Ambulatory monitoring of central arterial pressure, wave reflections, and arterial stiffness in patients at cardiovascular risk.

This paper reviews current 24 h ambulatory noninvasive technologies for pulse wave analysis (PWA) providing central arterial pressure, pulse wave velocity, and augmentation index and the scientific evidence supporting their use in the clinical management of patients with arterial hypertension or at risk for cardiovascular complications.The most outstanding value of these techniques lies in the fact that they are user-friendly, mostly operator independent, and enable the evaluation of vascular function during daily-life conditions, allowing to obtain repeated measurements in different out-of-office circumstances, less artificial than those of the laboratory or doctor's office.Studies performed so far suggest that 24 h PWA may represent a potentially promising tool for evaluating vascular function, structure, and damage in daily-life conditions and promoting early screening in subjects at risk. The current evidence in favor of such an approach in the clinical practice is still limited and does not recommend its routine use. In particular, at the moment, there is a shortage of long-term prognostic studies able to support the predictive value of 24 h PWA. Finally, the accuracy of the measures is strongly dependent on the type of technology and device employed with lack of interoperability among the devices that deeply affects comparability of results among studies using different technologies. It is thus mandatory in the near future to promote proper validation studies, for instance using the ARTERY protocol, and to plan well-designed long-term longitudinal studies that may prove the accuracy and high predictive value of PWA in ambulatory conditions.

Bluetooth Wireless Technology Cybersecurity and Diabetes Technology Devices.

Medical devices have transitioned from hospital into the home and consumer environments and have been shown to provide for mobility and quality-of-life improvements for chronic conditions such as diabetes. It is important to collect sensor and usage data while remotely connected in real time. The protection of these data is commonly called "cybersecurity." Bluetooth® wireless technology (Bluetooth is a registered trademark of the Bluetooth Special Interest Group, Inc.) is commonly used for low-cost medical devices to provide connections to other medical devices as well as compute and display devices such as smartphones. This paper provides a review of its use with respect to diabetes devices with a particular focus on cybersecurity.

EEG Electrode-induced Skin Injury among Adult Patients Undergoing Ambulatory EEG Monitoring.

Introduction: Ambulatory electroencephalography technology has improved in the last 40 years. Many clinicians believe that some skin injury is an unavoidable complication of prolonged EEG monitoring. In this study, we examined potential risk factors associated with electrode-induced skin injury in adult patients with AEEG monitoring. Methods: A cross-sectional observational study was conducted from December 2017 to October 2018, in the outpatient clinic at a teaching hospital in Sydney, Australia. Patients were included if they were older than 16 years of age and had been referred for AEEG monitoring of two to five days duration. Trained neurophysiology nurses completed a pre-application skin assessment before they applied the EEG electrodes. Daily assessments of the skin condition were conducted. The patients completed a questionnaire to assess comfort levels at the completion of the testing. Results: A total of 251 patients participated in this study. Two groups were established - those who were monitored for 2-3 days (Group 1; n = 92) and those who were monitored for 4-5 days (Group 2; n = 159). There was a significant acceleration in inflammation which occurred between day 2 and day 4/5. Cross-sectional analyses of patient characteristics showed that increasing age, fair skin color, dry skin texture and fine hair texture were the prevailing risk factors for greater inflammation scores. Conclusion: The patient discomfort and inflammatory burden associated with this procedure were high. Inflammation was shown to increase with the duration of electrode application.

Consensus-based guidelines for Video EEG monitoring in the pre-surgical evaluation of children with epilepsy in the UK.

PURPOSE: Paediatric Epilepsy surgery in the UK has recently been centralised in order to improve expertise and quality of service available to children. Video EEG monitoring or telemetry is a highly specialised and a crucial component of the pre-surgical evaluation. Although many Epilepsy Monitoring Units work to certain standards, there is no national or international guideline for paediatric video telemetry. METHODS: Due to lack of evidence we used a modified Delphi process utilizing the clinical and academic expertise of the clinical neurophysiology sub-specialty group of Children's Epilepsy Surgical Service (CESS) centres in England and Wales. This process consisted of the following stages I: Identification of the consensus working group, II: Identification of key areas for guidelines, III: Consensus practice points and IV: Final review. Statements that gained consensus (median score of either 4 or 5 using a five-point Likerttype scale) were included in the guideline. RESULTS: Two rounds of feedback and amendments were undertaken. The consensus guidelines includes the following topics: referral pathways, neurophysiological equipment standards, standards of recording techniques, with specific emphasis on safety of video EEG monitoring both with and without drug withdrawal, a protocol for testing patient's behaviours, data storage and guidelines for writing factual reports and conclusions. All statements developed received a median score of 5 and were adopted by the group. CONCLUSION: Using a modified Delphi process we were able to develop universally-accepted video EEG guidelines for the UK CESS. Although these recommendations have been specifically developed for the pre-surgical evaluation of children with epilepsy, it is assumed that most components are transferable to any paediatric video EEG monitoring setting.

Effectiveness of SmartGuard Technology in the Prevention of Nocturnal Hypoglycemia After Prolonged Physical Activity.

BACKGROUND: The prevention of postexercise nocturnal hypoglycemia after prolonged physical activity using sensor-augmented pump (SAP) therapy with predictive low-glucose management (PLGM) has not been well studied. We conducted a study at a pediatric diabetes camp to determine whether a SAP with PLGM reduces the frequency of nocturnal hypoglycemia after prolonged physical activity more effectively than a SAP with a carbohydrate intake algorithm. METHODS: During a 1-week sport camp, 20 children (aged 10-13 years) with type 1 diabetes (T1D) managed by SAP therapy either with (n = 7) or without PLGM (n = 13) were studied. The hypoglycemia management strategy and the continuous glucose monitoring (CGM)/PLGM settings were standardized. The incidence, severity, and duration of hypoglycemia and carbohydrate intake were documented and compared. RESULTS: The PLGM system was activated on 78% of all nights (once per night on average). No difference was found between the SAP and PLGM groups in the mean overnight glucose curve or mean morning glucose (7.8 ± 2 mmol/L vs. 7.4 ± 3 mmol/L). There was no difference in the frequency and severity of hypoglycemia. However, the SAP group consumed significantly more carbohydrates to prevent and treat hypoglycemia than those in the PLGM group; the values were 10 ± 2 and 1 ± 2 gS (P < 0.0001) in the SAP and PLGM groups, respectively. Moreover, the SAP group spent a significantly longer time in hypoglycemia (64 ± 2 min vs. 38 ± 2 min, P < 0.05). We observed a difference in the time distribution of nocturnal hypoglycemia (10 to 12 p.m. in the PLGM group and 3 to 7 a.m. in the SAP group, P < 0.05). CONCLUSION: With PLGM system, euglycemia after prolonged physical activity was largely maintained with a minimal carbohydrate intake.

Do patients need to stay in bed all day in the Epilepsy Monitoring Unit? Safety data from a non-restrictive setting.

PURPOSE: To assess whether injuries occur more often in an Epilepsy Monitoring Unit (EMU) where portable EEG amplifiers are used, and where patients can freely move within a large area during the monitoring. METHODS: Patients were monitored at the Danish Epilepsy Center, in an EMU specifically designed for this purpose, and they were under continuous surveillance by personnel dedicated to the EMU. Adverse events (AEs) - including injuries, were prospectively noted, as part of the safety policy of the hospital. Other data were retrospectively extracted from the electronic database, for a 5-year period (January 2012-December 2016). RESULTS: 976 patients were admitted to the EMU. Falls occurred in 19 patients (1.9%) but none of them resulted in injury. Only one serious AE occurred: a patient had a convulsive status epilepticus, which did not respond to first-line treatment in the EMU and was transferred to the intensive care unit. The rate of AEs were similar or lower than previously reported by other centers, where the mobility of the patients had been restricted during monitoring. CONCLUSION: In an EMU specially designed for this purpose, where patients are under continuous surveillance by personnel dedicated to the EMU, injuries can be avoided even when the mobility of the patients is not restricted.

Fear of hypoglycemia: Influence on glycemic variability and self-management behavior in young adults with type 1 diabetes.

PURPOSE: The purpose of this study was to examine how fear of hypoglycemia (FOH) is associated with glycemic variability (GV) and self-management behavior in young adults (aged 18-35) with type 1 diabetes (T1DM). PROCEDURES: Using a prospective repeated-measures design, in 35 young adults, within- and between-person and temporal associations of FOH, specific self-management behaviors, and GV were measured. The data were collected using questionnaires and real-time measures using daily diaries, insulin pump downloads, actigraphy, and continuous glucose monitoring. FINDINGS: FOH was associated with greater glycemic variability. Significant temporal associations emerged. Concurrent day (glucose SD, p=.011) and previous-evening fear levels were associated with GV (glucose SD, p=.007). FOH was also associated with greater calorie intake (r=.492, p=.003) and less physical activity (light activity, r=-.341, p=.045). CONCLUSIONS: The significant associations of FOH with GV, dietary patterns, and physical activity provide evidence for FOH as an important psychological factor associated with diabetes care.

Evaluation of a Predictive Low-Glucose Management System In-Clinic.

BACKGROUND: Predictions based on continuous glucose monitoring (CGM) data are the basis for automatic suspension and resumption of insulin delivery by a predictive low-glucose management feature termed "suspend before low," which is part of the Medtronic MiniMed® 640G combined insulin pump and CGM system. This study assessed the safety and performance characteristics of the system in an in-clinic setting at eight sites. MATERIALS AND METHODS: In-clinic standardized increases in basal insulin delivery rates were used to induce nocturnal hypoglycemia in subjects (14-75 years) with type 1 diabetes wearing the MiniMed 640G system. The "suspend before low" feature was set at 65 mg/dL, and as a result, the predictive algorithm suspended insulin delivery when the forecasted glucose was predicted to be ≤85 mg/dL in 30 min (a 20 mg/dL safety buffer). Reference plasma glucose values (Yellow Springs Instruments [YSI], Yellow Springs, OH) were used to establish hypoglycemia and were defined as ≥2 consecutive values ≤65 mg/dL. RESULTS: Eighty subjects were screened. Among the 69 successful completers, 27 experienced a hypoglycemic event and 42 did not, a prevention rate of 60%. The mean (±standard deviation) YSI value at the time of pump suspension was 101 ± 18.5 mg/dL, and the mean duration of the 68 "suspend before low" events was 105 ± 27 min. At 120 min after the start of the pump suspension events, the mean YSI value was 102 ± 34.6 mg/dL. CONCLUSION: The MiniMed 640G "suspend before low" feature prevented 60% of induced predicted hypoglycemic events without significant rebound hyperglycemia.

Safety of using real-time sensor glucose values for treatment decisions in adolescents with poorly controlled type 1 diabetes mellitus: a pilot study.

BACKGROUND: This study explored the safety of using real-time sensor glucose (SG) data for treatment decisions in adolescents with poorly controlled type 1 diabetes. METHODS: Ten adolescents with type 1 diabetes, HbA1c ≥9% on insulin pumps were admitted to the clinical research center and a continuous glucose sensor was inserted. Plasma glucose was measured at least hourly using Yellow Springs Instrument's (YSI) glucose analyzer. Starting at dinner, SG rather than YSI was used for treatment decisions unless YSI was <70 mg/dL (<3.9 mmol/L) or specific criteria indicating SG and YSI were very discordant were met. Participants were discharged after lunch the next day. RESULTS: Ten participants (seven males; 15.2-17.8 year old) completed the study. The range of differences between high glucose correction doses using SG vs YSI for calculations was -2 (SG < YSI dose) to +1 (SG > YSI dose); this difference was two units in only 2 of 23 correction doses given (all SG < YSI dose). There were five episodes of mild hypoglycemia in two patients, two of which occurred after using SG for dose calculations. There was no severe hypoglycemia and no YSI glucose >350 mg/dL (19.4 mmol/L). Mean (±SE) pre- and postmeal YSI glucose were 163 ± 11 and 183 ± 12 mg/dL (9.1 ± 0.6 and 10.2 ± 0.7 mmol/L), respectively. CONCLUSION: Use of real-time continuous glucose monitoring for treatment decisions was safe and did not result in significant over- or undertreatment. Use of SG for treatment decisions under supervised inpatient conditions is a suitable alternative to repeated fingerstick glucose monitoring. Outpatient studies using SG in real-time are needed.

Heart rate informed artificial pancreas system enhances glycemic control during exercise in adolescents with T1D.

OBJECTIVE: To evaluate the safety and performance of using a heart rate (HR) monitor to inform an artificial pancreas (AP) system during exercise among adolescents with type 1 diabetes (T1D). MATERIALS AND METHODS: In a randomized, cross-over trial, adolescents with T1D age 13 - 18 years were enrolled to receive on separate days either the unmodified UVa AP (stdAP) or an AP system connected to a portable HR monitor (AP-HR) that triggered an exercise algorithm for blood glucose (BG) control. During admissions participants underwent a structured exercise regimen. Hypoglycemic events and CGM tracings were compared between the two admissions, during exercise and for the full 24-hour period. RESULTS: Eighteen participants completed the trial. While number of hypoglycemic events during exercise and rest was not different between visits (0.39 AP-HR vs 0.50 stdAP), time below 70 mg dL -1 was lower on AP-HR compared to stdAP, 0.5±2.1% vs 7.4±12.5% (P = 0.028). Time with BG within 70-180 mg dL -1 was higher for the AP-HR admission vs stdAP during the exercise portion and overall (96% vs 87%, and 77% vs 74%), but these did not reach statistical significance (P = 0.075 and P = 0.366). CONCLUSIONS: Heart rate signals can safely and efficaciously be integrated in a wireless AP system to inform of physical activity. While exercise contributes to hypoglycemia among adolescents, even when using an AP system, informing the system of exercise via a HR monitor improved time <70 mg dL -1 . Nonetheless, it did not significantly reduce the total number of hypoglycemic events, which were low in both groups.

The AngelMed Guardian system: Is there a role for implantable devices for early detection of coronary artery occlusion?

The AngelMed Guardian System is an implantable device similar to a single chamber pacemaker that continuously monitors the intracardiac electrogram for evidence of ST segment shift indicating acute coronary artery occlusion. The system aims to reduce time to presentation by alerting patients to present to a medical facility whether symptoms are present or not. In March 2016, the US Food and Drug Administration (FDA) assembled a meeting of the Circulatory System Devices Panel to review the results of the AngelMed for Early Recognition and Treatment of STEMI (ALERTS) pivotal trial and the accompanying premarket approval (PMA) application for regulatory approval of the AngelMed Guardian System in the US. In this review, we examine the ALERTS trial methodology and results, and describe the FDA panel's deliberations and recommendations.

Diabetes Technology-Continuous Subcutaneous Insulin Infusion Therapy and Continuous Glucose Monitoring in Adults: An Endocrine Society Clinical Practice Guideline.

OBJECTIVE: To formulate clinical practice guidelines for the use of continuous glucose monitoring and continuous subcutaneous insulin infusion in adults with diabetes. PARTICIPANTS: The participants include an Endocrine Society-appointed Task Force of seven experts, a methodologist, and a medical writer. The American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology co-sponsored this guideline. EVIDENCE: The Task Force developed this evidence-based guideline using the Grading of Recommendations, Assessment, Development, and Evaluation system to describe the strength of recommendations and the quality of evidence. The Task Force commissioned one systematic review and used the best available evidence from other published systematic reviews and individual studies. CONSENSUS PROCESS: One group meeting, several conference calls, and e-mail communications enabled consensus. Committees and members of the Endocrine Society, the American Association for Clinical Chemistry, the American Association of Diabetes Educators, and the European Society of Endocrinology reviewed and commented on preliminary drafts of these guidelines. CONCLUSIONS: Continuous subcutaneous insulin infusion and continuous glucose monitoring have an important role in the treatment of diabetes. Data from randomized controlled trials are limited on the use of medical devices, but existing studies support the use of diabetes technology for a wide variety of indications. This guideline presents a review of the literature and practice recommendations for appropriate device use.

Do we need to monitor the percentage of biventricular pacing day by day?

BACKGROUND: Incidence and clinical significance of transient, daily fluctuations of biventricular pacing percentage (CRT%) remain unknown. We assessed the value of daily remote monitoring in identifying prognostically critical burden of low CRT%. METHODS AND RESULTS: Prospective, single-centre registry encompassed 304 consecutive heart failure patients with cardiac resynchronization therapy defibrillators (CRT-D). Patients with 24-h episodes of CRT% loss<95% were assigned to quartiles depending on cumulative time spent in low CRT%: quartile 1 (1-8days), 2 (9-20days), 3 (21-60days) and quartile 4 (>60days). During median follow-up of 35months 51,826 transmissions were analysed, including 15,029 in 208 (68.4%) patients with episodes of low CRT%. Overall, mean CRT%≥95% vs. <95% resulted in a 4-fold lower mortality (17.3 vs. 68.2%; p<0.001). Fifty-four percent of patients experienced episodes of CRT% loss, despite 85.6% having mean CRT%≥95%. Mortality was lowest in quartile 1 (7.7%), while longer periods of CRT% loss resulted in significantly higher death rates (25.0 vs. 34.6 vs. 57.7%; quartiles 2-4 respectively, p<0.001), despite mean CRT% still being ≥95% in quartiles 1-3. Cumulative low CRT% burden was the independent risk factor for death (HR 1.013; 95% CI 1.006-1.021; p<0.001). Mortality rose by 1.3 and 49% with every additional day and quartile of CRT% loss, respectively. CONCLUSIONS: Daily remote monitoring allows one to detect 24-h episodes of CRT% loss<95% in over two-thirds of CRT-D recipients during median observation of 3years. Cumulative low CRT% burden (in days) independently predicts mortality before mean CRT% drop.

Chronic tissue response to untethered microelectrode implants in the rat brain and spinal cord.

OBJECTIVE: Microelectrodes implanted in the central nervous system (CNS) often fail in long term implants due to the immunological tissue response caused by tethering forces of the connecting wires. In addition to the tethering effect, there is a mechanical stress that occurs at the device-tissue interface simply because the microelectrode is a rigid body floating in soft tissue and it cannot reshape itself to comply with changes in the surrounding tissue. In the current study we evaluated the scar tissue formation to tetherless devices with two significantly different geometries in the rat brain and spinal cord in order to investigate the effects of device geometry. APPROACH: One of the implant geometries resembled the wireless, floating microstimulators that we are currently developing in our laboratory and the other was a (shank only) Michigan probe for comparison. Both electrodes were implanted into either the cervical spinal cord or the motor cortices, one on each side. MAIN RESULTS: The most pronounced astroglial and microglial reactions occurred within 20 µm from the device and decreased sharply at larger distances. Both cell types displayed the morphology of non-activated cells past the 100 µm perimeter. Even though the aspect ratios of the implants were different, the astroglial and microglial responses to both microelectrode types were very mild in the brain, stronger and yet limited in the spinal cord. SIGNIFICANCE: These observations confirm previous reports and further suggest that tethering may be responsible for most of the tissue response in chronic implants and that the electrode size has a smaller contribution with floating electrodes. The electrode size may be playing primarily an amplifying role to the tethering forces in the brain whereas the size itself may induce chronic response in the spinal cord where the movement of surrounding tissues is more significant.

Real-time mobile detection of drug use with wearable biosensors: a pilot study.

While reliable detection of illicit drug use is paramount to the field of addiction, current methods involving self-report and urine drug screens have substantial limitations that hinder their utility. Wearable biosensors may fill a void by providing valuable objective data regarding the timing and contexts of drug use. This is a preliminary observational study of four emergency department patients receiving parenteral opioids and one individual using cocaine in a natural environment. A portable biosensor was placed on the inner wrist of each subject, to continuously measure electrodermal activity (EDA), skin temperature, and acceleration. Data were continuously recorded for at least 5 min prior to drug administration, during administration, and for at least 30 min afterward. Overall trends in biophysiometric parameters were assessed. Injection of opioids and cocaine use were associated with rises in EDA. Cocaine injection was also associated with a decrease in skin temperature. Opioid tolerance appeared to be associated with a blunted physiologic response as measured by the biosensor. Laterality may be an important factor, as magnitude of response varied between dominant and nondominant wrists in a single patient with bilateral wrist measurements. Changes in EDA and skin temperature are temporally associated with intravenous administration of opioids and cocaine; the intensity of response, however, may vary depending on history and extent of prior use.

Outpatient safety assessment of an in-home predictive low-glucose suspend system with type 1 diabetes subjects at elevated risk of nocturnal hypoglycemia.

OBJECTIVE: Nocturnal hypoglycemia is a common problem with type 1 diabetes. In the home setting, we conducted a pilot study to evaluate the safety of a system consisting of an insulin pump and continuous glucose monitor communicating wirelessly with a bedside computer running an algorithm that temporarily suspends insulin delivery when hypoglycemia is predicted. RESEARCH DESIGN AND METHODS: After the run-in phase, a 21-night randomized trial was conducted in which each night was randomly assigned 2:1 to have either the predictive low-glucose suspend (PLGS) system active (intervention night) or inactive (control night). Three predictive algorithm versions were studied sequentially during the study for a total of 252 intervention and 123 control nights. The trial included 19 participants 18-56 years old with type 1 diabetes (hemoglobin A1c level of 6.0-7.7%) who were current users of the MiniMed Paradigm® REAL-Time Revel™ System and Sof-sensor® glucose sensor (Medtronic Diabetes, Northridge, CA). RESULTS: With the final algorithm, pump suspension occurred on 53% of 77 intervention nights. Mean morning glucose level was 144±48 mg/dL on the 77 intervention nights versus 133±57 mg/dL on the 37 control nights, with morning blood ketones >0.6 mmol/L following one intervention night. Overnight hypoglycemia was lower on intervention than control nights, with at least one value ≤70 mg/dL occurring on 16% versus 30% of nights, respectively, with the final algorithm. CONCLUSIONS: This study demonstrated that the PLGS system in the home setting is safe and feasible. The preliminary efficacy data appear promising with the final algorithm reducing nocturnal hypoglycemia by almost 50%.