Linking NHS data for pediatric pharmacovigilance: Results of a Delphi survey

Background: Adverse drug events are a major cause of patient safety incidents. Current systems of pharmacovigilance under-report adverse drug reactions (ADRs), especially in children, leading to delays in their identification. This is of particular concern, as children especially have an increased vulnerability toADRs. Objectives: The objective was to seek consensus among healthcare professionals (HCPs) about barriers and facilitators to the linkage of routinely collected health data for pediatric pharmacovigilance in Scotland. Methods: A Delphi survey was conducted with a random sample of HCPs including nurses, pharmacists and doctors, working in primary or secondary care, in Scotland. Participants were identified from sampling frames of the target professionals such as an NHS workforce list for general practitioners and recruited by postal invitation. A total of 819 HCPs were invited to take part. Those agreeing to participate were given the option of completing the questionnaires online or as hard copy. Reminders were sent twice at a fortnightly interval. Questions content included description of professional role as well as testing for the willingness to support the proposed project and was informed by the Theoretical Domains Framework of Behavior Change (TDF) and earlier qualitative work. Three Delphi rounds were administered, including a first round for item generation. Results: 121 of those invited agreed to take part (15%). The first round of the Delphi study included 21 open questions and generated over a 1000 individual statements from 61 participants that returned the questionnaires (50.4%). These were rationalized to 149 items for the second round in which participants rated their views on the importance (or not) of each item on a 9-point Likert scale (strongly disagree - strongly agree). After the third round, there was consensus on items that focused on professional standards, and practical requirements, overall there was support for data linkage and a multi-professional approach. Conclusions: It would be acceptable to stakeholders to introduce a data linkage system for pharmacovigilance as long as identified concerns are addressed. Concerns included adherence to current professional, legal and ethical standards, as well resolving practical issues

Integrated Circuits for 3D High-Frame-Rate Intracardiac Echocardiography Probes

This thesis describes the design of application-specific integrated circuits (ASICs) for high-frame-rate 3D intracardiac echocardiography (ICE) probes. The work follows the whole process from the analysis of the application to the testing of a prototype with all envisioned functionality. It starts with the evaluation of the main challenges posed by ultrasound imaging from the tip of a catheter with a diameter in the order of 3 mm and its implications on the circuit design. A broad literature review in the field of ICE probe development but also regarding general ultrasound electronics provides the basis for this work and motivates later design choices. A high-frame-rate 3D imaging scheme is developed based on the needs of the application and leads to the design targets of the imager array and electronics. The final ASIC architecture is reached over the course of two prototypes to enable the evaluation of block-level functionality and advanced debugging. The thesis provides a detailed description of the circuit implementation with introduced novelties and shows characterization results in the electrical as well as acoustic domain. In the following, the contents of each chapter of the main matter are summarized in one paragraph...

Integrated Circuits for 3D High-Frame-Rate Intracardiac Echocardiography Probes

This thesis describes the design of application-specific integrated circuits (ASICs) for high-frame-rate 3D intracardiac echocardiography (ICE) probes. The work follows the whole process from the analysis of the application to the testing of a prototype with all envisioned functionality. It starts with the evaluation of the main challenges posed by ultrasound imaging from the tip of a catheter with a diameter in the order of 3 mm and its implications on the circuit design. A broad literature review in the field of ICE probe development but also regarding general ultrasound electronics provides the basis for this work and motivates later design choices. A high-frame-rate 3D imaging scheme is developed based on the needs of the application and leads to the design targets of the imager array and electronics. The final ASIC architecture is reached over the course of two prototypes to enable the evaluation of block-level functionality and advanced debugging. The thesis provides a detailed description of the circuit implementation with introduced novelties and shows characterization results in the electrical as well as acoustic domain. In the following, the contents of each chapter of the main matter are summarized in one paragraph....Electronic Instrumentatio

Feasibility of High Frame Rate 3-D Intracardiac Echography using Fan-Beam Transmissions

ImPhys/Imaging PhysicsImPhys/Medical ImagingElectronic Instrumentatio

Imaging Scheme for 3-D High-Frame-Rate Intracardiac Echography: A Simulation Study

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is normally treated by RF ablation. Intracardiac echography (ICE) is widely employed during RF ablation procedures to guide the electrophysiologist in navigating the ablation catheter, although only 2-D probes are currently clinically used. A 3-D ICE catheter would not only improve visualization of the atrium and ablation catheter, but it might also provide the 3-D mapping of the electromechanical wave (EW) propagation pattern, which represents the mechanical response of cardiac tissue to electrical activity. The detection of this EW needs 3-D high-frame-rate imaging, which is generally only realizable in tradeoff with channel count and image quality. In this simulation-based study, we propose a high volume rate imaging scheme for a 3-D ICE probe design that employs 1-D micro-beamforming in the elevation direction. Such a probe can achieve a high frame rate while reducing the channel count sufficiently for realization in a 10-Fr catheter. To suppress the grating-lobe (GL) artifacts associated with micro-beamforming in the elevation direction, a limited number of fan-shaped beams with a wide azimuthal and narrow elevational opening angle are sequentially steered to insonify slices of the region of interest. An angular weighted averaging of reconstructed subvolumes further reduces the GL artifacts. We optimize the transmit beam divergence and central frequency based on the required image quality for EW imaging (EWI). Numerical simulation results show that a set of seven fan-shaped transmission beams can provide a frame rate of 1000 Hz and a sufficient spatial resolution to visualize the EW propagation on a large 3-D surface. Accepted Author ManuscriptImPhys/Imaging PhysicsImPhys/Medical ImagingElectronic Instrumentatio

A Pitch-Matched ASIC with Integrated 65V TX and Shared Hybrid Beamforming ADC for Catheter-Based High-Frame-Rate 3D Ultrasound Probes

Intra-cardiac echography (ICE) probes (Fig. 32.2.1) are widely used in electrophysiology for their good procedure guidance and relatively safe application. ASICs are increasingly employed in these miniature probes to enhance signal quality and reduce the number of connections needed in mm-diameter catheters [1]-[5]. 3D visualization in real-time is additionally enabled by 2D transducer arrays with, for each transducer element, a high-voltage (HV) transmit (TX) part, to generate acoustic pulses of sufficient pressure, and a receive (RX) path, to process the resulting echoes. To achieve the required reduction in RX channels, micro-beamforming (BF), which merges the signals from a subarray using a delay-and-sum operation, has been shown to be an effective solution [3], [4]. However, due to the frame-rate reduction that is associated with BF, these designs cannot serve emerging high-frame-rate imaging modes (1000 volumes/s) like 3D blood-flow and elastography imaging. In-probe digitization has recently been investigated to provide further channel-count reduction, make data transmission more robust, and enable pre-processing in the probe [1]-[3]. However, these earlier designs have either no TX functionality [2], [3] or only low-voltage (LV) TX [1] integrated. Combining BF and digitization with area-hungry HV transmitters in a pitch-matched scalable fashion while supporting high-frame-rate imaging remains an unmet challenge. The work presented in this paper meets this target, enabled by a hybrid ADC, the small die size of which allows for co-integration with 65V element-level pulsers.</p

Transceiver ASIC Design for High-Frame-Rate 3D Intracardiac Echocardiography

This work describes an ASIC design for high-frame-rate 3D intracardiac echocardiography probes. The chip is the first to combine element-level high-voltage pulsers and time-gain-compensation analog frontends as well as subarray beamformers and in-probe digitization in a pitch-matched fashion. The integration challenge is met by a shared hybrid beamforming ADC with the highest reported area and power efficiency. The achieved beamformer size of three elements enables acquisition at 1000 volumes/s while, in combination with a custom datalink, still providing sufficient channel-count reduction for catheter integration.Electronic InstrumentationImPhys/Imaging PhysicsImPhys/Medical Imagin

A Compact Integrated High-Voltage Pulser Insensitive to Supply Transients for 3-D Miniature Ultrasound Probes

In this letter, a compact high-voltage (HV) transmit circuit for dense 2-D transducer arrays used in 3-D ultrasonic imaging systems is presented. Stringent area requirements are addressed by a unipolar pulser with embedded transmit/receive switch. Combined with a capacitive HV level shifter, it forms the ultrasonic HV transmit circuit with the lowest reported HV transistor count and area without any static power consumption. The balanced latched-based level shifter implementation makes the design insensitive to transients on the HV supply caused by pulsing, facilitating application in probes with limited local supply decoupling, such as imaging catheters. Favorable scaling through resource sharing benefits massively arrayed architectures while preserving full individual functionality. A prototype of 8 × 9 elements was fabricated in the TSMC 0.18 μm HV BCD technology and a 160μm×160μm PZT transducer matrix is manufactured on the chip. The system is designed to drive 65-V peak-to-peak pulses on 2-pF transducer capacitance and hardware sharing of six elements allows for an area of only 0.008 mm2 per element. Electrical characterization as well as acoustic results obtained with the 6-MHz central frequency transducer are demonstrated.Accepted author manuscriptElectronic InstrumentationImPhys/Medical Imagin

A Pitch-Matched ASIC with Integrated 65V TX and Shared Hybrid Beamforming ADC for Catheter-Based High-Frame-Rate 3D Ultrasound Probes

Intra-cardiac echography (ICE) probes (Fig. 32.2.1) are widely used in electrophysiology for their good procedure guidance and relatively safe application. ASICs are increasingly employed in these miniature probes to enhance signal quality and reduce the number of connections needed in mm-diameter catheters [1]-[5]. 3D visualization in real-time is additionally enabled by 2D transducer arrays with, for each transducer element, a high-voltage (HV) transmit (TX) part, to generate acoustic pulses of sufficient pressure, and a receive (RX) path, to process the resulting echoes. To achieve the required reduction in RX channels, micro-beamforming (BF), which merges the signals from a subarray using a delay-and-sum operation, has been shown to be an effective solution [3], [4]. However, due to the frame-rate reduction that is associated with BF, these designs cannot serve emerging high-frame-rate imaging modes (1000 volumes/s) like 3D blood-flow and elastography imaging. In-probe digitization has recently been investigated to provide further channel-count reduction, make data transmission more robust, and enable pre-processing in the probe [1]-[3]. However, these earlier designs have either no TX functionality [2], [3] or only low-voltage (LV) TX [1] integrated. Combining BF and digitization with area-hungry HV transmitters in a pitch-matched scalable fashion while supporting high-frame-rate imaging remains an unmet challenge. The work presented in this paper meets this target, enabled by a hybrid ADC, the small die size of which allows for co-integration with 65V element-level pulsers.Accepted author manuscriptElectronic InstrumentationImPhys/Medical Imagin

An Ultrasound Matrix Transducer for High-Frame-Rate 3-D Intra-cardiac Echocardiography

Objective: Described here is the development of an ultrasound matrix transducer prototype for high-frame-rate 3-D intra-cardiac echocardiography. Methods: The matrix array consists of 16 × 18 lead zirconate titanate elements with a pitch of 160 µm × 160 µm built on top of an application-specific integrated circuit that generates transmission signals and digitizes the received signals. To reduce the number of cables in the catheter to a feasible number, we implement subarray beamforming and digitization in receive and use a combination of time-division multiplexing and pulse amplitude modulation data transmission, achieving an 18-fold reduction. The proposed imaging scheme employs seven fan-shaped diverging transmit beams operating at a pulse repetition frequency of 7.7 kHz to obtain a high frame rate. The performance of the prototype is characterized, and its functionality is fully verified. Results: The transducer exhibits a transmit efficiency of 28 Pa/V at 5 cm per element and a bandwidth of 60% in transmission. In receive, a dynamic range of 80 dB is measured with a minimum detectable pressure of 10 Pa per element. The element yield of the prototype is 98%, indicating the efficacy of the manufacturing process. The transducer is capable of imaging at a frame rate of up to 1000 volumes/s and is intended to cover a volume of 70° × 70° × 10 cm. Conclusion: These advanced imaging capabilities have the potential to support complex interventional procedures and enable full-volumetric flow, tissue, and electromechanical wave tracking in the heart.ImPhys/Verweij groupImPhys/Medical ImagingElectronic InstrumentationImPhys/De Jong grou