1 What type of training is required to properly use the device, to obtain reliable and valid measurements. How is training handled? DiaTecne s.r.l. provides the new Help/Tutorial that includes four sections: 1) Help: references to the various features of the software. 2) Quick Guide: tips and tricks on the use of PulsePen. 3) Tutorial: elements of theory and example videos. 4) User Manual: reference document for the installation and use of the instrument. It's included in the software package of the instrument but it can be also downloaded from the website. Our suggestion is to start using the PulsePen with all the information provided by the help/tutorial, which usually is enough combined with the steadiness and ability of the operator. In any case, the Customer can obviously ask us by email if he/she has specific questions/doubts using the device, and we will reply in a short time. It is also possible to export (.dbd format) and send us one or more examinations to obtain a valued opinion from tonometry experts about the signal quality. On request, DiaTecne s.r.l. provides training via video call. In-person training at the Customer’s location can eventually be arranged. Schedule and cost must be separately defined. 2 Do laboratory personnel assigned to measure PWV using your device require a specific level of professional training or background? For example, carotid IMT requires a highly skilled ultrasound technician. A specific level of professional training is not required for the use of the PulsePen. As far as we know, not only a medical doctor but also nurses, students, biologists, and engineers use the PulsePen device in all the world in daily clinical practice. Actually, when the operator uses the PulsePen he/she should know what "want to find", i.e. he/she should know the pulse waveforms in different clinical conditions. In order to learn quickly the elements of hemodynamics, we suggest reading the book “Pulse waves: how vascular hemodynamics affects blood pressure” (author: P. Salvi, published by Springer). 3 How long does the measurement process take for each assessment? An expert operator may assess PWV in 5-8 minutes (included the insertion of patient’s data in the computer). During epidemiological studies, a single operator assessed up to 186 PWV a day (El Meniaa Study in Algeria). In our experience, it is not difficult to become a skilled operator after 20-30 PWV measurements. 4 What posture is the participant in during the measurement? PulsePen measures not only PWV but also central and peripheral blood pressure, thus the patient needs to stay lying down. 5 Is there any discomfort? No discomfort for the patient. 6 What is the reliability of the measurement? PulsePen has been validated versus invasive method (P. Salvi, et al. Validation of a new non-invasive portable tonometer for determining arterial pressure wave and pulse wave velocity: the PulsePen device. J Hypertens. 2004; 22:2285-2293) and versus MRI (L. Joly, et al. Pulse wave velocity assessment by external noninvasive devices and phase-contrast magnetic resonance imaging in the obese. Hypertension. 2009; 54:421-426). PulsePen was widely used in epidemiological and clinical studies. Actually, the normal values of PWV in children and adolescents currently used in all the world were acquired with the PulsePen device (G. Reusz, et al. Reference values of pulse wave velocity in healthy children and teenagers. Hypertension. 2010; 56:217-224). Also, reference values of PWV in the elderly age were acquired with the PulsePen device (A. Cosmin, et al. Reference values of aortic pulse wave velocity in the elderly. J Hypertens. 2008; 26:2207-2212.). Because of the proliferation of methods for measurement of aortic PWV, the international scientific society ARTERY published in 2010 guidelines for the validation of the instruments used for this purpose (Wilkinson IB, et al. on behalf of the ARTERY Society. Artery society guidelines for validation of non-invasive hemodynamic measurement devices: Part 1, arterial pulse wave velocity. Artery Research. 2010;4:34-40). Below is the conclusive judgment of these guidelines.   The PulsePen is the only device on the market, at the moment, that fully satisfies all the requirements suggested by ARTERY: sampling rate of 1 kHz; registration of 10 cardiac cycles (other devices record 10 seconds); use of arterial tonometer (some other devices use mechanotransducers), transit time determined from the waveforms using an intersecting tangent algorithm (other devices use other algorithms). Registration up to 24 hrs in ASCII format of tonometric signals. 7 Can you provide research references in which measurements taken with your device are related to other preclinical CVD markers or are used to predict CVD outcomes? Pls see “References / Research Papers" 8 What age ranges are appropriate for these measurements? No limit of age exists for the use of PulsePen tonometer. PulsePen has been widely used in children (as highlighted above, the normal values of PWV in children and adolescents currently used in all the world were acquired with the PulsePen device) and in the elderly (as highlighted above, reference values of PWV in the elderly were acquired with the PulsePen device). The longitudinal multicenter “PARTAGE” study included prospectively 1130 elderly subjects aged older than 80 years living in nursing homes. 9 How to improve the quality of the captured pressure waves ? During the exam recording, the Superposition Index - S.I. [%] - is calculated in real time for each waveform, while at the end of the recording, the Quality Index - Q.I. - is calculated for all recorded pressure waves. These indices are based on the waveform overlap criteria. They are intended to assist the operator, but cannot replace them in defining a good or poor quality waveform. For example, in the presence of extrasystoles, the traffic light will normally be red, but the operator can manually disable the corresponding waveforms to prevent them from contributing to the parameter calculation. On the other hand, a good Q.I. (green) does not automatically mean that the waveforms are correct, but simply that they are similar to each other with good overlap. It is important to note that the software cannot know the expected waveforms, which depend on the condition of the arteries, any pathologies, etc. Reasons for having a low Q.I. typical causes include: Operator muscle tremors: follow the suggestions in the Quick Guide and Tutorial. Incorrect probe grip: see the Operator Tips in the Quick Guide. Improper probe placement over the artery: locate the highest pulse with your fingers and then position the probe in that position, holding it with your fingers, as shown in the operator and patient suggestions in the Quick Guide. If in doubt, we recommend that all our customers export the waveforms (.dbd format) and send them to us for evaluation by our clinical experts. This is a free service. 10 What sort of maintenance or service is required for the device? What is the number of measurements before service is required? No particular periodic maintenance or calibration operations are necessary on the instrument. In the case of prolonged non-use, remove the batteries. Cleaning should be done before each use on a new patient and before storing the instrument in the case. wRs1, wEc1: use a soft, clean cloth slightly soaked in alcohol, avoiding infiltration inside. CV010: use a soft, clean cloth lightly soaked in alcohol for the cables, the “crocodiles” and the connectors at the ends. wTn1: use a soft, clean cloth slightly soaked in alcohol for the plastic shell, avoiding infiltration inside. Clean the metal disc of the sensor with the same cloth, acting gently and without pressing, avoiding infiltration inside. In the case normal cautions are applied during the instrument’s use (like avoiding that the probe falls down, correctly inserting the battery, … and all precautions listed in the user manual), thousands of measurements are possible with no service required. 11 How is service for the device handled? In case of problems with the device, the Customer needs to contact DiaTecne s.r.l. by email and if necessary to send the apparatus following our instructions, using international express couriers (DHL, UPS, FedEx, ..). In few days the device will be repaired and sent back to the Customer. 12 How to deal with radio interference with other devices ? Use the device away from electromagnetic interference sources such as for example “cordless” telephones operating at radio frequency, cellular phones, hotspots” / WiFi devices, Bluetooth / Zigbee devices or other devices that emit high frequency electromagnetic waves and any type of transmitter in the 2.4 GHz frequency band. Make sure that the WiFi and Bluetooth of the computer and mobile phones are Turned Off while using the PulsePen, or alternatively activate the 'airplane mode' on these devices. If it is not possible to activate 'airplane mode' on the computer and/or turn off WiFi and Bluetooth, use a USB extender cable to connect the wRs1 unit, in order to keep the latter away from the computer itself. If you are near a WiFi hotspot antenna in the building, it is suggested to move away from it. You can also try changing the radio channel in use with the PulsePen system. Follow instructions in Help - Software - WPulsePen - Options and Tools - Device Programming - Parameters Setup. 13 How much does the device cost? Are there discounts for research uses (as opposed to clinical uses in revenue-generating health care settings)? Are there discounts for purchasing multiple units? Pls, ask for a quote. At the moment the main PulsePen device’s field of application is the research and our Customers are mainly Research Centers and Universities. Discounts are applied in the case of multiple purchasing units: ask for a special quote related to the number of the involved units. 14 Are there costs for service? Only the shipping costs during the Guarantee period (2 years) are applied. After this period the cost depends on the damaged parts. Normally in case of minor repair service, only the shipping costs are applied. 15 What is the guarantee? The guarantee period is 2 years.