. The main circuit board  487  is configured to transfer power and/or control to the auxiliary circuit board  451 . The auxiliary circuit board  451  is configured to use some of this power to drive the pump  453 . A microcontroller  419  is carried on the main circuit board  487 , but may alternatively be carried on the auxiliary circuit board  451 . The microcontroller  419  may be programmed or programmable to control the operations of any of the functions of the wearable blood pressure control system  400 . The microcontroller  419  may control parameters such as start time, stop time, rise time, intensity, or any RAM timing parameters (memory timing parameters), such as column address strobe (CAS) latency, row address to column address delay, row pre-charge time, or row active time. 
     Additional electrodes  445 ,  443  are carried within circular depressions  437 ,  435  in sides  441 ,  439  of the main housing  450 , respectively. And are electrically coupled to one or both of the main circuit board  487  or auxiliary circuit board  451 . In some embodiments, one or both of the circuit boards  487 ,  451  may be configured to receive input from the electrodes  480   a - d  and one or more of the electrodes  445 ,  443  in order to obtain electrocardiographic data (ECG). In use, a subject places the wearable blood pressure control system  400  onto a first limb, for example, by wrapping the bands  404 ,  408  around the subject’s left wrist, and securing them. The subject then initiates an electrocardiographic measurement via the user interface  410 , and then touches either one of the electrodes  445 ,  443  of the main housing  450  with a finger of the subject’s right hand. The electrodes  480   a - d ,  445  (or electrodes  480   a - d ,  443 , or other combinations) together create multiple ECG vectors to allow for useful cardiovascular data. The incorporation of both the left wrist and the right hand (via at least one finger), provides the bilateral input important for a reliable and physiologically indicative electrocardiogram (ECG). In some embodiments, the touching of the finger to the electrode  445  or electrode  443  automatically initiates the electrocardiographic measurement, without requiring the use of the touch buttons  469 ,  467 ,  465  of the user interface  410 . In some embodiments, the control circuitry can be configured or programmed such that the touch of one of the electrodes  445 ,  443  with a finger initiates and maintains ECG measurement, and the removal of that finger stops ECG measurement. 
       FIGS.  20 A and  20 B  illustrates the connections between the bladder  416  and the pump  453 . The pump  453  includes an outlet port  371  that is secured into inner cylindrical cavity  375  in the main housing  450 . An o-ring  369  carried around the outlet port  371  provides a seal between the pump  453  and the main housing  450 , as the o-ring  369  seals the communication between the outlet port  371  and the cavity  375 . An exhaust port  367 , having an o-ring  365   therearound seals into an inner cylindrical cavity  363  in the main housing  450 . Thus, air being emptied from the bladder  416  will exit through the auxiliary circuit  451 , and into the interior of the housing  402 . A solenoid  361  ( FIG.  17   ) carried on the auxiliary circuit  451  may be controlled by the microcontroller  419  to close or open the solenoid  361 , to keep air within the bladder  416  or allow air to exit the bladder  416 . A snapping bracket  399  is secured to the lower side  397  of the main housing  450  by inserting tabs  395 ,  393  of the snapping bracket  399  in slots  391 ,  389  of the main housing  450 , respectively, and then tightening a screw (not shown) through a hole  387  in the snapping bracket  399  and into a threaded hole  385  in the lower side  397  of the main housing  450 . The ports  434 ,  436  of the bladder  416  are snapped into the holes  383 ,  381 , respectively, of the snapping bracket  399 . The tapered snap wings  442 ,  444  allow the lead-in of the ports  434 ,  436  into the holes  383 ,  381 , and secure attachment with the snapping bracket  399  and the main housing  450  (and thus, the housing  402 ). In some embodiments, the tapers of the tapered snap wings  442 ,  444  is only on the lead-in side (as shown), and so the bladder  416  can be attached to the housing  402 , but not detached. In other embodiment, there may also be tapers on the lower sides of the tapered snap wings  442 ,  444 , and so the bladder  416  can be attached to and detached from the housing  402 . The bladder  416  and first band  404  can thus be configured to be disposable and replaceable in some embodiments. In these embodiments, the first band  404  and second band  408  may be removably connectable to each other, for example with snaps, hooks and loops, rib and groove configurations, or adhesive attachment. When the ports  434 ,  436  are snapped through the holes  383 ,  381 , tapered hubs  379 ,  377  having the extension of the inner cavities  375 ,  373  sealingly engage into the inner diameters  440  of the ports  434 ,  436 . This completes the sealing communication between the pump  453  and the bladder  416 . 
     The adjustable internal surface  406  of the first band  404  is configured to automatically inflate to an appropriate size (e.g., by the bladder  416  being inflated by the pump  453  with a particular volume of air) such that it applies the appropriate amount of snugness (radially-applied pressure) to the limb at the site of attachment. The microcontroller  419  can be programmed or programable to initiate a bladder inflation cycle using feedback from any two of the electrodes  480 . The electrodes  480  may additionally or alternatively be located on the contact surface  432  of the lower band  420 , instead of only on the second band  408 . Two electrodes  480  can be configured to measure an impedance of the limb tissue between them. Thus, as the bladder  416  is inflated, the measured impedance makes a sudden change (spike) with the two electrodes  480  each become substantially coupled to the skin. This occurs with the two electrodes  480  each have at least a nominal normal force against the skin. This sudden change in the impedance measurement when an impedance through the limb tissue is being measured, with air no longer an impedance component, can be used by the microcontroller  419  to signal the pump  453  to stop injecting air into the bladder  416 . The bladder  416  is now adjusted for the appropriate or desired “fit” of the first band  404 . In a band  404  Alternatively, the internal pressure of the bladder  416  may be measured with an internal pressure transducer (not shown). The bladder pressure can be monitored, and the microcontroller  419  will signal pump  453  to stop injecting air into the bladder  416  when a spike in the pressure is detected. 
     The user interface  410  is shown in more detail in  FIG.  21   . The display  412  includes a first line  433  configured to display a current or latest-measured value of systolic blood pressure, for example, systolic arterial blood pressure. The display  412  includes a second line  431  for a current or latest-measured value of diastolic blood pressure, for example, diastolic arterial blood pressure. Alternatively, in place of these two lines of text  433 ,  431 , a graph of blood pressure may be displayed, with time in the x-axis and pressure in the y-axis. In other embodiments, the two lines of text  433 ,  431  may be replaced by a single line (or may be augmented by an additional line) showing a current or latest-measured value for mean pressure, for example mean arterial pressure (MAP). The blood pressure may be displayed, whether a value or a graph, by units of mm Hg, or by other units. The display  412  includes a third line  429  for a current or latest-measured value of pulse or heart rate, e.g., beats per minute. A secondary or alternative display location on the display  412  may indicate heart rate variability. 
     Controls  414  in  FIG.  21    are assigned to: an on/off button  465  by which a user turns the user interface  410  on or off; a start/stop button  467 , by which a user stops or starts a program of treatment application, with or without automatic intermittent blood pressure measurement (depending on programmed status); and a blood pressure measurement button  469 , by which a user initiates a blood pressure measurement cycle. Alternatively, the button  469  can be configured to initiate a pulse (heat rate) measurement cycle. Though not shown, an additional button may be configured to notify emergency medical personnel. Alternatively, the holding down of one of more of the controls  414  may achieve this task. The wearable blood pressure control system  400  may be configured to communicate with a mobile phone or other mobile device to make the call to an emergency system, or to a preprogrammed medical professional. Indicator lights  427 , which may comprise LEDs, include: an on/off status indicator  425 ; an indicator of active status of applied electrical stimulation  423 ; an indicator of active status of applied vibration/ultrasound  421 ; and an ECG indicator  413 , which indicates when ECG is being measured. In other embodiments, the ECG indicator  413  may alternatively be configured to indicate when electrodes are not sufficiently coupling to skin, or may even indicate when the measured ECG is critical or indicates arrythmias in the subject. Any additional indicator lights  427  may be added to achieve these or other functions. 
       FIG.  22    illustrates a wearable blood pressure control system  500  having multi-mode energy delivery therapy including both vibration and electrical stimulation. The wearable blood pressure control system  500  is configured to be wrapped around a limb of a subject, as shown in  FIGS.  25  and  27   . A band  502  having a first end  504  and a second end  506  includes an inner-facing side  510  and an outer-facing side  512 . The band  502  further includes an elastic clasp  508  having a first hook/loop area  514  configured to be secured to a second hook/loop area  516 . The elastic clasp  508  comprises an elastic sheet configured to stretch longitudinally, such that the band  502  will fit on a variety of limb diameters. When the band  502  is secured to the limb, an additional band  518  maybe secured around the band  502  for additional securement, but in some embodiments, the band  502  alone is utilized. The additional band  518  may be similar to the second band  408  of  FIG.  19   , though without any of the active components (piezoelectric discs  478 , electrodes  480 ). In some embodiments, the additional band  518  may comprise a band  404  having a bladder  416 . The wearable blood pressure control system  500  includes eight conductive hydrogel electrodes  520  carried on the inner-facing side  510  of the band  502 , and eight piezoelectric discs  522  ( FIG.  28   ) embedded below the electrodes  520 . The eight piezoelectric discs  522  are each acoustically coupled by the hydrogel such that they are able to be operable when the electrodes  520  are contacting the skin of the user. An adjustable internal surface  406  such as that of the wearable blood pressure control system  400  of  FIG.  15    may alternatively be incorporated, and the two or more of the electrodes  520  may be used to measure impedance of the limb tissue, for an automatic inflation of the bladder  416 , and automatic fitting optimization. A multi-terminal connector  524  includes magnetic clasps  526 ,  528  that are configured to magnetically locate a mating multi-terminal (e.g., multi-pin) connector, which may be attached to a smart watch, health tracker, fitness tracker, or a smart phone, or other mobile control system, such as a system carried on one’s person or on clothing, or as part of the clothing. Multiple contacts  530  allow for various electrical connections in a small area. Sixteen contacts are shown, but any number is possible, including two to  32 , four to sixteen, or six to twelve, for example. The pins of a multi-pin terminal may include spring-loaded electrical contact pins. 
     A receptable  560  is configured for placement of an electronic identification device, such as an RFID chip, an EPROM, an EEPROM, or a resistor for a Wheatstone Bridge. 
     Turning to  FIG.  28   , disc-shaped conductive hydrogel electrode  520  extends from the inner-facing side  510  of the band  502 . The hydrogel electrode  520  can be flexible and stretchable, but these characteristics are less needed if the electrodes  520  are small. Thus, the size (e.g., diameter) of the electrodes  520  can be varied, depending on the particular geometry of the array. The electrode  520  is coupled to a first surface  534  of a flexible substrate  531  (e.g., polyimide flex circuit material) via a conductive paint  532 . The conductive paint  532  is electrically connected to a trace  552  on the first surface  534  of the flexible substrate  531 . In some embodiments, the conductive paint  532  comprises a silver-silver chloride (Ag-AgCl). In other embodiments, the conductive paint (ink) may comprise copper or gold, or other silver-based materials. A first portion  542  of a piezoelectric disc  536  is bonded to a first trace  546  on a second surface  538  of the flexible substrate  531  with a conductive epoxy  540 . The piezoelectric disc  536  may comprise a PZT material (lead zirconate titanate (Pb[Zr(x)Ti(1-x)]O3)), or another appropriate ceramic material configured to vibrate in response to an applied voltage. A second portion  544  of the piezoelectric disc  536  is electrically coupled to a conductive tab  548  which in turn is electrically coupled to a second trace  550  on the second surface  538  of the flexible substrate  531 . Thus, the electrode  520  is electrically coupled to a circuit on the first surface  534  of the flexible substrate and the piezoelectric disc  536  is electrically coupled to a circuit on the second surface  538  of the flexible substrate  531 . The flexible substrate  531  may comprise one or more thin strips within the band  502  (for example, between an upper sheet  554  and a lower sheet  556  of the band  502  that are bonded together. Each element (electrode or piezoelectric) of each of the eight electrode 520/piezoelectric disc  536  layered pairs  558  may be operated independently, or in some instances, both elements of the layered pair  558  may be operated in unison. 
     The electrodes  520  may be electrically connected and arrayed on the band  502  in a variety of combinations in order to achieve a particular effect. In the wearable blood pressure control system 500′ of  FIGS.  24 - 25   , the band  502  includes a first row  562  of four anode electrodes  520   a  and a second row  564  of four cathode electrodes  520   c . When the band  502  is attached to the wrist  38  of a user  42 , as in  FIG.  25   , each anode-cathode pair  566   a - d  is substantially aligned along the general longitudinal axis  568  of the median nerve  43 , such that the application to the skin  570  of a negative charge from the cathodes  520   c  and the positive charge from the anodes  520   a  at substantially longitudinally-aligned locations  572 ,  574  is configured to create an effect on the conductive properties of the median nerve  43 . In some cases, the conduction of the median nerve  43  is increased by the operation of the anode-cathode pair  566   a - d , and in other cases, the conduction of the median nerve  43  is decreased or disrupted by the by the operation of the anode-cathode pair  566   a - d . In use, a user may achieve acceptable results with the orientation of the band  502  as shown in  FIG.  25   , with a first lateral edge  576  of the band  502  located proximally and a second lateral edge  578  of the band  502  located distally. In other cases, the results may not be desirable, and the user my remove and reattach the band  502  such that the first lateral edge  576  of the band  502  is located distally and the second lateral edge  578  of the band  502  is located proximally, wherein the results are improved. The traces  552 ,  546 ,  550  for each electrode  520  and piezoelectric disc  536  of the flexible substrate  531  flex circuit  580  ( FIG.  28   ) can be fabricated in a variety of patterns to achieve different electrical connections. The contacts  530  of the multi-terminal connector  524  may be assigned independently to also allow for different electrical connection configurations. Though the median nerve  43  is often the target, in other cases, the effect may be focused, or shared, on the radial nerve or the ulnar nerve. The band  502  may alternatively be located in other positions (around upper arm, around upper forearm) to get the desired effect, or even around a portion of the leg. 
     In the wearable blood pressure control system 500″ of  FIGS.  26 - 27   , the band  502  includes a first row  582  of four common-grounded electrodes  520   m  and a second row  584  of four electrodes  520   w ,  520   x ,  520   y ,  520   z  that are configured to be excited independently of each other. When the band  502  is attached to the wrist  38  of a user  42 , as in  FIG.  27   , the common-grounded electrodes  520   m  are located proximally and each of the independent electrodes  520   w - z  are located distally. Because they are independently connected with respect to each other, the independent electrodes  520   w - z  can be operated in a wide range of different patterns. 
     In alternative embodiments, the electrodes  520  and piezoelectric discs  536  may each have unequal numbers (e.g., six electrodes  520  and four piezoelectric discs  536 , etc.) or equal numbers. Some pairs  566  may exist in some portions of the band  502 , while single electrodes  520  or single piezoelectric discs  536  may exist in other portions of the band  502 . Though the bands  502  of the wearable blood pressure control systems  500 , 500′, 500″ are shown without a bladder  416 , in other embodiments, each of the wearable blood pressure control systems  500 , 500′, 500″ may incorporate a bladder  416 , either for one-size-fits-all sizing, or for sphygmomanometry, or for therapeutic compression. The arrays of electrodes  520  and piezoelectric discs  536  presented herein allow for multiple touch points on the skin or around the limb, which can lead to a faster reduction of blood pressure. 
     In alternative a wearable blood pressure control system  600  is illustrated in  FIG.  29   , and includes a housing  602  (similar to housing  402 ) and a band  604 . The band  604  has a bracelet-like structure comprising five individual flex circuit sections  606   a - e . The flex circuit sections  606   a - e  each have conductive tracings  608  coupled to components (e.g., electrodes, piezoelectric elements-not shown). The components may in some embodiments be arranged as in the layered pair  558  of  FIG.  28   . A hinge joint  610  between each adjacent flex circuit section  606   a - e  includes one or more conductor  612  linking them together electrically. The hinge joint  610  may in some embodiments include an elastic matrix, to allow some elastic separation and recoil (stretch) between adjacent flex circuit sections  606   a - e . Though five flex circuit sections  606   a - e  are shown in  FIG.  29   , any number may be used, for example, between three and sixteen or between four and ten. The low-profile and light weight structure of the flex circuit sections  606   a - e , as well as the modular architecture and ease of fabrication, increase affordability and allow for an easy to wear system. 
     While the foregoing is directed to embodiments of the present invention, other and further embodiments of the invention may be devised without departing from the basic scope thereof. Though not described in detail above, the wearable blood pressure control system  400  of  FIG.  15   , the wearable blood pressure control system  500  of  FIGS.  22 - 23   , and the wearable blood pressure control system  600  of  FIG.  29    may also be utilized according to the method described in relation to  FIG.  14   . 
     The ranges disclosed herein also encompass any and all overlap, sub-ranges, and combinations thereof. Language such as “up to,” “at least,” “greater than,” “less than,” “between,” and the like includes the number recited. Numbers preceded by a term such as “approximately”, “about”, and “substantially” as used herein include the recited numbers (e.g., about 10%=10%), and also represent an amount close to the stated amount that still performs a desired function or achieves a desired result. For example, the terms “approximately”, “about”, and “substantially” may refer to an amount that is within less than 10% of, within less than 5% of, within less than 1% of, within less than 0.1% of, and within less than 0.01% of the stated amount.