Clinical system for closure surgery in patients with refractory epilepsy accompanied by high-flow shunt PFO

Abstract

The present invention relates to the field of epilepsy, and more specifically, discloses a clinical system for closure surgery in patients with refractory epilepsy accompanied by high shunt flow PFOs. The system comprises a patient medical record information acquisition and storage module for acquiring and storing electronic medical record data of epilepsy patients, wherein the types of electronic medical record data include sex, age at surgery, age of epilepsy onset, seizure frequency, normality of 24-hour EEG examination, and seizure duration, and the electronic medical record data includes sample data from a sample population and subject data from a subject; a patient selection module for selecting subjects who may be suitable for PFO closure surgery; and a preoperative efficacy evaluation module for evaluating the effectiveness of the subject if they undergo the PFO closure surgery. The clinical system provided by the present invention has a complete and normative evaluation system for patient selection and exclusion, and is useful for guiding the selection, decision-making, and postoperative management of epilepsy patients suitable for application of PFO closure surgery.

Description

Technical Field

[0001] This application claims the priority of Chinese Patent Application No. 2023104865029, titled "Diagnostic and Treatment System for the Closure of Refractory Epilepsy Patients with High-Flow Shunt PFO", filed with the China National Intellectual Property Administration on May 4, 2023, the entire content of which is incorporated herein by reference in its entirety.

[0002] The present invention relates to the field of epilepsy, and specifically to a diagnostic and treatment system for the closure of refractory epilepsy patients with high-flow shunt PFO.

Background Art

[0003] The foramen ovale is a passage that directly connects the circulations of both atria during the fetal period, and most anatomically close within 1 year under normal physiological conditions. If it does not close even after exceeding 3 years old, it is called Patent Foramen Ovale (PFO). According to reports, PFO is the most common congenital heart disease in adults, and its incidence rate is about 25%. PFO is a potential passage. When the right atrial pressure exceeds the left atrial pressure (for example, when pulmonary hypertension, cough, sneeze, strong emotion, or loud laughter occurs), a right-to-left shunt (RLS) appears. PFO allows small molecules such as microthrombi, air, inflammatory mediators, cholinergic compounds, glutamine, and some anoxic venous blood to avoid metabolism by the pulmonary circulation and directly enter the systemic circulation, causing dysfunction of cerebrovascular endothelial cells or changes in cortical excitability, and ultimately causing stroke, migraine, and obstructive sleep apnea (OSA). In recent years, percutaneous PFO closure has become one of the most common and simplest catheter intervention treatments in adult cardiology.

[0004] Drug-resistant epilepsy (or drug-tolerant epilepsy, or simply refractory epilepsy) generally refers to a type of epilepsy that is ineffective even after treatment with at least two or more antiepileptic drugs and more than two years of regular treatment. Refractory epilepsy accounts for approximately 40% of all epilepsy cases. Although refractory epilepsy represents only a relatively small proportion of all epilepsy cases, frequent and severe seizures severely impair the patient's physical health, reduce their quality of life, and significantly increase mortality. At the same time, refractory epilepsy imposes a heavy economic burden on families and society; according to World Health Organization statistics, even though only about 40% of epilepsy cases are refractory, refractory epilepsy accounts for 80% of the economic burden on all epilepsy patients.

[0005] A population-based case-control study in the UK reported that the prevalence of epilepsy in patients with congenital heart disease over long-term follow-up was 2.4%, compared to a total prevalence of only 0.62% in the normal population. Another study showed that 4–18% of newborns with congenital heart disease experienced seizures during the perioperative period of the condition, suggesting that epilepsy may be associated with more severe neurodevelopmental disorders in children with congenital heart disease, often manifesting as refractory epilepsy. Notably, because PFO patients often have milder clinical symptoms, they are less likely to undergo surgery in infancy, and therefore, the long-term effects of PFO inducing epilepsy may be overlooked.

[0006] Chinese patent CN113040835A discloses that epileptic seizures can be effectively controlled by performing PFO closure surgery on patients with PFOs. However, in the prior art, the recommendation of PFO closure surgery for PFO patients is often based on an anatomical evaluation of the PFO, and there is a lack of evaluation of its effectiveness for specific patient types (e.g., patients with refractory epilepsy). [Overview of the Initiative]

[0007] In a first embodiment, the present invention provides a medical system for closure of refractory epilepsy patients with high shunt flow PFO, the system being: A patient medical record information acquisition and storage module for acquiring and storing electronic medical record data of epilepsy patients, wherein the types of electronic medical record data include basic clinical data, epileptic seizure history data, and PFO examination data, the basic clinical data includes sex and age at surgery, the epileptic seizure history data includes age of epilepsy onset, seizure frequency, normality of 24-hour electroencephalogram (EEG) examination, and seizure duration, the PFO examination data includes presence or absence of PFO and grade of right-to-left shunt, and the electronic medical record data includes sample data from a sample population and subject data from a subject, A patient selection module for acquiring subject data via the patient medical record information acquisition and storage module, and selecting subjects who may be suitable for PFO closure surgery based on the subject data, A preoperative efficacy evaluation module for performing a preoperative efficacy evaluation of the PFO closure procedure on the subject selected by the patient selection module, the preoperative efficacy evaluation module comprising: a preoperative efficacy evaluation module that includes an evaluation submodule for acquiring subject data via the patient medical record information acquisition and storage module, calling an efficacy evaluation model to analyze the subject data, and thereby evaluating the efficacy of the subject undergoing the PFO closure procedure, wherein the efficacy is calculated by the following formula: S=β1×X1+β2×X2+β3×X3+β4×X4+β5×X5+β6×X6 β1, β2, ..., β6 represent the weights of the feature variables, S represents the overall effectiveness score, X1 represents the age classification at surgery, X2 represents the age classification at the onset of epilepsy, X3 represents the sex, X4 represents the seizure frequency classification, X5 represents the presence or absence of normality in the 24-hour EEG test, and X6 represents the seizure duration classification. β1 through β6 each represent the proportion of the odds ratio (OR) of X1 through X6 to the sum of the OR values ​​of the feature variables.

[0008] The system further comprises a postoperative management module for tracking the postoperative health status of the subject who underwent the PFO closure procedure, the postoperative management module including a health guidance submodule for providing reminder information to the subject who underwent the PFO closure procedure, the reminder information including medication reminders, health reminders, and examination reminders.

[0009] In some embodiments, the postoperative management module further includes a postoperative follow-up submodule for receiving and analyzing postoperative treatment efficacy data of the subject, the postoperative treatment efficacy data including epileptic seizure data, daily medication data, and closed device data.

[0010] In some embodiments, the medications in the daily medication data include antiplatelet agents and antiepileptic agents; the closure device data includes the location and function of the closure device, the presence or absence of occluding thrombi, the presence or absence of cardiac structural abnormalities, and residual shunts after surgery; and the epileptic seizure data includes the frequency and duration of epileptic seizures.

[0011] In some embodiments, the postoperative treatment effect data is obtained from the subject and / or supervisor.

[0012] In some embodiments, the patient selection module is Using selection criteria including (1) being between 9 and 55 years of age at the time of surgery, and (2) being an epileptic patient with PFO, epileptic patients who may be suitable to undergo the PFO closure procedure are identified. Patients unsuitable for PFO closure are excluded using exclusion criteria, which include (1) those who do not meet the selection criteria, (2) patients with secondary epilepsy caused by one or more of the following: tumor, traumatic brain injury, encephalitis, or neurotoxicity, and (3) those who are intolerant to antiplatelet drug therapy.

[0013] In some embodiments, the preoperative efficacy evaluation module further includes a model building submodule for constructing the efficacy evaluation model by performing statistical analysis on the sample data.

[0014] In some embodiments, the subject data and postoperative treatment effect data of the subject are used as new sample data to optimize the effectiveness evaluation model.

[0015] In some embodiments, the basic clinical data further includes one or more of the following: height, weight, BMI, diastolic blood pressure, systolic blood pressure, blood glucose indicators, blood cell count indicators, smoking history, alcohol consumption history, physical activity scale assessment, diet and nutrition scale assessment, mental health scale assessment, and history of past chronic diseases.

[0016] In some embodiments, the epileptic seizure history data further includes one or more of the following: family history of epilepsy, type of epileptic seizure, appearance of aura, appearance of motor epilepsy, characteristic appearance of epileptic seizures, standard duration of antiepileptic drug use, number of different antiepileptic drugs taken, history of antiepileptic drug use, severity of epileptic seizures, presence or absence of migraines, and presence or absence of normality on MRI examinations.

[0017] In some embodiments, the PFO examination data further includes the presence or absence of an occlusive thrombus and the relationship between the PFO and the surrounding tissue.

[0018] In some embodiments, the efficacy evaluation model scores the subjects, and subjects with an overall score exceeding 40, 50, 60, 70, 80, or 90 points are predicted to be beneficial to undergo the PFO closure procedure.

[0019] In some embodiments, subjects with a total score exceeding 60 points are predicted to benefit from undergoing the PFO closure procedure.

[0020] In some embodiments, the system further includes a surgical process standardization and management module.

[0021] In a second embodiment, the present invention further provides a method for constructing an efficacy evaluation model for evaluating the effectiveness of PFO closure in patients with refractory epilepsy accompanied by high shunt flow PFO, characterized in that the method is Step S1 involves obtaining sample data derived from a sample population, the types of sample data including basic clinical data, epileptic seizure history data, and PFO examination data. Step S2 involves performing a statistical analysis on the aforementioned sample data to select predictor variables, which include sex, age at surgery, age of epilepsy onset, seizure frequency, 24-hour EEG test results, and seizure duration. The process includes step S3, which involves constructing the effectiveness evaluation model based on the selected predictor variables.

[0022] In some embodiments, the statistical analysis method includes a two-stage analysis strategy and a bootstrap method.

[0023] Favorable effects In the prior art, the determination of whether a subject is suitable to undergo patent foramen ovale closure is often based solely on the anatomical structure of the subject's foramen ovale. In other words, even for certain types of patients (for example, patients with refractory epilepsy accompanied by patent foramen ovale, which is the subject of this invention), the prior art still relies on the anatomical structure of the foramen ovale and, in severe cases, is unable to determine at all whether the person is suitable to undergo patent foramen ovale closure.

[0024] The present invention provides a medical treatment system for the closure of a patent foramen ovale (PFO) in refractory epilepsy patients with a high shunt flow. The patient selection module of the medical treatment system provided by the present invention can perform a primary selection of epilepsy patients from hard conditions. On the other hand, the effectiveness evaluation model in the preoperative effectiveness evaluation module only requires the clinical basic information (age and gender at the time of surgery) and basic epilepsy history data (age of epilepsy onset, frequency of epileptic seizures, 24-hour EEG test results, and duration of epileptic seizures) of epilepsy patients, and can evaluate the subjects selected by the patient selection module (which can also be understood as soft conditions), and is helpful for epilepsy patients and doctors to predict and visualize the effectiveness of the patent foramen ovale closure surgery for refractory epilepsy patients in advance. The medical treatment system provided by the present invention breaks through the fixed concept of the existing technology that the decision to undergo patent foramen ovale closure surgery depends only on the anatomical structure of the foramen ovale based on the electronic medical record data of epilepsy patients, provides a new objective reference and decision-making concept for whether refractory epilepsy patients should undergo patent foramen ovale closure surgery, and is also useful for assisting clinical evaluation.

[0025] The postoperative management module of the medical treatment system provided by the present invention performs long-term postoperative follow-up on refractory epilepsy patients who have undergone patent foramen ovale closure surgery and obtains their postoperative treatment effect data. Here, the postoperative treatment effect data can be obtained from the subject himself and the supervisor (for example, medical staff in the hospital). By comparing the postoperative treatment effect data from the subject himself with the postoperative treatment effect data from the supervisor, the adherence of the subject can be further evaluated, and to a certain extent, the problem that the subject hides the true medication situation and epileptic seizures can be avoided. And the postoperative treatment effect data and the corresponding electronic medical record data of the subject (for example, the subject with a high comprehensive score who has undergone closure surgery, the subject with a low comprehensive score who has undergone closure surgery) can be used as new sample data to further optimize the effectiveness evaluation model of the present invention. Furthermore, the new sample data is fed back to the patient selection module to further clarify the selection criteria and exclusion criteria.

[0026] In summary, the medical treatment system provided by the present invention has a complete and standardized evaluation system for patient selection and exclusion, and is useful for guiding the selection, decision-making, and postoperative management of epilepsy patients suitable for receiving PFO closure surgery.

[0027] To more clearly explain the technical solutions in the embodiments of the present invention or the prior art, the drawings necessary for use in the description of the embodiments or the prior art are briefly introduced below. In all the drawings, similar elements or parts are generally denoted by similar reference numerals. In the drawings, each element or part is not necessarily drawn according to the actual scale. Obviously, the drawings in the following description are some embodiments of the present invention, and those skilled in the art can obtain other drawings based on these drawings without creative labor.

Brief Description of the Drawings

[0028] [Figure 1] It is a schematic diagram of the effectiveness evaluation model of Example 1 of the present invention. [Figure 2] It is a schematic diagram of the architecture of the medical treatment system of Example 2 of the present invention. [Figure 3] It is a schematic diagram of a certain module of the medical treatment system of Example 2 of the present invention. [Figure 4] It is a schematic diagram of a certain module of the medical treatment system of Example 2 of the present invention. [Figure 5] It is a schematic diagram of a certain module of the medical treatment system of Example 2 of the present invention. [Figure 6] It is a summary diagram of the 14-item clinical index-related information selected in Example 1 of the present invention. [Figure 7] It is the OR value information of the characteristic variables of the effectiveness evaluation model of Example 1 of the present invention.

Modes for Carrying Out the Invention

[0029] To further clarify the object, technical solution, and advantages of the embodiments of the present invention, the technical solution in the embodiments of the present invention will be clearly and completely described below with reference to the drawings of the embodiments. Clearly, the embodiments described are some, but not all, embodiments of the present invention. All other embodiments that a person skilled in the art could obtain without creative work based on the embodiments of the present invention are within the scope of the protection of the present invention.

[0030] In this specification, suffixes such as “module,” “part,” or “unit” used to represent elements are merely for the purpose of facilitating the explanation of the invention and do not have any specific meaning in themselves. Therefore, “module,” “part,” or “unit” may be used interchangeably.

[0031] In this specification, directions or positional relationships indicated by terms such as "up," "down," "inside," "outside," "front," "back," "one end," and "the other end" are based on the directions or positional relationships shown in the drawings and are merely for the purpose of describing and simplifying the invention, and do not indicate that the indicated or suggested device or element must have a specific orientation or be configured and operated in a specific orientation, and therefore should not be understood as a limitation to the invention. Furthermore, the terms "first" and "second" are used for descriptive purposes only and should not be understood as indicating or implying relative importance.

[0032] In this specification, "and / or" includes any and all combinations of one or more of the related items listed.

[0033] In this specification, "plural" means two or more, including two, three, four, five, and so on.

[0034] It is necessary to clarify that, in this specification, “equipment,” “includes,” or any other variation thereof, is intended to be non-exclusive inclusion, and therefore a process, method, article, or apparatus that includes a set of elements includes not only those elements but also other elements not explicitly listed, or elements specific to such process, method, article, or apparatus. An element limited by the phrase “includes one…” does not preclude the presence of other identical elements in a process, method, article, or apparatus that includes that element, under less restrictive circumstances.

[0035] As used herein, the term “about” typically means ±5% of the value, more typically ±4% of the value, even more typically ±3% of the value, even more typically ±2% of the value, even more typically ±1% of the value, and even more typically ±0.5% of the value.

[0036] In this specification, certain embodiments may be disclosed in a form that falls within a certain range. Such “within a certain range” statements should be understood to be merely for convenience and brevity and not to be interpreted as a rigid limitation on the disclosed range. Accordingly, a range statement should be considered to specifically disclose all possible subranges and independent numerical values ​​within that range. For example, a range statement of 1 to 6 should be considered to specifically disclose subranges such as 1 to 3, 1 to 4, 1 to 5, 2 to 4, 2 to 6, 3 to 6, and individual numerical values ​​within this range such as 1, 2, 3, 4, 5, and 6. This rule applies regardless of the breadth of the range. [Examples]

[0037] This invention analyzes the clinical characteristics of 33 patients with refractory epilepsy and grade 2-3 right-to-left shunt (RLS) who underwent PFO closure surgery and were followed up for one year. Based on this data, a model for evaluating the effectiveness of PFO closure surgery for epilepsy patients (especially those with refractory epilepsy) was constructed.

[0038] Transthoracic echocardiography (TTE) was used to assess the presence of prostatic follicular formation (PFO) and the reflex level (RLS) grade. A contrast agent containing microbubbles was mixed with 8 mL of saline, 1 mL of blood, and 1 mL of air, and injected into the precubital vein to improve sensitivity. RLS was assessed at rest, during the Valsalva maneuver, and when the subject coughed. If two or more microbubbles appeared in the left atrium or left ventricle of a subject within three cardiac cycles after maximum right atrium opacity, the subject was considered to have a PFO. In semi-quantitative analysis, the degree of RLS was evaluated by TTE and quantified by the number of microbubbles (microembolus) detected per frame in the left atrium: Grade 0 = no microbubble signal (no RLS), Grade 1 = 1 to 20 microbubble signals (1 to 10 per side) (small amount of RLS), Grade 2 = more than 20 microbubble signals (more than 10 per side), not curtain-like (moderate amount of RLS), Grade 3 = microbubble signal exhibits a curtain-like or shower-like pattern (large amount of RLS). In this invention, "high shunt flow rate" refers to an RLS grade of 2 or 3.

[0039] Next, this embodiment employs a two-stage analysis strategy. In the initial stage, clinical information and prognostic outcomes (i.e., marked improvement group ("surgery effective") and no marked improvement group ("surgery ineffective")) of the above-mentioned patients with refractory epilepsy were classified and compared. The primary outcome was the percentage reduction in the average number of epileptic seizures in the year after PFO closure compared to the average number of epileptic seizures in the year before surgery. A reduction of more than 30% was considered marked improvement ("surgery effective"). In this example, 14 clinical indicators were selected and included in the variable validation model. These 14 clinical indicators include sex, RLS grade, age at surgery, age of epilepsy onset, epilepsy history, appearance of aura (aura classification), standard antiepileptic drug use duration, frequency of epileptic seizures in the year prior to surgery, duration of epileptic seizures in the year prior to surgery, number of types of antiepileptic drugs taken, severity of epileptic seizures (presence or absence of other serious symptoms), presence or absence of migraines, normality of 24-hour EEG examination, and normality of MRI examination (Figure 6).

[0040] In the validation phase, this embodiment employed the bootstrap method, and after 200 sampling validations, under conditions where the test level was set to 0.1, the proportion of significant models (in this invention, this can be understood as the proportion of a certain feature variable that maintains significance even after 200 sampling validation analyses) was calculated. A PFO closure efficacy evaluation model was constructed, with a threshold of over 15% being used for efficacy. It is important to note that the efficacy prediction model provided by this invention can be further enhanced and optimized by combining it with newly acquired sample data for analysis.

[0041] The characteristic variables of the PFO closure efficacy evaluation model in this embodiment include age at surgery, age of epilepsy onset, sex, frequency of epileptic seizures in the year prior to surgery, duration of epileptic seizures in the year prior to surgery, and presence or absence of normality in 24-hour EEG testing (Figure 7). Here, OR represents the odds ratio (OR) of these characteristic variables. The OR value is a statistic that quantifies the strength of the association between two events, and represents the ratio of the odds of the outcome occurring after exposure (in this invention, this refers to the characteristic variable being examined; the same applies hereinafter) to the odds of the outcome occurring without the same exposure.

[0042] The PFO closure efficacy evaluation model allows for scoring the effectiveness of PFO closure for a subject before the procedure is performed. In some embodiments, the PFO closure efficacy evaluation model is S=β1×X1+β2×X2+β3×X3+β4×X4+β5×X5+β6×X6 Here, β1, β2, ..., β6 represent the weights of the characteristic variables, S represents the overall effectiveness score, X1 represents the age classification at surgery, X2 represents the age classification at the onset of epilepsy, X3 represents the sex, X4 represents the classification of the average epileptic seizure frequency in the year prior to surgery, X5 represents the presence or absence of normality in the 24-hour EEG examination, and X6 represents the classification of the average epileptic seizure duration in the year prior to surgery.

[0043] In some embodiments, the weight of a feature variable is the proportion of the OR value of that feature variable to the total OR value of the feature variables. Specifically, β1 represents the proportion of the OR value of X1 to the total OR value of the feature variables, β2 represents the proportion of the OR value of X2 to the total OR value of the feature variables, β3 represents the proportion of the OR value of X3 to the total OR value of the feature variables, β4 represents the proportion of the OR value of X4 to the total OR value of the feature variables, β5 represents the proportion of the OR value of X5 to the total OR value of the feature variables, and β6 represents the proportion of the OR value of X6 to the total OR value of the feature variables.

[0044] Specifically, the formulas for calculating the weights of each feature variable are as follows:

[0045]

number

[0046]

number

[0047]

number

[0048]

number

[0049]

number

[0050]

number

[0051]

number

[0052] In some embodiments, a subject's overall score (with a maximum score of 100 points) can be calculated based on the following formula, and this overall score indicates the effectiveness of the subject receiving PFO closure treatment (Figure 1).

[0053] In some embodiments, the PFO closure effectiveness evaluation model was S=15×X1+19×X2+14×X3+11×X4+15×X5+7.5×X6 That is the case.

[0054] Specifically, the range of values ​​for the above feature variables is as follows:

[0055] If the patient's age at surgery is over 18 years, the value of the age classification (X1) at surgery is 0; if the patient's age at surgery is 18 years or younger, the value of the age classification (X1) is 1.

[0056] If the age of epilepsy onset is over 18 years, the value of the epilepsy onset age classification (X2) is 0, and if the age of epilepsy onset is 18 years or younger, the value of the epilepsy onset age classification (X2) is 1.

[0057] If the gender is female, the value of gender(X3) is 0, and if the gender is male, the value of gender(X3) is 1.

[0058] If the average seizure frequency in the year prior to surgery is >1 seizure per week or daily, the average seizure frequency classification (X4) value for the year prior to surgery is 0; if the average seizure frequency in the year prior to surgery is >1 seizure per month, the average seizure frequency classification (X4) value for the year prior to surgery is 1; and if the average seizure frequency in the year prior to surgery is ≤1 seizure per month, the average seizure frequency classification (X4) value for the year prior to surgery is 2.

[0059] If the 24-hour EEG test is abnormal, the value of the 24-hour EEG test normality (X5) is 0. If the 24-hour EEG test is normal, the value of the 24-hour EEG test normality (X5) is 1.

[0060] If the average duration of an epileptic seizure in the year prior to surgery is less than 1 minute per seizure, the average seizure duration classification (X6) value for the year prior to surgery is 0. If the average duration of an epileptic seizure in the year prior to surgery is between 1 and 3 minutes per seizure, the average seizure duration classification (X6) value for the year prior to surgery is 1. If the average duration of an epileptic seizure in the year prior to surgery is more than 3 minutes per seizure, the average seizure duration classification (X6) value for the year prior to surgery is 2.

[0061] In some cases, subjects with a preoperative efficacy score exceeding 40, 50, 60, 70, 80, or 90 points were evaluated as likely to benefit from a favorable postoperative therapeutic effect by undergoing PFO closure surgery. In some cases, subjects with a preoperative efficacy score exceeding 60 points were evaluated as likely to benefit from a favorable postoperative therapeutic effect by undergoing PFO closure surgery. [Examples]

[0062] Based on the above PFO closure effectiveness evaluation model, and by combining electronic medical record data of epilepsy patients, the PFO closure surgical process, and postoperative management and follow-up data, the present invention provides a closure treatment system for refractory epilepsy patients with high shunt flow PFOs.

[0063] Referring to Figure 2, Figure 2 is a schematic diagram of one selectable architecture of a clinical system for closure of refractory epilepsy patients with high shunt flow PFOs, provided by an embodiment of the present invention. To support the exemplary application, terminals (shown as a first terminal 302 and a second terminal 304, for example) are connected to the clinical system via a network 306. The network according to the present invention may be a wide area network, a local area network, or a combination thereof, and data transmission is achieved using wireless links. The terminals according to the present invention may be various types of user terminals, such as smartphones, tablet computers, and notebook computers. The terminals may be used to display an input interface for subject data and / or sample data, as well as a display interface for evaluation results of the clinical system.

[0064] The following describes an exemplary structure of the medical treatment system of the present invention. In some embodiments, as shown in Figure 3, the medical treatment system 100 is: The system includes a patient medical record information acquisition and storage module 102 for acquiring and storing electronic medical record data of epilepsy patients, wherein the types of electronic medical record data include basic clinical data, epileptic seizure history data, and PFO examination data, and the electronic medical record data includes sample data derived from a sample population and subject data derived from the subject.

[0065] In some embodiments, the basic clinical data includes sex and age at surgery; the epileptic seizure history data includes age of epilepsy onset, seizure frequency, normality of 24-hour EEG examination, and seizure duration; and the PFO examination data includes presence or absence of PFO and grade of right-to-left shunt.

[0066] In some embodiments, the basic clinical data includes sex, age at surgery, height, weight, BMI, diastolic blood pressure, systolic blood pressure, blood glucose indicators, blood cell count indicators, smoking history, alcohol consumption history, physical activity scale assessment, diet and nutrition scale assessment, mental health scale assessment (e.g., including scale assessments for depression, anxiety, loneliness, and sleep quality), and a history of chronic diseases (e.g., including hypertension, diabetes, cognitive impairment, sleep disorders, history of traumatic brain injury, or other neurological disorders). In some cases, the epileptic seizure history data includes family history of epilepsy, age of epilepsy onset, type of epileptic seizure, appearance of aura, appearance of motor epilepsy, frequency of epileptic seizures in the year prior to surgery, duration of epileptic seizures in the year prior to surgery, characteristic appearance of epileptic seizures, standard duration of antiepileptic drug use, number of types of antiepileptic drugs taken, history of antiepileptic drug use, severity of epileptic seizures, presence or absence of migraines, normality of 24-hour EEG examination, and normality of MRI examination. In some cases, the PFO examination data includes the presence or absence of PFO, grade of right-to-left shunt, presence or absence of thrombus, and relationship between PFO and surrounding tissue.

[0067] The electronic medical record data can be transmitted to the patient medical record information acquisition and storage module 102 via the network 306 through the first terminal 302 and / or the second terminal 304. In some embodiments, the first terminal 302 may be a hospital-side terminal, and the second terminal 304 may be a patient-side terminal. In some embodiments, the basic clinical data can be obtained through self-reporting by epilepsy patients and completion of corresponding scales (e.g., physical activity scale, dietary nutrition scale, mental health scale). In some embodiments, the epileptic seizure history data can be obtained through self-reporting by epilepsy patients, the performance of corresponding tests (e.g., 24-hour EEG and MRI), and recording in a preoperative epilepsy diary. In some embodiments, the PFO examination data can be obtained by epilepsy patients performing corresponding tests (e.g., transthoracic right cardiac acoustics, transesophageal echocardiography, pulmonary artery pressure measurement, and PFO anatomical evaluation).

[0068] The patient selection module 104 is used to select subjects who are likely to be suitable for PFO closure surgery based on the electronic medical record data (which may specifically be basic clinical data and PFO examination data).

[0069] In some embodiments, the patient selection module 104 is Selection criteria for identifying epileptic patients who may be suitable to undergo the PFO closure procedure, the selection criteria including (1) being between 9 and 55 years of age at the time of surgery, and (2) being an epileptic patient with PFO, Exclusion criteria for excluding persons unsuitable for undergoing the PFO closure procedure, the exclusion criteria further include: (1) persons who do not meet the selection criteria; (2) patients with secondary epilepsy caused by one or more of the following: tumor, traumatic brain injury, encephalitis, or neurotoxicity; and (3) persons who are intolerant to antiplatelet drug therapy.

[0070] The preoperative efficacy evaluation module 106 is used to evaluate the preoperative efficacy of the PFO closure procedure for the subjects selected by the patient selection module 104. The preoperative efficacy evaluation module 106 includes an evaluation submodule 202, which acquires subject data via the patient information acquisition and storage module 102, calls an efficacy evaluation model to analyze the subject data, and thereby evaluates the efficacy of the subject undergoing the PFO closure procedure.

[0071] In some embodiments, the characteristic variables of the efficacy evaluation model include the duration of epileptic seizures, normality of 24-hour EEG tests, frequency of epileptic seizures, sex, age of onset, and age at surgery.

[0072] In some embodiments, the efficacy evaluation model scores the subjects, and subjects whose overall score exceeds 40, 50, 60, 70, 80, or 90 points are predicted to be beneficial to undergo the PFO closure procedure.

[0073] In some embodiments, subjects with a total score exceeding 60 points are predicted to benefit from undergoing the PFO closure procedure.

[0074] In some embodiments, the preoperative efficacy evaluation module 106 further includes a model building submodule 204 for constructing the efficacy evaluation model by performing statistical analysis on the sample data.

[0075] In some embodiments, as shown in Figure 4, the medical system 100 may further include a postoperative management module 108 for tracking the postoperative health status of the subject who underwent the PFO closure procedure.

[0076] In some embodiments, the postoperative management module 108 includes a health guidance submodule 208. The health guidance submodule 208 is used to provide reminder information to the subject who has undergone the PFO closure procedure. In some embodiments, the reminder information includes medication reminders, health reminders, and examination reminders. In some embodiments, the health reminders include regular exercise, healthy eating, and improvement of unhealthy habits (e.g., quitting smoking and moderate drinking). In some embodiments, the health reminders further include reminding the subject to stay at home for one month after the PFO closure procedure and to avoid strenuous exercise and lifting heavy objects. In some embodiments, the medications for the medication reminders include antiplatelet drugs and antiepileptic drugs. In some specific embodiments, the medication plan for the antiplatelet drugs includes taking 100 mg / day of aspirin and 75 mg / day of clopidogrel in combination for six months postoperatively, and taking 100 mg / day of aspirin from the seventh to the twelfth month postoperatively. In some embodiments, the medication schedule for the antiepileptic drug is to maintain the subject's preoperative antiepileptic drug treatment plan. In some specific embodiments, the health guidance submodule 208 provides medication reminders at a specific frequency (e.g., once a day, twice a day) based on the subject's medication schedule. In some embodiments, the reminder times for the medication reminders can be pre-set, for example, to one or more medication times (e.g., 9:00, 14:00, 20:00). In some embodiments, the examination reminders include epilepsy-related examinations and PFO-related examinations. In some embodiments, the reminder times for the examination reminders can be pre-set, for example, to every three months postoperatively.

[0077] In some embodiments, the postoperative management module 108 further includes a postoperative follow-up submodule 206. The postoperative follow-up submodule 206 is used to receive and analyze postoperative treatment efficacy data of the subject. In some embodiments, the postoperative treatment efficacy data includes epileptic seizure data, daily medication data, and occlusion device data. In some embodiments, the postoperative treatment efficacy data is obtained from the subject. In some embodiments, the postoperative treatment efficacy data is obtained from a supervisor, e.g., a healthcare professional. In some embodiments, the medications in the daily medication data include antiplatelet drugs and antiepileptic drugs. In some embodiments, the medications in the daily medication data may further include other medications. In some embodiments, the epileptic seizure data includes epileptic seizure frequency and epileptic seizure duration. In some embodiments, the occlusion device data includes the location and function of the occlusion device, presence or absence of occlusion thrombus, presence or absence of cardiac structural abnormalities, and postoperative residual shunt.

[0078] If a predetermined event occurs, the postoperative follow-up submodule 206 provides feedback information to the subject and the supervisor. In some embodiments, the predetermined event may include one or more of the following: (1) abnormalities in daily medication data (e.g., failure to receive data on the administration of the antiplatelet drug and / or the antiepileptic drug at a predetermined time (e.g., 20:00) (i.e., missed dose), or the subject taking a drug unsuitable for administration); (2) abnormalities in epileptic seizure data (e.g., increased seizure frequency and / or seizure duration (i.e., worsening of seizures)); (3) abnormalities in occlusion device data (e.g., appearance of occlusion thrombus); or (4) failure to receive postoperative treatment effectiveness data from the supervisor within a certain period (e.g., within two weeks) after the occurrence of the above predetermined event or after a predetermined examination reminder time. In some embodiments, the feedback information may be provided to the subject via video message, voice message, or other possible means. The subject should promptly visit the hospital after receiving the feedback information, and after the visit, postoperative treatment effectiveness data from the subject's supervisor is transmitted to the postoperative follow-up submodule 206. In some embodiments, the postoperative follow-up submodule 206 can also compare the postoperative treatment effectiveness data from the subject with the postoperative treatment effectiveness data from the supervisor to assess the subject's adherence to their current medication plan.

[0079] In some other embodiments, the feedback information may further include information that encourages the subject to maintain the current medication plan.

[0080] As shown in Figure 5, in some embodiments, the postoperative follow-up submodule 206 transmits the postoperative treatment effect data to the model building submodule 204. The subject's postoperative treatment effect data and subject data can be used as newly acquired sample data (which may also be classified into "marked improvement group" and "no marked improvement group") to further optimize the efficacy evaluation model.

[0081] In some embodiments, the postoperative follow-up submodule 206 may also transmit the postoperative treatment effect data to the patient selection module 104, which further updates the exclusion and selection criteria (for example, excluding certain epilepsy patient groups unsuitable for PFO surgery).

[0082] In some embodiments, the medical treatment system 100 may further include a surgical process standardization management module 110, which specifically includes the following steps.

[0083] Device insertion procedure S401: Under local anesthesia, the femoral vein is punctured and a guidewire is placed. An appropriate model of closure device is selected according to the size of the foramen ovale. The sheath is advanced along the guidewire through the foramen ovale to the left atrium under ultrasound guidance, and the patent foramen ovale closure plug is released.

[0084] Positioning procedure S402: Use transthoracic echocardiography to confirm that the closure device is correctly positioned in the foramen ovale.

[0085] Closure device placement procedure S403: Slowly release the closure device (the closure plug is mesh-like, and tissue will gradually fill the holes in the mesh, closing the foramen ovale) and continue until it completely fills and closes the foramen ovale.

[0086] Examination procedure S404: Use transthoracic echocardiography again to confirm that the closure device has successfully closed the foramen ovale.

[0087] Device Removal Procedure S405: After the surgery is complete, slowly remove the catheter and device from the groin and apply pressure to the femoral vein puncture site.

[0088] Perioperative observation procedure S406: The patient is transferred to the recovery room and observed for 7 days to ensure that no complications occur.

[0089] The medical system provided by the present invention has a complete patient selection and exclusion evaluation system and standardized management, and is useful for guiding the selection, decision-making, and postoperative management of epilepsy patients suitable for PFO closure.

[0090] The following shows one specific application scenario of the present invention.

[0091] Patient A is a patient with refractory epilepsy accompanied by PFO. Patient A's electronic medical record data is entered via the first terminal 302 and then transmitted via the network 306 to the patient medical record information acquisition and storage module 102 of the medical system 100. The patient medical record information acquisition and storage module 102 acquires and stores Patient A's electronic medical record data. If the patient selection module 104 selects Patient A as a suitable subject for PFO closure surgery based on pre-set selection and exclusion criteria, the preoperative efficacy evaluation module 106 (specifically the evaluation submodule 202) acquires Patient A's electronic medical record data, calls a pre-built efficacy evaluation model, analyzes Patient A's electronic medical record data, and evaluates the efficacy of PFO closure surgery for Patient A. As output, the preoperative efficacy evaluation module 106 generates a report indicating the efficacy of Patient A undergoing PFO closure surgery and can transmit the evaluation results via the network 306 to the first terminal 302 and / or the second terminal 304. If patient A's overall score exceeds a pre-set effectiveness score threshold (e.g., 60 points), patient A is recommended to undergo PFO closure surgery. If patient A undergoes PFO closure surgery, the postoperative management module 108 provides long-term guidance and follow-up to patient A. Patient A receives reminders from the health guidance submodule 208 and transmits postoperative treatment effectiveness data via the second terminal 304 to the postoperative follow-up submodule 206 through the network 306. Patient A should also regularly visit a recommended or affiliated hospital, which transmits postoperative treatment effectiveness data from patient A's supervisor to the postoperative follow-up submodule 206 via the first terminal 302. The postoperative follow-up submodule 206 tracks and analyzes the postoperative treatment effectiveness data and verifies that patient A's antiepileptic drug regimen and closure device are functioning correctly. If Patient A's postoperative epileptic seizure symptoms worsen and / or the closure device malfunctions, Patient A will be reminded to visit the hospital, where the hospital will conduct a thorough evaluation and adjust the treatment plan to control the epileptic seizures and / or maintain the closure device in proper function.The data from patient A (subject data + postoperative treatment effect data) can be used as new sample data to further optimize the efficacy evaluation model of evaluation submodule 202 and the exclusion / selection criteria of patient selection module 104.

[0092] Through the above description of embodiments, those skilled in the art will clearly understand that the methods of the above embodiments can be implemented using software and a necessary general-purpose hardware platform, and of course, through hardware, but in many cases the former is a better embodiment. Based on this understanding, the essence of the technical solutions of the present invention, or the part that contributes to the prior art, can be embodied in the form of a software product, which is stored in a storage medium (ROM / RAM, magnetic disk, optical disk, etc.) and includes a plurality of instructions for causing a computer terminal (which may be a mobile phone, computer, server, or network device, etc.) to perform the methods of each embodiment of the present invention.

[0093] Although embodiments of the present invention have been described above in conjunction with the drawings, the present invention is not limited to the above-described specific embodiments, and the above-described specific embodiments are merely illustrative and not limiting. Those skilled in the art will be able to make many forms under the revelation of the present invention without departing from the spirit of the invention and the scope protected by the claims, and all of these fall within the scope of protection of the present invention.

[0094] [References] PT Hagen, DG Scholz, WD Edwards. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts. MAYO CLIN PROC 1984;59(1):17-20. doi: 10.1016 / s0025-6196(12)60336-x pmid:66944271984-01-01]. P. A. Calvert, B. S. Rana, A. C. Kydd, L. M. Shapiro. Patent foramen ovale: anatomy, outcomes, and closure. NAT REV CARDIOL 2011;8(3):148-60. doi: 10.1038 / nrcardio.2010.224 pmid:212831482011-03-01]. S. F. Rimoldi, S. Ott, E. Rexhaj, et al. Patent Foramen Ovale Closure in Obstructive Sleep Apnea Improves Blood Pressure and Cardiovascular Function. HYPERTENSION 2015;66(5):1050-57. doi: 10.1161 / HYPERTENSIONAHA.115. 06303 pmid:26418025.[(c) 2015 American Heart Association, Inc.:*2015-11-01]. WG Rd Kussmaul. Different Strokes. ANN INTERN MED 2020;172(11):761-62. doi: 10.7326 / M20-1879 pmid:324220672020-06-02]. S. Kutty, P. P. Sengupta, B. K. Khandheria. Patent foramen ovale: the known and the to be known. J AM COLL CARDIOL 2012;59(19):1665-71. doi: 10.1016 / j.jacc.2011.09.085 pmid:22554596.[Copyright (c) 2012 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.:*2012-05-08]. K. I. Strauss, K. V. Elisevich. Brain region and epilepsy-associated differences in inflammatory mediator levels in medically refractory mesial temporal lobe epilepsy. J Neuroinflammation 2016;13(1):270. doi: 10.1186 / s12974-016-0727-z pmid:277377162016-10-13]. J. Detour, C. Bund, C. Behr, et al. Metabolomic characterization of human hippocampus from drug-resistant epilepsy with mesial temporal seizure. EPILEPSIA 2018;59(3):607-16. doi: 10.1111 / epi.14000 pmid:29341105.[Wiley Periodicals, Inc. (c) 2018 International League Against Epilepsy.:*2018-03-01]. M. Puligheddu, M. Melis, G. Pillolla, et al. Rationale for an adjunctive therapy with fenofibrate in pharmacoresistant nocturnal frontal lobe epilepsy. EPILEPSIA 2017;58(10):1762-70. doi: 10.1111 / epi.13863 pmid:28766701.[Wiley Periodicals, Inc. (c) 2017 International League Against Epilepsy.:*2017-10-01]. M. Eickhoff, S. Kovac, P. Shahabi, et al. Spreading depression triggers ictaform activity in partially disinhibited neuronal tissues. EXP NEUROL 2014;253:1-15. doi: 10.1016 / j.expneurol.2013.12.008 pmid:24368193.[Copyright (c) 2013 Elsevier Inc. All rights reserved.:*2014-03-01]. L. Zhang, X. Zhu, X. Qiu, et al. Relationship between right-to-left shunt and migraine in patients with epilepsy: a single-centre, cross-sectional study in China. BMJ OPEN 2018;8(10):e24144. doi: 10.1136 / bmjopen-2018-024144 pmid:30297353.[(c) Author(s) (or their employer(s)) 2018. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.:*2018-10-08]. Madhkour R, Wahl A, Praz F, Meier B. Amplatzer patent foramen ovale occluder: safety and efficacy. EXPERT REV MED DEVIC 2019;16(3):173-82. doi: 10.1080 / 17434440.2019.1581060. Billett J, Cowie MR, Gatzoulis MA, Vonder Muhll IF, Majeed A. Comorbidity, healthcare utilisation and process of care measures in patients with congenital heart disease in the UK: cross-sectional, population-based study with case-control analysis. Heart (British Cardiac Society) 2008;94(9):1194-99. doi: 10.1136 / hrt.2007.122671. B. Desnous, M. Lenoir, A. Doussau, et al. Epilepsy and seizures in children with congenital heart disease: A prospective study. Seizure 2019;64:50-53. doi: 10.1016 / j.seizure.2018.11.011 pmid:30557820.[Copyright (c) 2018 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.:*2019-01-01]. [Explanation of Symbols]

[0095] 100 Medical Systems 102 Patient medical record information acquisition and storage module 104 Patient Selection Module 106 Preoperative efficacy evaluation module 108 Postoperative Management Module 110 Surgical Process Standardization and Management Module 202 Evaluation Submodule 204 Model Building Submodule 206 Postoperative Follow-up Submodule 208 Health Guidance Submodule 302 First Terminal 304 Second Terminal Network 306.

Claims

1. A clinical system for closure surgery in patients with refractory epilepsy accompanied by high shunt flow PFO, A patient medical record information acquisition and storage module for acquiring and storing electronic medical record data of epilepsy patients, wherein the types of electronic medical record data include basic clinical data, epileptic seizure history data, and PFO examination data, the basic clinical data includes sex and age at surgery, the epileptic seizure history data includes age of epilepsy onset, seizure frequency, normality of 24-hour electroencephalogram (EEG) examination, and seizure duration, the PFO examination data includes presence or absence of PFO and right-to-left shunt grade, and the electronic medical record data includes sample data from a sample population and subject data from a subject, A patient selection module for acquiring subject data via the patient medical record information acquisition and storage module, and selecting subjects who are potentially suitable for PFO closure surgery based on the subject data, A preoperative efficacy evaluation module for performing a preoperative efficacy evaluation of the PFO closure procedure on the subject selected by the patient selection module, the preoperative efficacy evaluation module includes an evaluation submodule for acquiring subject data via the patient medical record information acquisition and storage module, calling an efficacy evaluation model to analyze the subject data, and thereby evaluating the efficacy of the subject if the subject undergoes the PFO closure procedure, Equipped with, The aforementioned effectiveness is calculated by the following formula: S=β 1 ×X 1 +b 2 ×X 2 +b 3 ×X 3 +b 4 ×X 4 +b 5 ×X 5 +b 6 ×X 6 β １ , β ２ , ..., β ６ represents the weight of the feature variable, S represents the overall effectiveness score, and X represents the weight of the feature variable. １ The 'X' indicates the age classification at the time of surgery. ２ The 'X' indicates the age classification for epilepsy onset, X ３ X indicates gender. ４ The symbol indicates the classification of epileptic seizure frequency, X ５ X indicates whether the 24-hour EEG test is normal or not. ６ This shows the classification of epileptic seizure duration, β １ or β ６ These are X １ or X ６ This shows the proportion of each individual odds ratio (OR) to the sum of the OR values ​​of the feature variables. Medical system.

2. The system further comprises a postoperative management module for tracking the postoperative health status of the subject who underwent the PFO closure procedure, The system according to claim 1, wherein the postoperative management module includes a health guidance submodule for providing reminder information to the subject who has undergone the PFO closure procedure, the reminder information including medication reminders, health reminders, and examination reminders.

3. The system according to claim 2, wherein the postoperative management module further comprises a postoperative follow-up submodule for receiving and analyzing postoperative treatment efficacy data of the subject, the postoperative treatment efficacy data comprising epileptic seizure data, daily medication data, and closed device data.

4. The drugs in the aforementioned daily drug use data include antiplatelet drugs and antiepileptic drugs. The aforementioned closure device data includes the location and function of the closure device, the presence or absence of occluding thrombus, the presence or absence of cardiac structural abnormalities, and residual shunt after surgery. The system according to claim 3, wherein the epileptic seizure data includes the frequency of epileptic seizures and the duration of epileptic seizures.

5. The system according to claim 3, wherein the postoperative treatment effect data is obtained from the subject and / or supervisor.

6. The aforementioned patient selection module is Using selection criteria including (1) being between 9 and 55 years of age at the time of surgery, and (2) being an epileptic patient with PFO, epileptic patients who may be suitable to undergo the PFO closure procedure are identified. The system according to claim 1, wherein persons unsuitable for PFO closure are excluded using exclusion criteria including (1) persons who do not meet the selection criteria, (2) patients with secondary epilepsy caused by one or more of the following: tumor, traumatic brain injury, encephalitis, or neurotoxicity, and (3) persons who are intolerant to antiplatelet drug therapy.

7. The system according to claim 1, wherein the preoperative efficacy evaluation module further includes a model building submodule for constructing the efficacy evaluation model by performing statistical analysis on the sample data.

8. The system according to claim 3, wherein the subject data and postoperative treatment effect data of the subject are used as new sample data to optimize the effectiveness evaluation model.

9. The system according to claim 1, characterized in that the effectiveness evaluation model scores the subjects, and subjects whose overall score exceeds 40, 50, 60, 70, 80, or 90 points are predicted to be effective in undergoing the PFO closure procedure.

10. The system according to claim 9, characterized in that the subject whose overall score exceeds 60 points is predicted to be beneficial to undergo the PFO closure procedure.

Images