Assessment of volume flow rate in arteriovenous fistulas with a novel ultrasound Doppler device (earlybird): Trend analysis, comparison of methods, and inter- and intra-rater reliability.

BACKGROUND: An accessible tool is required to analyze volume flow trends in arteriovenous fistulas for hemodialysis. Earlybird, an easy-to-place ultrasound Doppler device, has shown comparable accuracy to duplex ultrasound. In this study, we compared volume flow measurements obtained with duplex ultrasound and the dilution technique to an enhanced earlybird device, featuring a dual Doppler probe system, eliminating the requirement for a known insonation angle. METHODS: Nine patients with a distal radiocephalic arteriovenous fistula were monitored for 12 months with regular volume flow measurements. Correlation and inter- and intra-class reliability analyses were conducted. RESULTS: An overall moderate correlation was observed between earlybird and duplex ultrasound or dilution technique (intraclass correlation coefficient = 0.606 (95% confidence interval 0.064, 0.721) and 0.581 (0.039, 0.739), respectively). Duplex ultrasound compared to dilution measurements, demonstrated an overall moderate correlation (0.725 (0.219, 0.843)). Correlation between earlybird and duplex ultrasound was stronger for the arteriovenous fistula (0.778 (0.016, 0.901)) than the brachial artery (0.381 (-0.062, 0.461)). For earlybird, inter-rater reliability was excellent for the arteriovenous fistula (0.907 (0.423, 0.930)) and poor for the brachial artery (0.430 (0.241, 0.716)). Duplex ultrasound showed a good inter-rater reliability (arteriovenous fistula: 0.843 (0.610, 0.871), brachial artery: 0.819 (0.477, 0.864)). The overall intra-rater reliability was good for duplex ultrasound (rater A: 0.893 (0.727, 0.911); rater B: 0.853 (0.710, 0.891)), while excellent for earlybird (rater A: 0.905 (0.819, 0.928); rater B: 0.921 (0.632, 0.969)). CONCLUSION: We observed a weaker correlation in the measurements of volume flow rates in arteriovenous fistulas when obtained using earlybird compared to dilution technique, unlike the comparison between duplex ultrasound and the dilution technique. However, inter-rater reliability for the arteriovenous fistula was excellent with earlybird and good with duplex ultrasound, indicating the potential of earlybird as a tool for frequent measurements, enabling trend surveillance and predicting adverse outcomes.

Peri-Operative Mortality and Survival After Repair of Abdominal Aortic Aneurysm in Advanced Age Patients: A National Study from the Norwegian Registry for Vascular Surgery Focused on Nonagenarians.

OBJECTIVE: Treatment of abdominal aortic aneurysm (AAA) in nonagenarians has become more frequent. This national observational cohort study aimed to investigate peri-operative mortality and survival after AAA surgery in nonagenarians in Norway. METHODS: All AAA repairs registered in the Norwegian Registry for Vascular Surgery from 2015 to 2021 were identified and stratified into nonagenarians > 90 years old (n = 77), octogenarians 80 - 89 years old (n = 1 362), and patients < 80 years old (n = 4 590). The patient characteristics and comorbidities were recorded, and the 30 and 90 day mortality rates were calculated. Kaplan-Meier analysis was performed to obtain the estimated median survival and survival curves. RESULTS: In the nonagenarians, the 30 day mortality rates were 2.5% in asymptomatic patients, 33.3% in symptomatic patients, and 59.1% in the patients with a ruptured AAA (rAAA). The estimated median survival (years) were 3.3 (95% confidence interval [CI] 1.95 - 4.59) for asymptomatic AAA, 2.9 (interquartile range [IQR] 2.82, 5.80) for symptomatic AAA, and 0.1 for rAAA (IQR 0.01, 3.04). For nonagenarians surviving the first 90 days, the estimated median survival (years) were 4.2 (95% CI 2.56 - 5.88) for asymptomatic AAA, 3.4 (IQR 2.86, 5.80) for symptomatic AAA, and 3.8 (IQR 1.49, 4.85) for rAAA. The 90 day mortality rates were 100.0%, 80.0%, and 62.5% for asymptomatic, symptomatic, and rAAA, respectively, after open surgical repair (OSR), and 5.1%, 10.0%, and 50.0%, respectively, after endovascular aortic repair (EVAR). CONCLUSION: Peri-operative mortality and survival results after AAA surgery in nonagenarians support treatment of selected asymptomatic patients. The 90 day survivors had an expected survival of more than three years, enabling balanced decision making regarding surgical vs. conservative treatment options in this challenging cohort. EVAR is the treatment method of choice for AAA in nonagenarians because most of them would probably live longer untreated than if treated by OSR.

The Effect of 12-Week Treatment with Intermittent Negative Pressure on Blood Flow Velocity and Flowmotion, Measured with a Novel Doppler Device (Earlybird). Secondary Outcomes from a Randomized Sham-Controlled Trial in Patients with Peripheral Arterial Disease.

BACKGROUND: Treatment with intermittent negative pressure (INP) is proposed as an adjunct to standard care in patients with peripheral arterial disease (PAD). The aims of this study were to evaluate the applicability of a novel ultrasound Dopplerdevice (earlybird) to assess blood flow characteristics in patients with PAD during a treatment session with INP, and whether certain flowproperties could determine who could benefit from INP treatment. METHODS: Secondary outcomes of data from a randomized sham-controlled trial were explored. Patients were randomized to 12 weeks of treatment with 40 mm Hg or 10 mm Hg INP, for one hour twice daily. Earlybird blood flow velocity recordings were made before and after the 12-week treatmentperiod and consists of a 5-min recording in rest, 3-min during INP treatment and 5-min recording after ended INP test-treatment. Mean blood flow velocity (vmean), relative changes in flow and frequency spectrum by Fourier-transform of the respective bandwidths of endothelial, sympathetic, and myogenic functions, were analyzed for the different series of blood flow measurements. RESULTS: In total, 62 patients were eligible for analysis, where 32 patients were treated with 40 mm Hg INP. The acquired recordings were of good quality and were used for descriptive analyses of flow characteristics. An immediate increase in vmean during the negative pressure periods of the INP test-treatment was observed in the 40 mm Hg INP treatment group at both pre- and post-test. There was a significant difference between the treatment groups, with a difference between the medians of 13.7 (P < 0.001) at pre-test and 10.7 (P < 0.001) at posttest. This finding was confirmed with spectrum analysis by Fourier-transform of the bandwidth corresponding to INP treatment. The change in amplitude corresponding to myogenic function after 12-weeks of treatment, was significantly different in favor of the 40 mm Hg INP treatment group. We were not able to detect the specific flow characteristics indicating who would benefit INP-treatment. CONCLUSIONS: Earlybird is an applicable tool for assessing blood flow velocity in patients with PAD. Analysis of the flow velocity recordings shows that INP induces an immediate increase in blood flow velocities during INP. The positive effects of INP may be attributed to recruitment of arterioles, and thereby, increasing blood flow. In these analyses, no flow characteristics were determined which could predict who would benefit INP treatment.

Quality of Life (QoL) Assessment in the Patients Operated with Either Laparoscopic or an Open Aortobifemoral Bypass for Aortoiliac Occlusive Disease (AIOD): 2 Years Results of a Randomized Controlled Trial.

BACKGROUND: QoL assessment within surgical treatment is seldom investigated and sparsely reported in the medical literature. This study aimed to compare QoL in a randomized fashion in the patients treated with either a laparoscopic aortobifemoral bypass (LABFB) or an open aortobifemoral bypass (OABFB) for the treatment of AIOD. PATIENTS AND METHODS: Seventy-one consecutive patients with AIOD, Trans-Atlantic Inter-Society Consensus II Type D lesions (TASC II, Type D) were randomized to LABFB or OABFB. Thirty-five patients in the LABFB and thirty-six in the OABFB groups were compared for the changes in the QoL, with the short-form health survey (SF-36), EuroQol 5 dimensions (EQ-5D), and EQ-5D visual analog scale (VAS) preoperatively, and postoperatively at 1, 3, 6, 12 and 24 months. Mann-Whitney U-Test and Wilcoxon sign-rank test were used for group comparison. Mixed model analysis was performed to examine the effect of different variables on the QoL. RESULTS: In the patients treated with LABFB, physical component score (PCS) and mental component score (MCS) in SF-36 were significantly higher than OABFB, at 1 and 3 months postoperatively. PCS was also significantly higher in the LABFB group than OABFB at 24 months postoperatively. The preoperative QoL scores for both the laparoscopy and the open group were significantly lower than the age-matched general Norwegian population. EQ-5D median scores were significantly higher in the LABFB at all postoperative follow-up time points up to 12 months. The patients in the LABFB group also had a statistically significant increase in EQ-5D VAS compared to OABFB, at 1 and 12 months postoperatively (p = 0.005, and p = 0.037, respectively). CONCLUSION: QoL seems better in patients treated with LABFB than OABFB, particularly during the early months after surgery.

Patient and clinician experiences and opinions of the use of a novel home use medical device in the treatment of peripheral vascular disease - a qualitative study.

BACKGROUND: Peripheral vascular diseases have a significant impact on functional quality of life. Previous research has demonstrated the complex, limiting and costly economic implications of these conditions such as lower limb ulceration chronicity and ischaemic amputation. These complex, limb and life threatening conditions demand the development of novel interventions with objective research as part of that development. Hence, a novel intermittent negative pressure medical device in the form of a wearable boot (FlowOx™) was developed. As part of the development process, this study aimed to explore patient and clinician opinions of the boot. METHODS: A qualitative approach was used to collect patient and clinician experiences in Norway. An advisory group informed the semi-structured questions used in seven patient interviews and one clinician focus group (n = 5). The data were recorded digitally and transcribed verbatim. Patient and clinician data were analysed as distinct groups using a thematic process. RESULTS: Data analysis resulted in five themes from the patients which gave insight into; the impact of the disease process; practicalities of using the boot, positive experiences of use; perceived outcomes; reflecting on use. Six themes were created from the clinicians. These gave insight into; ideal outcomes and how to measure them; ways to potentially use the boot; using research in healthcare; positives of the device; observed effects and next steps; potential improvements to the device. CONCLUSION: This study provides insight into the experiences and opinions of FlowOx™. Patients and clinicians were positive about the device due to its ease of use. Those patients with peripheral arterial disease experienced significantly more benefit, especially for ischaemic ulceration than those with a chronic venous condition. Clinicians placed value on the patient reported outcomes in the treatment decision-making process. This preliminary study into experiences of FlowOx™ use provides valuable feedback that will inform design modification and ongoing research into implementation points and prospective user groups. FlowOx™ demonstrates potential as a conservative therapy offering users a convenient, home use, self-care management solution for improving symptomatic peripheral arterial disease and quality of life.

Validation of a novel ultrasound Doppler monitoring device (earlybird) for measurements of volume flow rate in arteriovenous fistulas for hemodialysis.

BACKGROUND: Controversy exists regarding surveillance of arteriovenous fistulas for hemodialysis to increase patency. A significant reduction in volume flow rate (VFR) should lead to diagnostic evaluation and eventually intervention. Several methods are available for VFR measurements, but all of them are associated with low reproducibility. VFR trend analysis is suggested as an improved solution. It is therefore a need to find user-friendly, cost and time-effective modalities. We present a novel Doppler ultrasound device (earlybird) which could bridge this gap. It includes an easy-to-use and light-weight single element transducer. METHODS: In an experimental and clinical setting, we compared earlybird to duplex ultrasound to assess VFR. In a closed circuit of blood-mimicking fluid, 36 paired calculations of calibrated, duplex ultrasound and earlybird VFR was measured. In addition, 23 paired recordings of duplex ultrasound and earlybird VFR was measured in 16 patients with underarm arteriovenous fistulas. Pearson correlation, intraclass correlation coefficient, root-mean-square and Bland-Altman plots were analyzed. RESULTS: Strong correlation (r = 0.991, p < 0.001), and excellent level of agreement (ICC = 0.970 (95% CI 0.932 - 0.985), p < 0.001) between earlybird and the calibrated VFR was found in the experimental setup. This was confirmed in the clinical setting, with a strong correlation (r = 0.781, p < 0.001) and moderate to good level of agreement (ICC = 0.750 (95% CI 0.502-0.885), p < 0.001) between earlybird and duplex ultrasound VFR measured at the arteriovenous fistulas outflow veins. In the Bland-Altman plot-analysis for the experimental setup, we found smaller limits of agreement, a smaller consistent and proportional bias, as well as greater accuracy of earlybird than DUS when compared to the calibrated VFR. CONCLUSION: Earlybird is a feasible tool for VFR measurements and could be a future promising device for easy assessment and surveillance of AVF for hemodialysis.

Effects of intermittent negative pressure treatment on circulating vascular biomarkers in patients with intermittent claudication.

The aim of this study was to investigate the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour twice daily for 12 weeks, on circulating vascular biomarkers in patients with intermittent claudication. Patients were randomized to treatment with -40 mmHg INP (treatment group), or -10 mmHg INP (sham control group). Venous blood samples were collected at baseline and after 12 weeks, and concentrations of vascular adhesion molecule-1 (VCAM-1), intracellular adhesion molecule-1 (ICAM-1), E-selectin, P-selectin, von Willebrand factor (vWF), l-arginine, asymmetric dimethylarginine (ADMA), and symmetric dimethylarginine (SDMA) were analyzed. A larger proportion of the patients in the treatment group (25/31) had a reduction in vWF levels after 12 weeks, compared to the sham control group (17/30) (p = 0.043). Within the treatment group there was a significant mean (SEM) reduction in the concentration of vWF of -11% (4) (p = 0.019), whereas there was no significant change in the levels of vWF in the sham control group (1% (6); p = 0.85). There were no significant differences in the change of any of the biomarker levels between the groups after 12 weeks of treatment. In conclusion, there were no differences in the change of the circulating levels of the measured biomarkers between the treatment group and the sham control group after 12 weeks of INP treatment. However, the observed changes in vWF might indicate a beneficial effect of INP treatment on endothelial activation and endothelial injury. Clinicaltrials.gov Identifier: NCT03640676.

A randomized controlled trial of treatment with intermittent negative pressure for intermittent claudication.

OBJECTIVE: We investigated the effects of lower extremity intermittent negative pressure (INP) treatment for 1 hour two times daily for 12 weeks on the walking distance of patients with intermittent claudication (IC). METHODS: Patients with IC were randomized to treatment with -40 mm Hg INP (treatment group) or -10 mm Hg INP (sham control group). Pain-free walking distance (PWD) and maximal walking distance (MWD) on a treadmill, resting and postexercise ankle-brachial index, resting and postischemic blood flow (plethysmography), and quality of life (EQ-5D-5L and Vascuqol-6) were measured at baseline and after 12 weeks of treatment. RESULTS: A total of 72 patients were randomized, and 63 had data available for the intention-to-treat analyses. The between-group comparisons showed a significant change in the PWD, favoring the treatment group over the sham control group (estimated treatment effect, 50 m; 95% confidence interval [CI], 11-89; P = .014). The PWD had increased by 68 m (P < .001) in the treatment group and 18 m (P = .064) in the sham control group. No significant difference was found in the change in the MWD between the two groups (estimated treatment effect, 42 m; 95% CI, -14 to 97; P = .139). The MWD had increased by 62 m (P = .006) in the treatment group and 20 m (P = .265) in the sham control group. For patients with a baseline PWD of <200 m (n = 56), significant changes had occurred in both PWD and MWD between the two groups, favoring the treatment group (estimated treatment effect, 42 m; 95% CI, 2-83; P = .042; and estimated treatment effect, 62 m; 95% CI, 5-118; P = .032; respectively). Both overall and for the group of patients with a PWD <200 m, no significant differences were found in the changes in the resting and postexercise ankle-brachial index, resting and postischemic blood flow, or quality of life parameters between the two groups. CONCLUSIONS: Treatment with -40 mm Hg INP increased the PWD compared with sham treatment in patients with IC. For the patients with a baseline PWD of <200 m, an increase was found in both PWD and MWD compared with sham treatment.

Lower Extremity Intermittent Negative Pressure for Intermittent Claudication. Follow-Up after 24 Weeks of Treatment.

BACKGROUND: Treatment with lower extremity intermittent negative pressure (INP) of -40 mm Hg for one hour twice daily for 12 weeks, increases walking capacity in patients with intermittent claudication (IC). However, the effects of INP treatment beyond 12 weeks have not been elucidated. The aim of the present study was to investigate the clinical effects of INP treatment after 24 weeks in patients with IC. METHODS: This was a follow-up study after a randomized sham-controlled trial, where patients randomized to the active treatment group were offered to continue treatment for 12 additional weeks (24 weeks in total). Treatment with -40 mm Hg INP was applied in a pressure chamber sealed around the lower leg, and the patients were instructed to treat themselves at home one hour in the morning and one hour in the evening. Pain free walking distance (PWD), maximal walking distance (MWD), resting ankle-brachial index (ABI) and post exercise ABI were measured at baseline, after 12 and 24 weeks. RESULTS: Ten out of 32 patients (31%) from the active treatment group in the initial trial were included in this follow-up study. At baseline, PWD was (mean ±SD) 151 ± 91 m and MWD was 362 ±159 m. There was a significant increase in both PWD and MWD after 24 weeks of treatment, compared to baseline (ANOVA; P= 0.006 and P= 0.012, respectively). Post hoc tests revealed that PWD increased significantly from baseline to 12 weeks (mean 81 m; 95% CI [6, 156]; P = 0.032), and that MWD increased significantly from 12 to 24 weeks (mean 145 m; 95% CI [22, 268]; P = 0.018). There were no significant changes in resting ABI or post exercise ABI during the 24-week treatment period (ANOVA; P= 0.157 and P= 0.450, respectively). CONCLUSION: Both PWD and MWD improved after treatment with - 40 mm Hg INP for one hour twice daily for 24 weeks, compared to baseline. The main improvement in PWD occurred during the first 12 weeks of treatment, whereas the main improvement in MWD occurred between 12 and 24 weeks of treatment.

Validation of a novel ultrasound Doppler monitoring device (earlybird) for detection of microvascular circulatory changes.

OBJECTIVE: In this proof-of-concept study we aim to validate a novel ultrasound Doppler monitoring device for evaluating microcirculation (earlybird) against LDF and pulsed Doppler. METHODS: In ten healthy subjects, we measured microcirculatory function at rest and during different autonomic tests (forced respiration, isometric exercise, Valsalva maneuver and cold pressor). Earlybird, LDF and pulsed Doppler were recorded simultaneously. We performed a ZNCC to determine correlation. RESULTS: The curves for earlybird and LDF or pulsed Doppler correlates visually well. Overall median ZNCC 0.87 (interquartile range 0.77 -0.91) between the LDF and earlybird measurements, and 0.90 (0.82 - 0.95) for pulsed Doppler and earlybird. Median ZNCC for baseline and each provocation test for earlybird against LDF and pulsed Doppler were calculated; baseline: LDF 0.87 (0.73 - 0.97) pulsed Doppler 0.91 (0.81 - 0.94), forced respiration: LDF 0.87 (0.28 - 0.90) pulsed Doppler 0.90 (0.85 - 0.96), isometric exercise: LDF 0.82 (0.59 - 0.90) pulsed Doppler 0.87 (0.68 - 0.94), Valsalva maneuver: LDF 0.88 (0.82 - 0.91) pulsed Doppler 0.94 (0.92 - 0.97) and cold pressor: LDF 0.90 (0.85 - 0.95) pulsed Doppler 0.89 (0.65 - 0.94). CONCLUSION: Earlybird records vasoconstrictions in healthy subjects as well as LDF and pulsed Doppler.

Vestibulospinal component of postural control (vestibular function) in very preterm infants (25 to 27 weeks) at 3, 6, and 12 months corrected age.

Postural control, which is important for the development of all movement, balance, and locomotion, depends a great deal on the vestibulospinal component of vestibular function in early childhood. Vestibulospinal input is important for muscle power regulation, which, in turn, influences postural control. The aim of this study was to focus particularly on this component of vestibular function during the first year of life in 67 infants with a very short gestational age (25-27 weeks), to search for possible neonatal confounders, and to see whether it influences the course of muscle power development in preterm infants. Outcome was described as being optimal, suspect, or abnormal. The infants were categorized into the Neonatal Medical Index according to the severity of neonatal illness and separately into three groups for neonatal brain ultrasonography findings (normal to severe abnormalities). At the age of 3 months, 20 infants performed optimally on all items testing vestibular function, increasing to 40 at 6 months and 48 at 12 months. This significant improvement (also seen in muscle power regulation) was primarily caused by better head control (during the traction response and prone position), whereas less shoulder retraction and hyperextension were found in the sitting position. Vestibular function was significantly related to brain ultrasonography classification but not to gestational age, birthweight, the Neonatal Medical Index, or gender.