Innovative air mattress for the prevention of pressure ulcers in neonates.

OBJECTIVE: Pressure ulcers (PUs) severely impact health outcomes in neonatal intensive care, with up to 28% prevalence and doubled mortality rates. Due to their only partially developed stratum corneum, neonates are highly susceptible to PUs because of a lack of adequate support surfaces. The occipital region of the head and hip are the main risk areas due to immobility and newborn body proportions. The main goal of the study was to investigate the impact of reduction in local pressure in these body areas by two air mattress designs and different filling states. METHOD: Two innovative air-filled mattress prototypes (prototype 1 and prototype 2), consisting of three different segments (head, trunk and feet regions), were developed to reduce local interface pressures by optimising pressure distribution, and were assessed with three air pressure filling states (0.2kPa, 0.4kPa and 0.6kPa). A baby doll was used to investigate pressure distribution and local pressure impact. It measured 51cm and the weight was modified to be 1.3kg, 2.3kg and 3.3kg, representing premature to term newborn weights, respectively. A specialised foam mattress and an unsupported surface were considered as controls. RESULTS: The interface pressures at the hip region for newborn models could be reduced by up to 41% with mattress prototype 1 and 49% with prototype 2 when filled with 0.2kPa air pressure. It was found that the size and the pressure inside air segments was crucial for interface pressure. CONCLUSION: Our results demonstrated that air mattresses achieved lower interface pressures compared to conventional support surfaces, and that the benefit of the air mattresses depended on their filling status. The importance of using innovative, segmented designs that were tailored to meet the specific needs of highly vulnerable paediatric patients was demonstrated.

Exploring the thermally-controlled fentanyl transdermal therapy to provide constant drug delivery by physics-based digital twins.

Transdermal drug delivery is suitable for low-molecular-weight drugs with specific lipophilicity, like fentanyl, which is widely used for cancer-induced pain management. However, fentanyl's transdermal therapy displays high intra-individual variability. Factors like skin characteristics at application sites and ambient temperature contribute to this variation. In this study, we developed a physics-based digital twin of the human body to cope with this variability and propose better adapted setups. This twin includes an in-silico skin model for drug penetration, a pharmacokinetic model, and a pharmacodynamic model. Based on the results of our simulations, applying the patch on the flank (side abdominal area) showed a 15.3 % higher maximum fentanyl concentration in the plasma than on the chest. Additionally, the time to reach this maximum concentration when delivered through the flank was 19.8 h, which was 10.3 h earlier than via the upper arm. Finally, this variation led to an 18 % lower minimum pain intensity for delivery via the flank than the chest. Moreover, the impact of seasonal changes on ambient temperature and skin temperature by considering the activity level was investigated. Based on our result, the fentanyl uptake flux by capillaries increased by up to 11.8 % from an inactive state in winter to an active state in summer. We also evaluated the effect of controlling fentanyl delivery by adjusting the temperature of the patch to alleviate the pain to reach a mild pain intensity (rated three on the VAS scale). By implementing this strategy, the average pain intensity decreased by 1.1 points, and the standard deviation for fentanyl concentration in plasma and average pain intensity reduced by 37.5 % and 33.3 %, respectively. Therefore, our digital twin demonstrated the efficacy of controlled drug release through temperature regulation, ensuring the therapy toward the intended target outcome and reducing therapy outcome variability. This holds promise as a potentially useful tool for physicians.

Implementing physics-based digital patient twins to tailor the switch of oral morphine to transdermal fentanyl patches based on patient physiology.

Fentanyl transdermal patches are widely implemented for cancer-induced pain treatment due to the high potency of fentanyl and gradual drug release. However, transdermal fentanyl up-titration for opioid-naïve patients is difficult, which is why opioid treatment is often started with oral/iv morphine. Based on the daily dose of morphine, the initial dose of the fentanyl patch is decided upon. After reaching a stable level of pain, the switch is made from oral/iv morphine to transdermal fentanyl. There are standard calculation tools for transferring from oral/iv morphine to transdermal fentanyl, which is the same for all patients. By considering the variations in the physiology of the patients, a unique switching strategy cannot meet the needs of different patients. This study explores the outcome in terms of pain relief and minute ventilation during opioid therapy. For this, we used physics-based simulations on a virtually-generated population of patients, and we applied the same therapy to all patients. We could show that patients' physiology, such as gender, age, and weight, greatly impact the outcome of the therapy; as such, the correlation coefficient between pain intensity and age is 0.89, and the correlation coefficient between patient's weight and maximum plasma concentration of morphine and fentanyl is -0.98 and -0.97. Additionally, a different combination of the duration of overlap between morphine and fentanyl therapy with different doses of fentanyl was considered for the virtual patients to find the best opioid-switching strategy for each patient. We explored the impact of combining physiological features to determine the best-suited strategy for virtual patients. Our findings suggest that tailoring morphine and fentanyl therapy only based on a limited number of features is insufficient, and increasing the number of impactful physiological features positively influences the outcome of the therapy.

Use of a novel pressure distribution system for severely ill neonates: a clinical pilot study carried out by the PREPICare consortium.

BACKGROUND: Pressure Injuries are not exclusively an adult phenomenon; various risk factors contribute to a high prevalence rate of 43% in the neonatal and pediatric intensive care population. Effective preventive measures in this population are limited. METHODS: We performed a pilot study to analyze the distribution and localization of support surface interface pressures in neonates in a pediatric intensive care unit (PICU). The hypothesis was that pressure redistribution by a novel air mattress would reduce pressure peaks in critical neonates. The measurements were conducted in a 27-bed level III PICU between November and December 2020. This included measuring pressure distribution and pressure peaks for five neonates positioned on either a state-of-the-art foam mattress or a new prototype air mattress. RESULTS: We confirmed that the pressure peaks were significantly reduced using the prototype air mattress, compared with the state-of-the-art foam mattress. The reduction of mean pressure values was 9-29%, while the reduction of the highest 10% of pressure values was 23-41%. CONCLUSIONS: The journey to an effective, optimal, and approved product for severely ill neonates to reduce Pressure Injuries is challenging. However, a crucial step was completed by this pilot study with the first pressure measurements in a real-world setting and the successful realization of a decrease in pressure peaks obtained using a prototype air mattress.

An individualized digital twin of a patient for transdermal fentanyl therapy for chronic pain management.

Fentanyl transdermal therapy is a suitable treatment for moderate-to-severe cancer-related pain. The inter-individual variability of the patients leads to different therapy responses. This study aims to determine the effect of physiological features on the achieved pain relief. Therefore, a set of virtual patients was developed by using Markov chain Monte Carlo (MCMC) based on actual patient data. The members of this virtual population differ by age, weight, gender, and height. Tailored digital twins were developed using these correlated, individualized parameters to propose a personalized therapy for each patient. It was shown that patients of different ages, weights, and gender have significantly different fentanyl blood uptake, plasma fentanyl concentration, pain relief, and ventilation rate. In the digital twins, we included the virtual patients' response to the treatment, namely, pain relief. Therefore, the digital twin was able to adjust the therapy in silico to have more efficient pain relief. By implementing digital-twin-assisted therapy, the average pain intensity decreased by 16% compared to conventional therapy. The median time without pain increased by 23 h over 72 h. Therefore, the digital twin can be successfully used in individual control of transdermal therapy to reach higher pain relief and maintain steady pain relief. (Created with BioRender.com).

Predicting transdermal fentanyl delivery using physics-based simulations for tailored therapy based on the age.

Transdermal fentanyl patches are an effective alternative to the sustained release of oral morphine for chronic pain management. Due to the narrow therapeutic range of fentanyl, the concentration of fentanyl in the blood needs to be carefully monitored. Only then can effective pain relief be achieved while avoiding adverse effects such as respiratory depression. This study developed a physics-based digital twin of a patient by implementing drug uptake, pharmacokinetics, and pharmacodynamics models. The twin was employed to predict the in-silico effect of conventional fentanyl transdermal in a 20-80-year-old virtual patient. The results show that, with increasing age, the maximum transdermal fentanyl flux and maximum concentration of fentanyl in the blood decreased by 11.4% and 7.0%, respectively. However, the results also show that as the patient's age increases, the pain relief increases by 45.2%. Furthermore, the digital twin was used to propose a tailored therapy based on the patient's age. This predesigned therapy customized the duration of applying the commercialized fentanyl patches. According to this therapy, a 20-year-old patient needs to change the patch 2.1 times more frequently than conventional therapy, which leads to 30% more pain relief and 315% more time without pain. In addition, the digital twin was updated by the patient's pain intensity feedback. Such therapy increased the patient's breathing rate while providing effective pain relief, so a safer treatment. We quantified the added value of a patient's physics-based digital twin and sketched the future roadmap for implementing such twin-assisted treatment into the clinics.

Nano-3D-Printed Photochromic Micro-Objects.

Molecular photoswitches that can reversibly change color upon irradiation are promising materials for applications in molecular actuation and photoresponsive materials. However, the fabrication of photochromic devices is limited to conventional approaches such as mold casting and spin-coating, which cannot fabricate complex structures. Reported here is the first photoresist for direct laser writing of photochromic 3D micro-objects via two-photon polymerization. The integration of photochromism into thiol-ene photo-clickable resins enables rapid two-photon laser processing of highly complex microstructures and facile postmodification using a series of donor-acceptor Stenhouse adduct (DASA) photoswitches with different excitation wavelengths. The versatility of thiol-ene photo-click reactions allows fine-tuning of the network structure and physical properties as well as the type and concentration of DASA. When exposed to visible light, these microstructures exhibit excellent photoresponsiveness and undergo reversible color-changing via photoisomerization. It is demonstrated that the fluorescence variations of DASAs can be used as a reporter of photoswitching and thermal recovery, allowing the reading of DASA-containing sub-micrometric structures in 3D. This work delivers a new approach for custom microfabrication of 3D photochromic objects with molecularly engineered color and responsiveness.

Reversible Oxygen Sensing Based on Multi-Emission Fluorescence Quenching.

Oxygen is ubiquitous in nature and it plays a key role in several biological processes, such as cellular respiration and food deterioration, to name a few. Currently, reversible and non-destructive oxygen sensing is usually performed with sensors produced by photosensitization of phosphorescent organometallic complexes. In contrast, we propose a novel route of optical oxygen sensing by fluorescence-based quenching of oxygen. We hereby developed for the first time a set of multi-emissive purely organic emitters. These were produced through a one-pot hydrothermal synthesis using p-phenylenediamine (PPD) and urea as starting materials. The origin of the multi-emission has been ascribed to the diversity of chemical structures produced as a result of oxidative oligomerization of PPD. A Bandrowski's base (BB, i.e., trimer of PPD) is reported as the main component at reaction times higher than 8 h. This indication was confirmed by electrospray-ionization quadrupole time-of-flight (ESI-QTOF) and liquid chromatography-mass spectrometry (LC-MS) analysis. Once the emitters are embedded within a high molecular weight poly (vinyl alcohol) matrix, the intensities of all three emission centers exhibit a non-linear quenching provoked by oxygen within the range of 0-8 kPa. The detection limit of the emission centers are 0.89 kPa, 0.67 kPa and 0.75 kPa, respectively. This oxygen-dependent change in fluorescence emission is reversible (up to three tested 0-21% O2 cycles) and reproducible with negligible cross-interference to humidity. The cost-effectiveness, metal-free formulation, cross-referencing between each single emission center and the relevant oxygen range are all appealing features, making these sensors promising for the detection of oxygen, e.g., in food packaged products.

Need for mechanically and ergonomically enhanced tremor-suppression orthoses for the upper limb: a systematic review.

INTRODUCTION: Tremor is the most common movement disorder, affecting 5.6% of the population with Parkinson's disease or essential tremor over the age of 65. Conventionally, tremor diseases like Parkinson's are treated with medication. An alternative non-invasive symptom treatment is the mechanical suppression of the oscillation movement. The purpose of this review is to identify the weaknesses of past wearable tremor-suppression orthoses for the upper limb and identify the need for further research and developments. METHOD: A systematic literature search was conducted by performing a keyword combination search of the title, abstract and keyword sections in the four databases Web of Science, MedLine, Scopus, and ProQuest. Initially, the retrieved articles were selected by title and abstract using selection criteria. The same criteria were then applied to the full publication text. After the selection process, relevant information on the retrieved orthoses was isolated, sorted and analysed systematically. RESULTS: Forty-six papers, representing 21 orthoses, were identified and analysed according to the mechanical and ergonomic properties. The identified orthoses can be divided into 5 concepts and 16 functional prototypes, then subdivided further based upon their use of passive, semi-active, or active suppression mechanisms. Most of the orthoses concentrate on the wrist and elbow flexion and extension. They mainly rely on rigid structures and actuators while having tremor-suppression efficacies for tremorous subjects from 30 to 98% using power spectral density or other methods. CONCLUSION: The comparison of tremor-suppression orthoses considered and mapped their various mechanical and ergonomic properties, including the degrees of freedom, weight, suppression characteristics, and efficacies. This review shows that most of the orthoses are bulky and heavy, with a non-adapted human-machine interface which can cause rejection by the user. The main challenge of the design of an effective, minimally intrusive and portable tremor-suppressing orthosis is the integration of compact, powerful, lightweight, and non-cumbersome suppression mechanisms. None of the existing prototypes combine all the desired characteristics. Future research should focus on novel suppression orthoses and mechanisms with compact dimensions and light weight in order to be less cumbersome while giving a good tremor-suppression performance.

Biophysical skin properties of grade 1 pressure ulcers and unaffected skin in spinal cord injured and able-bodied persons in the unloaded sacral region.

AIM OF THE STUDY: To examine biophysical skin properties in the sacral region in spinal cord injury (SCI) patients suffering from a grade 1 pressure ulcer (PU) defined as non-blanchable erythema (SCI/PU), SCI patients in the post-acute phase (SCI/PA) and able-bodied participants (CON). Also, for SCI/PU patients, both the affected skin and healthy skin close to the PU were examined. STUDY DESIGN: An experimental controlled study with a convenience sample. SETTING: A Swiss acute care and rehabilitation clinic specializing in SCIs. MATERIALS AND METHODS: We determined hydration, redness, elasticity and perfusion of the unloaded skin in the sacral region of 6 SCI/PU patients (affected and healthy skin), 20 SCI/PA patients and 10 able-bodied controls. These measures were made by two trained examiners after the patients were lying in the supine position. RESULTS: The affected skin of SCI/PU patients showed elevated redness: median 595.5 arbitrary units (AU) (quartiles 440.4; 631.6) and perfusion: 263.0 AU (104.1; 659.4), both significantly increased compared to the healthy skin in SCI/PA patients and CON (p < 0.001). Similarly, healthy skin of SCI/PA patients showed elevated redness (p = 0.016) and perfusion (p < 0.001) compared to CON. On the other hand, differences in redness and perfusion between the affected and unaffected skin in SCI/PU patients were not significant. The results for skin hydration and skin elasticity were similar in all groups. CONCLUSIONS: Skin perfusion and redness were significantly increased in grade 1 PUs and for healthy skin in both SCI/PA patients and CON participants; thus, these are important in understanding the pathophysiology of PUs and skin in SCI.

Validation of the thermophysiological model by Fiala for prediction of local skin temperatures.

The most complete and realistic physiological data are derived from direct measurements during human experiments; however, they present some limitations such as ethical concerns, time and cost burden. Thermophysiological models are able to predict human thermal response in a wide range of environmental conditions, but their use is limited due to lack of validation. The aim of this work was to validate the thermophysiological model by Fiala for prediction of local skin temperatures against a dedicated database containing 43 different human experiments representing a wide range of conditions. The validation was conducted based on root-mean-square deviation (rmsd) and bias. The thermophysiological model by Fiala showed a good precision when predicting core and mean skin temperature (rmsd 0.26 and 0.92 °C, respectively) and also local skin temperatures for most body sites (average rmsd for local skin temperatures 1.32 °C). However, an increased deviation of the predictions was observed for the forehead skin temperature (rmsd of 1.63 °C) and for the thigh during exercising exposures (rmsd of 1.41 °C). Possible reasons for the observed deviations are lack of information on measurement circumstances (hair, head coverage interference) or an overestimation of the sweat evaporative cooling capacity for the head and thigh, respectively. This work has highlighted the importance of collecting details about the clothing worn and how and where the sensors were attached to the skin for achieving more precise results in the simulations.

Challenges to measure hydration, redness, elasticity and perfusion in the unloaded sacral region of healthy persons after supine position.

AIM OF THE STUDY: To combine measurement methods of biophysical skin properties in a clinical setting and to measure baseline values in the unloaded sacral region of healthy persons after lying 30 min in supine position. METHODS: Hydration (Corneometer® CM 825), redness (Mexameter® MX 18), elasticity (Cutometer® MPA 580) and perfusion (PeriFlux System 5000) of the skin in the sacral region of 10 healthy participants (median age: 26.9 years) were measured consecutively in the laying position by two trained examiners. RESULTS: The assessment duration for all four parameters lasted about 15 min. Intra-class correlation coefficients were overall moderate to strong (hydration r = 0.594, redness r = 0.817, elasticity r = 0.719, perfusion r = 0.591). Hydration (median 27.7 arbitrary units (AU)) mainly indicated dry skin conditions. Redness (median 158.5 AU) was low. Elasticity (median 0.880 AU) showed similar values as in the neck region. Perfusion (median 17.1 AU) showed values in the range of results reported in the literature. CONCLUSION: Biophysical skin properties in the sacral region after supine position can be measured within periods of 15 min. The results provide baseline data for the skin of healthy persons as well as insights into skin-physiological variations. But it remains challenging to optimize measurement procedures and test protocols when transferring preclinical tests in a clinical application.

Prediction of human core body temperature using non-invasive measurement methods.

The measurement of core body temperature is an efficient method for monitoring heat stress amongst workers in hot conditions. However, invasive measurement of core body temperature (e.g. rectal, intestinal, oesophageal temperature) is impractical for such applications. Therefore, the aim of this study was to define relevant non-invasive measures to predict core body temperature under various conditions. We conducted two human subject studies with different experimental protocols, different environmental temperatures (10 °C, 30 °C) and different subjects. In both studies the same non-invasive measurement methods (skin temperature, skin heat flux, heart rate) were applied. A principle component analysis was conducted to extract independent factors, which were then used in a linear regression model. We identified six parameters (three skin temperatures, two skin heat fluxes and heart rate), which were included for the calculation of two factors. The predictive value of these factors for core body temperature was evaluated by a multiple regression analysis. The calculated root mean square deviation (rmsd) was in the range from 0.28 °C to 0.34 °C for all environmental conditions. These errors are similar to previous models using non-invasive measures to predict core body temperature. The results from this study illustrate that multiple physiological parameters (e.g. skin temperature and skin heat fluxes) are needed to predict core body temperature. In addition, the physiological measurements chosen in this study and the algorithm defined in this work are potentially applicable as real-time core body temperature monitoring to assess health risk in broad range of working conditions.