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Background: Flowmotion is the rhythmical variations in measured skin blood flow that arise due to global and local regulation of the vessels and can be studied using frequency analysis of time-resolved blood flow signals. It has the potential to reveal clinically useful information about microvascular diseases, but the spatial heteroge-neous nature of the microvasculature makes interpretation difficult. However, recent technological advances in multi-exposure laser speckle contrast imaging (MELSCI) enable new possibilities for simultaneously studying spatial and temporal variations in flowmotion.Aim: To develop a method for flowmotion analysis of MELSCI perfusion images. Furthermore, to investigate the spatial and temporal variations in flowmotion in forearm baseline skin perfusion.Method: In four healthy subjects, forearm skin perfusion was imaged at 15.6 fps for 10 min in baseline. The time -trace signal in each pixel was analyzed using the wavelet transform and summarized in five physiologically relevant frequency intervals, resulting in images of flowmotion. Furthermore, a method for reducing the effect of motion artifacts in the flowmotion analysis was developed.Results: The flowmotion images displayed patterns of high spatial heterogeneity that differed between the fre-quency intervals. The spatial variations in flowmotion, quantified as the coefficient of variation, was between 11 % and 31 % in four subjects. Furthermore, significant temporal variations in flowmotion were also observed, indicating the importance of a spatiotemporal analysis.Conclusion: The new imaging technique reveals significant spatial differences in flowmotion that cannot be ob-tained with single-point measurements. The results indicate that global statistics of flowmotion, such as the mean value in a large region of interest, is more representative of the microcirculation than data measured only in a single point. Therefore, imaging techniques have potential to increase the clinical usef, Funding Agencies|Swedens Innovation Agency VINNOVA [2019-01522]; Swedish Society of Medicine [SLS-961560]; Swedish government and the county councils [RO-960844]

Vital signs reflect circulatory function and hence hemodynamics on a macroscopic scale and are often unreliable or late indicators of hemodynamic instability. Previous studies support that alterations in the microcirculation may provide early indicators of deterioration and impending shock. Microcirculation is also restored late in the recovery process. Hence, monitoring microcirculation is important since treatments based on normalizing classical vital signs will not always restore microvascular hemodynamics and the microcirculation may remain in shock although e.g., blood pressure seems normal. The aim of this study was to investigate alterations in skin microcirculation dynamics during lower body negative pressure as a model of shock and central hypovolemia. By using spatial frequency domain imaging (SFDI) and polarized reflectance imaging, we investigated the association between micro- and macrovascular function during these conditions. Furthermore, we evaluated microvascular reactivity using the capillary refill test. A cohort of 9 subjects were subjected to a progressive lower body negative pressure (LBNP) protocol. At baseline and at LBNP = -20mmHg, -30mmHg and -40mmHg, SFDI images were acquired and analyzed for tissue hemoglobin content and oxygenation. Superficial hemoglobin content was estimated by polarized reflectance imaging. We found that microcirculatory reactivity was prolonged during LBNP, but recovered after end of the protocol. These results indicate a correlation between negative pressure and microcirculatory function and that may provide a basis for early detection of shock in emergency care settings.

The high-density microneedle array patch (HD-MAP) is a promising alternative vaccine delivery system device with broad application in disease, including SARS-CoV-2. Skin reactivity to HD-MAP applications has been extensively studied in young individuals, but not in the >65 years population, a risk group often requiring higher dose vaccines to produce protective immune responses. The primary aims of the present study were to characterise local inflammatory responses and barrier recovery to HD-MAPs in elderly skin. In twelve volunteers aged 69-84 years, HD-MAPs were applied to the forearm and deltoid regions. Measurements of transepidermal water loss (TEWL), dielectric permittivity and erythema were performed before and after HD-MAP application at t = 10 min, 30 min, 48 h, and 7 days. At all sites, TEWL (barrier damage), dielectric permittivity (superficial water);, and erythema measurements rapidly increased after HD-MAP application. After 7 days, the mean measures had recovered toward pre-application values. The fact that the degree and chronology of skin reactivity and recovery after HD-MAP was similar in elderly skin to that previously reported in younger adults suggests that the reactivity basis for physical immune enhancement observed in younger adults will also be achievable in the older population., Funding Agencies|Department of Dermatology, Linkoping University Hospital, Linkoping, Sweden; Vaxxas, LTD, Brisbane, Australia

The molecular composition of human skin is altered due to diseases, which can be utilized for non-invasive sampling of biomarkers and disease diagnostics. For this to succeed, it is crucial to identify a sampling formulation with high extraction efficiency and reproducibility. Highly hydrated skin is expected to be optimal for increased diffusion of low-molecular-weight biomarkers, enabling efficient extraction as well as enhanced reproducibility as full hydration represents a well-defined endpoint. Here, the aim was to explore water-based formulations with high water activities, ensuring satisfactory skin hydration, for non-invasive sampling of four analytes that may serve as potential biomarkers, namely tryptophan, tyrosine, phenylalanine, and kynurenine. The included formulations consisted of two hydrogels (chitosan and agarose) and two different liquid crystalline cubic phases based on the polar lipid glycerol monooleate, which were all topically applied for 2 h on 35 healthy subjects in vivo. The skin status of all sampling sites was assessed by electrical impedance spectroscopy and transepidermal water loss, enabling explorative correlations between biophysical properties and analyte abundancies. Taken together, all formulations resulted in the successful and reproducible collection of the investigated biomarkers. Still, the cubic phases had an extraction capacity that was approximately two times higher compared to the hydrogels.

Monitoring of respiration is a central task in clinical medicine, crucial to patient safety. Despite the uncontroversial role of altered respiratory frequency as an important sign of impending or manifest deterioration, reliable measurement methods are mostly lacking outside of intensive care units and operating theaters. Photoplethysmography targeting the central blood circulation in the sternum could offer accurate and inexpensive monitoring of respiration. Changes in blood flow related to the different parts of the respiratory cycle are used to identify the respiratory pattern. The aim of this observational study was to compare photoplethysmography at the sternum to standard capnography in healthy volunteers. Bland Altman analysis showed good agreement (bias -0.21, SD 1.6, 95% limits of agreement -3.4 to 2.9) in respiratory rate values. Photoplethysmography provided high-quality measurements of respiratory rate comparable to capnographic measurements. This suggests that photoplethysmography may become a precise, cost-effective alternative for respiratory monitoring.

Background The high-density microarray patch (HD-MAP) promises to be a robust vaccination platform with clear advantages for future global societal demands for health care management. The method of action has its base not only in efficient delivery of vaccine but also in the reliable induction of a local innate physical inflammatory response to adjuvant the vaccination process. The application process needs to induce levels of reactivity, which are acceptable to the vaccine, and from which the skin promptly recovers. Materials and methods 1 x 1 cm HD-MAP patches containing 5000, 250-mu m long microprojections were applied to the skin in 12 healthy volunteers. The return of skin barrier function was assessed by transepidermal water loss (TEWL) and reaction to topical histamine challenge. Results Skin barrier recovery by 48 h was confirmed for all HD-MAP sites by recovered resistance to the effects of topical histamine application. Conclusions Our previous observation, that the barrier disruption indicator TEWL returns to normal by 48 h, is supported by this papers demonstration of return of skin resistance to topical histamine challenge in twelve healthy subjects.

Introduction As frailty among the elderly is receiving increasing attention in emergency departments (EDs) around the world, the use of frailty assessment tools is growing. An often used such tool is the Clinical Frailty Scale (CFS), whose inter-rater reliability has been sparingly investigated in ED settings. No inter-rater reliability study regarding CFS has previously been performed within the Scandinavian ED context. The primary aim of this study was to evaluate the inter-rater reliability of the CFS in a Swedish ED setting. Methods This was a prospective observational study conducted at three Swedish EDs. Patients >= 65 years were independently assessed with CFS by their responsible physician, registered nurse, and assistant nurse. Demographic information for each assessor was collected, along with frailty status (frail/not frail) on the basis of clinical judgment. Inter-rater reliability was calculated using intraclass correlation coefficient (ICC), whereas agreement of frailty assessed by CFS (dichotomized between frail/not frail, cutoff at >= 5 points) versus solely by clinical judgment was calculated by using cross-tabulation. Results One-hundred patients were included. We found inter-rater reliability to be moderate to good (ICC 0.78, 95% confidence interval [CI] 0.72-0.84), regardless of whether the care team included an emergency physician (ICC 0.74, 95% CI 0.62-0.83) or an intern/resident from another specialty (ICC 0.83, 95% CI 0.74-0.89). The agreement of clinically judged frailty compared to frailty according to CFS was 84%. In the opposing cases, staff tended to assess patients as frail to a higher extent using clinical judgment than by applying CFS on the same patient. Conclusions The CFS appears to have a moderate to good inter-rater reliability when used in a clinical ED setting. When guiding clinical decisions, we advise that the CFS score should be discussed within the team. Further research needs to be performed on the accuracy o

Background Exudative wounds cause discomfort for patients. Introduction of a moisture sensor to dressings could facilitate change of dressings only when needed. The aim of this pilot study was to evaluate the ability of a newly developed moisture sensor to detect moisture in relation to the absorbing capacity of the dressing. Materials and Methods In five patients, with one leg ulcer each, three dressing changes per patient were observed. Interval of dressing change was according to clinical need and healthcare professionals decision. Sensor activation, dressing weight and complications were registered. To investigate the effect of dressing on sensor activation, half of the observations were made without an extra layer of non-woven between the dressing and sensor (Variant A), and half with (Variant B). Results The sensor indicated time for dressing change in six out of fifteen observations. Variants A and B did not differ regarding activation or the timing of the activation. Conclusions The addition of a moisture sensor for facilitating management of exudative wounds is promising. We recommend future larger studies evaluating the potential clinical benefits and risks of the addition of a moisture sensor. We also recommend evaluation of potential home monitoring of wounds by a moisture sensor., Funding Agencies|Absorbest AB

Background The efficiency of transdermal drug delivery may be increased by pretreating the skin with microneedles, but distinct effects of microneedles and the microneedle-enhanced delivery of vasoactive drugs on the skin microvasculature are still not well investigated. Materials and Methods In eight healthy human subjects, we measured the microvascular response to microneedle-induced microtraumas in the skin microvasculature using polarized light spectroscopy imaging (Tissue Viability imaging, TiVi). The microvascular response was assessed for up to 48 hours for three microneedle sizes (300 mu m, 500 mu m, and 750 mu m) and for different pressures and application times. Results In our results, microneedle application increased the local red blood cell (RBC) concentration for up to 24 hours dependent on the needle lengths, applied time, and force. Conclusion Optimization of microneedles size, pressure, and application time should be taken into account for future protocols for drug delivery and experimental provocations.

Background Capillary refill (CR) time is traditionally assessed by naked-eye inspection of the return to original colour of a tissue after blanching pressure. Few studies have addressed intra-observer reliability or used objective quantification techniques to assess time to original colour. This study compares naked-eye assessment with quantified CR (qCR) time using polarisation spectroscopy and examines intra-observer and interobserver agreements in using the naked eye. Method A film of 18 CR tests (shown in a random fixed order) performed in healthy adults was assessed by a convenience sample of 14 doctors, 15 nurses and 19 secretaries (Department of Emergency Medicine, Linkoping University, September to November 2017), who were asked to estimate the time to return to colour and characterise it as fast, normal or slow. The qCR times and corresponding naked-eye time assessments were compared using the Kruskal-Wallis test. Three videos were shown twice without observers knowledge to measure intra-observer repeatability. Intra-observer categorical assessments were compared using Cohens Kappa analysis. Interobserver repeatability was measured and depicted with multiple-observer Bland-Altman plotting. Differences in naked-eye estimation between professions were analysed using ANOVA. Results Naked-eye assessed CR time and qCR time differ substantially, and agreement for the categorical assessments (naked-eye assessment vs qCR classification) was poor (Cohens kappa 0.27). Bland-Altman intra-observer repeatability ranged from 6% to 60%. Interobserver agreement was low as shown by the Bland-Altman plotting with a 95% limit of agreement with the mean of +/- 1.98 s for doctors, +/- 1.6 s for nurses and +/- 1.75 s for secretaries. The difference in CR time estimation (in seconds) between professions was not significant. Conclusions Our study suggests that naked-eye-assessed CR time shows poor reproducibility, even by the same observers, and differs from an objective measure o, Funding Agencies|Region Ostergotland [LIO-532001, LIO-700271]

Introduction: In a patient going into shock, blood is redistributed from the periphery to the central circulation, making an assessment of skin perfusion useful in a prehospital setting. Capillary refill time (CRT) is the time required for a pressure blanched skin site to reperfuse. Currently, CRT is tested by manually applying pressure for 5s to the skin and observing the time before reperfusion. Guidelines state that CRT should be 2-3s in a healthy patient. Shortcomings in this procedure include lack of standardization of pressure, subjective assessment of the time for reperfusion, and not accounting for the patient’s skin temperature. Aim: To develop a standardized objective procedure for testing CRT in the prehospital setting. Method: The study protocol was approved by the Ethics Committee at Linköping University (M200-07, 2015-99-31). An electro-pneumatic device exerting constant force (9N) over 5s was developed. CRT was measured using the Tissue Viability Imager (Wheelsbridge AB, Sweden) which relies on polarization spectroscopy. To simulate hypothermic conditions, healthy volunteers were subjected to low ambient temperature (8°C). Blood loss was simulated using a custom-built lower body negative pressure (LBNP) chamber. In both scenarios, the CRT test was carried out on three test sites (finger pulp, forehead, and sternum). Results: CRT on the finger pulp and sternum was shown to be increased following the hypothermic conditions, but not on the forehead. Skin temperature on the three sites followed the same pattern, with the forehead being virtually unchanged. Tests performed during LBNP revealed an apparent effect on CRT following the simulated blood loss, with prolonged CRT for all sites tested. Discussion: A successful methodology for objective assessment of CRT was developed, which was validated on healthy volunteers following hypothermia or simulated blood loss. Ongoing work will investigate a combination of hypothermia and blood loss to more accurately

Vital sign assessment is a common task in emergency medicine, but resources for continuous monitoring are restricted, data is often recorded manually, and entangled wires cause frustration. Therefore, we designed a small, wireless photoplethysmographic device capable of continuously assessing pulse, respiratory frequency and oxygen saturation on the sternum and tested the performance and feasibility in an emergency department setting. Fifty (56.3 20.2 years), consenting emergency patients (29 male) were recruited. Heart rate, respiratory rate and oxygen saturation were recorded simultaneously using the device and standard monitoring equipment. Data was compared using Bland-Altman plotting (heart rate, respiratory rate) and mean difference (oxygen saturation). The bias for heart- and respiratory rate was 0.4 (limits of agreements -11.3, 12.2 and -6.1, 7.0). Mean difference for oxygen saturation was -0.21 +/- 2.35%. This may be the first wireless device to use photoplethysmography on the sternum for vital sign assessment. We noted good agreement with standard monitors, but lack of standardization in data processing between monitoring systems may limit the generalizability of these findings. Although further improvements are needed, the feasibility of this approach provides proof of concept for a new paradigm of large scale, wireless patient monitoring., Funding Agencies|Region Ostergotland [LIO-532001, LIO-700271]