Oral use of intraoral appliances in the treatment of dysphagia

Abstract

Disclosed is a method for treating dysphagia, comprising fitting a patient suffering from dysphagia with a TRP oral retainer-based appliance having an arch for restricting tongue movement, the appliance being worn by the patient for at least 8 hours at night and during sleep, beginning around bedtime; providing instructions to the patient to wear the appliance nightly as directed for a period of about 2 to about 18 months (the "wearing period"); and monitoring the patient's tongue pressure at one or more time points during the wear period, where an increase in tongue strength, e.g., as measured by tongue pressure (TP), compared to baseline or compared to a previous monitoring time point during the wear period indicates the patient is benefiting from wearing the appliance. Increases in tongue strength have been shown to be closely associated with relief of oropharyngeal dysphagia and its associated symptoms and pathologies.

Description

[Technical Field]

[0001] The effect of the tongue position corrector (TRP) on tongue pressure: Use for the treatment of dysphagia

[0002] The present disclosure relates to methods of treating dysphagia, particularly oropharyngeal dysphagia. [Background technology]

[0003] Aging itself and many age-related degenerative diseases can cause dysphagia [1], which is one of the most life-threatening factors in older adults because it can lead to dehydration, malnutrition, choking, and aspiration pneumonia [2, 3].

[0004] Feeding and swallowing can be divided into five stages: preparatory, oral, pharyngeal, and esophageal.[4] In these processes, the tongue plays a key role in mastication, tasting, salivation induction, bolus formation, and bolus propagation into the pharynx. A significant amount of tongue strength (tongue pressure) is thought to be required for the preparatory and oral stages to mix food with saliva into a bolus and pass it to the pharynx.[5] Dysphagia has been shown to result from a reduced ability of the tongue to propel the bolus into the pharynx. Therefore, assessing tongue strength is an important factor in feeding and swallowing rehabilitation.

[15]

[0005] The tongue plays an important role in chewing and swallowing, working in cooperation with the lips, mandible, pharynx, and larynx. Therefore, tongue dysfunction adversely affects chewing and swallowing, which can result in dysphagia, or difficulty swallowing.

[42] Dysphagia is common among the elderly. Consequently, it can cause choking or aspiration of food into the airways. Both are potentially life-threatening through aspiration, often leading to serious and potentially fatal airway and lung infections.

[0006] Quantitative assessment of tongue function is essential for dysphagia rehabilitation, and tongue pressure (TP) is a convenient and quantitative indicator of tongue strength. Decreased TP is associated with impaired swallowing and masticatory function [1, 2]. TP can also be reduced by aging and pathologies associated with dysphagia, such as vascular disease [3], neuromuscular dysfunction [4], Parkinson's disease [5], and sarcopenia [6, 41]. Therefore, decreased TP is a useful indicator for the rehabilitation of dysphagia symptoms, particularly oropharyngeal dysphagia [15, 40]. Regarding the relationship between clinical symptoms and TP, prolonged mealtimes, reduced food intake [7], aspiration [8], and pharyngeal residue [9] have been associated with decreased TP. Therefore, improving TP during rehabilitation is necessary. Conventional rehabilitation treatment plans include exercises such as balloon tongue resistance training

[10] , tongue protrusion training

[11] , and tongue pressure resistance training

[12] . However, dysphagic patients often have little or no motivation and / or ability to exercise, especially on a sustained basis, resulting in low patient compliance.

[0007] Decreased tongue pressure (TP) levels have been associated with impaired swallowing and related conditions, such as dysphagia. Tongue position correction (TRP) devices have been used as intraoral devices to treat conditions such as obstructive sleep apnea (OSA), snoring, tongue dysfunction, malocclusion, and lip dislocation. The effects of TRP on OSA may be associated with improved perioral muscle function. However, the effectiveness of the device in addressing insufficient swallowing function, particularly that associated with dysphagia, has not been fully investigated and remains unclear. Accordingly, the present invention aims to investigate the effects of TRP on tongue strength and function in patients with dysphagia and to use TRP to increase tongue strength in such patients, thereby alleviating swallowing difficulties and reducing swallowing risk.

[0008] The TRP device and its previous use In addition to being used for tongue and oral remodeling, the TRP device has previously been used to treat sleep apnea and snoring. It has also been used to treat bruxism and certain orthodontic problems, such as malocclusion. Some suitable embodiments of the TRP device are described in International (PCT) Patent Application PCT / IB2017 / 054130, published as WO / 2018 / 008002. Earlier versions of the device are described in patent applications published as WO / 2010 / 015685 and WO / 2012 / 085672, and in principle, such devices could also be used. The specific device used in the testing that gave rise to this disclosure is further described below.

[0009] Prior to the study disclosed herein, TRP has not been used to treat dysphagia. Moreover, the patient populations in which TRP has been used previously are different from the dysphagia population. For example, dysphagia is not associated with children or teenagers. Furthermore, even elderly patients who may suffer from apnea do not necessarily also have dysphagia. Summary of the Invention [Means for solving the problem]

[0010] Disclosed is a method for treating oropharyngeal dysphagia, comprising fitting a patient suffering from dysphagia with a TRP oral retainer-based appliance having an arch for restricting tongue movement, the appliance being worn by the patient for at least 8 hours at night and during sleep, beginning around bedtime; providing instructions to the patient to wear the appliance nightly as directed for a period of about 2 months to about 18 months (the "wearing period"); and monitoring the patient's tongue strength at one or more time points during the wearing period, where an increase in tongue strength, as measured, for example, by tongue pressure (TP), compared to baseline or compared to a previous monitoring time point during the wearing period indicates that the patient is benefiting from wearing the appliance. Wearing the appliance can be discontinued once the desired TP is achieved, or it can be continued, even indefinitely, or resumed as needed to substantially maintain or further improve the benefits achieved in tongue strength. The appliance can optionally be adjusted during the wearing period as needed by replacing the arch with one having a different geometry and / or arch orientation. Alternatively, the entire appliance can be replaced with another appliance having a different orientation and / or geometry. Suitable appliances are illustrated in Figures 8A-8C, 10A-10C, and 11A-11C of International PCT Patent Publication WO / 2018 / 008002, reproduced below along with its description. Indeed, if tongue strength has not improved at the end of the initial appliance wear period, e.g., 1-3 months, the TRP can be adjusted or replaced. The new TRP arch or arches can have a different length and / or width and / or angle relative to the patient's occlusal plane and / or a different orientation (posterior or anterior).

[0011] More specific embodiments included in the present disclosure include, without limitation:

[0012] 1. A method for treating dysphagia, comprising: providing a patient suffering from dysphagia with a TRP oral retainer-based appliance to be worn overnight and during sleep, preferably for at least 8 hours, beginning around bedtime; Providing instructions to the patient to wear the device nightly for a period of approximately 2 to 18 months (wearing period) as directed based on the strength of the patient's tongue; Monitoring the patient's tongue pressure at one or more time points during the wearing period Including, an increase in tongue strength compared to baseline or compared to a previous monitoring time point during the wear period indicates that the patient is benefiting or continuing to benefit from wearing the appliance and that the patient's dysphagia is thereby treated; and The TRP device is for stimulating the tongue by restricting the movement of the anterior or posterior zone of the tongue while allowing the anterior or posterior zone and lateral border of the tongue, respectively, to perform the movements necessary for speech and swallowing; and an attachment mechanism adapted to removably attach the TRP device to a patient's tooth, comprising: a first surface adapted to be positioned on the vestibular side of the patient's upper teeth in the alveolar arch; and a pair of second surfaces including a left second surface and a right second surface, each second surface facing a first surface and adapted for positioning along and on the lingual side of at least one and up to four molars of the wearer; and a connector for coupling the left edge of the first surface with the left second surface and a connector for coupling the right edge of the first surface with the right second surface; an attachment mechanism, A tongue constraint mechanism, first and second ends of the restraining mechanism, each end optionally removably secured to a corresponding second surface of the attachment mechanism; and a tongue constraint mechanism having an anteriorly or posteriorly facing component that intersects and spans between the first and second surfaces and is positioned at or at an angle relative to the patient's occlusal plane, the angle being within a range of +0 to -30 degrees below the occlusal plane, and configured to restrict movement of a corresponding zone of the tongue, thereby restricting the range of tongue movement to a more restricted three-dimensional space within the patient's mouth than would be the case absent the device; Includes:

[0013] In the method described in the preceding embodiment, the dysphagia is oropharyngeal dysphagia.

[0014] In the method described in one or more of the preceding embodiments, tongue strength is assessed by measuring tongue pressure (TP).

[0015] In the method described in one or more preceding embodiments, the TRP is positive.

[0016] In the method described in one or more preceding embodiments, wherein the TRP device is adjustable, the method further includes adjusting the TRP by axially adjusting the position of the components back and forth during the wear period to re-anchor the ends of the constraint mechanism to the left and right second surfaces, respectively, or by removing the constraint mechanism and replacing it with a second constraint mechanism having a different geometry and / or orientation than the first constraint mechanism to enhance the effect of the TRP device on tongue strength, thereby enhancing the treatment of dysphagia.

[0017] In the method described in one or more preceding embodiments, where the TRP device is not adjustable, the method may further include replacing the entire TRP device with one having a restraining mechanism with a different orientation and / or geometry to enhance the effect of the TRP on tongue strength, thereby enhancing the treatment of dysphagia.

[0018] In the method described in one or more of the preceding embodiments, the wear period ranges from 6 months to 18 months.

[0019] In the method described in one or more of the preceding embodiments, the wearing period continues until the TP reaches and remains at normal values ​​of at least 30 and up to 55 kPa.

[0020] The method as described in one or more of the preceding embodiments, wherein the component includes an arch.

[0021] The method as described in one or more of the preceding embodiments, wherein the component includes an arch, the arch having a tip.

[0022] The method as described in one or more of the preceding embodiments, wherein the arch has a central bead.

[0023] In the method described in one or more of the preceding embodiments, the attachment mechanism is an annular retainer band.

[0024] The method described in one or more of the preceding embodiments, wherein the connectors are integrated into the first and second surfaces. [Brief explanation of the drawings]

[0025] [Figures 1A-1C] Photographs of examples of tongue position correctors such as those employed in the studies detailed in this disclosure. Figure 1A shows an occlusal view taken from underneath the posterior arch device, and Figure 1B shows an occlusal view taken from underneath the anterior arch device. Figure 1C shows a perspective view of the anterior arch device as shown in Figure 1B. [Figure 2] 1 is a series of plots of tongue pressure between baseline and follow-up values ​​for each subject. Each number within a circle represents the number assigned to each subject as further shown in Table 1. [Figure 3] This is a series of box plots showing the results of the study. The top left panel is a box plot of TP. The bottom of the box is the starting value and the top is the value at evaluation. The cross indicates the mean value and the horizontal bar indicates the median value. DETAILED DESCRIPTION OF THE INVENTION

[0026] The Tongue Position Corrector (TRP) device (illustrated in Figure 1) is an intraoral device originally developed for orthodontic treatment

[13] , but it has also been used to reshape the palate and oral topology more generally. Because the TRP repositions the tongue intraorally, it is also used in patients with obstructive sleep apnea (OSA)

[14] . The device partially blocks anterior-posterior tongue thrust and also prevents the tongue from exerting vertical pressure against the palate. Therefore, the inventors hypothesized that the strength of swallowing-related muscles, including the tongue muscles, could be increased to compensate for blocked tongue movement. Previous studies have reported that the TRP (an earlier version of the device used to generate the data reported in this disclosure) increases the strength of suprahyoid muscles, such as the genioglossus (GG), geniohyoid (GH), styloglossus (SG), and stylohyoid (SH) muscles

[13] , in patients without dysphagia. Therefore, the inventors further hypothesized that TRP could potentially be used to improve tongue muscle strength by selecting the arch and / or its orientation and duration of treatment. To the inventors' knowledge, the study disclosed herein is the first study of the effect of TRP on tongue strength and function in patients with dysphagia.

[0027] material and method This single-arm study was conducted according to the Declaration of Helsinki of 1975, revised in 2013, and approved by the Ethics Committee of the Tokyo Medical and Dental University (D2020-023). Written informed consent was obtained from all participants.

[0028] Participants were enrolled among patients with dysphagia who visited a university dental hospital between September 2020 and September 2021. Inclusion criteria were (i) at least three of the six maxillary anterior teeth remaining, (ii) at least two of the six maxillary molars remaining on both sides, (iii) a non-short lingual frenulum, (iv) ability to handle TRP use, and (v) consent to participate in the study. Exclusion criteria were (i) inability to follow instructions, (ii) altered consciousness, and (iii) tracheostomy. Eight male patients with a mean age of 58.8 ± 12.3 years underwent TRP treatment. Patients suffered from various dysphagia-related conditions, as detailed in Table 1 below.

[0029] The measured variables included TP as the primary outcome, as well as changes in lip and tongue movement, peak nasal inspiratory flow, and ultrasound-based changes in tongue and suprahyoid muscle area as secondary outcomes. Each participant was asked to use the TRP, as shown in Figure 1B, for at least 8 hours nightly for 2 months. The measured variables before and after treatment were compared using paired t-tests and Wilcoxon signed-rank tests.

[0030] TRP The type of TRP used (provided by Tongue Lab Japan, Kyoto, Japan, and commercially available through the company or its parent company, Tongue Lab Europe Ltd.) is disclosed in detail in International (PCT) Patent Application PCT / IB2017 / 054130, published as WO / 2018 / 008002 (incorporated by reference) by Tongue Lab Europe Ltd. The device was provided by Tongue Lab Japan, Kyoto, Japan, and provided to all participants. The particular TRP device used in this study was a removable retainer-based intraoral appliance custom-made for each patient, including a transverse arch 2′ featuring a central bead 3′ encasing a resin retainer 1′ and arch 2′ (see particularly FIGS. 1A-1C, 1B, and 1C). The device was positioned along the maxillary dental arch 4', with a transverse arch 2' extending between the left and right sides of the maxilla and with the tip of the arch 5' approximately at the mesial level of the first molars and flush with the occlusal edges of the upper teeth 6' (close to the occlusal plane, not shown). A bead 3' was placed in the center of the arch to help the arch resist tongue movement. The arch 2' can be removed by loosening the screws 7' (one on each side) and withdrawing it. A replacement arch (not shown) can then be used, which may have the same or different orientation (posterior as in FIG. 1A or anterior as in FIGS. 1B and 1C) and dimensions (length of the base of the arch and distance of the tip from the base of the arch) and angle relative to the wearer's occlusal plane.

[0031] In the attached appendix, excerpted from PCT application WO / 2018 / 008002, exemplary arches of various shapes, angles, and dimensions for insertion into the second surface of a TRP device are set forth in Figures 8, 10, and 11 of the aforementioned PCT application.

[0032] Further adjustments to the arch can be made by adjusting loops 8' (one on each side). However, it should be noted that the loops are not necessary, as the arch can already be adjusted through screws 7' (and corresponding nuts, not shown) or removed and replaced with an arch of a different size or angle. Furthermore, this disclosure uses the described version of the TRP as merely illustrative. Previous TRP devices (described in WO / 2010 / 015685 and WO / 2012 / 085672) can be used, as can plastic disposable TRP devices.

[0033] Generally, a posterior-facing TRP device (illustrated in FIG. 1A ) is intended to restrict movement of the posterior zone of a wearer's tongue while allowing the anterior zone and lateral edge of the tongue to perform the movements necessary for speech and swallowing. Conversely, an anterior-facing TRP device (illustrated in FIGS. 1B and 1C ) is intended to restrict movement of the anterior zone of a person's tongue while allowing the posterior zone and lateral edge of the tongue (and tongue tip) to perform the movements necessary for speech and swallowing. In either case, the TRP includes an attachment mechanism, such as a retainer band (1 or 1′), adapted to attach the dental appliance over the teeth in the wearer's mouth. The attachment mechanism includes a first surface (1a or 1a′) and left and right second surfaces or returns (1b or 1b′) adapted to be positioned on the vestibular sides of the wearer's upper teeth in the alveolar arch.

[0034] Each second surface (1b or 1b') faces the first surface and is attached along at least one corresponding left or right molar tooth, respectively, on the lingual side of the teeth. The second surfaces can extend along the lingual sides of two, three, or four of the wearer's rear molars.

[0035] Each second surface is connected to the first surface by a connector (8 or 8'), which can be integrated into the first and second surfaces or can be a separate element. In Figures 1A and 1B, the connectors are made of metal wire and are therefore different from the resin material of the attachment mechanism (retainer).

[0036] The second surfaces are attached to a tongue restraining mechanism having a component (commonly referred to as an arch) that is fixed, optionally removably, to the attachment mechanism and spans between the pair of second surfaces. The arch can be thought of as having a tip at a center 5 or 5'. The component has a first end attached to the first surface and a second end attached to the second surface. The component (arch) can be anterior-facing (FIG. 1B) or posterior-facing (FIG. 1A).

[0037] The components are configured to be attached generally at or at an angle to a person's occlusal plane (the angle at the tip can be up to 30 degrees below the occlusal plane) and to restrict the movement of the corresponding zone of the tongue (anterior or posterior) while allowing at least the unconstrained zone of the tongue (anterior zone in the case of a posterior-facing appliance and posterior zone in the case of an anterior-facing appliance) and the lateral edge of the tongue to perform the movements necessary for speech and swallowing (the constraint is most pronounced in the middle of the tongue where the tip of the component is located), thereby confining the range of tongue movement to a more restricted three-dimensional space than would be possible without the TRP device. The components prevent the constrained portion of the tongue from touching the palate.

[0038] An antegrade TRP appliance was used in this study. It was thought that older patients would be more easily adapted to it. However, it is anticipated that a retrograde appliance would also be useful. Indeed, there is reason to predict that a retrograde appliance may be more effective in strengthening the tongue and treating dysphagia because the arches within such an appliance more directly affect the muscles at the base of the tongue that are directly involved in the passage and swallowing of food boluses.

[0039] The attachment mechanism or retainer or perimeter band is adapted to be fastened onto a person's upper teeth / alveolar arch to removably secure the device onto the upper teeth / alveolar arch.

[0040] The restraining or attachment mechanism optionally includes an adjustment mechanism for adjusting: (i) the angle of the component relative to the person's occlusal plane when the device is worn, thereby controlling the degree of restriction of tongue movement; or (ii) the position of the component along the longitudinal axis of the device, thereby controlling the posterior tongue zone to which the constraint is applied; or (iii) both the angle and position. In Figures 1A-1C, the adjustment mechanism is a screw (7 or 7') and nut combination.

[0041] The restraining mechanism is secured to the attachment mechanism. Alternatively, as in the case of disposable TRP devices, there is no adjustment mechanism and the restraining mechanism can be integrated with the second surface. If present, the adjustment mechanism includes a fastening mechanism, preferably a nut-and-screw or nut-and-bolt combination, with each end of the component slidably attached to the fastening mechanism and secured in an anterior-posterior and longitudinally adjustable manner. Adjustment of the component relative to the occlusal plane can be achieved by changing the angle of the component end or by removing the component and replacing it with another component having a different preset angle. In Figures 1A-1C, the component ends (9 and 9') are secured to the second surface (1b and 1b') using a combination of screws (7 or 7') and nuts (not shown).

[0042] Testing During the study, participants were asked to return to the clinic three times for treatment. At the first visit, dental impressions were taken to create plaster casts that were sent to a dental laboratory (Tongue Lab) to create personalized TRP devices. Participants who received their TRPs were informed of their usage at the second visit and asked to wear the devices at night and for at least 8 hours while sleeping. Participants were also asked to return for a follow-up visit two months later to evaluate the effects of TRP use. Participants did not perform any active tongue exercises, such as tongue training, during the period between the second visit and the follow-up visit.

[0043] result Outcome variables were assessed at the start of the study and at the 2-month follow-up visit. TP was the primary outcome, and secondary outcomes included tongue and lip velocity, peak nasal inspiratory flow (PNIF), and ultrasound measurements of swallowing muscles. TP after treatment (31.5 ± 13.1 kPa) was significantly higher than TP before treatment (23.0 ± 13.4 kPa) (p < 0.034, Figure 3A). However, other measured variables did not significantly improve (Figures 3B-3D). Although participants did not actively train, most participants in this study showed improved TP. Therefore, these findings indicate that the TRP device can significantly improve TP even after only 2 months of use, especially considering the small number of subjects. It should also be noted that only anterior arch devices were used in this study; posterior arch devices were not used. Results with the posterior arching device (see Appendix Figures 8A-8C, 10A-10C, and 11A-11C, the latter two figures for the posterior arching device, and Figure 1A herein) predict that it may be even more effective because it more specifically targets the tongue base. Similarly, other parameters measured in this preliminary study may improve with longer treatment periods.

[0044] measurement Measurements were performed by a dentist affiliated with the Department of Swallowing Rehabilitation at Tokyo Medical and Dental University Hospital who was familiar with the use of the measurement devices. Before the measurements, the dentist inspected the use of all measurement devices used in this study.

[0045] Tongue pressure TP was assessed using a TPM-01 tongue pressure measurement device (JMS Co. Ltd., Hiroshima, Japan). Accordingly, the TP values ​​provided herein are based on measurements with this device. Measurements with other devices may yield different values. For example, a TPM-01 value of 30-50 kPa corresponds to an IOPI value of 47.5-69 kPa when measured with an IOPI device. See https: / / doi.org / 10.1016 / j.jds.2020.06.005 for a comparison of the Iowa Oral Performance Instrument and the JMS tongue pressure measurement device.

[0046] Participants were asked to place the device's balloon in their mouth while sitting, bite the plastic pipe with their upper and lower central incisors, and close their lips. A dentist held the probe in place while recording measurements. Participants were then asked to press the balloon with their tongue against the hard palate with maximum pressure for 7 seconds. TP was measured three times, and the average was recorded as previously described [15, 16].

[0047] Tongue and lip movement speed Tongue and lip movement speed was assessed using oral diadochokinesis (ODK). ODK was measured using the KENKO-KUN Handy oral function measurement device (Takei Scientific Co., Ltd., Niigata, Japan). Participants were asked to speak monosyllabic words as quickly as possible for 5 seconds. The device recorded the number of repetitions for each syllable to calculate the number of syllables produced per second. The monosyllabic words "pa," "ta," and "ka" were used to assess the performance of the lips, tongue tip, and tongue back, respectively [17, 18].

[0048] Ultrasonographic evaluation of swallowing muscles The cross-sectional area of ​​the geniohyoid muscle (CSA of the GH) and tongue thickness were assessed using an ultrasound measuring device (SonoSite M-turbo, Fujifilm, Tokyo, Japan) in B-mode [19, 20] to evaluate swallowing-related muscles. The geniohyoid muscle (GH) was selected to represent the suprahyoid muscle. To assess the CSA of the GH, participants were asked to gently close their mouths while seated and facing forward. A probe with ultrasound gel was placed in the center of the floor of the mouth, covering the geniohyoid muscle (sagittal), and it was sufficiently attached to the skin without applying pressure to the tissue. To assess tongue thickness, the probe was placed perpendicular to the Frankfurt plane on a line connecting the left and right first mandibular molars, including the second premolar. The probe was placed in close contact with the inferior surface of the mandible, which was covered with ultrasound gel [20, 21]. A cross-section of the tongue was presented to the participant in a static, seated, forward-facing position.

[0049] To assess inter-examiner reliability, intraclass correlation coefficients (ICC) (1,1) and (2,1) were calculated. ICCs (1,1) 0.925 and (2,1) 0.966 were used for measurements of GH CSA, and ICCs (1,1) 0.936 and (2,1) 0.925 were used for measurements of tongue thickness, revealing their high reliability. ImageJ software (National Institutes of Health, Bethesda, MD, USA) was used for image processing. GH CSA and tongue thickness were measured three and two times, respectively, and the mean values ​​were recorded. During analysis, examiners were blinded to information including participant names and whether the images were taken at baseline or follow-up.

[0050] Peak nasal inspiratory flow (PNIF) PNIF was assessed using a handheld In-Check® PNIF meter (Clement Clarke International, Harlow, Essex, UK). Participants were asked to inhale as quickly as possible through the mask, starting from the end of full inflation, with their mouths tightly closed while sitting and holding their head perpendicular to the floor. Reliability has been previously established [22, 23], with correlation coefficients of up to 92%

[24] . Measurements were performed three times and the mean values ​​were recorded as previously described

[25] .

[0051] Other measurements Participants' Barthel Index (BI) and FOIS (functional oral intake scale) scores were recorded. The BI is a 10-question index of activities of daily living with a score ranging from 0 to 100. Higher scores are associated with better physical function

[26] . The 7-point FOIS was recorded to assess oral intake levels, with higher scores associated with higher intake levels. The reliability of the BI and FOIS has been previously validated [6, 27, 28].

[0052] statistical analysis The Shapiro-Wilk test was used to examine the normality of all data. Subsequently, the paired t-test and the Wilcoxon signed-rank test were used using the Japanese version of SPSS for Windows (version 25J; IBM Japan, Ltd., Tokyo, Japan) for the analysis of parametric and nonparametric data, respectively. A difference with a corrected p-value < 0.05 was considered significant. Post hoc analysis was performed to calculate the effect size (ES) of each variable using G*Power 3.1 (Kiel University, Kiel, Germany). ES was defined as large for r > 0.5, medium for 0.3 < r < 0.5, small for 0.1 < r < 0.3, and no effect for r < 0.1.

[0053] Results Eight participants (all male, mean age 58.8 ± 12.3 years) were enrolled in this study. Table 1 shows the characteristics of the participants. Diseases causing dysphagia included neuromuscular diseases (n = 3) and cerebrovascular diseases (n = 2). The median BI and FOIS scores of the participants were 85 (25 - 100) and 6.5 (2 - 7), respectively. Table 2 shows the differences in TP, ODK, PNIF, and ultrasound examination evaluations of swallowing-related muscles before and after TRP use. There was a significant improvement in TP (p = 0.034, r = 0.84). The ES of each measurement item was also calculated. Among the eight participants, the ODK of one participant with cerebral infarction could not be evaluated due to post-stroke expressive aphasia. There was no other missing data. Figure 2 shows the comparison of TP between the baseline and follow-up observations of each participant. Among the eight participants, seven showed improvement in TP. Figures 3A - 3D show the box plots of the measurement parameters (TP, ODK / pa / , ODK / ka / , and PNIF, respectively) that were significantly improved between the baseline TP value and the TP value at the time of evaluation. The remaining parameters did not show improvement in this study.

[0054] In Figure 3, the left and right box plots for each measurement item ( ) indicate baseline and follow-up values, respectively. The upper and lower vertical lines indicate maximum and minimum values, respectively, and the central box indicates the interquartile range. The light gray central horizontal line indicates the median, and the cross indicates the mean. TP, tongue pressure; ODK, oral diadochokinesis; PNIF, peak nasal inspiratory flow.

[0055] The TRP was first employed in patients with dysphagia, demonstrating that TP improved after two months of use. Interestingly, TP improved even in three participants with progressive diseases (amyotrophic lateral sclerosis, spinocerebellar degeneration, and progressive supranuclear palsy). Thus, this device can serve as a valuable tool for restoring tongue function in patients with oropharyngeal dysphagia, even if due to an underlying degenerative disease.

[0056] A decrease in TP was observed in only one of the eight participants. However, this participant's baseline TP was 40.8 kPa, which was not very low despite the presence of dysphagia, and the decrease was only 0.8 kPa. Therefore, TRP may not have been very useful in this case, or the treatment interval was too short. However, based on the data, TRP can be said to be suitable for dysphagia associated with low tongue strength.

[0057] There have been no reports of a relationship between TRP and TP improvement, and therefore, no mechanism for such has been proposed. Without wishing to be bound by theory, a possible explanation may be the lingual-hypoglossal reflex. When the filiform papillae on the tongue are mechanically stimulated, the tip of the tongue bends upward, the tongue bends its lateral border upward, concaves to the left and right, and the posterior portion is depressed [29, 30]. TRP may trigger this reflex and increase the strength of the anterior intrinsic and extrinsic muscles of the tongue, particularly the genioglossus (GG), which plays a role in protrusion and retraction. At a minimum, tongue protrusion has been reported to be involved in swallowing. Improved tongue muscles may be responsible for the improvement in TP. A relationship between tongue protrusion strength and upper airway patency in the awake state has been previously reported

[31] . TP assessment suggests that TRP improves GG muscle strength, contributing to tongue protrusion. The GG is a pharyngeal dilator muscle, which may explain why TRP has been used to manage OSA

[14] .

[0058] Ultrasound evaluation revealed that GH CSA did not improve in this study (p = 0.484, r = 0.25). Although a link between TP and the geniohyoid muscle has been reported

[13] , the mechanism by which TP improved with TRP use may be due to strengthened GG and SG tongue muscles rather than the suprahyoid muscles. Whether TRP improved GH muscle function in this study remains unclear due to the small number of patients and short treatment interval; therefore, further investigation is needed to clarify the effectiveness of TRP on GH muscle function in larger, longer-term studies. Tongue thickness did not increase despite the improvement in TP (p = 0.588, r = 0.21). Tongue muscle strength increases without muscle hypertrophy at the onset of muscle movement due to neural adaptation

[32] . The improvement in TP in this study may be due to this phenomenon, and a longer study period, optionally and preferably using or switching to a TRP device with a posterior arch as in Figure 1B, would likely also lead to increased muscle strength.

[0059] ODK and PNIF were also measured. ODK "Pa" (r = 0.45) and PNIF (r = 0.48) tended to increase during follow-up visits, but were not significantly different when compared with those at baseline. Future studies with a larger sample size and / or longer study duration may show significant differences between baseline and follow-up values. In this study, the incidence of some patients with progressive disease should have been adjusted or homogenized. Although the improvement was not significant, PNIF scores increased. This result is consistent with previous studies, although the previous study did not involve dysphagia or measure tongue pressure

[33] . Similarly, ODK "Pa" also increased. However, the reasons behind this result remain unclear. A possible explanation may be a decrease in mouth breathing resulting from improvement in nasal obstruction and associated PNIF. Previously, adult mouth breathers have been shown to have reduced nasal congestion and lower PNIF than nasal breathers

[34] . In particular, mouth breathing is associated with weaker lip muscle strength

[35] . Accordingly, improved lip closure may be reflected in the ODK Pa and PNIF. Future studies should also measure lip closure strength.

[0060] In contrast, the ODK "ta" and "ka" scores showed slight declines. Four participants, including three with progressive neuromuscular disease, showed increases in the ODK "ta" score, while the scores of the other two participants decreased. Two participants' "ka" scores decreased, while the remaining participants' scores remained unchanged. The improvement in "ta," as well as the improvement in TP, may be explained by increased genioglossal muscle strength. However, "ka" scores remained stable or decreased. Of the two participants whose "ka" scores decreased, one had progressive disease and the other had a history of stroke. The ODK "ta" and "ka" reflect anterior and posterior tongue movement, respectively. In both cases, TRP may maintain anterior tongue movement despite the presence of progressive disease.

[0061] This study had several limitations. First, only eight participants were included. Therefore, more studies with more male and female participants are needed to clarify the reasons behind the effectiveness of TRP use in improving oral function. Second, although TP improved, ultrasound assessment did not show improvement, suggesting that muscle characteristics did not change after wearing the TRP for 2 months. Third, the improvement in TP may be due to the lingual-hypoglossal reflex. However, it was difficult to prove that the reflex actually occurred. Most importantly, because the wearing period was significantly shorter than the optimal wearing period for other TRP uses (6 to 18 months), it is expected that benefits may increase with longer-term use, and muscle strength gains may be further observed after longer TRP use and, optionally, with or by switching to a posterior-arch appliance.

[0062] This is the first study to examine swallowing function in TRP users with dysphagia. A randomized controlled trial should be conducted to elucidate the effectiveness of TRP in dysphagia and its associated abnormalities in the parameters measured in this study. Considering the ES of TP in this study was 0.84, future studies will recruit 48 participants, including 24 who used TRP and a placebo oral appliance (α = 0.05, power = 0.8). The length of treatment could be extended to at least 4 months, preferably 6 months to 1 year, if other indicators of TRP benefit continue to improve. Furthermore, future studies should include swallowing assessment using radiographic videography or video endoscopy.

[0063] Numerous exercises have been proposed to improve TP [12, 38, 39]. However, the most important thing is for patients to follow instructions. In contrast, most participants in this study showed improvement in TP, even though they did not perform active exercises.

[0064] The TRP is a non-invasive, removable device worn entirely inside the mouth, making it useful for patients with swallowing disorders who are unable or unwilling to actively train, allowing them to continue active exercise therapy. Additionally, caregiver assistance is required, if at all, only during device insertion and removal. Therefore, the TRP can be used even in situations where assistance is limited. No adverse events were reported in this study.

[0065] table [Table 1]

[0066] [Table 2] All cited references are incorporated by reference in their entirety for all purposes.

[0067] References 1. Aoki Y, Kabuto S, Ozeki Y, Tanaka T, Ota K (2015) The effect of tongue pressure strengthening exercise for dysphagic patients.Jpn J Compr Rehabil Sci 6:129-136.https: / / doi.org / 10.11336 / jjcrs.6.129 2.Hara K, Tohara H, Kenichiro K, Yamaguchi K, Ariya C, Yoshimi K, Nakane A, Minakuchi S (2019) Association between tongue muscle strength and masticatory muscle strength. J Oral Rehabil 46:134-139. https: / / doi.org / 10.1111 / joor.12737 3.Nakamori M,Hosomi N,Ishikawa K,Imamura E,Shishido T,Ohshita T,Yoshikawa M,Tsuga K,Wakabayashi S,Maruyama H,Matsumoto M (2016) Prediction of pneumonia in acute stroke patients using tongue pressure measurements.PLOS ONE 11:e0165837.https: / / doi.org / 10.1371 / journal.pone.0165837 4.Umemoto G,Tsuboi Y,Kitashima A,Furuya H,Kikuta T (2011) Impaired food transportation in Parkinson‘s disease related to lingual bradykinesia.Dysphagia 26:250-255.https: / / doi.org / 10.1007 / s00455-010-9296-y 5.Minagi Y,Ono T,Hori K,Fujiwara S,Tokuda Y,Murakami K,Maeda Y,Sakoda S,Yokoe M,Mihara M,Mochizuki H (2018) Relationships between dysphagia and tongue pressure during swallowing in Parkinson‘s disease patients.J Oral Rehabil 45:459-466.https: / / doi.org / 10.1111 / joor.12626 6.Maeda K,Akagi J (2015) Decreased tongue pressure is associated with sarcopenia and sarcopenic dysphagia in the elderly.Dysphagia 30:80-87.https: / / doi.org / 10.1007 / s00455-014-9577-y 7.Namasivayam AM,Steele CM,Keller H (2016) The effect of tongue strength on meal consumption in long term care.Clin Nutr 35:1078-1083.https: / / doi.org / 10.1016 / j.clnu.2015.08.001 8.Nakamori M,Ishikawa K,Imamura E,Yamamoto H,Kimura K,Ayukawa T,Mizoue T,Wakabayashi S (2021) Relationship between tongue pressure and dysphagia diet in patients with acute stroke.PLOS ONE 16:e0252837.https: / / doi.org / 10.1371 / journal.pone.0252837 9.Ono T,Kumakura I,Arimoto M,Hori K,Dong J,Iwata H,Nokubi T,Tsuga K,Akagawa Y (2007) Influence of bite force and tongue pressure on oropharyngeal residue in the elderly.Gerodontology 24:143-150.https: / / doi.org / 10.1111 / j.1741-2358.2007.00172.x 10.Robbins J,Gangnon RE,Theis SM,Kays SA,Hewitt AL,Hind JA (2005) The effects of lingual exercise on swallowing in older adults.J Am Geriatr Soc 53:1483-1489.https: / / doi.org / 10.1111 / j.1532-5415.2005.53467.x 11.Fujiu-Kurachi M,Fujiwara S,Tamine KI,Kondo J,Minagi Y,Maeda Y,Hori K,Ono T (2014) Tongue pressure generation during tongue-hold swallows in young healthy adults measured with different tongue positions.Dysphagia 29:17-24.https: / / doi.org / 10.1007 / s00455-013-9471-z 12.Namiki C,Hara K,Tohara H,Kobayashi K,Chantaramanee A,Nakagawa K,Saitou T,Yamaguchi K,Yoshimi K,Nakane A,Minakuchi S (2019) Tongue-pressure resistance training improves tongue and suprahyoid muscle functions simultaneously.Clin Interv Aging 14:601-608.https: / / doi.org / 10.2147 / CIA.S194808 13.Mauclaire C,Vanpoulle F,Saint-Georges-Chaumet Y (2015) Saint-Georges-Chaumet Y.Physiological correction of lingual dysfunction with the ‘Tongue Right Positioner’:Beneficial effects on the upper airways.Int Orthod 13:370-389.https: / / doi.org / 10.1016 / j.ortho.2015.06.007 14. Wullman P, Belattar A, Coulson S, Vanpoulle F, Mauclaire C, Saint-Georges-Chaumet Y (2019) Effect of lingual reeducation with Tongue Right Positioner on SAOS. Med Sommeil 16:43 (French). https: / / doi.org / 10.1016 / j.msom.2019.01.065. See also International PCT Patent Publication WO / 2018 / 008002. 15.Utanohara Y,Hayashi R,Yoshikawa M,Yoshida M,Tsuga K,Akagawa Y (2008) Standard values ​​of maximum tongue pressure taken using newly developed disposable tongue pressure measurement device.Dysphagia 23:286-290.https: / / doi.org / 10.1007 / s00455-007-9142-z [ PubMed ] 16.Shimizu A,Fujishima I,Maeda K, Wakabayashi H,Nishioka S,Ohno T,Nomoto A,Shigematsu T,Kayashita J;Japanese Working Group on Sarcopenic Dysphagia (2021). 90:111295.https: / / doi.org / 10.1016 / j.nut.2021.111295 [ PMC free article ] [ PubMed ] 17. Ito K, Yoshihara A, Takano N, Ishigami K, Seida Y, Inoue M, Kitahara M, Miyazaki H (2009). https: / / doi.org / 10.11259 / jsg.24.48 18.Ziegler W (2002) Task-related factors in oral motor control:Speech and oral diadochokinesis in dysarthria and apraxia of speech.Brain Lang 80:556-575.https: / / doi.org / 10.1006 / brln.2001.2614 19.Yabunaka K,Konishi H,Nakagami G,Sanada H,Iizaka S,Sanada S,Ohue M (2012) Ultrasonographic evaluation of geniohyoid muscle movement during swallowing:A study on healthy adults of various ages.Radiol Phys Technol 5:34-39.https: / / doi.org / 10.1007 / s12194-011-0132-3 20.Ogawa N,Mori T,Fujishima I,Wakabayashi H,Itoda M,Kunieda K,Shigematsu T,Nishioka S,Tohara H,Yamada M,Ogawa S (2018) Ultrasonography to measure swallowing muscle mass and quality in older patients with sarcopenic dysphagia.J Am Med Dir Assoc 19:516-522.https: / / doi.org / 10.1016 / j.jamda.2017.11.007 21.Yoshimi K,Hara K,Tohara H,Nakane A,Nakagawa K,Yamaguchi K,Kurosawa Y,Yoshida S,Ariya C,Minakuchi S (2018) Relationship between swallowing muscles and trunk muscle mass in healthy elderly individuals:A cross-sectional study.Arch Gerontol Geriatr 79:21-26.https: / / doi.org / 10.1016 / j.archger.2018.07.018 22.Cho SI, Hauser R, Christiani DC (1997) Reproducibility of nasal peak inspiratory flow among healthy adults:Assessment of epidemiologic utility.Chest 112:1547-1553.https: / / doi.org / 10.1378 / chest.112.6.1547 23.Teixeira RUF,Zappelini CEM,Alves FS,da Costa EA (2011) Peak nasal inspiratory flow evaluation as an objective method of measuring nasal airflow. Braz J Otorhinolaryngol 77:473-480.https: / / doi.org / 10.1590 / S1808-86942011000400011 24.Starling-Schwanz R,Peake HL,Salome CM,Toelle BG,Ng KW,Marks GB,Lean ML,Rimmer SJ (2005) Repeatability of peak nasal inspiratory flow measurements and utility for assessing the severity of rhinitis.Allergy 60:795-800.https: / / doi.org / 10.1111 / j.1398-9995.2005.00779.x 25.Sawa A,Suzuki H,Niwa H,Oguchi S,Yagi T,Iwata Y,Makiyama Y,Chow CM,Komiyama O (2020) Assessment of screening for nasal obstruction among sleep dentistry outpatients with obstructive sleep apnea.Dent J (Basel)8:119.https: / / doi.org / 10.3390 / dj8040119 26.Mahoney FI, Barthel DW (1965) Functional evaluation:The Barthel index.Md State Med J 14:61-65 27.Sainsbury A,Seebass G,Bansal A,Young JB (2005) Reliability of the Barthel index when used with older people.Age Ageing 34:228-232.https: / / doi.org / 10.1093 / ageing / afi063 28.Crary MA,Mann GDC,Groher ME (2005) Initial psychometric assessment of a functional oral intake scale for dysphagia in stroke patients.Arch Phys Med Rehabil 86:1516-1520.https: / / doi.org / 10.1016 / j.apmr.2004.11.049 29.John RR,Chandrasekaran B,Murugadoss P (2019) Lingual hypoglossal reflex:An unusual reflex of head and neck.J Maxillofac Oral Surg 18:366-370.https: / / doi.org / 10.1007 / s12663-018-1157-5 30.Miller AJ (2002) Oral and pharyngeal reflexes in the mammalian nervous system:Their diverse range in complexity and the pivotal role of the tongue.Crit Rev Oral Biol Med 13:409-425.https: / / doi.org / 10.1177 / 154411130201300505 31.Kanezaki M, Ogawa T, Izumi T (2015) Tongue protrusion strength in arousal state is predictive of airway patency in obstructive sleep apnea 32.Cullins MJ,Krekeler BN,Connor NP (2018) Differential impact of tongue exercise on intrinsic lingual muscles.Laryngoscope 128:2245–2251 33.Mauclaire C,Vanpoulle F,Belattar A (2017) Saint-Georges-Chaumet Y.Importance of lingual reeducation by the right tongue positioner on upper airways permeability in young orthodontic patients. Sleep Med 24:161-165 34.Trevisan ME,Bellinaso JH,Pacheco Ade Ade B,Auge LB,Silva AM,Correa EC (2015) Respiratory mode,nasal patency and palatine dimensions.CoDAS.Brazilian Society of Speech and Audiology 2015.Codas 27:201-206[sin Protuguese].https: / / doi.org / 10.1590 / 2317-1782 / 20152014177 35.Ismail AMA (2021) Oral rehabilitation using the lip muscle trainer:A narrative review. PTJ 11:139-144.https: / / doi.org / 10.32598 / ptj.11.3.486.1 36.Horibe Y,Matsuo K,Ikebe K,Minakuchi S,Sato Y,Sakurai K,Ueda T (2022) Relationship between two pressure-sensitive films for testing reduced occlusal force in diagnostic criteria for oral hypofunction.Gerodontology 39:3-9. https: / / doi.org / 10.1111 / ger.12538 37.Yanagida R,Hara K,Iida T,Tohara T,Tamada Y,Minakuchi S,Namiki C,Okumura T,Tohara H (2022) Jaw-opening force as a useful index for dysphagia:A cross-sectional and multi-institutional study.Gerontology:1-8.https: / / doi.org / 10.1159 / 000521392 38.Park T,Kim Y (2016) Effects of tongue pressing effortful swallow in older healthy individuals.Arch Gerontol Geriatr 66:127-133.https: / / doi.org / 10.1016 / j.archger.2016.05.009 39.Oh JC (2021) Effects of resistive jaw-opening exercise with elastic resistance bands on suprahyoid muscle activation and tongue strength in the elderly:A pilot study.Folia Phoniatr Logop 73:376-383.https: / / doi.org / 10.1159 / 000509441 40.Sakamoto,Y.et al,Effect of tongue pressure decreased on dysphagia and survival rate in elderly people requiring long-term care. (2022) Journal of Dental Sciences 17:856-862 41. Sakai, K, et al, Association of Oral Function and Dysphagia with Frailty and Sarcopenia in Community-Dwelling Older Adults: A Systematic Review and Meta-Analysis. Cells (2022) 11,2199. https: / / doi.org / 10.3390 / cells11142199 42.Milazzo,M.et al,Tongue Rehabilitation Device for Dysphagic Patients.Sensors (2019)19,4657;doi:10.3390 / s19214657

[0068] Appendix of TRP orientations, widths, lengths, and angles relative to the occlusal plane that can be considered for use in patients with dysphagia, extracted from International PCT Patent Publication WO / 2018 / 008002 [Table 3] JPEG2025537623000005.jpg134132JPEG2025537623000006.jpg120132

[0069] 8A-8C illustrate an exemplary restraint mechanism having forward-facing horizontal loops, according to one or more embodiments. FIG. 8A illustrates exemplary lengths of a short forward-facing restraint mechanism (FwS) and a long forward-facing restraint mechanism (FwL), according to one or more embodiments. FIG. 8B illustrates a front perspective view of an exemplary forward-facing restraint mechanism with horizontal loops, and FIG. 8C illustrates a rear view of an exemplary forward-facing restraint mechanism, according to one or more embodiments.

[0070] 10A-10C illustrate an exemplary rearward (backward) facing restraint mechanism, according to one or more embodiments. FIG. 10A illustrates exemplary lengths of a short rearward facing restraint mechanism (BwS) and a long rearward facing restraint mechanism (BwL), according to one or more embodiments. FIG. 10B illustrates a front view of the exemplary rearward facing restraint mechanism, and FIG. 10C illustrates a top view of the exemplary rearward facing restraint mechanism, according to one or more embodiments.

[0071] 11A-11C illustrate exemplary restraint mechanisms with rearward-facing horizontal loops, according to one or more embodiments. FIG. 11A illustrates exemplary lengths of a short rearward-facing restraint mechanism (BwS) and its components and a long rearward-facing restraint mechanism (BwL) and its components, according to one or more embodiments. FIG. 11B illustrates a front view of an exemplary rearward-facing restraint mechanism with horizontal loops, and FIG. 11C illustrates a top view of an exemplary rearward-facing restraint mechanism, according to one or more embodiments.

Claims

1. 1. A method for treating dysphagia, comprising: providing a patient suffering from dysphagia with a TRP oral retainer-based appliance for wear overnight and during sleep, preferably for at least 8 hours, beginning around bedtime; providing instructions to the patient to wear the device for a period of about 2 to about 18 months (wear period) as directed based on the patient's tongue strength; monitoring the patient's tongue pressure at one or more times during the wearing period; Including, an increase in tongue strength compared to baseline or compared to a previous monitoring time point during the wear period indicates that the patient is benefiting or continuing to benefit from wearing the device and that the patient's dysphagia is thereby treated; and the TRP device is for stimulating the tongue by restricting movement of the posterior or anterior zone of the tongue while allowing the anterior or posterior zone and lateral edge of the tongue, respectively, to perform the movements necessary for speech and swallowing; an attachment mechanism adapted to removably attach the TRP device to the patient's tooth, a first surface adapted to be positioned on the vestibular side of the patient's upper teeth in the alveolar arch; and a pair of second surfaces including a left second surface and a right second surface, each second surface facing the first surface and adapted to be positioned along at least one and up to four molar teeth of the wearer on the lingual sides of the molars; and a connector for coupling a left edge of the first surface with the left second surface and a connector for coupling a right edge of the first surface with the right second surface; an attachment mechanism comprising: A tongue constraint mechanism, first and second ends of the restraining mechanism, each end optionally removably secured to a corresponding second surface of the attachment mechanism; and a tongue constraint mechanism having an anteriorly or posteriorly facing component intersecting and spanning the first and second surfaces, positioned at or at an angle relative to the patient's occlusal plane, the angle being within a range of +0 to -30 degrees below the occlusal plane, and configured to restrict movement of the corresponding zone of the tongue, thereby restricting the range of tongue movement to a more restricted three-dimensional space within the patient's mouth than would be the case absent the device; Including, method.

2. 10. The method of claim 1, wherein the swallowing disorder is oropharyngeal dysphagia.

3. 10. The method of claim 1, wherein tongue strength is assessed by measuring tongue pressure (TP).

4. The method of claim 1 , wherein the TRP is forward-looking.

5. 10. The method of claim 1, wherein the TRP device is adjustable, and the method further comprises adjusting the TRP during the wearing period by axially adjusting the position of the components back and forth to re-secure the ends of the constraint mechanisms to the respective left and right second surfaces, or by removing the constraint mechanisms and replacing them with second constraint mechanisms having a different geometry and / or orientation than the first constraint mechanisms, to enhance the effect of the TRP device on tongue strength, thereby enhancing the treatment of dysphagia.

6. 10. The method of claim 1, wherein the TRP device is not adjustable, and the method further comprises replacing the entire TRP device with one having a restraining mechanism with a different orientation and / or geometry to enhance the effect of the TRP on tongue strength, thereby enhancing the treatment of dysphagia.

7. 10. The method of claim 1, wherein the wearing period ranges from 6 to 18 months.

8. 10. The method of claim 1, wherein the wearing period continues until TP reaches and remains at normal values ​​of at least 30 and up to 55 kPa.

9. The method of claim 1 , wherein the component is an arch.

10. The method of claim 8 , wherein the arch has a tip.

11. The method of claim 9 , wherein the arch has a central bead.

12. The method of claim 1 , wherein the attachment mechanism is an annular retainer band.

13. The method of claim 1 , wherein the connectors are integrated into the first and second surfaces.

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