Rapid cycle compression device for preventing thrombosis

Abstract

A DVT prevention and / or mitigation device includes a wearable band having an inflatable bladder with an inflatable portion. When the wearable band is disposed about a user's leg, a majority of the inflatable portion of the inflatable bladder is positionable between the user's knee and a midpoint of the user's gastrocnemius muscle. The inflatable bladder is also inflatable to apply pressure to a portion of the user's gastrocnemius muscle, and a source of compressed air is coupled to the wearable band to deliver continuous compression cycles to the inflatable bladder at a frequency of at least 3 cycles per minute, each compression cycle having a compression period and a peak inflation pressure to induce cyclic flow in the user's venous valve sinuses from each successive inflation.

Description

[0001] Cross-reference to related applications

[0002] This application claims the benefit of U.S. Provisional Patent Application No. 63 / 091,858, filed October 14, 2020, entitled “Rapid Cycling Compression Device For The Prevention of Thrombosis”; U.S. Provisional Patent Application No. 63 / 167,603, filed March 29, 2021, entitled “Rapid Cycling Compression Device For The Prevention of Thrombosis”; and U.S. Provisional Patent Application No. 63 / 209,980, filed June 12, 2021, entitled “Rapid Cycling Compression Device For The Prevention of Thrombosis”, each of which is incorporated herein by reference in its entirety. Technical Field

[0003] The present invention generally relates to a compression device, and more specifically to a rapid circulatory compression device for preventing deep vein thrombosis in the lower extremities. Background Technology

[0004] Deep vein thrombosis (DVT) occurs when a blood clot forms in the downstream sinusoids of a venous valve. DVT can lead to pulmonary embolism (PE), which occurs when fragments of the primary blood clot rupture and travel into the arterial system of the lungs, obstructing blood flow and causing tissue damage and death. DVT and PE are collectively referred to as venous thromboembolism (VTE) and are a leading cause of preventable death in US hospitals, with 300,000–600,000 cases annually, resulting in an estimated 60,000 premature deaths.

[0005] Hospitalized patients are at particularly high risk of developing VTE due to increased systemic blood clotting caused by inflammation, surgery, cancer, and other prothrombotic disease states, as well as due to increased immobility (a long-established risk factor for VTE formation).

[0006] Anticoagulation using low molecular weight heparin or oral anticoagulants is a common prophylactic treatment for VTE in hospitals. However, anticoagulants carry a significant bleeding risk, making them unsuitable for some patients, such as postoperative patients, trauma patients, and patients with hemorrhagic stroke. The use of prophylactic anticoagulants also has limited ability to prevent DVT; despite widespread use, DVT often still develops in treated patients and remains a common complication. Furthermore, mechanical compression can be used to prevent DVT by increasing venous flow in the patient to prevent blood stasis. Despite the use of mechanical compression and anticoagulant prophylaxis, alone or concurrently (often in synergy), VTE remains a major complication in hospitalized patients.

[0007] VTE is associated with immobility and subsequent reduction in venous blood flow. The effects of immobility are visible in the venous valvular sinuses, where VTE clots typically form. During periods of immobility, the valvular sinuses exhibit very little blood flow, leading to blood stagnation and susceptibility to clotting. Until recently, the molecular mechanisms linking reduced venous flow to VTE formation were poorly understood. However, recent studies have shown that oscillating flow within the venous valvular sinuses (i.e., flow with both antegrade and retrograde venous flow at different times) helps prevent clot formation. The aspects of the subject matter disclosed herein provide devices and methods for treating and preventing VTE by generating oscillating flow in the venous valvular sinuses of immobile individuals through systems, devices, and methods for generating oscillating flow in the lower extremity venous valves from which DVT formation originates. Summary of the Invention

[0008] In one embodiment, there is a DVT prevention and / or mitigation device comprising: a wearable band including an inflatable bladder having an inflatable portion, wherein when the wearable band is positioned around a user's leg, a large portion of the inflatable portion of the inflatable bladder is positioned between the user's knee and the midpoint of the user's gastrocnemius muscle, the inflatable bladder being inflatable to apply pressure to a portion of the user's gastrocnemius muscle; and a compressed air source coupled to the wearable band to deliver continuous compression cycles to the inflatable bladder at a frequency of at least 3 cycles per minute, each compression cycle having a compression period and a peak inflation pressure to induce circulatory flow in the user's venous valvular sinuses from each continuous inflation.

[0009] In some embodiments, the venous flow velocity in the user's deep veins between successive compression cycles is substantially equivalent to the user's resting baseline venous flow velocity in the deep veins. The venous flow velocity in the user's deep veins between successive compression cycles may return to the resting baseline venous flow velocity within 1 to 10 seconds after each compression period.

[0010] In some embodiments, the frequency is at least 5 cycles per minute. Continuous compression cycles can produce substantially equivalent hemodynamic effects for each compression cycle. Continuous compression cycles can induce a pulse of positive flow in the user's deep veins, which in turn induces a period of reverse flow in the venous valvular sinuses.

[0011] In some embodiments, the frequency, peak inflation pressure, and duration of the compression period are selected to stimulate endothelial FOXC2 expression in the endothelium of the valvular sinus.

[0012] In some embodiments, the inflatable bladder applies pressure to the user's calf muscle within one of the following areas: i) less than 60 square inches; ii) about 55 square inches; iii) less than 30 square inches; iv) about 25 square inches; v) less than 15 square inches; or vi) about 12.5 square inches.

[0013] In some embodiments, the time for the bladder to reach peak inflation is one of the following: i) 30 ms or less, ii) 100 ms or less, iii) 300 ms or less.

[0014] In some embodiments, the bladder inflation period is one of the following: i) 50 ms or less; ii) 150 ms to 250 ms; or iii) 300 ms to 400 ms. The peak inflation pressure may be one of the following: i) 35 mmHg to 70 mmHg; ii) 70 mmHg to 130 mmHg; or iii) 100 mmHg to 200 mmHg.

[0015] In some embodiments, i) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​less than 60 square inches or about 55 square inches, the bladder has an inflation period of 50 ms or less, and a peak inflation pressure of 35 mmHg to 70 mmHg; ii) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​less than 30 square inches or about 25 square inches, the bladder has an inflation period of 150 ms to 250 ms, and a peak inflation pressure of 70 mmHg to 130 mmHg; or iii) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​less than 15 square inches or about 12.5 square inches, the bladder has an inflation period of 300 ms to 400 ms, and a peak inflation pressure of 100 mmHg to 200 mmHg.

[0016] In some embodiments, i) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 55 square inches, the bladder has an inflation period of 25 ms to 50 ms, and a peak inflation pressure of 45 mmHg to 60 mmHg; ii) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 25 square inches, the bladder has an inflation period of 150 ms to 250 ms, and a peak inflation pressure of 80 mmHg to 100 mmHg; or iii) the bladder applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 12.5 square inches, the bladder has an inflation period of 300 ms to 400 ms, and a peak inflation pressure of 150 mmHg to 175 mmHg.

[0017] In some embodiments, the inflation period includes a compression hold period of 400 ms or less. The pressure within the inflatable bladder can dissipate substantially throughout the compression hold period. The inflation period may include a peak inflation period defined by the duration for which peak inflation pressure is reached.

[0018] In some embodiments, the compressed air source includes a valve that alternately directs compressed air to a compressed air tank and a bladder. In some embodiments, the DVT prevention and / or mitigation device includes a valve that alternately allows compressed air to flow to the compressed air tank in a first configuration and to the bladder in a second configuration.

[0019] In some embodiments, a compressed air source delivers compressed air to the bladder during a compression cycle having a ramp-up period, a pulse period, a compression hold period, and a deflation period. The compressed air source may include an air pump that pumps air into the bladder during the ramp-up period. The air pump may be configured to pump air into a compressed air reservoir. The maximum inflation pressure during the ramp-up period may be less than the maximum inflation pressure during the pulse period. The duration of the ramp-up period may be greater than the duration of the pulse period. The duration of the compression hold period may be equal to or greater than the duration of the pulse period and less than the ramp-up period.

[0020] In some embodiments, the duration of the deflation phase is equal to or greater than the duration of the ramp phase. The compression hold phase may be characterized by a pressure drop curve having at least one shoulder. The compression hold phase may be characterized by a pressure drop rate less than the inflation rate during the pulse phase. The ramp phase may begin approximately 5 ms after the end of the deflation phase.

[0021] In some embodiments, the inflatable bladder comprises multiple bladders. The inflatable bladders may be coupled to a wearable strap such that inflation of the inflatable bladders causes the wearable strap to tighten around the user's legs. The inflatable bladders have a total length that decreases as the inflatable bladders inflate, causing the wearable strap to tighten.

[0022] In some embodiments, the compression period includes an inflation period of less than 500 ms. The compression period may include an inflation period of less than 400 ms. The peak inflation pressure may be from approximately 1 PSI to approximately 3 PSI.

[0023] In some embodiments, DVT prevention and / or mitigation may include a flexible outer covering disposed on at least a portion of the bladder and secured to a band, the flexible outer covering being configured to tighten the band during bladder inflation.

[0024] In some embodiments, the inflatable bladder includes a longitudinal axis and elastomeric sidewalls about the longitudinal axis and radially disposed between opposite ends of the elastomeric sidewalls, wherein inflation of the inflatable bladder causes the elastomeric sidewalls to expand away from the longitudinal axis and push the opposite ends of the elastomeric sidewalls toward each other. The flexible outer covering may include a mesh covering.

[0025] In some embodiments, the venous valve sinuses are located in deep veins near the user's groin.

[0026] In some embodiments, both peak positive venous flow and peak negative venous flow occur during the balloon inflation period.

[0027] Another embodiment of the invention provides a method for inducing reverse flow in a venous valve sinus region, the method comprising: applying an inflatable bladder having a majority portion of an inflatable portion positionable between the user's knee and the midpoint of the user's gastrocnemius muscle, the inflatable bladder being inflatable to apply pressure to a portion of the user's gastrocnemius muscle; inflating the inflatable bladder to deliver a peak inflation pressure of compressed air at a compression period and frequency to induce circulatory flow in the user's venous valve sinuses at a frequency of at least 3 cycles per minute during continuous compression cycles of the inflatable bladder, wherein inflating the inflatable bladder comprises the steps of: inflating the inflatable bladder to a target ramp pressure during a ramp period; inflating the inflatable bladder to the peak inflation pressure during a pulse period following the ramp period; maintaining the pressure of the inflatable bladder within a holding pressure range during a holding period following the pulse period; and deflating the inflatable bladder to a minimum pressure less than the target ramp pressure after the holding period.

[0028] In some embodiments, the inflatable bladder applies pressure to the user's gastrocnemius muscle (in some embodiments, the midpoint of the gastrocnemius muscle) within one of the following areas: i) less than 60 square inches; ii) about 55 square inches; iii) less than 30 square inches; iv) about 25 square inches; v) less than 15 square inches; or vi) about 12.5 square inches. The inflation period of the inflatable bladder may be one of the following: i) 50 ms or less; ii) 150 ms to 250 ms; or iii) 300 ms to 400 ms. The inflation pressure may be one of the following: i) 35 mmHg to 70 mmHg; ii) 70 mmHg to 130 mmHg; or iii) 100 mmHg to 200 mmHg. Inflating an inflatable bladder may include i) applying pressure to the user's gastrocnemius muscle over an area of ​​less than 60 square inches or about 55 square inches for an inflation period of 50 ms or less and a peak inflation pressure of 35 mmHg to 70 mmHg; ii) applying pressure to the user's gastrocnemius muscle over an area of ​​less than 30 square inches or about 25 square inches for an inflation period of 150 ms to 250 ms and a peak inflation pressure of 70 mmHg to 130 mmHg; or iii) applying pressure to the user's gastrocnemius muscle over an area of ​​less than 15 square inches or about 12.5 square inches for an inflation period of 300 ms to 400 ms and a peak inflation pressure of 100 mmHg to 200 mmHg.

[0029] In some embodiments, inflating the inflatable bladder includes i) applying pressure to the user's gastrocnemius muscle over an area of ​​approximately 55 square inches for an inflation period of 25 ms to 50 ms and a peak inflation pressure of 45 mmHg to 60 mmHg; ii) applying pressure to the user's gastrocnemius muscle over an area of ​​approximately 25 square inches for an inflation period of 150 ms to 250 ms and a peak inflation pressure of 80 mmHg to 100 mmHg; or iii) applying pressure to the user's gastrocnemius muscle over an area of ​​approximately 12.5 square inches for an inflation period of 300 ms to 400 ms and a peak inflation pressure of 150 mmHg to 175 mmHg.

[0030] In some embodiments, the inflation period includes a compression hold period of 400 ms or less. The pressure within the inflatable bladder can dissipate substantially throughout the compression hold period. The inflation period may include a peak inflation period defined by the duration for which peak inflation pressure is reached.

[0031] In some embodiments, inflating the inflatable cuff includes cyclically inflating the cuff to alternate between peak inflation pressure and subsequent peak inflation pressure at least 6 cycles per minute. The venous valve sinus region may be located at the junction of the user's saphenous vein and the user's femoral vein.

[0032] In some embodiments, continuous inflation of the bladder includes a first compression at the venous valve sinus causing a first peak reverse flow velocity index and a subsequent compression at the venous valve sinus causing a subsequent peak reverse flow velocity index, wherein the magnitude of the first peak reverse flow velocity index is 50% to 150% of the magnitude of the subsequent peak reverse flow velocity index.

[0033] In some embodiments, the first compression causes a first forward flow that occurs substantially simultaneously with the first reverse flow, and all subsequent compressions cause subsequent forward flows that occur substantially simultaneously with the reverse flow.

[0034] Another embodiment of the invention provides a treatment method comprising: selecting a subject from a population with impaired venous valves; applying an inflatable bladder having a majority portion of an inflatable portion that can be positioned between the subject's knee and the midpoint of the subject's gastrocnemius muscle, the inflatable bladder being inflatable to apply pressure to a portion of the subject's gastrocnemius muscle; inflating the inflatable bladder to deliver a peak inflation pressure of compressed air at a compression period and frequency to induce circulatory flow in the subject's venous valve sinuses at a frequency of at least 3 cycles per minute during continuous compression cycles of the inflatable bladder, wherein inflating the inflatable bladder comprises the steps of: rapidly inflating the bladder to the peak inflation pressure during a pulse period; and maintaining the pressure of the bladder within a holding pressure range during a holding period following the pulse period.

[0035] In some embodiments, inflating the inflatable bladder further includes the steps of: inflating the inflatable bladder to a target climb pressure during the climb phase; and deflating the inflatable bladder to a minimum pressure less than the target climb pressure after the hold phase.

[0036] In some embodiments, frequency, peak inflation pressure, and compression duration are selected to stimulate endothelial FOXC2 expression in the endothelium of the valvular sinus. Attached Figure Description

[0037] Figure 1 An exemplary rapid cycle compression device (RCCD) for use by a patient is shown according to an embodiment.

[0038] Figure 2 An exploded view of an exemplary air control system for RCCD according to an embodiment is shown.

[0039] Figure 3 An exemplary schematic diagram of an exemplary air control system for an RCCD according to an embodiment is shown.

[0040] Figures 4A-4C An exemplary wearable inflatable device for RCCD according to an embodiment is shown.

[0041] Figures 5A-5B An exemplary inflatable bladder design for wearable inflatable devices is shown.

[0042] Figure 6A Another exemplary inflatable bladder design according to an embodiment is shown.

[0043] Figures 6B-6D An example of having Figure 6A The inflatable bladder design allows for the placement of the wearable, inflatable garment around the user's lower limbs.

[0044] Figure 7 This is a graph showing the pressure change over time for an exemplary RCCD.

[0045] Figure 8A These are a series of ultrasound images of the venous valve sinus region during the use of an exemplary RCCD.

[0046] Figures 8B-8E This is a diagram showing the forward and reverse flow during the use of an exemplary RCCD.

[0047] Figure 8F and Figure 8G This is a graph of the normalized average flow volume index (“flow index”) and various durations during the use of an exemplary RCCD.

[0048] Figure 9A and Figure 9B This is a graph showing the relationship between canister pressure and bladder pressure during the use of an exemplary RCCD.

[0049] Figure 9C and Figure 9D This is a graph showing the normalized average flow index and various tank pressures during the use of an exemplary RCCD.

[0050] Figure 10A This is a graph showing the flow index and various tank pressures and holding durations during the use of an exemplary RCCD.

[0051] Figure 10B This is a table showing the tank pressure, holding time, and percentage of individuals experiencing backflow during the use of an exemplary RCCD.

[0052] Figure 11A This is a graph of peak bladder pressure based on the inflation rate of an exemplary RCCD.

[0053] Figure 11B and Figure 11C This is a graph of the normalized peak flow index and various inflation rates for an exemplary RCCD.

[0054] Figure 12AThese are a series of ultrasound images of the venous valve sinus region during use of exemplary RCCDs and commercially available devices.

[0055] Figure 12B This is a chart showing the percentage of subjects with reverse venous flow during use of the exemplary RCCD and commercially available devices.

[0056] Figure 13A This is a diagram illustrating the forward and reverse flow during the use of an exemplary RCCD.

[0057] Figure 13B This is a diagram illustrating exemplary forward and reverse flow during use of a commercially available device.

[0058] Figure 14 The effectiveness of an exemplary RCCD in generating oscillatory flow in the valvular sinus is shown compared to commercially available devices.

[0059] Figure 15A These are a series of ultrasound images of the venous valve sinus region taken at different inflation times during the use of an exemplary RCCD.

[0060] Figure 15B This is a graph showing the forward and reverse flow during three compression cycles of an exemplary RCCD.

[0061] Figure 16 This is a graph reflecting experimental data on normalized FOXC2 expression in human endothelial cells cultured under reversed flow conditions under different conditions.

[0062] Figures 17A-17C These are ultrasound images of venous flow based on baseline during lower leg flexion and during the use of the exemplary RCCD.

[0063] Figure 17D-17I It is a graph of the positive and negative flow based on baseline during lower leg flexion and during the use of the exemplary RCCD.

[0064] Figure 18 This is a table comparing the number of compression cycles that occurred during the use of the exemplary RCCD and commercially available devices under 30% compliance.

[0065] Figure 19A This is a graph showing the average system pressure over time for compliant, non-compliant, and sleeve-separated applications using an exemplary RCCD.

[0066] Figure 19B This is a graph showing the normalized system pressure over time for compliant, non-compliant, and sleeve-separated applications using an exemplary RCCD.

[0067] Figure 20AThis is a graph showing the change of bladder pressure over time during a compression period, provided by an exemplary RCCD.

[0068] Figure 20B This is a graph showing the change of bladder pressure over time for three consecutive compression periods, provided by an exemplary RCCD.

[0069] Figures 21A-21B This is an illustration of the expansion of an inflatable bladder according to an exemplary RCCD.

[0070] Figure 21C-21D This is an illustration of pneumatic muscle expansion based on an exemplary RCCD. Detailed Implementation

[0071] Embodiments of this disclosure include systems, apparatus, and methods for utilizing rapid compression to generate oscillatory flow in the valvular sinuses of deep veins. In further embodiments of this disclosure, a system, apparatus, and method are provided that includes a compression device optimized for a limited reduction in venous flow volume within the compression region to allow for rapid return to baseline pressure, thereby enabling rapid re-application of compression and continuous initiation of oscillatory flow multiple times per minute to match physiological hemodynamics, while preserving antithrombotic genetic programs that prevent VTE.

[0072] Endothelial cells of the lining venous valvular sinuses and adjacent valvular leaflets (the site of conventional VTE clot formation) experience reverse or oscillatory flow when bursts of venous flow create eddies in the downstream sinus region. These bursts of flow are generated in response to “normal” muscle movements that occur during activity. Valvular sinus endothelial cells sense oscillatory shear forces and, in response, upregulate the expression of the transcription factors FOXC2 and PROX1. PROX1 and FOXC2 regulate the expression of numerous target genes, including six genes associated with thrombosis. Endothelial cells expressing FOXC2 and PROX1 have 1 / 10–1 / 5 times higher levels of von Willebrand factor (vWF), undetectable levels of surface P-selectin, and 1 / 20–1 / 5 times higher levels of intercellular adhesion molecule 1 (ICAM1), all of which are prethrombotic proteins. Furthermore, these identical endothelial cells exhibited 2-3 times higher levels of the antithrombotic proteins thrombomodulin (THBD), endothelial protein C receptor (EPCR), and tissue factor pathway inhibitor (TFPI) compared to endothelial cells that did not express FOXC2 and PROX1. Deletion of the FOXC2 or PROX1 gene in mice revealed the loss of antithrombotic gene programming at the valve site and spontaneous DVT formation. Similar responses were observed when venous blood flow was restricted in mice. Finally, the results indicate that local cells at the site of VTE clot formation in human patients have lost expression of PROX1 and FOXC2, and the expression pattern of antithrombotic proteins has also been lost, suggesting that the loss of this pathway is associated with clinical VTE formation.

[0073] In summary, these results demonstrate that immobility contributes to the formation of VTE blood clots not only by reducing total venous flow, but also by specifically reducing the bursts of venous flow that generate valvular sinus oscillations and stimulation of local endothelial cells, thereby upregulating the PROX1 and FOXC2 transcription factors. This, in turn, regulates the genetic program that effectively inhibits clot formation through multiple biochemical pathways.

[0074] See Figure 1-6D This disclosure may include a rapid cycle compression device (“RCCD”) 100. In some embodiments, the RCCD 100 may include a head unit 101, an air conduit 102, and one or more (e.g., two) wearable inflatable wearables 103. Each wearable inflatable wearable or wearable 103 may each include a bladder configured to inflate. For example, embodiments of wearables 103, 300, 600 may include bladders 301, 405, or 601, each of which is interchangeable herein. The head unit 101 may be configured to generate and control a compressed air flow to inflate bladders 301, 405, or 601 of the wearable inflatable wearable 103. Bladders 301, 405, and 601 may be coupled to the head unit 101 via the air conduit 102. The wearable inflatable wearable 103 may be secured in place around a portion of a user or patient. For example, the wearable inflatable wearable 103 may be secured around the lower limb of a patient requiring treatment. In some embodiments, the wearable inflatable wearable 103 is secured around the user's lower leg. The wearable inflatable wearable 103 may be secured around different parts of the patient's lower limb. In some embodiments, the wearable inflatable wearable 103 is configured to secure around other parts of the patient, such as the upper limb.

[0075] In some embodiments, the RCCD100 includes one or more air compressors configured to fill an air canister to a set pressure (e.g., 1.5-7.5 psi) and / or inflate bladders 301, 405, or 601. The RCCD100 may include one or more valves, such as solenoid valves, and the air canister may be opened electronically by connecting the air canister to a tubing connected to a bladder disposed in one of the wearable inflatable wearables 103. In some embodiments, for example, after 100-200 milliseconds, the valve may close, and the air compressor may restore the canister pressure, allowing a bladder in another wearable inflatable wearable 103 to inflate. This process continues with one wearable inflatable wearable 103 inflating every 3-10 seconds and alternating between the left and right calves.

[0076] In some embodiments, the RCCD 100 is configured to provide one or more compression periods of 500 ms or less, such as less than 300 ms. A compression period can be the time from the start of inflation to the end of deflation. For example, a compression period can be the time from the start of inflation of bladders 301, 405, or 601 to the completion of deflation of bladders 301, 405, or 605. The RCCD 100 can be configured to provide alternating compression to each lower limb. For example, the RCCD 100 can be configured to provide compression to a portion of each lower limb (such as the calf) every 3 seconds, resulting in the RCCD 100 providing compression to a single lower limb every 6 seconds. In some embodiments, the RCCD 100 can be configured to provide compression to the user's lower limbs by inflating the wearable inflatable wearable 103 to a pressure ranging from 1 PSI to approximately 5 PSI. In some embodiments, the RCCD100 is configured to provide compressions lasting 500 ms or less (such as about 300 ms) at a balloon pressure ranging from about 1.5 PSI to about 2.5 PSI in a 6-second compression cycle, alternating between the patient's lower limbs.

[0077] In one embodiment, the RCCD 100 includes a bladder disposed within a wearable, inflatable garment 103 that wraps around a user's lower limb, such as around the calf (e.g., between the knee and the widest part of the calf). The RCCD 100 can be configured to provide compression to desired anatomical areas of the user's lower limb (e.g., the calf). The bladder 301, 405, or 601 can be inflated and deflated to provide compression to desired anatomical areas. In some embodiments, the size and shape of the bladder 301, 405, or 601 are configured to provide compression to desired anatomical areas. For example, the bladder 301, 405, or 601 can be sized to completely cover the calf, cover half of the calf, or be a band disposed around the calf.

[0078] In some embodiments, the inflatable bladder 301, 405, or 601 is selected based on the size or area of ​​the bladder 301, 405, or 601 that provides compression to the desired anatomical area of ​​the user. For example, the bladder 301, 405, or 601 may be selected from sizes of 45 square inches to 65 square inches, 15 square inches to 35 square inches, or 5 square inches to 15 square inches. A wearable inflatable wearable 103 may be pneumatically coupled to a head unit 101 that compresses air and releases the air into the bladder to generate pulses of compressive force. The RCCD 100 may be performed via compression cycles, each of which induces a venous return pulse (e.g., blood flowing back towards the heart through the venous system), which generates circulatory or oscillating flow in the valvular sinus region of the venous valves in the patient's lower extremities. The sustained generation of oscillating flow in the valvular sinuses is believed to preserve the natural hemodynamic mechanisms of VTE prevention associated with muscle activity in active individuals.

[0079] References are for illustrative purposes and not for limitation. Figure 1 The illustration shows an exemplary RCCD 100 used by a user (e.g., a patient). In some embodiments, the RCCD 100 is configured to prevent and / or reduce the occurrence of VTE. The RCCD 100 may include a head unit 101, pneumatic air tubing 102, and a wearable inflatable wearable 103 having a bladder 601. Bladders 301, 400, 405, and 601 ( Figures 4A-6A Any of the features described herein may also be applied to any of the sacs 301, 400, 405, and 601. As shown, the wearable 103 is worn around the user's lower limbs (e.g., between the knee and the widest part of the calf), and the air duct 102 connects the head unit 101 to the wearable wearable 103.

[0080] In some embodiments, the head unit 101 is configured to compress air and release air into a bladder disposed within a wearable inflatable wearable 103 to generate pressure pulses around the user's lower limb (e.g., near or around the user's calf). The wearable inflatable wearable 103 may be pneumatically coupled to the head unit 101 via an air conduit 102. In some embodiments, the RCCD 100 may be performed via compression cycles, each of which induces venous return pulses (e.g., blood flowing back towards the heart through the venous system), which generate circulatory or oscillating flow in the valvular sinus regions of the venous valves within the patient's lower limb. In some embodiments, the sustained generation of circulatory or oscillating flow in the valvular sinuses preserves the natural hemodynamic mechanisms of VTE prevention associated with muscle activity in active individuals.

[0081] References are for illustrative purposes and not for limitation. Figure 2An exploded view is provided, illustrating an exemplary head unit air control system 101 (“head unit 101”) and components according to certain embodiments. In some embodiments, the head unit 101 includes a housing made of, for example, two pieces of molded plastic 201 and 202. In some embodiments, the housing has one or more (e.g., two) hooks 203 on its rear portion, allowing the head unit 101 to be suspended near a patient. For example, during use of the RCCD 100, the hooks 203 can be used to suspend the head unit 101 at an end of a bed. The head unit 101 may include a power switch 204 configured to control the head unit 101. For example, the RCCD 100 may preferably be electronically powered and activated by engaging or actuating the power switch 204. The housing may also include two external ports 205 for connecting air ducts 102. In some embodiments, the head unit 101 includes a handle 206 for carrying and transporting the head unit 101. The external ports 205 may be configured to allow air to flow from the head unit 101 through the air ducts 102 to external devices, such as a bag 601. The head unit 101 may be powered by a power supply 207 configured to be plugged into a standard wall socket. The head unit 101 may include an air control system housed within a housing. In some embodiments, the air control system includes an air reservoir 208, an air compressor 209, and one or more solenoid valves 210. For example, the air control system may include two solenoid valves 210. The solenoid valves 210 may generate, store, and control the release of compressed air from the air control system. Compressed air may be delivered from the head unit 101 via pneumatic lines 211. The RCCD 100 may be configured to compress air entering the air reservoir 208 to a set pressure and release the air via the solenoid valves 210 at set time periods and / or at set intervals. In some embodiments, the release of compressed air is controlled by a PCB or control board 212. In some embodiments, the PCB 212 includes a microprocessor. The PCB 212 may include one or more pressure sensors. In some embodiments, the PCB 212 is coupled to one or more pressure sensors.

[0082] See Figure 3This document provides an exemplary architecture of head unit 101 and an illustration of the pneumatic function of RCCD 100. In some embodiments, head unit 101 includes one or more sensors. For example, head unit 101 may include a sensor 220 disposed within an air reservoir 208. Sensor 220 may be a pressure sensor to monitor air pressure within air reservoir 208. Head unit 101 may also include a sensor 221 for monitoring post-solecular pressure in the patient's left and / or right lower extremities. For example, sensor 221 may be positioned near one or more solenoid valves 210 disposed within head unit 101. One or more solenoid valves 210 may be located along an air passage between air reservoir 208 and bladder 601. One or more solenoid valves 210 may regulate the inflation and deflation of bladder to provide compression to the patient. Sensor 221 may be a pressure sensor that monitors air pressure released from one or more solenoid valves 210. In some embodiments, RCCD 100 includes an external sensor 222 for measuring pressure within the bladder coupled to head unit 101. For example, external sensor 222 can be used to ensure that the pressure inside the bladder connected to head unit 101 is within the desired range.

[0083] In some embodiments, the head unit 101 is configured to insert into a standard wall socket, and during operation, a switch on the front of the head unit 101 changes from "off" to "on". In some embodiments, the head unit 101 may include one or more status indicators, which may include visual and / or auditory indicators. In some embodiments, an LED indicator may turn on when the head unit 101 is powered on, and may display blue, for example, if the system is operating normally. The RCCD 100 may include additional lighting features and / or audio alarms to indicate inappropriate pressure levels that could cause injury or discomfort to the user. For example, if the RCCD 100 becomes unable to properly output / distribute air from / in the air tank 208, the pressure in the air tank 208 may rise to a dangerous or inappropriate level. Once the pressure remains above a predetermined normal range, audio and visual alarms may be activated to alert the user and / or operator (e.g., a medical professional) to the inappropriate pressure. The LED indicator on the head unit 101 may change from green to red, for example, and an audible alarm will sound. For a "high pressure" alarm, the audible alarm may be configured to generate a continuous noise. In some embodiments, to prevent overfilling of the air canister 208, the air canister 208 includes a check valve configured to discharge air above 10 psi to prevent continuous pressure buildup within the canister 208. If the check valve is deactivated or malfunctions and the pressure continues to rise, the air compressor may automatically shut down, and the RCCD100 may be configured to automatically stop operating.

[0084] In some embodiments, the RCCD100 includes one or more air compressors. For example, the RCCD100 may include a first air compressor connected via an air line to the inflatable bladder 601 and a second air compressor connected to the air canister 208. The first air compressor may be configured to inflate the inflatable bladder 601 to a desired pressure, and the second air compressor may be configured to fill the air canister 208 before the valve 210 opens, thereby causing a pressure increase. In some embodiments, an RCCD100 having one or more air compressors allows the RCCD100 to use one air compressor to slowly inflate the inflatable bladder 601 to a first desired pressure, and then use another air compressor and / or the air canister 208 to rapidly inflate the inflatable bladder 601 to a second desired pressure. Alternatively, one or more air compressors may operate simultaneously to inflate both the inflatable bladder 601 and the air canister 208. In one embodiment, a single air compressor may be configured to directly supply the inflatable bladder 601 and / or supply the air canister 208. In some embodiments, the RCCD100 includes a valve configured to alternately direct compressed air (e.g., from a single air compressor or more than one air compressor) to the air tank and bladder.

[0085] In the illustrated example, the dimensions of the air reservoir 208 and the set pressure of the reservoir 208 are calibrated based on the dimensions of the bladder 601 disposed within the wearable inflatable garment 103. For example, the RCCD 100 can be configured to inflate the bladder 601 to a desired pressure (e.g., an air pressure of 1.5-2.5 PSI in use) within a selected time period (e.g., 30 ms from the start of filling the bladder 601 to reaching peak pressure). The RCCD 100 can also be configured to repressurize the reservoir in less than 5 seconds (e.g., from the time the solenoid valve 210 closes) to allow for rapid cycles of subsequent inflation.

[0086] In one embodiment, the RCCD 100 is configured to inflate the bladder 601 to a desired pressure of approximately 1.5 PSI in less than 1 second. For example, the RCCD 100 may be configured to deliver air to the bladder 601 to inflate it to the desired pressure in less than 500 ms. In some embodiments, the RCCD 100 is configured to deliver air to the bladder 601 in 100 ms or less. For example, the RCCD 100 may be configured to deliver air to the bladder 601 in approximately 30 ms. The RCCD 100 may be configured to sequentially inflate the bladder 601 to the desired pressure during repeated compression cycles. Each compression cycle may include a compression period. For example, a single compression cycle may be from the beginning of one compression period to the beginning of a subsequent compression period. The time between compression periods may be included in the compression cycle. In other words, a compression cycle may be from the beginning of a first compression period to the beginning of a subsequent second compression period, including the time between the first and second compression periods. The time between subsequent compression periods may be referred to herein as the residence time.

[0087] In some embodiments, a compression cycle may be a period from the peak of one compression period to the peak of a subsequent compression period. A compression period may be defined as the time from the start of inflation to the end of deflation. In some embodiments, the RCCD100 may have a first baseline pressure at the start of inflation and a second baseline pressure at the end of deflation. The first baseline pressure may be substantially equal to the second baseline pressure. In some embodiments, the patient may or may not feel compression throughout the compression period. For example, an early phase of the compression period may be characterized by inflation of the bladder 601, where little or no compression is applied to the user, resulting in the patient not feeling compression at the start of the compression period. Similarly, in some embodiments, the patient may hardly feel the increased compression during the final phase / stage of the compression period. In some embodiments, the duration of a compression period is less than 300 ms. However, the duration of a compression period may be 500 ms or less, 400 ms or less, 300 ms or less, 200 ms or less, or 100 ms or less. The time from the peak pressure of one compression period to the peak pressure of a subsequent compression period (e.g., a compression cycle) may be from 3 seconds to 20 seconds. For example, the RCCD100 can be configured to provide repetitive compression cycles, thereby achieving peak pressure in increments ranging from 3 seconds to 20 seconds. For example, peak pressure can be achieved in increments of 3 seconds, 6 seconds, 10 seconds, 15 seconds, 20 seconds, or any increment between 3 seconds and 20 seconds.

[0088] In practice, the RCCD100 can be configured to provide alternating compression cycles between different limbs of a patient. For example, a first compression cycle may be applied to the patient's first lower limb, and a subsequent compression cycle (e.g., a second compression cycle in the next compression cycle in a series) may then be applied to the patient's second lower limb. The time interval between the peak of the first compression cycle (e.g., the first leg) and the peak of the second compression cycle (e.g., the second leg) can range from 3 seconds to 20 seconds. In some embodiments, for example, although compression cycles occur every 3 seconds, each leg may experience a compression cycle every 6 seconds or longer (e.g., in cases where there is a predetermined delay between pairs of compression cycles applied to a single limb).

[0089] In one embodiment, the RCCD100 is configured to include a specific volume ratio of air tank 208 to bladder 601. For example, a volume ratio of at least 2:1 for air tank 208 to bladder 601 is selected to prevent air tank 208 (tank 208) from depressurizing to a point where the set pressure of tank 208 is slowly rebuilt within, for example, 3-5 seconds. The volume ratio of tank 208 to bladder 601 may be 1:1 or less. In some embodiments, the ratio between the internal volume of bladder 601 and the internal volume of tank 208 is 1:3.

[0090] In some embodiments, a larger volume canister 208 allows for faster repressurization, which helps maintain the inflation pressure at the desired level. In some embodiments, a smaller volume canister 208 may be used with an air compressor selected to produce greater output and / or have a longer runtime capability (e.g., continuous operation). The set canister pressure (e.g., the pressure that head unit 101 is programmed to maintain in air canister 208) is also calibrated based on the volume of bladder 601. For example, the set pressure of canister 208 may be calibrated to enable bladder 601 to inflate rapidly to the desired peak pressure. For example, the peak pressure within bladder 601 may range from 1.5 to 2.5 PSI. The set canister pressure of canister 208 may also be calibrated to allow bladder 601 to inflate rapidly to peak pressure in less than, for example, 150 ms. However, the set canister pressure can be calibrated to allow the bladder 601 to inflate rapidly to peak pressure within 50 ms or less, 100 ms or less, 200 ms or less, 300 ms or less, 400 ms or less, 500 ms or less, 600 ms or less, 700 ms or less, 800 ms or less, 900 ms or less, or 1000 ms or less. In a preferred embodiment, the set canister pressure calibration allows the bladder 601 to inflate rapidly to peak pressure within approximately 30 ms.

[0091] See Figures 9A-9DVarious pressures can be used in canister 208 to achieve the desired hemodynamic effect of generating oscillating flow. For example, canister 208 may have canister pressures ranging from 1 to 5 PSI. During experimental testing of the RCCD100, canister 208 was used with pressures of 1 PSI, 2 PSI, 3 PSI, and 4 PSI, all of which resulted in reverse venous flow at the venous valve sinus region at the junction of the saphenous and femoral veins (e.g., the saphenofemoral junction). In some embodiments, canister 208 has a canister pressure of 3 PSI. A canister 208 with a canister pressure of 3 PSI may be desirable because it represents the lowest pressure and is most comfortable for the patient, and it also generates reverse venous flow higher than that generated by activities the patient engages in, such as dorsiflexion of the lower leg. Figure 9A A graph showing the pressure at sensor 221 measured at various tank pressures in tank 208 during inflation after solenoid valve 210 is opened. Figure 9B A graph showing the linear relationship between the tank pressure of tank 208 and the pressure of RCCD100 monitored by sensor 221 is presented. Figure 9A As shown, a canister 208 with a canister pressure of 3 PSI results in a peak pressure of approximately 2 PSI for the bladder 601, and Figure 9B The pressure increase at outlet tank 208 leads to an increase in pressure at bladder 601.

[0092] Figure 9C-9D For forward flow ( Figure 9C ) and reverse flow ( Figure 9D This paper presents quantified hemodynamic data from healthy subjects, measuring flow in the venous valve sinus region during immobility (baseline), active lower leg flexion (active), and compression provided by the RCCD100 at various canister pressures (1 PSI, 2 PSI, and 3 PSI) in canister 208. The graphs show the mean flow index during peak flow normalized to the peak during active movement to minimize inter-subject variability. Comparison Figure 9C and Figure 9D The graphs show that increasing the pressure of canister 208 (e.g., from 1 PSI to 2 PSI to 3 PSI) does not have a strong effect on the generation of forward flow in the venous valvular sinus region at the saphenofemoral junction, compared to the effect on the normalized mean flow index of reverse flow when canister pressure is increased to 3 psi. The data also indicate that canister 208 with a canister pressure of 1 PSI resulted in some subjects exhibiting similar levels of reverse venous flow in the valvular sinus as during activity. Furthermore, canister 208 with a canister pressure of 3 PSI resulted in a significant increase in compression-induced reverse venous flow compared to activity, 1 PSI, and 2 PSI. Figure 9C and Figure 9D The error bars shown represent standard errors.

[0093] See Figures 10A-10BThe data demonstrates the effectiveness of RCCD100. Figures 10A-10B The data showed that, except when canister 208 had a canister pressure of 3 PSI and was held for 150 ms, all patients using the RCCD100 achieved greater reverse venous flow compared to baseline when canister 208 had a canister pressure of 2 PSI and was held for 250 ms. The data also showed that, for Figure 10B For each instance provided in the table, the reverse venous flow index induced by compression provided by the RCCD100 was higher than the mean reverse venous flow index during immobility (baseline, dashed line). The additional duration of maintaining compression for 250 ms at 2PSI increased the response compared to 150 ms at 2PSI. Furthermore, at a canister pressure of 3PSI in canister 208, 100% of patients had a reverse flow index greater than the baseline value at 150 ms inflation. These data indicate that canister 208 pressure at 3PSI and a holding time of 150 ms are sufficient to achieve reverse venous flow. In some embodiments, canister 208 with a pressure of 2PSI can also be used while increasing the holding time (e.g., 250 ms), which prolongs the duration of the compression phase. Figures 10A-10B The patients in the data provided are adults from the general population. Figure 10A Each point represents a single individual.

[0094] In some embodiments, the RCCD100 is configured (e.g., by selecting a target pressure for canister 208) to achieve a desired bladder filling cycle time, defined by the amount of time required to fully fill and inflate bladder 601. For example, a higher pressure canister 208 may be selected to allow bladder 601 to fill and inflate more quickly. For example, the pressure setting of canister 208 may be in the range of 1 PSI to 5 PSI to achieve the desired bladder filling cycle time within a selected filling time of less than 100 ms (such as about 30 ms). Canister 208 may be configured to continuously maintain the pressure setting or may be configured to cyclically refill to the desired pressure. In some embodiments, the pressure of canister 208 is from 1 PSI to 5 PSI. In a preferred embodiment, the pressure of canister 208 is about 3 PSI. In some embodiments, the selected filling time for refilling canister 208 between inflated bladder 601 periods (e.g., between compression periods) may be less than 250 ms, about 500 ms, about 600 ms, about 1 second, about 3 seconds, about 5 seconds, or from 0.01 seconds to 5 seconds. In some embodiments, the exemplary system is configured to adjust the selected fill time from any of the aforementioned fill times, or to any of the aforementioned fill times.

[0095] In some embodiments, the RCCD 100 is configured to achieve a desired pressure distribution within bladders 301, 405, or 601 disposed within a wearable inflatable wearable 103. The RCCD 100 may be configured to reach a midpoint pressure within a preselected time period after inflation begins. The midpoint pressure may be the pressure between a baseline pressure (e.g., the initial pressure of bladder 601) and a peak pressure. In some embodiments, the midpoint pressure within bladder 601 is 2 PSI at a point approximately 30 ms after bladder 601 begins inflation. However, it may be desirable to reach the midpoint pressure within bladder 601 within a time range of 0.01 to 2 seconds after bladder 601 begins inflation, and then reach the desired peak pressure after reaching the midpoint pressure. In some embodiments, increasing the pressure of canister 208 may reduce the time required to reach the midpoint pressure (e.g., the aforementioned 2 PSI) within bladder 601.

[0096] In one embodiment, the RCCD100 is configured to reach a midpoint pressure within the range of 2 to 3 PSI 30 ms after bladder 301, 405, or 601 begins inflation. In another embodiment, the RCCD100 is configured to reach a midpoint pressure within the range of 2 to 3 PSI 30 ms after bladder 301, 405, or 601 begins inflation. In yet another embodiment, the RCCD100 is configured to reach a midpoint pressure within the range of 2 to 3 PSI 100 ms after bladder 301, 405, or 601 begins inflation. In yet another embodiment, the RCCD100 is configured to reach a midpoint pressure within the range of 2 to 3 PSI 250 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD 100 is configured to reach a midpoint pressure in the range of 2 to 3 PSI 300 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD 100 is configured to reach a midpoint pressure in the range of 2 to 3 PSI 350 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD 100 is configured to reach a midpoint pressure in the range of 2 to 3 PSI 400 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD is configured to reach a midpoint pressure in the range of 2 to 3 PSI 450 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD 100 is configured to reach a midpoint pressure in the range of 2 to 3 PSI 500 ms after bladder 301, 405, or 601 begins inflation. In one embodiment, the RCCD100 is configured to reach a midpoint pressure in the range of 2 to 3 PSI 525 ms after the bladder 301, 405 or 601 begins inflation.

[0097] References are for illustrative purposes and not for limitation. Figure 4A This document provides a schematic diagram illustrating an exemplary inflatable wearable or garment 300. In some embodiments, the inflatable wearable 300 is substantially similar to garment 103. Garment 300 may include an inflatable bladder 301, 405, or 601 housed within a padding portion 302. In some embodiments, the inflatable bladder 301 is approximately 4 inches to approximately 10 inches long (e.g., from the furthest point to the nearest point of the inflatable bladder 301 when worn by a patient) and approximately 5 inches wide at its widest point, tapering to match the shape of a typical human calf. During use of the RCCD 100, the padding portion 302 may be positioned on the calf of the leg and may accommodate additional padding to reduce pressure from the weight of the leg during use. In some embodiments, the padding portion 302 is 5 inches wide to match the physiological width of the widest portion of a typical calf. In some embodiments, the size and construction of garment 300 are configured to completely wrap around the patient's calf. The wearable 300 may include two wings 303 and 304 of fabric extending from either side of the padding portion 302. In some embodiments, wing 304 includes a hook material 305 for attaching to a loop of fabric material on the outside of the wearable 300. In some embodiments, wings 303 and 304 are from 7 inches to 9 inches to allow for a universal fit to typical maximum and minimum calf diameters (e.g., 10 inches to 22 inches).

[0098] In some embodiments, the size of the bladder 301, 405, or 601 is determined based on the desired anatomical region to which compression should be applied (referred to herein as the compression zone). For example, the size of the inflatable bladder 301, 405, or 601 may be configured to extend along the entire posterior portion of the lower leg (full lower leg), from the knee to the widest part of the lower leg (half lower leg), or along a band designed to be positioned between the knee and the widest part of the lower leg (lower leg band). In some embodiments, the size of the bladder 301, 405, or 601 is a factor in peak inflation pressure and / or compression duration. For example, changing the size of the bladder 301, 405, or 601 will result in different pressure distributions applied to the patient and the compression zone while keeping all other operating parameters the same. The size (e.g., area) of the bladder 301, 405, or 601 may be selected to allow the bladder 301, 405, or 601 to deliver compression to the compression zone. The size of the bladder 301, 405, or 601 may range from 5 square inches to 65 square inches. In some embodiments, the area of ​​bladder 301, 405, or 601 is selected based on the region of the gastrocnemius muscle to be compressed (e.g., a compression region). For example, bladder 301, 405, or 601 may be from 45 square inches to 65 square inches for a compression region including most or all of the gastrocnemius muscle (e.g., a full calf bladder). Inflatable bladder 301, 405, or 601 may be from 45 square inches to 15 square inches for a compression region including approximately half of the gastrocnemius muscle (e.g., a half calf bladder). Inflatable bladder 301, 405, or 601 may include from 15 square inches to 3 square inches for a compression region including a small portion of the gastrocnemius muscle (e.g., a calf band bladder).

[0099] In some embodiments, a smaller size (e.g., area) of the bladder 301, 405, or 601 results in a larger peak inflation pressure to produce a desired hemodynamic effect (e.g., generating oscillating flow). For example, when the inflatable bladder 301, 405, or 601 is a full calf bladder with an area of, for example, 55 square inches, the peak inflation pressure may be from 35 mmHg to 70 mmHg to achieve the desired hemodynamic effect. In some embodiments, when the inflatable bladder 301, 405, or 601 is a full calf bladder, the peak inflation pressure is from 45 mmHg to 60 mmHg to achieve the desired hemodynamic effect. In another example, when the inflatable bladder 301, 405, or 601 is a half calf bladder with an area of, for example, 25 square inches, the peak inflation pressure may be from 70 mmHg to 130 mmHg to achieve the desired hemodynamic effect. In some embodiments, when the inflatable bladder 301, 405, or 601 is a semi-calf bladder, the peak inflation pressure is from 80 mmHg to 100 mmHg to achieve the desired hemodynamic effect. As another example, when the inflatable bladder 301, 405, or 601 is a semi-calf bladder with, for example, an area of ​​12.5 square inches, the peak inflation pressure may be from 100 mmHg to 200 mmHg to achieve the desired hemodynamic effect. In some embodiments, when the inflatable bladder 301, 405, or 601 is a calf bladder, the peak inflation pressure is from 150 mmHg to 175 mmHg to achieve the desired hemodynamic effect.

[0100] In some embodiments, smaller-sized bladders 301, 405, or 601 (e.g., having a smaller compressible area) require longer inflation periods for the inflatable bladders 301, 405, or 601 to produce the desired hemodynamic effects (e.g., generating oscillating flow). For example, when bladders 301, 405, or 601 are full-calf bladders with, for example, an area of ​​55 square inches, the inflation period may be 50 ms or less to achieve the desired hemodynamic effect. In another instance, when inflatable bladders 301, 405, or 601 are half-calf bladders with, for example, an area of ​​25 square inches, the inflation period may be from 150 ms to 250 ms to achieve the desired hemodynamic effect. As yet another example, when inflatable bladders 301, 405, or 601 are calf band bladders with, for example, an area of ​​12.5 square inches, the inflation duration may be from 300 ms to 400 ms to achieve the desired hemodynamic effect.

[0101] In some embodiments, the RCCD100 is based on one or more of the following features: the bladder 601 applies pressure to the user's gastrocnemius muscle in an area of ​​less than 60 square inches or about 55 square inches, the bladder 601 has an inflation period of 50 ms or less, and a peak inflation pressure of 35 mmHg to 70 mmHg; the bladder 601 applies pressure to the user's gastrocnemius muscle in an area of ​​less than 30 square inches or about 25 square inches, the bladder 601 has an inflation period of 150 ms to 250 ms, and a peak inflation pressure of 70 mmHg to 130 mmHg; or the bladder 601 applies pressure to the user's gastrocnemius muscle in an area of ​​less than 15 square inches or about 12.5 square inches, the bladder 601 has an inflation period of 300 ms to 400 ms, and a peak inflation pressure of 100 mmHg to 200 mmHg.

[0102] In some embodiments, the RCCD100 is selected based on one or more of the following features: the bladder 601 applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 55 square inches, the bladder 601 has an inflation period of 25 ms to 50 ms, and a peak inflation pressure of 45 mmHg to 60 mmHg; the bladder 601 applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 25 square inches, the bladder 601 has an inflation period of 150 ms to 250 ms, and a peak inflation pressure of 80 mmHg to 100 mmHg; or the bladder 601 applies pressure to the user's gastrocnemius muscle over an area of ​​approximately 12.5 square inches, the bladder 601 has an inflation period of 300 ms to 400 ms, and a peak inflation pressure of 150 mmHg to 175 mmHg.

[0103] The RCCD100 may also include an adapter tube 306 that connects to the inflatable bladder 301 and extends beyond the wear 300, for example, between 2 and 5 inches, and provides a port from the head unit 101 to a pneumatic line for pneumatically connecting the head unit 101 and the wear 300. In some embodiments, the adapter tube 306 is coupled to a line 102 to attach the bladder 301 to the head unit 101. The inner diameter of the adapter tube 306 may be from 3 / 8 inch to 1 inch to allow the rapid airflow required to inflate the bladder 301 to the desired pressure within approximately 400 ms. Figure 4B It provides examples of how to apply wearable device 300 to the lower limbs, and Figure 4CThe illustration shows how the wearable 300 can be fitted and secured to the lower limb. For example, the wearable 300 can be attached to the patient's lower leg such that it is positioned around the widest part of the lower leg. However, the wearable 300 can also be positioned on the lower leg between the knee and the widest part of the lower leg. The wearable 300 should be secured to the patient's lower limb so that it will not inadvertently move or slip off the patient's lower limb. Furthermore, the wearable 300 should be secured around the lower limb such that inflation of the bladder 301 causes pressure to be applied to the patient's lower limb near the bladder 301.

[0104] For illustrative purposes and not for limitation, Figure 5A A schematic diagram of an exemplary pattern of an inflatable bladder 400 within a wearable 300 is provided. The bladder 400 may be similar to the bladder 301, but the bladder 400 may include two inflatable regions 401 positioned on the sides of a padding portion 402 and connected by a narrower region of a bladder conduit 403. A hook-and-loop system 404 may also be used to secure the wearable 300 around the lower limb. In some embodiments, the bladder 400 applies pressure primarily to the sides and back of the lower leg in the region of the bladder conduit 403. This configuration of the bladder 400 reduces compressive pressure on the weight-bearing portion of the lower leg, thereby reducing common clinical complications associated with skin abrasions at weight-bearing sites during hospitalization. In some embodiments, the bladder conduit 403 is 5 inches long, and the larger inflatable region 401 is 3 inches in diameter, positioning the bladder 400 away from the back of the lower leg and, for most users, on the side of the lower leg, without extending onto the tibia of the least active user.

[0105] Figure 5B An iteration is provided where the inflatable bladder 405 extends across the padding portion 406 and into the two fabric wings 411 and 413. The wear 300 may include a hook-and-loop closure 407 to secure the wear 300 around the lower limb. In some embodiments, the inflatable bladder 405 allows compression to be applied around most of the calf to create a maximum compressive surface area. The inflatable bladder 405 may be 4-5 inches high and 10 inches wide to prevent the bladder from extending beyond the calf circumference of the smallest user.

[0106] Figures 6A-6DAnother embodiment of the wearable and pouch configuration is shown. Wearable 600 and pouch 601 may be similar to wearable 300 and pouches 301, 400 and 405, respectively, but may differ in size, shape and position on the patient. Pouches 301, 400, 405 and pouch 601 may be used interchangeably throughout this disclosure. In some embodiments, wearable 600 includes pouch 601 such that pouch 601 is secured within or attached to wearable 600. Wearable 600 may include a first end 603, a second end 605 and a middle portion 607. Pouch 601 may be disposed on or within the middle portion 607. Wearable 600 may be secured around an anatomical region of the patient, such as the lower limb. In some embodiments, wearable 600 is configured to be secured around the patient's upper lower leg. Wearable 600 may be secured around the patient's upper lower leg near the patient's knee. In some embodiments, the wearable 600 is secured between the patient's knee and the widest part of the patient's lower leg, such that the middle portion 607 and the sac 601 contact the patient between the knee and the widest part of the lower leg. See also Figure 6C The wearable device 600 can be placed in the patient's area (*) between the knee and the thickest part (#) of the patient's lower leg. When using the RCCD100, the thickest part of the lower leg may bear the greatest weight; therefore, keeping the compressive forces on the patient's lower limb away from this area reduces the total force felt by the patient during RCCD100 use. This configuration reduces potential skin damage and discomfort, and improves compliance with RCCD100 use. In some embodiments, during RCCD100 use, the venous valve sinus regions inducing reverse and forward flow by the RCCD100 are each located at the saphenofemoral junction 1.

[0107] In some embodiments, the wearable 600 is disposed around the upper part of a patient's lower limb. The wearable 600 can be secured in place by attaching a second end 605 to a first end 603. For example, the second end 605 may be configured to be secured to the first end 603 such that a middle portion 607 and / or a portion of the first end 603 and the second end 605 contact the patient's upper lower leg. The middle portion 607 may include a pouch 601, which may be attached to a head unit 101 (e.g., connected to an air tube 102) via a conduit 602. In some embodiments, the conduit 602 is attached to the wearable 600 such that air flows from the head unit 101 through the conduit 602, into the wearable 600, and into the pouch 601. However, the conduit 602 may be directly attached to the pouch 601. In some embodiments, the pouch 601 includes a protruding corner 609 attached to the conduit 602. The protruding corner 609 may be positioned near the periphery of the pouch 601 and may allow air to flow into and out of the pouch 601 and through the conduit 602. In some embodiments, the convex angle 609 provides patient comfort and makes connection to the air tube easier.

[0108] Figures 21A-21BAn exemplary expansion configuration of the bladder 601 is shown. In one embodiment, during inflation, the bladder 601 begins to bulge outward, thus causing the width of the bladder 601 to be pushed to a smaller size. Since the bladder 601 is attached to the wear 600, as the bladder 601 inflates and its width decreases, the wear 600 tends to tighten around the leg of the user to which it is attached, and thus tightens around the user's leg due to the pull of the bladder 601 on the wear 600.

[0109] Figure 21C-21D Another embodiment of the inflatable bladder used in the RCCD100 is shown. The inflatable bladder 701 is attachable to a wearable 700, which is positioned around a user's leg. The inflatable bladder 701 may include a longitudinal axis 702 and sidewalls 703 arranged radially around the longitudinal axis. In some embodiments, the sidewalls 703 may be made of an elastomeric material. In use, inflation of the bladder 701 causes the sidewalls 703 to expand away from the longitudinal axis 702 and pushes opposite ends of the sidewalls 703 toward each other. This pushing of opposite ends of the sidewalls 703 toward each other causes the wearable 700 to tighten, thereby tightening the wearable 700 around the user's leg. The wearable 700 may include one or more inflatable bladders 701. The bladder 701 may include a flexible outer covering disposed on at least a portion of the bladder 701. In some embodiments, the flexible outer covering is attached to the wearable 700 and configured to shorten and tighten the wearable 700 when the bladder 701 is inflated. The flexible outer covering may include a mesh cover.

[0110] In some embodiments, the air bladder 701 provides direct compression to the surface of the user's legs and causes a reduction in the size (e.g., circumference) of the wearable 700 to increase the feeling of compression on the user's legs. The use of the air bladder 700 allows the compression device to achieve the desired results while requiring significantly less air volume (e.g., compared to a non-constricting device). By requiring less air, the size and weight of the head unit 101 can be reduced, thereby enhancing the portability of the head unit 101. In some embodiments, the RCCD 100 is a wearable device.

[0111] In some embodiments, the RCCD100 is configured to increase venous blood flow in a stationary person by rapidly compressing a part of the body (e.g., the lower limb). For example, the rapid compression provided by the RCCD100 can generate a circulatory flow pattern consisting of forward and reverse venous blood flow in the venous valve sinus region at the junction of the saphenous and femoral veins (e.g., the saphenofemoral junction), which, in addition to providing protection against blood clots and DVT, also mimics the venous blood flow that occurs during active movement (such as walking or foot dorsiflexion).

[0112] In some embodiments, the RCCD100 mimics the dynamics of muscle activity (where muscle contractions occur on a timescale of less than 1 second) and / or the frequency of muscle activity during activity (where a typical human gait results in 1-2 steps per second and an average person may walk between 1,000 and 10,000 steps per day). This can result in hemodynamic effects that maximize oscillatory flow input to the valvular sinus endothelium to support the expression of protective gene programs and the expression of PROX1 and FOXC2. In one embodiment, the RCCD100 inflates the sac 601 to provide optimized compression force and power to generate oscillatory flow in the deep venous valves during each compression cycle, and can cycle rapidly, for example, up to one compression cycle per lower limb every 5-6 seconds. Furthermore, the RCCD100 may allow one compression cycle per lower limb every 5 to 20 seconds. For example, the RCCD100 may provide up to one compression cycle per lower limb every 5 seconds, 6 seconds, 12 seconds, 15 seconds, or 20 seconds. In some embodiments, the RCCD100 is inflated to a target pressure between 1 PSI and 3 PSI, with an inflation time of 10 ms to 300 ms and an inflation cycle every 5-6 seconds. In some embodiments, the RCCD100 alternately provides compression between each of the user's lower limbs. In some embodiments, frequent compression cycles lead to the expression of PROX1 and FOXC2 in the venous valve sinus endothelium.

[0113] The RCCD100 can be configured to inflate the bladder 601 in repetitive compression cycles, such that the bladder 601 repeatedly provides compression to an anatomical region of the patient (e.g., the user's leg). The RCCD100 can provide compression to the patient via the bladder 601 in repetitive compression cycles, each including a compression period. The compression period may include inflating the bladder 601 from a first baseline pressure to a peak pressure and deflating the bladder 601 to a second baseline pressure. The first baseline pressure may be substantially the same as the second baseline pressure. In some embodiments, at least a portion of the repetitive compression cycle induces anterograde and reverse venous flow in the patient's deep veins near the venous valve sinuses. Deep veins may include the common femoral vein, deep femoral vein, deep femoral vein, popliteal vein, peroneal vein, anterior tibial vein, and / or posterior tibial vein above the knee in the thigh / groin region. The anterograde and reverse venous flow within the venous valve sinuses may each have a corresponding peak value, which occurs within approximately 100 ms of each other. Both peak anterograde and peak reverse venous flow may occur during the inflation period of the compression bladder 601. Peak reverse venous flow may have a reverse flow volume index that is greater than that of the reverse flow volume index during the stationary period.

[0114] In some embodiments, inflating the bladder 601 within a repetitive compression cycle includes applying a first compression to the patient and applying a subsequent second compression to the patient in the next compression cycle. The first compression may induce a first reverse flow at the venous valve sinus region, and the subsequent second compression may induce a second reverse flow at the venous valve sinus region. In some embodiments, the first reverse flow has a volume index that is substantially equal to the volume index of the subsequent reverse flow. The first reverse flow has a volume index that is substantially equal to 100% of the volume index of the subsequent reverse flow. However, the first reverse flow may have a volume index between 75% and 100% of the volume index of the subsequent reverse flow. In some embodiments, the first compression induces a first forward flow that occurs substantially simultaneously with the first reverse flow, and the second compression induces a second forward flow that occurs substantially simultaneously with the second reverse flow. Both the first and second forward flows may occur at the cryptofemoral junction. The volume index of the first forward flow may be substantially equal to the volume index of the second forward flow, and the volume index of the first forward flow may be 10% to 300% of the volume index of the first reverse flow. In some embodiments, positive venous flow in the venous valve sinus region may decrease after sac 601 is inflated. In some embodiments, after sac 601 is compressed, the positive flow in the valve sinus does not decrease to less than 10% of the pre-compression flow for a period of longer than 2 seconds. In some embodiments, the positive venous flow may be reduced compared to the positive venous flow induced by a method with the same pressure lasting longer than 300 ms.

[0115] See Figure 7 In some embodiments, each compression period of the repeated compression cycle may include Phase I, Phase II, and Phase III. The duration of each compression period (e.g., from the start of inflation (Phase I) to the end of deflation (Phase III)) may be less than 500 seconds, or in some embodiments less than 300 ms. The duration of the compression period may be from the start of Phase I to the end of Phase III. In some embodiments, Phase I spans the inflation of bladder 601. Phase II spans a holding period during which the pressure within bladder 601 is maintained within a desired range of peak pressure. In some embodiments, the pressure within bladder 601 is constant or substantially constant during the holding period (e.g., at or near peak pressure or some other selected pressure level). In some embodiments, Phase III is demarcated by the termination of the holding period and the end of deflation of bladder 601 (e.g., at or near baseline pressure).

[0116] In one example, during Phase II, the pressure within bladder 601 can be maintained in the range of 1.5 PSI to approximately 2.5 PSI. In some embodiments, Phase II is approximately at valve 210 of RCCD100 ( Figure 2-3Phase II begins when the bladder 601 is opened (as shown in the diagram), and Phase III begins approximately when valve 210 of RCCD 100 is closed. In some embodiments, the pressure curve for Phase II may have a downward trend slope starting from a point at or near the peak pressure at the start of the holding period, which in some embodiments immediately follows the end of the inflation period of bladder 601. In some embodiments, the pressure of bladder 601 decreases by no more than 33% of the peak pressure during the holding period. In some embodiments, the lowest pressure point of the holding period (e.g., the holding end point) decreases by no more than 25%, 20%, 15%, 10%, or 5% of the peak pressure. In some embodiments, during Phase II, air may be released from bladder 601 via valve 210, or bladder 601 may be pumped out to cause bladder 601 to deflate.

[0117] Phase I (inflation period) may have a duration of approximately 30 ms. Phase I may have a duration from approximately 10 ms to approximately 150 ms, from approximately 20 ms to approximately 120 ms, or from approximately 50 ms to approximately 100 ms. Phase II may have a duration of approximately 150 ms. However, Phase II (holding period) may have a duration from approximately 100 ms to approximately 350 ms, from approximately 125 ms to approximately 300 ms, or from approximately 100 ms to approximately 200 ms. Phase III (deflation period) may have a duration of approximately 60 ms. However, Phase III may have a duration from approximately 30 ms to approximately 350 ms, from approximately 50 ms to approximately 300 ms, or from approximately 60 ms to approximately 250 ms. In some embodiments, Phase III has a duration from approximately 60 ms to approximately 210 ms.

[0118] In some embodiments, the hold period has a duration of 150 ms or less. The inventors have discovered that in some embodiments, because reverse venous flow occurs when blood initially passes through the valve, additional hold compression only increases forward flow. This additional forward flow is not optimal because it prolongs the time required between repeated compression cycles.

[0119] See Figure 8A During compression provided by an exemplary RCCD100 with an inflation period of approximately 30 ms and a hold time of approximately 150 ms, ultrasound images of venous flow at the valvular sinuses in healthy human subjects are shown at various time points during the hold time: 0 ms (indicating the start of the hold period), 70 ms, and 140 ms. Figure 8AThe data presented show that the peak of reverse venous flow (red) occurs in the range of 0 ms to 70 ms, indicating that additional compression time greater than, for example, 70 ms does not affect the level of reverse venous flow, and that reverse venous flow only occurs when the initial clump of high-velocity blood passes through the valve leaflets in the venous valve sinus region, thereby causing eddies and oscillating shear flow, leading to the expression of antithrombotic proteins.

[0120] Figures 8B-8C A quantitative example of positive venous flow (black dots) and negative venous flow (white dots) in the venous valve sinus region of a patient is shown, wherein compression is held for 100 ms. Figure 8B ) and 300ms Figure 8C ).For example, Figures 8B-8C It shows that after 30ms of inflation, it remains inflated for 150ms. Figure 8B ) and hold for 250ms after 30ms inflation. Figure 8C The flow volume index (“flow index”) of reverse and forward venous flow over time during the period. This data indicates that a prolonged hold of compression of 100 to 150 ms provided by the RCCD does not significantly increase the magnitude of the flow index of reverse venous flow in the subject.

[0121] Figure 8D-8E Exemplary quantifications of forward flow (black dots) and reverse venous flow (white dots) in the venous valve sinus region of a patient are shown, with compression hold (holding time) of 100 ms. Figure 8D ) and 300ms Figure 8E This data indicates that the extended hold time of the 100ms compression provided by the RCCD100 did not significantly increase the subject's reverse venous flow.

[0122] See Figure 8B Positive venous flow may have a baseline velocity occurring at the peak positive flow volume index prior to balloon 601 inflation. Positive venous flow may have an increased positive flow volume index during balloon 601 inflation and may decrease back to the baseline velocity after balloon 601 inflation. In some embodiments, the peak positive flow volume index of positive venous flow after balloon 601 inflation may be reduced by no more than 10% compared to the peak positive flow volume index or baseline velocity of positive venous flow before balloon 601 inflation. In some embodiments, the peak positive flow volume index of positive venous flow after balloon 601 inflation may be reduced by no more than 10% for a period not exceeding 2 seconds compared to the peak positive flow volume index of positive venous flow before balloon 601 inflation. Positive venous flow after balloon 601 inflation may return to the baseline velocity within a range of approximately 2 seconds to approximately 10 seconds. The peak positive flow volume index after balloon inflation may return to the baseline velocity within less than or equal to 2 seconds.

[0123] See Figure 20A and Figure 20B Each compression phase of a compression cycle may include an inflation phase, a holding phase, and a deflation phase. The inflation phase may include a ramp phase and a pulse phase. In some embodiments, the ramp phase occurs before the pulse phase. See also... Figure 20A The bladder 601 may be configured to slowly inflate during the ramp-up phase (phase A), then rapidly inflate to peak pressure during the pulse phase (phase B), then maintain pressure in a higher pressure range during the hold phase (phase C), and then deflate to baseline pressure during the deflation phase (phase D). In some embodiments, the RCCD 100 utilizes a first air compressor during the ramp-up phase and a second air compressor or a stored air source during the pulse phase.

[0124] In some embodiments, the effect on venous flow is not immediate when the bladder 601 inflates to peak pressure. In some embodiments, inflation of the bladder 601 during the ascending phase (phase A) causes the wearer 600 and the bladder 601 to further abut and compress the skin, closing any gaps between the wearer 600 and the skin. Furthermore, inflation of the bladder 601 during the ascending phase (phase A) also begins to compress the soft tissue of the leg without significantly affecting venous flow. In some embodiments, peak pressure is reached during the pulsating phase (phase B), resulting in the desired hemodynamic response that generates oscillating flow. The benefits of the ascending phase (phase A) include informing the user of the impending compression of their skin during the compression phase. The user is less likely to be startled by sudden, rapid compression. Additionally, the ascending phase (phase A) allows for a shorter duration of rapid pulse compression (e.g., the pulsating phase (phase B)) to reduce discomfort and improve tolerance.

[0125] A ramp-up phase (phase A) may begin at a first baseline pressure and may terminate at a target ramp-up pressure. In some embodiments, the ramp-up phase (phase A) reaches the target ramp-up pressure over a duration ranging from 0.5 seconds to 2 seconds. The target ramp-up pressure may be the pressure within bladder 601 at the end of the ramp-up phase (phase A). A pulse phase (phase B) may be defined by a rapid increase in pressure from the target ramp-up pressure to the peak pressure. In some embodiments, the pulse phase (phase B) may have a duration ranging from 0.03 seconds to 0.05 seconds. The pulse phase (phase B) may be defined by the target ramp-up pressure and the peak pressure of the compression phase. In some embodiments, a hold phase (phase C) follows the pulse phase (phase B) and is defined by bladder 601 that maintains the pressure within a hold pressure range. The hold pressure range may include a pressure as a percentage of the peak pressure. For example, the hold pressure range may include pressure from 80% to 99% of the peak pressure. In some embodiments, the hold pressure range is from the peak pressure to the hold endpoint (e.g., the lowest pressure within the hold pressure range). The duration of the holding period (phase C) can be from the peak pressure to the holding end, and the holding end can be a percentage of the peak pressure. The duration of the holding period (phase C) may depend on the size of the bladder 601. For example, the smaller the size of the bladder 601, the longer the duration of the holding period (phase C). In some embodiments, the pressure within the bladder 601 may dissipate substantially throughout the holding period (phase C). The venting period (phase D) may occur at the end of the holding period (phase D). The venting period (phase D) may begin at the end of the holding pressure range (e.g., the holding end) and may terminate at a second baseline pressure. The second baseline pressure may be substantially equivalent to the first baseline pressure.

[0126] In some embodiments, when the bladder 601 is a full calf bladder, the duration of the holding period (phase C) is less than 50 ms. However, when the bladder 601 is a half calf bladder, the duration of the holding period (phase C) is 150 ms to 250 ms. When the bladder 601 is a calf bladder, the duration of the holding period (phase C) is 300 ms to 400 ms. The deflation period (phase D) may have a duration of 0.2 seconds to 2.5 seconds. The target deflation pressure at the end of the deflation period (phase D) may be a pressure less than the peak pressure and / or the holding pressure range. For example, the target deflation pressure may be 0 mmHg.

[0127] In some embodiments, each of the ramp-up phase (phase A), pulse phase (phase B), and hold phase (phase C) has a target pressure or range that depends on the size of the inflatable bladder 601. For example, the target ramp-up pressure may be selected based on the size of the bladder 601. In some embodiments, the target ramp-up pressure is from 10 mmHg to 15 mmHg when the bladder 601 is a full calf bladder, and from 10 mmHg to 40 mmHg when the bladder 601 is a half calf bladder or a calf band bladder. The peak pressure at the end of the pulse phase may also be selected based on the size of the bladder 601. In some embodiments, the peak pressure is from 35 mmHg to 75 mmHg when the bladder 601 is a full calf bladder, from 70 mmHg to 130 mmHg when the bladder 601 is a half calf bladder, or from 100 mmHg to 200 mmHg when the bladder 601 is a calf band bladder. Furthermore, the hold pressure range during the hold phase may depend on the size of the bladder 601. In some embodiments, when the bladder 601 is a full calf bladder, the pressure range is from 28 mmHg to 52 mmHg; when the bladder 601 is a half calf bladder, the pressure range is from 70 mmHg to 130 mmHg; or when the bladder 601 is a calf bladder, the pressure range is from 100 mmHg to 200 mmHg.

[0128] The bladder 601 can deliver peak inflation pressure during a compression phase to induce circulatory flow in the user's venous valve sinuses at a predetermined frequency during continuous compression cycles. In some embodiments, the predetermined frequency is at least 3 cycles per minute. The inflatable bladder 601 can inflate to a target ramp pressure during a ramp phase and then inflate to peak inflation pressure during a pulse phase following the ramp phase. The pulse phase may have a significantly shorter duration than the ramp phase. The bladder 601 can maintain pressure within a holding pressure range during a hold phase following the pulse phase and can then deflate to baseline or minimum pressure after the hold phase. In some embodiments, the minimum pressure is less than the target ramp pressure. This process can be repeated at a predetermined frequency.

[0129] In some embodiments, the reverse venous flow induced by the RCCD100 has a peak reverse flow volume index that is greater than the peak reverse flow volume index when the patient is stationary and the RCCD100 is not being used. For example, the peak reverse flow volume index of the reverse venous flow induced by compression provided by the RCCD100 may be greater than the peak reverse flow volume index of the reverse flow when the patient is stationary and the RCCD100 is not being used. In some embodiments, the first peak reverse flow volume index induced by the first compression provided by the RCCD100 may be substantially equal to the subsequent peak reverse flow volume index induced by subsequent compression provided by the RCCD100. In some embodiments, the first peak reverse flow volume index may be 50% to 150% of the subsequent peak reverse flow volume index.

[0130] In some embodiments, the RCCD100 induces reverse venous flow simultaneously with antegrade venous flow. For example, a first compression provided by the RCCD100 during a first compression cycle can induce eddies in the venous valve sinus region, causing the first antegrade flow and the first reverse flow provided by the first compression of the first compression cycle to occur substantially simultaneously. Furthermore, a second compression in a subsequent second compression cycle following the first compression cycle, provided by the RCCD100, can induce a second antegrade flow that occurs substantially simultaneously with the second reverse flow. In some embodiments, the peak volume index of the first antegrade flow induced by the RCCD100 is substantially equal to the peak volume index of the second antegrade flow, and the peak volume index of the first antegrade flow is 10%–300% of the peak volume index of the first reverse flow. In some embodiments of the RCCD100, the peak reverse flow volume index of the reverse venous flow in the venous valve sinus region caused by inflation of the bladder 601 ranges from 50% to 150% of the peak antegrade flow volume index of the antegrade venous flow that occurs substantially simultaneously with the reverse venous flow. After the balloon 601 is inflated, the peak positive flow volume index of the RCCD100 in the venous valve sinus region is not less than the peak positive flow volume index in the same venous valve sinus region before the balloon 601 is inflated for a period of more than 2 seconds.

[0131] Figure 8F-8G The mean forward flow is shown. Figure 8F ) and mean reverse venous flow ( Figure 8G The peak flow index of active muscle movement (“active”) was averaged and normalized across multiple subjects. For example, the average flow index values ​​for “active” were normalized so that their average flow index had a value of 1, and the “baseline,” “150ms duration,” and “250ms duration” were each normalized accordingly. The data indicate that although increasing the length of holding the compression from 150ms to 250ms increases positive flow ( Figure 8F(250ms vs. 150ms), but it does not increase reverse venous flow ( Figure 8G (250ms vs. 150ms). In some embodiments, active muscle movement includes dorsiflexion of the patient's foot. For example, see Figure 8D-8E “Active” can refer to active muscle movement, which may include the patient being in a prone position and dorsiflexing their feet to simulate activity.

[0132] In some embodiments, reducing the holding time of the compression provided by the RCCD100 also reduces distal blood stasis. For example, reducing the holding time of the compression from 250 ms to 150 ms results in reduced venous flow below the wearer 600 due to the compression pressure applied to downstream veins obstructing flow. Blood stasis can cause congestion in veins in the area below the compression site. This blood stasis may increase the risk of lower leg clotting in some patients. Reducing blood stasis can decrease the likelihood of distal blood stasis or prevent distal blood stasis altogether.

[0133] In some embodiments, the RCCD100 is configured to provide repetitive compression cycles to induce reverse venous flow at the saphenofemoral junction to alleviate or prevent deep vein thrombosis (DVT). In one embodiment, the RCCD100 is selected based on one or more of the following characteristics: placement of the bladder 601 between the widest part of the patient's lower leg and the knee; the duration of the compression phase, e.g., less than 500 ms, less than 400 ms, and / or less than 300 ms; the inflation pressure of the bladder 601, e.g., 4 PSI or less, 3 PSI or less, 2 PSI or less, and / or 1 PSI or less; and the inflation time of the bladder 601, e.g., 10 ms or less, 50 ms or less. The duration of pressure retention within bladder 601, such as 100ms or less, 150ms or less, and / or 250ms or less; the duration of deflation of bladder 601, such as 30ms or less, 90ms or less, 210ms or less, and / or 250ms or less; and the frequency of compression periods per minute, such as 6 cycles or less per minute, 10 cycles or less per minute, and / or 15 cycles or less per minute.

[0134] In some embodiments, the RCCD100 has an inflation time ranging from 10 ms to 150 ms, a hold time ranging from 100 ms to 350 ms, a deflation time ranging from 30 ms to 350 ms, a cycle frequency ranging from 6 cycles per minute to 20 cycles per minute, and an inflation pressure ranging from 50 mmHg to 250 mmHg.

[0135] In some embodiments, the venous flow velocity within the venous valves returns to the baseline venous flow velocity between compression cycles. For example, venous flow at the venous valve sinuses may have a baseline flow velocity, and the venous flow velocity may return to the baseline flow velocity between each compression period. In some embodiments, the venous flow velocity returns to the baseline flow velocity within less than 10 seconds after each compression period. However, the venous flow velocity may return to the baseline flow velocity within less than 20 seconds, less than 15 seconds, less than 8 seconds, less than 5 seconds, or less than 3 seconds after each compression period.

[0136] As described above, the RCCD100 is configured to generate rapid compression pulses in the patient's / wearer's lower limb during repetitive compression cycles. For example, the RCCD100 may generate peak pressures ranging from 2 PSI to 3 PSI. However, the RCCD100 may generate peak pressures ranging from 1 PSI to 10 PSI, from 2 PSI to 8 PSI, or from 3 PSI to 7 PSI. In some embodiments, the pressure in the sac 301 of the RCCD100 does not exceed approximately 3 PSI due to discomfort to the wearer and the effect of blood drainage from the site of pressure application, which may increase the residence time required to restore venous pressure.

[0137] The RCCD100 may also have a baseline (minimum) pressure at which the pressure of the bladder 301 is maintained before inflation. In some embodiments, the peak pressure achieved in the bladder 301 is based on the baseline (minimum) pressure. For example, the peak pressure may be at least 15 mmHg greater than the baseline pressure. However, the peak pressure may be at least 5 mmHg, 15 mmHg, 25 mmHg, 50 mmHg, 100 mmHg, 150 mmHg, or 200 mmHg greater than the baseline pressure. The baseline pressure may range from 0 mmHg to 250 mmHg, from 50 mmHg to 200 mmHg, or from 75 mmHg to 150 mmHg. In some embodiments, the baseline pressure is 10 mmHg or less. For example, the baseline pressure may be approximately 5 mmHg.

[0138] The baseline pressure can be the maximum pressure within the sac 301 that does not reduce venous flow. For example, when pressure is applied by the sac 301, the baseline pressure can be as high as possible without causing a reduction in venous flow in the saphenofemoral junction venous valve sinus region.

[0139] The RCCD100 can achieve the desired hemodynamic effect of generating oscillatory flow using a predefined inflation rate of the balloon 601. For example, the RCCD100 can be configured to increase the pressure of the balloon 601 to 10 mmHg above the baseline pressure in 0.5 seconds or less. For example, the RCCD100 can be configured to inflate the balloon 601 to a desired pressure ranging from 30 ms to 60 ms. In some embodiments, the RCCD100 is configured to increase the pressure of the balloon 601 to approximately 65 mmHg above the baseline pressure in less than 0.2 seconds or less than 0.3 seconds. In some embodiments, the RCCD100 is configured to increase the pressure of the balloon 601 to approximately 100 mmHg above the baseline pressure in less than 0.2 seconds or 0.3 seconds.

[0140] In some embodiments, the RCCD100 is configured for passive deflation of the bladder. For example, the bladder 601 may be configured to deflate and release into the atmosphere. In some embodiments, the bladder 601 is configured to immediately depressurize from peak inflation pressure to baseline pressure within five seconds or less (preferably within 0.5 seconds). For example, the bladder 601 may be configured to deflate in the range of 60 ms to 210 ms. In some embodiments, the bladder 601 is configured to deflate within approximately 60 ms. The longest deflation time for the bladder 601 may be from 1 second to 3 seconds. In some embodiments, the deflation time is characterized by the time between the peak pressure and the pressure at which the bladder 601 no longer affects venous flow. This pressure may be the baseline pressure or may be greater than the baseline pressure. In some embodiments, the deflation time may be characterized by the time between the peak pressure and half the difference between the peak pressure and the baseline pressure.

[0141] In some embodiments, the RCCD 100 is configured to rapidly inflate the bladder 610 from a baseline pressure to a desired peak pressure. For example, the RCCD 100 may be configured to inflate the bladder 601 from a baseline pressure of, for example, 0.2 PSI to a peak pressure of, for example, 1.5 PSI within approximately 30 ms. The RCCD 100 may be configured to inflate the bladder 601 from a baseline pressure to a peak pressure within 150 ms or less, 120 ms or less, 90 ms or less, 60 ms or less, or less than or equal to 30 ms. In a preferred embodiment, the RCCD 100 may be configured to inflate the bladder 601 from a baseline pressure to a peak pressure within approximately 30 ms. In some embodiments, the inflation rate of the bladder 601 is based on the pressurization of the air tank. For example, the higher the pressure of the air tank, the faster the bladder 601 fills with air and thus inflates. In some embodiments, the bladder 601 is configured to rapidly inflate from a non-zero baseline pressure (such as 5 mmHg) to a peak pressure. However, the bladder 601 can be configured to rapidly inflate to the desired peak pressure from a non-zero baseline pressure greater than 0.1 PSI, about 0.2 PSI or greater, about 0.5 PSI or greater, or about 1 PSI or greater.

[0142] See Figure 11A The inflation times of the 601 capsule were compared between 30 ms and 488 ms. Figure 11A The graph shows the time required for bladder 601 to reach peak pressure with inflation times of 30 ms and 488 ms. The 488 ms inflation period results in bladder 601 reaching peak pressure significantly after the 30 ms inflation period. Figure 11B and Figure 11C This shows the average positive venous flow (NPV) across multiple subjects during each subject's activity (“active”) and normalized to the peak flow index. Figure 11B ) and mean reverse venous flow ( Figure 11C Data shows that extending the inflation time (e.g., 488 ms) increases positive flow ( Figure 11B 488ms inflation versus 30ms inflation) but reduces reverse venous flow in the valvular sinus region ( Figure 11C (488ms inflation vs. 30ms inflation). This indicates that shorter inflation times (such as 30ms) result in better reverse venous flow in the venous valve sinus region compared to longer inflation times (such as 488ms).

[0143] As indicated above, the compression period and the time between deflation and subsequent inflation of bladder 601 (e.g., dwell time) can comprise the entire compression cycle. For example, a compression cycle may include a compression period followed by a dwell time. In some embodiments, the duration of a compression cycle may be the elapsed time from the peak pressure of one inflation to the peak inflation of the next bladder inflation. A compression cycle may include a dwell time between compression periods. In some embodiments, the dwell time between compression periods may be 20 seconds or less. For example, each compression period may have a duration of less than 500 ms, and each compression cycle may have a duration of, for example, approximately 6 seconds, resulting in a dwell time, for example, from approximately 5.5 seconds to approximately 6 seconds. In some embodiments, the dwell time is less than 1 second.

[0144] In some embodiments, the desired physiological effect is achieved by reducing the residence time and the presence of the ramp phase. For example, a desired hemodynamic effect (e.g., generating oscillatory flow) can be achieved by reducing the residence time and adding or increasing the ramp phase. In some embodiments, the desired hemodynamic effect is achieved by increasing the residence time and reducing or eliminating the ramp phase. The residence time may be the time between the end of the deflation phase (phase D) of the first compression cycle and the beginning of the ramp phase (phase A) of the subsequent second compression cycle. In some embodiments, the residence time is the duration for which the pressure within the sac 601 is at baseline pressure or at minimum pressure.

[0145] In some embodiments, the duration of a compression cycle is 5 seconds or less. However, the time interval between the start of inflation of bladder 601 from one compression period to the start of inflation of bladder 601 in a subsequent compression period can range from 6 seconds to 20 seconds. In some embodiments, the number of compression cycles per minute can be based on the duration of each compression cycle. For example, the duration of a compression cycle can range from 6 seconds to 20 seconds, resulting in 10 compression cycles per minute (6-second intervals of compression cycles) to 3 compression cycles per minute (20-second intervals of compression cycles).

[0146] In some embodiments, the duration of the compression cycle is 10 seconds or less. In practice, a compression cycle with a duration of approximately 5 seconds results in 12 compression cycles per minute. For example, a 5-second compression cycle results in compression periods occurring every 5 seconds. The RCCD100 can be configured to provide compression cycles at a frequency ranging from 6 cycles per minute to 20 cycles per minute. In other words, the RCCD100 can be configured to provide cycles ranging from every 10 seconds (5 seconds per leg alternation) to every 3 seconds (1.5 seconds per leg alternation). In some embodiments, the RCCD100 can be configured to deliver compression cycles at a frequency of at least 3 compression cycles per minute, resulting in compression cycles with a duration of 20 seconds or less. However, the RCCD100 can be configured to deliver compression cycles at a frequency of at least 5 cycles per minute, at least 7 cycles per minute, or at least 10 cycles per minute.

[0147] In some embodiments, the RCCD100 is configured to deliver substantially equivalent hemodynamic effects during each compression phase of a repetitive compression cycle. For example, a first compression phase may produce substantially the same hemodynamic effect as a second subsequent compression phase. The frequency, peak inflation pressure, and duration of the compression phase can be selected to stimulate endothelial FOXC2 expression in the endothelium of the valvular sinus.

[0148] For illustrative purposes and not for limitation, Figure 12A Exemplary data from 2D color Doppler experiments are provided, illustrating blood flow patterns generated at the junction of the saphenous and femoral veins (e.g., the saphenofemoral junction) compared to commercially available devices 1 and 2 during use of the RCCD100 in healthy human volunteers. Furthermore, Table 1 shows a comparison of the RCCD100 with commercially available devices 1, 2, and 3. The RCCD100 can be placed on the upper calf (e.g., between the widest part of the calf and the knee), while commercially available devices 1, 2, and 3 are placed on the calf, such as between the widest part of the calf or between the foot and the widest part of the calf.

[0149]

[0150] Table 1: Comparison of RCCD with commercially available devices 1, 2 and 3

[0151] For testing purposes, ultrasound imaging of the saphenofemoral junction using the RCCD100 was compared with that of commercially available devices. The saphenofemoral junction is the region of the deep venous system in the groin, a typical area for clinically significant VTE blood clot formation. The images show blood flow captured during compression events of each device, and reverse venous flow was detected by color Doppler detection distinguishing between flow directions. Reverse venous flow within the venous valve sinuses (white circles) indicates oscillating flow periods. This reverse venous flow pattern was observed during the use of the aforementioned RCCD100 (indicated by white stars).

[0152] Figure 12B Quantifications are provided of the percentage of studied subjects observed with reverse venous flow in the valvular sinus region during use of each of the following devices: RCCD100, commercially available device 1, commercially available device 2, and commercially available device 3. In this experiment, 100% of subjects had reverse venous flow when using the RCCD100 described herein, compared to less than 100% of subjects using the other commercially available devices: commercially available device 1, commercially available device 2, and commercially available device 3. These results indicate that compression of the lower limb with the RCCD100 is sufficient to generate oscillatory flow in the valvular sinus region at the saphenofemoral junction, which substantially replicates active muscle movement in 100% of the tested subjects, while commercially available device 1 generated oscillatory flow in approximately 11% of the tested subjects, commercially available device 2 generated oscillatory flow in 0% of the tested subjects, and commercially available device 3 generated oscillatory flow in approximately 75% of the tested subjects.

[0153] Figure 13A and Figure 13B This shows the results of using RCCD100 ( Figure 13A ) and commercially available device 1 ( Figure 13B The exemplary velocity flow index traces of reverse and forward venous flow from the venous valve sinus region during compression are provided. (*) Indicated by RCCD100 ( Figure 13A ) and commercially available device 1 ( Figure 13B The device compression start time is provided. In addition to the rapid recovery of the baseline flow level, Figure 13A The traces also show rapid forward and reverse venous flow caused by compression provided by the RCCD100. Figure 13BThe trace shown in the commercially available device 1 indicates a prolonged increase in venous flow after compression, followed by a period of decreased baseline venous flow due to the reduction in venous flow. This is a common phenomenon with commercially available compression devices, where venous pressure needs to return to pre-compression levels after compression before additional compression can be applied to produce a similar increase in flow. Data from the RCCD100 test indicates that brief compression applied to a patient does not produce a significant period of decreased venous pressure.

[0154] Furthermore, these findings demonstrate why commercially available devices with extended compression periods require a 30-60 second dwell time between compression cycles to allow venous pressure to return to normal. Without venous pressure restoration, subsequent compression events will not stimulate the same hemodynamic effects, thus limiting the benefits of the commercially available devices and the ability of compression to induce the valvular sinus oscillatory flow required to stimulate antithrombotic gene programs. For example, as cited in U.S. Patent No. 5,588,955, another commercially available device (e.g., commercially available device 3) specifies a minimum of 30 seconds between compression events in each lower limb to maintain hemodynamic efficacy.

[0155] Studies using Doppler ultrasound in the deep veins of the groin (typical sites of proximal DVT formation, such as the cephalic femoral junction or common femoral valve) have shown that commercially available devices (such as commercially available devices 1 and 2) may not generate valvular sinus oscillatory flow at these valves because many tested subjects had slower compression rates.

[0156] Figure 14 The commercially available device 3 was shown to generate oscillatory flow in some subjects during initial compression imaging. The device 3 inflates from baseline pressure to peak pressure within 0.5 to 1 second and provides prolonged compression, which does not prolong or enhance the oscillatory flow signal. Furthermore, the device 3's inflation cycle is once per minute per leg to allow venous pressure to return to normal levels, ensuring that subsequent compressions will induce hemodynamic effects, which limits the amount of total oscillatory flow generated over time.

[0157] Figure 15AThis demonstrates how the RCCD100 cycles rapidly, generating oscillatory flow at the valvular sinuses during each compression event in a single lower limb at 10-second intervals. In some embodiments, this is six times the rate of oscillatory flow generation of a commercially available device with a typical compression frequency (such as commercially available device 3). Active muscle activity generates oscillatory flow within the venous valvular sinuses; therefore, to replicate the number of oscillatory flow pulses generated by 15 minutes of walking (assuming 1.5 steps per second during the walk), it would require 11.25 hours of continuous use with a typical compression system, compared to only 1.875 hours with the RCCD100. Given the well-known poor patient compliance with mechanical compression devices, this suggests that even at the expected level of compliance, a system that generates maximum oscillatory flow over a shorter time period is more likely to be clinically effective.

[0158] See Figure 15B The graph shows that the amount of oscillating flow did not change significantly across the three compression cycles. For example, Figure 15B The graphs include positive flow (black dots) and negative flow (white dots) in the venous valvular sinuses during three consecutive compressions. The data show that baseline flow did not decrease after compression, and each compression provided by the RCCD100 generated robust negative venous flow in the valvular sinuses. This consistent finding indicates that the rapid cyclic compression provided by the RCCD100 does not reduce hemodynamic efficiency even at inflation rates up to 6 times faster than other commercially available devices, such as the commercially available device 3.

[0159] also, Figures 15A-15B The data provided shows no increase in flow during deflation, a measure of blood retention. When other commercially available devices deflate, flow briefly increases, followed by a period of low flow as the vein needs to be refilled. The RCCD100 limits or prevents these retention and refilling effects.

[0160] Human lymphovascular endothelial cells (LECs) have previously been used as a model for oscillatory shear stress-induced FOXC2 activation. FOXC2 is a transcription factor responsible for an antithrombotic gene program expressed in the endothelium of venous valvular sinuses in healthy individuals. These studies used a reverse flow frequency of 1 / s to activate FOXC2 expression in human LECs and demonstrated that the reverse flow pattern was sufficient to activate FOXC2. Figure 16Experimental results testing the RCCD100 method are shown, in which human LECs were cultured for 24 hours under static, simulated immobile, or flowing conditions. For cells cultured under flowing conditions, the flow was reversed at a frequency of 0.1 / s for less than 1 s to simulate the recirculating flow induced by RCCD100 and compared to a flow reversal frequency of 1 / s (the current model frequency at which FOXC2 expression is induced by flow). A frequency of 0.1 / s (such as the frequency used for RCCD100 in some embodiments) increased FOXC2 expression compared to static (e.g., immobile) conditions, which did not induce reverse flow across cells. Furthermore, the degree of FOXC2 stimulation did not differ significantly between the 1 / s and 0.1 / s frequencies. This demonstrates that, in some embodiments, the compression frequency provided by RCCD100 is sufficient to stimulate FOXC2 activation, a pathogenic molecular event that activates antithrombotic gene programs and prevents DVT.

[0161] The RCCD100 can generate reverse venous flow in the valvular sinuses, which is produced by “vortices” that appear as initial pulses of blood flowing through the valvular leaflets generated by rapid balloon inflation. However, in some embodiments, increasing the duration of compression is not expected to significantly contribute to this effect. In one embodiment, the RCCD100 does not maintain compression for several seconds after inflation. For example, the RCCD100 may maintain compression for 500 ms or less, 400 ms or less, 300 ms or less, 200 ms or less, or 100 ms or less. Some embodiments provide the RCCD100 with the ability to generate a maximum number of oscillating flow pulses through pneumatic efficiency to allow for rapid refilling of the air canister to allow for an inflation event every 3 seconds. In some embodiments, the RCCD100 provides the ability to optimize compression force and compression area to prevent venous pressure depletion, resulting in a consistent hemodynamic effect on blood flow from rapid circulation, which, according to studies of commercially available devices, is a limiting factor in their circulation rate.

[0162] In some embodiments, the RCCD100 is configured to generate eddies (e.g., eddies as described above) located near the venous valve sinuses. In one instance, the eddies are located slightly downstream of the valve toward the heart. In some embodiments, the eddies may be positioned between the valve leaflets and the vessel wall downstream of the valve. In some embodiments, the RCCD100 is configured to generate eddies extending downstream (proximal) from the valve over a length equivalent to approximately two valve leaflet dimensions. In some embodiments, the eddies generated near the venous valve occur where the valve leaflets abut against the vein wall when the valve is open. Although the effects and eddies caused by the RCCD100 are shown at the valves of the femoral and popliteal veins, the effects and eddies caused by the RCCD100 may also be shown at other deep vein valves. In some embodiments, the use of the RCCD100 results in the presence of eddies at venous valves positioned between the wearer's knee and hip.

[0163] In one embodiment of the systems, apparatus, and methods disclosed herein, the flow pulses are generated with a cycle time of 3 to 10 seconds. However, flow pulses may be generated with cycle times ranging from 3 to 20 seconds, from 6 to 15 seconds, or from 8 to 12 seconds. Rapid flow pulses allow oscillatory flow stimulation of the antithrombotic gene program to occur, for example, once every 10 seconds per lower limb. In some embodiments, the RCCD100 is configured to allow oscillatory flow stimulation of the antithrombotic gene program to occur at greater than 10 times per minute, greater than 5 times per minute, or greater than 3 times per minute. Molecular studies have shown that frequent flow oscillations are a physical stimulus to the activation of PROX1 and FOXC2 in human endothelial cells, and that those transcription factors activate the antithrombotic program that prevents VTE.

[0164] Figures 17A-17C This demonstrates how venous flow at the deep vein valves is affected during active calf flexion or during RCCD compression, compared to baseline flow during immobility. Figure 17D-17F The mean positive venous flow index (black dots) and negative venous flow index (white dots) are shown for individual subjects during baseline immobile flow, during active lower leg flexion (* indicates the time of movement), and during RCCD compression (* indicates the time of compression). Figure 17G-17H The average peak positive index (API) across multiple subjects is shown. Figure 17G ) and peak reverse flow index ( Figure 17H ). Figure 17IAs shown, compression increased the reverse flow index in all tested RCCD subjects compared to immobility, with each subject shown as a pair of black dots corresponding to the flow response for each treatment. Data showed that compression with a duration of 30 ms inflation, 150 ms hold, and 60 ms deflation provided by the RCCD100 produced significantly more reverse venous flow than during immobility and during activity (such as leg flexion). Furthermore, data showed that compression with a duration of 30 ms inflation, 150 ms hold, and 60 ms deflation provided by the RCCD100 produced significantly more forward flow than during immobility, and less forward flow than during activity (such as leg flexion). However, as described herein, optimizing reverse flow provides a greater antithrombotic effect compared to optimizing forward flow, particularly in the valvular sinus region.

[0165] Figure 18 A table is provided showing a comparison of the number of compression events experienced by a user under the assumption of 30% compliance. Compliance is reported as a percentage, indicating the time a patient uses the device relative to the time required by the patient's treatment regimen. For example, a healthcare professional might prescribe a treatment regimen for a patient to use the RCCD100 for a predetermined amount of time (e.g., 3 hours) within a given time period (e.g., daily). In this example, a patient using the RCCD100 for 1 hour would be 33% compliant. The low circulation time provided by the RCCD100 (e.g., 5-6 cycles per minute) allows for a higher number of compressions to generate an increased number of flow volume pulses, which provides an activation signal for molecular processes and physically flushes the valvular sinuses, thus providing physical and biochemical protection. For example, under a typical 24-hour DVT prevention treatment regimen with 30% compliance, the RCCD100 provides approximately 5184 compressions per day, compared to only 432 compressions provided by commercially available device 1 and only 864 compressions provided by commercially available devices 2 and 3. Therefore, compared to commercially available device 1 or commercially available device 2, users operating with 30% compliance will need to use RCCD100 for a shorter duration to obtain the same amount of compression and benefits, such as generating antithrombotic pathways for reverse flow.

[0166] Figures 19A-19B Compliance tracking is shown when using RCCD100. Figure 19A The diagram shows graphs of the average system pressure readings provided by sensor 221 during the inflation of bladder 601 by RCCD 100 when the sleeve is fully hooked and applied to the patient's leg (compliant), hooked but not applied to the patient's leg (non-compliant), and when the sleeve is not properly attached to head unit 101 causing air leakage (sleeve not connected). Under these various conditions, the pressure monitored by sensor 221 changes during the Phase II hold period of RCCD 100.

[0167] Figure 19B A normalized curve is shown showing the pressure decay from the peak pressure provided by the RCCD100 to the end of the Phase II hold period. During both compliant and non-compliant use, the peak pressure is reached at 60 ms, 30 ms after the initial 30 ms inflation period. The pressure decay during Phase II is consistent and readily matches a Phase I exponential decay curve. The RCCD100 may include a processor that analyzes these curves and detects patient compliance and system leaks to alert healthcare personnel using alarms and indicators. The RCCD100 may also allow for prescription use. For example, if it is determined that 10,000 compressions per day are sufficient to achieve maximum DVT protection, the RCCD100 may count 10,000 compliant compressions over a 24-hour window and cease activity upon reaching that count. This reduces the time patients need to use and / or interact with the RCCD100, allowing for reduced sleep disruption and contributing to compliance, which will be rewarded with goal achievement and device removal.

[0168] In some embodiments, the RCCD100 may be configured to monitor compliance. For example, the RCCD100 may determine the pressure of the bladder 601 during repeated compression periods and compare the pressure of the bladder 601 with the pressure of a non-compliant bladder. The non-compliant bladder pressure may be the pressure of the bladder when it is not applied to an anatomical area or during an air leak. The RCCD100 may be configured to alert a patient or user (or another person, such as a physician or caregiver) if the pressure of the bladder 601 is less than or equal to the non-compliant bladder pressure within a predetermined amount of non-compliant inflation during a predetermined compliance period. In some embodiments, the predetermined compliance period is twenty-four hours. However, the predetermined time may be 1 hour, 6 hours, 12 hours, 24 hours, 36 hours, 48 ​​hours, 72 hours, 1 hour or less, less than 24 hours or greater than 24 hours. In some embodiments, the alert or alarm may indicate compliance with the patient's treatment protocol for using the RCCD101. In one embodiment, compliance with the treatment protocol indicates that the patient does not need to use the RCCD100 during the predetermined compliance period (such as 24 hours). In some embodiments, adherence to a treatment regimen includes meeting predetermined thresholds within a predetermined time period to indicate that the threat of DVT has been prevented or mitigated.

[0169] Unless otherwise indicated, the images from the study provided in this article (e.g., such as...) Figure 8A and 15AThe images are taken at the femoral junction or the common trigeminal junction. These are the usual sites of venous valve imaging. 2D color Doppler imaging is used to analyze venous flow via ultrasound to obtain the direction of flow and the velocity at the site of the venous valve. Subjects were between 25 and 75 years old, had no history of venous disease, and were evenly matched in male and female ratios. The veins were examined in cross-section, and the valvular leaflets and turbulence in the venous sinuses were identified by observing them using dual ultrasound examination. Venous flow was measured using 2D color Doppler with the volunteers prone, either still, during active dorsiflexion of the foot, or during compression cycles of a compression device. Ultrasound was performed using a Mindray M9 portable ultrasound machine with an L12-4s linear array ultrasound transducer or a Phillips EPIC 7G with an L12-3 transducer.

[0170] In some cases, clots from deep vein thrombosis (DVT) obstruct flow in local veins, causing ductal dilation (usually in the form of varicose veins) and physically damaging the valves at the site of clot formation and other local valves in contact with the clot. Even after the DVT resolves, one or more of these valves may remain damaged and may be unable to prevent backflow for a prolonged period. This can lead to chronic pain, swelling, and redness in the affected limb, clinically known as postthrombotic syndrome or postphlebitis syndrome. RCCD100 can be configured to repair damaged venous valves. For example, RCCD100 can be configured to induce oscillatory flow based on the compression circulation generated by RCCD100. RCCD100 is configured to generate recirculation or oscillatory flow in the venous valvular sinuses, which is known to stimulate local expression of FOXC2 and PROX1. Both FOXC2 and PROX1 are responsible for local antithrombotic gene programs and are essential for valve formation and maintenance. Loss of FOXC2 and PROX1 leads to valve degeneration. Therefore, the loss of local flow conditions following DVT clot formation disrupts the natural endothelial expression of FOXC2 and PROX1 in the damaged valve endothelium, leading to irreparable damage and the formation of a defect-free valve. In some embodiments, the rapid compression provided by the repetitive compression cycles of the RCCD100 maximizes the number of recirculatory flow events in the user's body, thereby stimulating the recovery of FOXC2 and PROX1 in the damaged valve to drive valve recovery and symptom resolution.

[0171] In some embodiments, the use of RCCD100 repairs damaged venous valves in the subject. In practice, subjects can be selected from individuals with damaged venous valves. A bladder 601 can be applied to the subject between the knee and the midpoint of the subject's gastrocnemius muscle. The bladder 601 can be inflatable to apply pressure to a portion of the subject's gastrocnemius muscle. In some embodiments, the bladder 601 is inflated to deliver a peak inflation pressure of compressed air at a compression period and frequency to induce circulatory flow in the subject's venous valvular sinuses at a frequency of at least 3 cycles per minute during continuous compression cycles of the bladder 601. The bladder 601 can be inflated to a target ramp pressure during the ramp phase and then rapidly inflated to the peak inflation pressure during the pulse phase. During a hold period following the pulse phase, the pressure in the bladder 601 can be maintained within a hold pressure range. The pressure within the bladder 601 can be deflated to a minimum pressure after the hold period. In some embodiments, the minimum pressure is less than the target ramp pressure. The frequency, peak inflation pressure, and compression period can be selected to stimulate endothelial FOXC2 expression in the endothelium of the valvular sinuses.

[0172] The disclosed subject matter provides a rapidly circulating device for mitigating or preventing venous thromboembolism (DVT) to generate venous valve oscillatory flow at a physiological rate in the leg veins of a stationary person. In one embodiment, these devices are configured to increase oscillatory flow in the venous valve sinuses and adjacent valve leaflets to drive the expression of FOXC2 and PROX1 transcription factors. In some exemplary embodiments, the device includes an air pump controller pneumatically connected to an inflatable wearable device (referred to herein as a wearable) that rapidly inflates and deflates to compress the soft tissue of the leg to generate oscillatory flow at a high frequency in the valve sinuses. The rapid compression induced by the device generates venous valve oscillatory flow at various points in the leg veins of a stationary person to maintain the natural DVT prevention mechanism associated with muscle activity, and rapidly circulates at a rate that closely mimics the oscillatory flow periods occurring during walking.

[0173] In some embodiments, the inflatable wearable wraps around the user's calf, and the inflatable bladder is positioned on the posterior portion of the calf to effectively compress the soft tissue of the calf. In some exemplary embodiments, the area of ​​the bladder ranges from 6 to 60 square inches to provide sufficient compression area to generate blood flow pulses, which produce oscillating flow in the valvular sinuses of the deep veins during compression. In some embodiments, the compression area may be constituted by one or more bladders that inflate simultaneously or rapidly and sequentially. In some embodiments, the inflatable wearable is positioned around the user's leg such that a large portion of the inflatable bladder is positioned between the user's knee and the midpoint of the user's gastrocnemius muscle. The inflatable bladder may be configured to have different sizes based on the amount of calf compression the bladder is intended to provide. For example, the inflatable bladder may have sizes for the entire calf (e.g., 11” x 5”), half calf (e.g., 5” x 5”), or calf band (2.5” x 5”).

[0174] In some embodiments, the head unit further includes an air compressor and a compressed air tank, wherein the air compressor is adapted to fill the compressed air tank with compressed air to a predetermined pressure, and the compressed air tank is adapted to release compressed air to the inflatable bladder. In some embodiments, the compressed air inflates the inflatable bladder to a desired pressure in 0.5 seconds or less. In some embodiments, the compressed air inflates the inflatable bladder to a desired pressure within 0.4 seconds, 0.3 seconds, 0.2 seconds, or 0.1 seconds. In some embodiments, the head unit further includes a solenoid valve adapted to regulate the release of compressed air from the compressed air tank to the inflatable bladder. The head unit may include at least one pressure sensor adapted to monitor the pressure of the compressed air tank and restore the pressure to a predetermined level; and at least one pressure relief valve adapted to monitor the pressure of the inflatable bladder and prevent overinflation.

[0175] In some embodiments, the head unit compressed air canister is at least twice the volume of the inflatable bladder, allowing the canister to be rapidly refilled to the target pressure between inflations to allow for rapid cycling. In some embodiments, the solenoid valve opens for 50-300 milliseconds and then immediately closes to allow rapid bladder inflation and allows the bladder to depressurize rapidly upon closure. In some embodiments, the air canister pressure is set to 1.5-3 times the target pressure of the inflatable bladder. In some embodiments, setting the air canister pressure to 1.5 to 3 times the target pressure of the inflatable bladder allows the bladder to inflate rapidly to a pressure that generates sufficient compressive force on the surface area of ​​the bladder to stimulate rapid blood flow.

[0176] The inflatable bladder may be rectangular in shape and taper to match the contour of an exemplary calf to improve contact between the bladder and the calf. In some embodiments, the inflatable bladder wraps around the calf to apply pressure to the sides of the calf. The size and shape of the inflatable bladder may be determined based on the desired amount of calf coverage. For example, the size and shape of the inflatable bladder may be configured to completely cover the back of the calf, cover half of the back of the calf, or serve as a covering band on the calf.

[0177] Embodiments of this disclosure relate to a deep vein thrombosis mitigation device comprising a compression bladder connected via a catheter to an air compressor assembly, the compression bladder being configured to be worn by a patient at an anatomical region defined by the widest portion of the patient's knee and lower leg; and an air compressor assembly configured to deliver air via the catheter to inflate the compression bladder in repetitive compression cycles including compression periods. During each repetitive compression cycle, the pressure in the compression bladder increases from a baseline pressure to a peak pressure and decreases from the peak pressure to a baseline pressure within a predetermined time period referred to herein as the compression period. In some embodiments, the compression period is less than 500 milliseconds (ms). In some embodiments, the compression period is less than 300 ms.

[0178] In some embodiments, the compression period includes an inflation period, a holding period, and a deflation period. The inflation period may be defined as the period from the initial baseline pressure to the peak pressure. The holding period may be defined as the period from the peak inflation pressure to a holding endpoint before the pressure in the bladder returns to the baseline pressure. The deflation period may be defined as the period from the holding endpoint until the pressure in the bladder reaches a second baseline. It should be understood that the initial baseline pressure and the second baseline pressure may be substantially equivalent pressures. The inflation period may have a duration of approximately 10 ms to approximately 150 ms. The inflation period may be less than 250 ms. The holding period may have a duration of approximately 100 ms to approximately 350 ms. The holding period may be less than 500 ms. The deflation period may have a duration of approximately 30 ms to approximately 350 ms. The deflation period may have a duration of less than 500 ms. In some embodiments, the compression period also includes a ramp-up period and a pulse period. The inflation period may include a ramp-up period and a pulse period. The ramp-up period may have a longer duration than the holding period. In some embodiments, as described in further detail below, the compression period includes an ascent period, a pulse period, a holding period, and a deflation period.

[0179] In some embodiments, the peak pressure is from about 1 PSI to about 3 PSI. The compression bladder can maintain the pressure above the minimum pressure for about 150 ms.

[0180] In some embodiments, the compression bladder includes a convex angle coupled to the catheter, the convex angle being positioned close to the periphery of the compression bladder.

[0181] In some embodiments, the compression bladder is configured to be positioned on the patient's upper lower leg near the patient's knee.

[0182] In some embodiments, at least a portion of the repetitive compression cycle is configured to induce both forward and reverse venous flow at the venous valve sinus. The venous valve sinus may be located in a deep vein near the patient's groin. The forward and reverse venous flow within the venous valve sinus may each have a corresponding peak, which occurs within approximately 100 milliseconds of each other. Both peak forward and peak reverse venous flow may occur during the inflation of the compression balloon.

[0183] In some embodiments, venous flow has a baseline rate that occurs before balloon inflation. After balloon inflation, the venous flow volume index returns to the baseline rate within approximately 2 to approximately 10 seconds. The venous flow volume index returns to the baseline rate within less than or equal to 2 seconds after balloon inflation.

[0184] In some embodiments, the peak reverse velocity of the reverse venous flow is greater than the peak reverse velocity when the patient is stationary.

[0185] In some embodiments, the duration of the repetitive compression cycle is from 3 seconds to 20 seconds, and the duration of the repetitive compression cycle is the time from the peak inflation pressure of one compression period of the repetitive compression cycle to the peak inflation pressure of a subsequent compression period of the repetitive compression cycle.

[0186] In some embodiments, the compression bladder is configured to inflate cyclically to alternate between peak pressure and subsequent peak pressure at least 6 cycles per minute.

[0187] In some embodiments, the compression bladder is configured to inflate cyclically to alternate between 6 cycles per minute and 20 cycles per minute between peak pressure and subsequent peak pressure.

[0188] In some embodiments, the compression bladder is configured to depressurize from peak pressure to minimum pressure in less than one second.

[0189] In some embodiments, the compression bladder includes a first end, a middle portion, and a tapered second end, the tapered second end being configured to be fixed to the first end to position the middle portion close to the patient's upper lower leg.

[0190] In some embodiments, the size and dimensions of the compression bladder are configured to apply pressure across a limited portion of the patient's lower limb, wherein the limited portion is close to the patient's knee and along the patient's upper calf.

[0191] In some embodiments, the air compressor assembly includes a housing surrounding the air compressor, a compressed air reservoir, and a pressure control system operatively connected to the air compressor and the compressed air reservoir. The operating air reservoir can achieve a pressure between 1.5 PSI and 7.5 PSI. The ratio of the internal volume of the compression bladder to the internal volume of the air tank can be 1:3.

[0192] In some embodiments, the peak pressure in the bladder during inflation is from about 0.5 PSI to about 4 PSI.

[0193] In some embodiments, the peak pressure in the bladder during inflation is from about 1 to about 5.

[0194] In some embodiments, the device further includes a wearable material, wherein the compression bladder is disposed within the wearable material. When the wearable material is operatively positioned on a patient's lower leg, operation of the device can generate a repeatable flow pattern in the venous valve sinus region at the junction of the patient's saphenous vein and femoral vein, characterized by an increase in the flow volume index of both forward venous flow and reverse venous flow within the same circulatory period.

[0195] In some embodiments, repetitive compression cycles effectively generate an oscillating flow pattern in the patient's venous sinus region, which substantially replicates the oscillating flow pattern derived from active muscle movements. Active muscle movements may include dorsiflexion of the patient's feet.

[0196] In some embodiments, the frequency of repeated compression cycles effectively induces the expression of PROX1 and FOXC2 in human endothelial cells.

[0197] In some embodiments, when the compression bladder is operatively positioned on the patient's lower leg, repeated compression cycles effectively induce reverse flow in the venous valve sinus region at the junction of the patient's saphenous vein and femoral vein.

[0198] In some embodiments, when the compression bladder is operatively positioned on the patient's lower leg, repeated compression cycles effectively induce eddies in the venous valve sinus region at the junction of the patient's saphenous vein and femoral vein.

[0199] Another embodiment of this disclosure relates to a method for inducing reverse flow in a region of venous valvular sinuses. The method includes applying a compression bladder to an anatomical region between a patient's knee and the widest part of the patient's lower leg; and inflating the bladder in repetitive compression cycles, each compression cycle having a compression period. In some embodiments, the compression period is defined as an inflation period, a holding period, and a deflation period. The duration of the compression period may be less than 300 ms. The repetitive compression periods may have a peak pressure and a minimum pressure (e.g., baseline pressure).

[0200] In some embodiments, the elapsed time from the peak pressure of one compression period of a repetitive compression cycle to the peak pressure of a subsequent compression period of the repetitive compression cycle is selected from the group consisting of: 20 seconds or less, 15 seconds or less, 10 seconds or less, 6 seconds or less, 5 seconds or less, 2 seconds or less, and 3 seconds or less.

[0201] In some embodiments, inflating the bladder includes cyclically inflating the bladder to alternate between peak pressure and subsequent peak pressure at least 3 cycles per minute. Inflating the bladder also includes cyclically inflating the bladder to alternate between peak pressure and subsequent peak pressure at a rate between 3 and 20 cycles per minute.

[0202] In some embodiments, the compression bladder comprises a single bladder positioned at the patient's lower leg.

[0203] In some embodiments, the venous valve sinus region is located at the junction of the patient's saphenous vein and the patient's femoral vein.

[0204] In some embodiments, inducing reverse flow includes inducing activation of PROX1 and FOXC2 in human endothelial cells at the venous valve sinus region.

[0205] In some embodiments, inducing reverse flow includes inducing eddies in the venous valve sinus region.

[0206] In some embodiments, inflating the compression bladder in repeated compression cycles includes applying coherent compressions at anatomical regions, each coherent compression causing reverse flow at the venous valve sinus region.

[0207] In some embodiments, inflating the bladder in a repetitive compression cycle includes applying a first compression and a subsequent second compression, the first compression inducing a first reverse flow at the venous valve sinus region, and the subsequent second compression inducing a second reverse flow at the venous valve sinus region. The first reverse flow may have a peak volume index having a magnitude substantially equal to the magnitude of the peak volume index of the subsequent reverse flow. The magnitude of the peak volume index of the first reverse flow may be between 50% and 150% of the magnitude of the peak volume index of the subsequent reverse flow. The first compression may induce a first forward flow substantially simultaneously with the first reverse flow, and the second compression may induce a second forward flow substantially simultaneously with the second reverse flow.

[0208] In some embodiments, the magnitude of the peak volume index of the first forward flow is substantially equal to the magnitude of the peak volume index of the second forward flow, and the magnitude of the peak volume index of the first forward flow is 10%-300% of the magnitude of the peak volume index of the first reverse flow.

[0209] In some embodiments, the method further includes preventing a significant reduction in venous flow in the venous valve sinus region after inflating the compression bladder.

[0210] In some embodiments, the method further includes reducing the magnitude of the positive flow volume index of positive venous flow occurring in the venous valve sinus region after the balloon is inflated by no more than 10% compared to the magnitude of the positive flow volume index occurring before the balloon is inflated.

[0211] In some embodiments, the inflation period is between approximately 30 ms and approximately 150 ms. The holding period can be between approximately 150 ms and approximately 250 ms. The deflation period can be approximately 60 ms.

[0212] In some embodiments, inflating the balloon in the venous valve sinus region induces reverse venous flow with a peak reverse flow volume index that is larger than that when the patient is stationary. The peak reverse flow volume index of the reverse venous flow in the venous valve sinus region may have a value between 50% and 150% of the value of the peak forward flow volume index of the forward venous flow that occurs substantially simultaneously with the reverse venous flow.

[0213] In some embodiments, the peak positive flow volume index at the venous valve sinus region after the balloon is inflated is not less than the peak positive flow volume index at the venous valve sinus region before the balloon is inflated for a period of more than 2 seconds.

[0214] Another embodiment of this disclosure relates to a method for monitoring the compliance of a deep vein thrombosis mitigation device, the method comprising applying a compression bladder to an anatomical region substantially between the patient's lower leg and knee; inflating the compression bladder with repeated compression, inflation, hold, and deflation periods, the duration of the compression period being less than 300 ms; determining the bladder pressure during the repeated compression periods; comparing the bladder pressure with non-compliant bladder pressure; and alerting the patient if the bladder pressure is less than or equal to the non-compliant bladder pressure during a predetermined amount of non-compliant inflation within a predetermined compliance period.

[0215] In some embodiments, the method further includes automatically deactivating the deep vein thrombosis mitigation device if the balloon pressure is greater than a selected pressure within a predetermined inflation quantity.

[0216] In some embodiments, the predetermined compliance period is 24 hours.

[0217] In some embodiments, non-compliant bladder pressure is the pressure of the bladder when it is not applied to the anatomical region.

[0218] In some embodiments, non-compliant bladder pressure is the pressure of the bladder during an air leak.

[0219] Although the subject matter and its advantages have been described in detail, it should be understood that various changes, substitutions, and modifications may be made herein without departing from the spirit and scope of the disclosed subject matter as defined by the appended claims. Furthermore, the scope of this application is not intended to be limited to the specific embodiments of the processes, machines, manufactures, compositions of matter, means, methods, and steps described in the specification. As will be readily understood by those skilled in the art from the disclosure of the subject matter, existing or future processes, machines, manufactures, compositions of matter, and methods that perform substantially the same function or achieve substantially the same results as the corresponding embodiments described herein may be utilized according to the subject matter currently disclosed. Therefore, the appended claims are intended to include such processes, machines, manufactures, compositions of matter, and methods within their scope.

[0220] Patents, patent application announcements, product descriptions and solutions are cited throughout this application, and their disclosures are incorporated herein by reference in their entirety for all purposes.

[0221] The terminology used in the description of the various embodiments described herein is for the purpose of describing particular embodiments only and is not intended to be limiting. As used in the description of the various embodiments described and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms as well, unless the context clearly indicates otherwise. It should also be understood that the term “and / or” as used herein refers to and covers any and all possible combinations of one or more of the associated listed items. It should also be understood that the terms “comprising” and / or “including”, when used in this specification, indicate the presence of the indicated features, integers, steps, operations, elements, and / or components, but do not exclude the presence or addition of one or more other features, integers, steps, operations, elements, components, and / or combinations thereof.

[0222] Furthermore, the specific order of steps described herein should not be considered a limitation of the claims, given that the methods of this disclosure do not depend on such a specific order. Any claim relating to the methods of this disclosure should not be limited to performing the steps in the order written, and those skilled in the art will readily understand that these steps may vary but remain within the spirit and scope of this disclosure.

[0223] For illustrative purposes, the above description has been given with reference to specific embodiments. However, the exemplary discussion above is not intended to be exhaustive or to limit the scope of the claims to the precise forms disclosed. In view of the above teachings, many modifications and variations are possible. These embodiments were chosen to best explain the principles underlying the claims and their practical application, thereby enabling others skilled in the art to best utilize the embodiments with various modifications suitable for the intended particular use.

Claims

1. A device for the prevention and / or mitigation of deep vein thrombosis (DVT), comprising: A wearable strap including an inflatable bladder with an inflatable portion, wherein when the wearable strap is positioned around a user's leg, a large portion of the inflatable portion of the inflatable bladder is positioned between the user's knee and the midpoint of the user's gastrocnemius muscle, and the inflatable bladder is inflatable to apply pressure to a portion of the user's gastrocnemius muscle. as well as A compressed air source, connected to the wearable strap, delivers continuous compression cycles to the inflatable bladder at a frequency of at least 3 cycles per minute, each compression cycle having a compression period and a peak inflation pressure to induce circulatory flow in the user's venous valve sinuses from each continuous inflation. The device is configured to have a first baseline pressure at the start of inflation and a second baseline pressure at the end of deflation, wherein the first baseline pressure is substantially equal to the second baseline pressure.

2. The DVT prevention and / or mitigation device according to claim 1, wherein, Between the consecutive compression cycles, the venous flow velocity in the user's deep veins is substantially equal to the resting baseline venous flow velocity in the user's deep veins.

3. The DVT prevention and / or mitigation device according to claim 2, wherein, Between the continuous compression cycles, the venous flow rate in the user's deep veins returns to the resting baseline venous flow rate within 1 to 10 seconds after each compression period.

4. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The frequency is at least 5 cycles per minute.

5. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The continuous compression cycle produces substantially the same hemodynamic effect for each compression cycle.

6. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The continuous compression cycle induces a pulse of positive flow in the user's deep veins, and the pulse induces a period of reverse flow in the venous valve sinuses.

7. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The frequency, the peak inflation pressure, and the duration of the compression period are selected to stimulate endothelial FOXC2 expression in the endothelium of the valvular sinus.

8. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflatable bladder applies pressure to the user's gastrocnemius muscle within one of the following areas: i) less than 60 square inches; ii) 55 square inches; iii) less than 30 square inches; iv) 25 square inches; v) less than 15 square inches; vi) 12.5 square inches.

9. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The time for the bladder to reach peak inflation is one of the following: i) 30 ms or less; ii) 100 ms or less; iii) 300 ms or less.

10. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflation period of the bladder is one of the following: i) 50 ms or less; ii) 150 ms to 250 ms; iii) 300 ms to 400 ms.

11. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The peak inflation pressure is one of the following: i) 35 mmHg to 70 mmHg; ii) 70 mmHg to 130 mmHg; iii) 100 mmHg to 200 mmHg.

12. The DVT prevention and / or mitigation device according to claim 1, wherein: i) The bladder applies pressure to the user's gastrocnemius muscle in an area of ​​less than 60 square inches or 55 square inches, the bladder has an inflation period of 50 ms or less, and the peak inflation pressure is 35 mmHg to 70 mmHg. or ii) The bladder applies pressure to the user's gastrocnemius muscle in an area of ​​less than 30 square inches or 25 square inches, the bladder has an inflation period of 150 ms to 250 ms, and the peak inflation pressure is 70 mmHg to 130 mmHg. or iii) The bladder applies pressure to the user's gastrocnemius muscle in an area of ​​less than 15 square inches or 12.5 square inches, the bladder has an inflation period of 300 ms to 400 ms, and the peak inflation pressure is 100 mmHg to 200 mmHg.

13. The DVT prevention and / or mitigation device according to claim 1, wherein: i) The bladder applies pressure to the user's gastrocnemius muscle over an area of ​​55 square inches, the bladder has an inflation period of 25 ms to 50 ms, and the peak inflation pressure is 45 mmHg to 60 mmHg; or ii) The bladder applies pressure to the user's gastrocnemius muscle over an area of ​​25 square inches, the bladder has an inflation period of 150 ms to 250 ms, and the peak inflation pressure is 80 mmHg to 100 mmHg. or iii) The bladder applies pressure to the user's gastrocnemius muscle within an area of ​​12.5 square inches, the bladder has an inflation period of 300 ms to 400 ms, and the peak inflation pressure is 150 mmHg to 175 mmHg.

14. The DVT prevention and / or mitigation device according to any one of claims 12 to 13, wherein, The inflation period includes a compression holding period of 400ms or less.

15. The DVT prevention and / or mitigation device according to claim 14, wherein, The pressure inside the inflatable bladder dissipates substantially throughout the entire compression holding period.

16. The DVT prevention and / or mitigation device according to any one of claims 12 to 13, wherein, The inflation period includes a peak inflation period defined by the duration during which the peak inflation pressure is reached.

17. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, further comprising a valve that alternately allows compressed air to flow to a compressed air tank in a first configuration and to the bladder in a second configuration.

18. The DVT prevention and / or mitigation device according to claim 1, wherein, The compressed air source delivers compressed air to the bladder in a compression cycle that includes a ramp-up period, a pulse period, a compression holding period, and a deflation period.

19. The DVT prevention and / or mitigation device according to claim 18, wherein, The compressed air source includes an air pump that pumps air into the bladder during the ramp-up period.

20. The DVT prevention and / or mitigation device according to claim 19, wherein, The air pump is configured to pump air into a compressed air container.

21. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The maximum inflation pressure during the ramp phase is less than the maximum inflation pressure during the pulse phase.

22. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The duration of the ramp-up period is greater than the duration of the pulse period.

23. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The duration of the compression hold period is equal to or greater than the duration of the pulse period, and the duration of the compression hold period is less than the ramp period.

24. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The duration of the venting period is equal to or greater than the duration of the ramping period.

25. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The compression holding period is characterized by having a pressure reduction curve at least in the shoulder area.

26. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The rate of pressure reduction during the compression holding period is less than the rate of inflation during the pulse period.

27. The DVT prevention and / or mitigation device according to any one of claims 18 to 20, wherein, The ramp-up period begins within 5ms after the end of the venting period.

28. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflatable bladder consists of multiple bladders.

29. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflatable bladder is attached to the wearable strap, such that inflation of the inflatable bladder causes the wearable strap to tighten around the user's legs.

30. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflatable bladder has a total length that decreases as the inflatable bladder inflates, causing the wearable strap to tighten.

31. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The compression period includes an inflation period of less than 500 ms.

32. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The compression period includes an inflation period of less than 400 ms.

33. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The peak inflation pressure is 1 PSI to 3 PSI.

34. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, further comprising a flexible outer covering disposed on at least a portion of the bladder and secured to the band, the flexible outer covering being configured to tighten the band during bladder inflation.

35. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The inflatable bladder includes a longitudinal axis and elastomeric sidewalls, the elastomeric sidewalls being radially disposed around the longitudinal axis and between opposite ends of the elastomeric sidewalls, wherein inflation of the inflatable bladder causes the elastomeric sidewalls to expand away from the longitudinal axis and pushes the opposite ends of the elastomeric sidewalls toward each other.

36. The DVT prevention and / or mitigation device according to claim 34, wherein, The flexible outer covering includes a mesh covering.

37. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, The venous valve sinus is located in a deep vein near the user's groin.

38. The DVT prevention and / or mitigation device according to any one of claims 1 to 3, wherein, Both peak positive venous flow and peak negative venous flow occur during the period of sac inflation.

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