CN119173199A - 用于检测和监测心血管疾病的装置和方法 - Google Patents

用于检测和监测心血管疾病的装置和方法 Download PDF

Info

Publication number
CN119173199A
CN119173199A CN202380032946.3A CN202380032946A CN119173199A CN 119173199 A CN119173199 A CN 119173199A CN 202380032946 A CN202380032946 A CN 202380032946A CN 119173199 A CN119173199 A CN 119173199A
Authority
CN
China
Prior art keywords
sensor
sensor assembly
cardiac
processor
heart
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Pending
Application number
CN202380032946.3A
Other languages
English (en)
Chinese (zh)
Inventor
加埃塔诺·加尔吉洛
尼尔·劳伦斯·安德森
里塔班·杜塔
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
3 Target Intellectual Property Co ltd
Original Assignee
3 Target Intellectual Property Co ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from AU2022900926A external-priority patent/AU2022900926A0/en
Application filed by 3 Target Intellectual Property Co ltd filed Critical 3 Target Intellectual Property Co ltd
Publication of CN119173199A publication Critical patent/CN119173199A/zh
Pending legal-status Critical Current

Links

Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235Details of waveform analysis
    • A61B5/7246Details of waveform analysis using correlation, e.g. template matching or determination of similarity
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/02028Determining haemodynamic parameters not otherwise provided for, e.g. cardiac contractility or left ventricular ejection fraction
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/021Measuring pressure in heart or blood vessels
    • A61B5/02108Measuring pressure in heart or blood vessels from analysis of pulse wave characteristics
    • A61B5/02116Measuring pressure in heart or blood vessels from analysis of pulse wave characteristics of pulse wave amplitude
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/024Measuring pulse rate or heart rate
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/024Measuring pulse rate or heart rate
    • A61B5/02405Determining heart rate variability
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/024Measuring pulse rate or heart rate
    • A61B5/02438Measuring pulse rate or heart rate with portable devices, e.g. worn by the patient
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/024Measuring pulse rate or heart rate
    • A61B5/0245Measuring pulse rate or heart rate by using sensing means generating electric signals, i.e. ECG signals
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316Modalities, i.e. specific diagnostic methods
    • A61B5/318Heart-related electrical modalities, e.g. electrocardiography [ECG]
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/24Detecting, measuring or recording bioelectric or biomagnetic signals of the body or parts thereof
    • A61B5/316Modalities, i.e. specific diagnostic methods
    • A61B5/318Heart-related electrical modalities, e.g. electrocardiography [ECG]
    • A61B5/346Analysis of electrocardiograms
    • A61B5/349Detecting specific parameters of the electrocardiograph cycle
    • A61B5/35Detecting specific parameters of the electrocardiograph cycle by template matching
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/48Other medical applications
    • A61B5/4842Monitoring progression or stage of a disease
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235Details of waveform analysis
    • A61B5/7264Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271Specific aspects of physiological measurement analysis
    • A61B5/7275Determining trends in physiological measurement data; Predicting development of a medical condition based on physiological measurements, e.g. determining a risk factor
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7271Specific aspects of physiological measurement analysis
    • A61B5/7282Event detection, e.g. detecting unique waveforms indicative of a medical condition
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/74Details of notification to user or communication with user or patient; User input means
    • A61B5/746Alarms related to a physiological condition, e.g. details of setting alarm thresholds or avoiding false alarms
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B7/00Instruments for auscultation
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/08Clinical applications
    • A61B8/0883Clinical applications for diagnosis of the heart
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B8/00Diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/52Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves
    • A61B8/5215Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data
    • A61B8/5223Devices using data or image processing specially adapted for diagnosis using ultrasonic, sonic or infrasonic waves involving processing of medical diagnostic data for extracting a diagnostic or physiological parameter from medical diagnostic data
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H40/00ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices
    • G16H40/60ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices
    • G16H40/63ICT specially adapted for the management or administration of healthcare resources or facilities; ICT specially adapted for the management or operation of medical equipment or devices for the operation of medical equipment or devices for local operation
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/20ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for computer-aided diagnosis, e.g. based on medical expert systems
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/70ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for mining of medical data, e.g. analysing previous cases of other patients
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2560/00Constructional details of operational features of apparatus; Accessories for medical measuring apparatus
    • A61B2560/02Operational features
    • A61B2560/0223Operational features of calibration, e.g. protocols for calibrating sensors
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/02Details of sensors specially adapted for in-vivo measurements
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B2562/00Details of sensors; Constructional details of sensor housings or probes; Accessories for sensors
    • A61B2562/06Arrangements of multiple sensors of different types
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/02Detecting, measuring or recording for evaluating the cardiovascular system, e.g. pulse, heart rate, blood pressure or blood flow
    • A61B5/02007Evaluating blood vessel condition, e.g. elasticity, compliance
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61BDIAGNOSIS; SURGERY; IDENTIFICATION
    • A61B5/00Measuring for diagnostic purposes; Identification of persons
    • A61B5/72Signal processing specially adapted for physiological signals or for diagnostic purposes
    • A61B5/7235Details of waveform analysis
    • A61B5/7264Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems
    • A61B5/7267Classification of physiological signals or data, e.g. using neural networks, statistical classifiers, expert systems or fuzzy systems involving training the classification device
    • GPHYSICS
    • G16INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR SPECIFIC APPLICATION FIELDS
    • G16HHEALTHCARE INFORMATICS, i.e. INFORMATION AND COMMUNICATION TECHNOLOGY [ICT] SPECIALLY ADAPTED FOR THE HANDLING OR PROCESSING OF MEDICAL OR HEALTHCARE DATA
    • G16H50/00ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics
    • G16H50/30ICT specially adapted for medical diagnosis, medical simulation or medical data mining; ICT specially adapted for detecting, monitoring or modelling epidemics or pandemics for calculating health indices; for individual health risk assessment

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Biomedical Technology (AREA)
  • Public Health (AREA)
  • Medical Informatics (AREA)
  • General Health & Medical Sciences (AREA)
  • Pathology (AREA)
  • Surgery (AREA)
  • Animal Behavior & Ethology (AREA)
  • Molecular Biology (AREA)
  • Veterinary Medicine (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Physics & Mathematics (AREA)
  • Biophysics (AREA)
  • Cardiology (AREA)
  • Physiology (AREA)
  • Artificial Intelligence (AREA)
  • Signal Processing (AREA)
  • Computer Vision & Pattern Recognition (AREA)
  • Epidemiology (AREA)
  • Primary Health Care (AREA)
  • Psychiatry (AREA)
  • Data Mining & Analysis (AREA)
  • Databases & Information Systems (AREA)
  • General Business, Economics & Management (AREA)
  • Business, Economics & Management (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Radiology & Medical Imaging (AREA)
  • Vascular Medicine (AREA)
  • Evolutionary Computation (AREA)
  • Fuzzy Systems (AREA)
  • Mathematical Physics (AREA)
  • Measuring Pulse, Heart Rate, Blood Pressure Or Blood Flow (AREA)
  • Measurement And Recording Of Electrical Phenomena And Electrical Characteristics Of The Living Body (AREA)
CN202380032946.3A 2022-04-08 2023-04-05 用于检测和监测心血管疾病的装置和方法 Pending CN119173199A (zh)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
AU2022900926A AU2022900926A0 (en) 2022-04-08 A device and method for the early detection of heart failure
AU2022900926 2022-04-08
PCT/AU2023/050273 WO2023193053A1 (en) 2022-04-08 2023-04-05 A device and method for the detection and monitoring of cardiovascular disease

Publications (1)

Publication Number Publication Date
CN119173199A true CN119173199A (zh) 2024-12-20

Family

ID=88243645

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202380032946.3A Pending CN119173199A (zh) 2022-04-08 2023-04-05 用于检测和监测心血管疾病的装置和方法

Country Status (6)

Country Link
US (1) US20250248658A1 (https=)
EP (1) EP4504040A4 (https=)
JP (1) JP2025512817A (https=)
CN (1) CN119173199A (https=)
AU (1) AU2023249228A1 (https=)
WO (1) WO2023193053A1 (https=)

Family Cites Families (15)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2555807A1 (en) * 2004-02-12 2005-08-25 Biopeak Corporation Non-invasive method and apparatus for determining a physiological parameter
US8571643B2 (en) * 2010-09-16 2013-10-29 Flint Hills Scientific, Llc Detecting or validating a detection of a state change from a template of heart rate derivative shape or heart beat wave complex
US11350871B2 (en) * 2008-01-25 2022-06-07 Flint Hills Scientific, L.L.C. Contingent cardio-protection for epilepsy patients
US9420959B2 (en) * 2010-12-15 2016-08-23 Cardiac Pacemakers, Inc. Detecting heart failure by monitoring the time sequence of physiological changes
US9049994B2 (en) * 2011-09-21 2015-06-09 Siemens Medical Solutions Usa, Inc. System for cardiac arrhythmia detection and characterization
WO2013160537A1 (en) * 2012-04-23 2013-10-31 Turun Yliopisto Method and apparatus for determining information indicative of cardiac malfunctions and abnormalities
EP2769668B1 (fr) * 2013-02-26 2021-10-13 Sorin CRM SAS Ensemble pour le diagnostic adaptatif de l'insuffisance cardiaque moyennant des classifieurs et un arbre de décision booléen
KR102080113B1 (ko) * 2018-05-14 2020-02-21 전문석 디지털 ecg 전압 좌표 값을 이용한 혈압 측정 장치 및 방법
GB2582124A (en) * 2018-09-07 2020-09-16 Transf Ai Ltd Analysis of cardiac data
AU2020365762A1 (en) * 2019-10-18 2022-04-21 3 Aim Ip Pty Ltd Physiological parameter sensing systems and methods
JP6893002B1 (ja) * 2020-08-31 2021-06-23 国立大学法人 東京大学 情報処理システム及びプログラム
EP4014850B1 (en) * 2020-12-16 2024-07-24 Polar Electro Oy Method for measuring pre-ejection period
JP2024516573A (ja) * 2021-04-16 2024-04-16 3 エイム アイピー プロプライエトリー リミテッド 生理学パラメータ検知システム及び方法
US11496232B1 (en) * 2021-05-03 2022-11-08 Nihon Kohden Digital Health Solutions, Inc. Waveform synchronization system for data received from a network
EP4362782A4 (en) * 2021-05-25 2025-05-14 Sports Data Labs, Inc. Method and system for generating dynamic real-time predictions using heart rate variability

Also Published As

Publication number Publication date
JP2025512817A (ja) 2025-04-22
EP4504040A4 (en) 2026-03-25
US20250248658A1 (en) 2025-08-07
EP4504040A1 (en) 2025-02-12
AU2023249228A1 (en) 2024-09-26
WO2023193053A1 (en) 2023-10-12

Similar Documents

Publication Publication Date Title
US12213812B2 (en) Monitoring physiological status based on bio- vibrational and radio frequency data analysis
US20230082362A1 (en) Processes and methods to predict blood pressure
US7771364B2 (en) Method and system for cardiovascular system diagnosis
Kachuee et al. Cuff-less high-accuracy calibration-free blood pressure estimation using pulse transit time
US8473041B2 (en) Cardiography system and method using automated recognition of hemodynamic parameters and waveform attributes
US20230218178A1 (en) Construction method and application of digital human cardiovascular system based on hemodynamics
US20080045844A1 (en) Method and system for cardiovascular system diagnosis
US20070021673A1 (en) Method and system for cardiovascular system diagnosis
CN101801263A (zh) 监测生理状况和检测异常
CN118922128A (zh) 用于肥厚型心肌病估计的多传感器mems系统和机器学习分析方法
JP2003260033A (ja) 血管圧力波形検出装置、生体血管状態決定方法、および血管圧力波形検出装置の製造方法
US20250169700A1 (en) Machine learning techniques for estimating carotid-femoral pulse wave velocity and/or vascular age from single-site arterial waveform measurements
US20060224070A1 (en) System and method for non-invasive cardiovascular assessment from supra-systolic signals obtained with a wideband external pulse transducer in a blood pressure cuff
Hsiao et al. Design and implementation of auscultation blood pressure measurement using vascular transit time and physiological parameters
Iskandar et al. Design and implementation electronic stethoscope on smart chair for monitoring heart rate and stress levels driver
CN119173199A (zh) 用于检测和监测心血管疾病的装置和方法
A‐Mohannadi et al. Conventional Clinical Methods for Predicting Heart Disease
US20240298903A1 (en) Blood pressure estimation
Khosrow-Khavar Automatic and non-invasive delineation of the seismocardiogram signal for the estimation of cardiac time intervals with applications in diastolic timed vibration and early stage hemorrhage detection
Anisimov et al. Comparison of heart rate derived from ECG and pulse wave signals during controlled breathing test for biofeedback systems
Muehlsteff et al. Cardiac status assessment with a multi-signal device for improved home-based congestive heart failure management
Fainzilberg Generalized approach to building computer’s tools of preventive medicine for home using
Salman et al. Minimally Invasive and Non‐Invasive Sensor Technologies for Predicting Heart Failure: An Overview
Paiva Beat-to-beat cardiac output inference using heart sounds
JP2024546697A (ja) A/v比を自動的に計算するためのlap信号処理

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination