Proof of stability of an RSV Controlled Human Infection Model challenge agent.

In 2018, SGS Belgium NV developed RSV-NICA (Respiratory Syncytial Virus-Nasobronchial Infective Challenge Agent), an RSV type A challenge agent for use in RSV Controlled Human Infection Model (CHIM) studies.It is widely recognized that the stability of RSV can be influenced by a variety of environmental parameters, such as temperature and pH. Consequently, our objective was to evaluate the stability of the viral titer of RSV-NICA following five years of controlled storage and to determine the uniformity of the viral titers across different vials of a GMP-qualified batch of RSV-NICA. In addition, we examined the capacity of RSV-NICA to infect human primary airway epithelial cells (MucilAir™), the principal target cells of RSV, and evaluated the influence of single and recurrent freeze-thaw cycles on the infectious viral titer of the challenge agent.The aliquoted RSV-NICA virus stock was subjected to standard virological and molecular methods to gather data on the titer and consistency of the viral titer contained within 24 representative vials of the stock. Our findings illustrate that over a span of five years of cryo-storage, the infectious viral titer in 75% of the tested vials exhibited a comparable average infectious viral titer (4.75 ± 0.06 vs 4.99 ± 0.11; p-value = 0.14). A considerable reduction down to an undetectable level of infectious virus was observed in the remaining vials. RSV-NICA demonstrated its capacity to effectively infect differentiated human airway epithelial cells, with active virus replication detected in these cells through increasing RSV genome copy number over time. Virus tropism for ciliated cells was suggested by the inhibition of cilia beating coupled with an increase in viral RNA titers. No discernable impact on membrane barrier function of the epithelial lung tissues nor cytotoxicity was detected. Pooling of vials with infectious titers > 4.0 log10 TCID50/ml and freeze-thawing of these combined vials showed no deterioration of the infectious titer. Furthermore, pooling and re-aliquoting of vials spanning the entire range of viral titers (including vials with undetectable infectious virus) along with subjecting the vials to three repeated freeze-thaw cycles did not result in a decrease of the infectious titers in the tested vials.Taken together, our findings indicate that long-term cryo-storage of vials containing RSV-NICA challenge agent may influence the infectious viral titer of the virus, leading to a decrease in the homogeneity of this titer throughout the challenge stock. However, our study also demonstrates that when heterogeneity of the infectious titer of an RSV stock is observed, rounds of pooling, re-aliquoting and subsequent re-titration serve as an effective method not only to restore the homogeneity of the infectious titer of an RSV-A stock, but also to optimize patient-safety, scientific and operational aspects of viral inoculation of study participants during at least the period of one RSV CHIM trial. RSV-NICA is a stable, suitable CHIM challenge agent that can be utilized in efficacy trials for RSV vaccines and antiviral entities.

Pro-opiomelanocortin and ACTH-cortisol dissociation during pediatric cardiac surgery.

In critically ill adults, high plasma cortisol in face of low ACTH coincides with high pro-opiomelanocortin (POMC) levels. Glucocorticoids further lower ACTH without affecting POMC. We hypothesized that in pediatric cardiac surgery-induced critical illness, plasma POMC is elevated, plasma ACTH transiently rises intraoperatively but becomes suppressed post-operatively, and glucocorticoid administration amplifies this phenotype. From 53 patients (0-36 months), plasma was obtained pre-operatively, intraoperatively and on post-operative day 1 and 2. Plasma was also collected from 24 healthy children. In patients, POMC was supra-normal pre-operatively (p<0.0001) but no longer thereafter (p<0.05). ACTH was never high in patients. While in glucocorticoid-naive patients ACTH became suppressed by post-operative day 1 (p<0.0001), glucocorticoid-treated patients had suppressed ACTH already intraoperatively (p≤0.0001). Pre-operatively high POMC, not accompanied by increased plasma ACTH, suggests a centrally-activated HPA-axis with reduced pituitary processing of POMC into ACTH. Increasing systemic glucocorticoid availability with glucocorticoid treatment accelerated the suppression of plasma ACTH.

Selective Replacement of Cholesterol with Cationic Amphiphilic Drugs Enables the Design of Lipid Nanoparticles with Improved RNA Delivery.

The delivery of RNA across biological barriers can be achieved by encapsulation in lipid nanoparticles (LNPs). Cationic amphiphilic drugs (CADs) are pharmacologically diverse compounds with ionizable lipid-like features. In this work, we applied CADs as a fifth component of state-of-the-art LNPs via microfluidic mixing. Improved cytosolic delivery of both siRNA and mRNA was achieved by partly replacing the cholesterol fraction of LNPs with CADs. The LNPs could cross the mucus layer in a mucus-producing air-liquid interface model of human primary bronchial epithelial cells following nebulization. Moreover, CAD-LNPs demonstrated improved epithelial and endothelial targeting following intranasal administration in mice, without a marked pro-inflammatory signature. Importantly, quantification of the CAD-LNP molar composition, as demonstrated for nortriptyline, revealed a gradual leakage of the CAD from the formulation during LNP dialysis. Altogether, these data suggest that the addition of a CAD prior to the rapid mixing process might have an impact on the composition, structure, and performance of LNPs.

Vitamin D insufficiency in infants with increased risk of developing type 1 diabetes: a secondary analysis of the POInT Study.

BACKGROUND: Vitamin D insufficiency (VDI) may be a factor in the development of type 1 diabetes (T1D). The aim of this study is to investigate the presence and persistence of VDI in a large cohort of infants with increased risk of developing T1D, in light of the differences in local supplementation guidelines. METHODS: In the POInT Study, a multicentre primary prevention study between February 2018 and March 2021 in Germany, Poland, Belgium, England and Sweden, including infants aged 4-7 months at high genetic risk of developing ß-cell autoantibodies, vitamin D levels were analysed at each study visit from inclusion (4-7 months) until 3 years, with an interval of 2 months (first three visits) or 4-6 months (visits 4-8). The protocol actively promotes vitamin D sufficiency to optimise immune tolerance. VDI was defined as a concentration below 30 ng/mL and was treated according to local guidelines of participating centres. Recovery from VDI was defined as a concentration above or equal to 30 ng/mL on the subsequent visit after VDI. RESULTS: 1050 infants were included, of which 5937 vitamin D levels were available for analyses. VDI was observed in 1464 (24.7%) visits and 507 (46.1%) of these were not resolved at the next visit. The risk of having VDI was independently associated with season (higher in winter), weight (higher with increased weight), age (higher with increased age) and country (higher in England). The risk of not recovering from VDI was independently associated with the season of the previously determined VDI, which was higher if VDI was identified in winter. CONCLUSIONS: VDI is frequent in infants with increased risk of developing T1D. Treatment guidelines for VDI do not seem effective. Increasing supplementation dosages in this patient population seems warranted, especially during winter, and increasing dosages more aggressively after VDI should be considered.

Pigmented hypertrichosis with insulin-dependent diabetes mellitus syndrome: A case series.

INTRODUCTION: Pigmented hypertrichosis with insulin-dependent diabetes mellitus (PHID) syndrome is a rare disease, and part of the cluster Histiocytosis-lymphadenopathy plus syndrome (H syndrome), which is associated with mutations in the SLC29A3 gene. Patients with PHID show clinical features of H syndrome, but also have insulin-dependent diabetes mellitus. The PHID associated diabetes has previously been described as predominantly in absence of pancreatic autoantibodies. Case Series Presentation: Through an open call in two international diabetes registers, clinical and genetic characteristics of 7 PHID patients in 6 treatment centres were collected after informed consent. All of them had consanguinity in their families, and their origins were located in North-African and Middle Eastern regions. 4 out of 7 patients had at least one positive pancreatic autoantibody. DISCUSSION AND CONCLUSION: Our case series reveals that PHID exhibits a wide range of clinical symptoms and signs. When consanguinity is present in a patient with newly diagnosed diabetes, and/or if other atypical symptoms such as dysmorphic features, skin lesions, haematological abnormalities and developmental delay are present; threshold for genetic analysis should be low. Moreover, the presence of autoantibodies should not withhold genetic testing, as our case series contradicts the previous observation of predominant auto-antibody absence in PHID.

Differential alternative splicing analysis links variation in ZRSR2 to a novel type of oral-facial-digital syndrome.

PURPOSE: Oral-facial-digital (OFD) syndromes are genetically heterogeneous developmental disorders, caused by pathogenic variants in genes involved in primary cilia formation and function. We identified a previously undescribed type of OFD with brain anomalies, ranging from alobar holoprosencephaly to pituitary anomalies, in 6 unrelated families. METHODS: Exome sequencing of affected probands was supplemented with alternative splicing analysis in patient and control lymphoblastoid and fibroblast cell lines, and primary cilia structure analysis in patient fibroblasts. RESULTS: In 1 family with 2 affected males, we identified a germline variant in the last exon of ZRSR2, NM_005089.4:c.1211_1212del NP_005080.1:p.(Gly404GlufsTer23), whereas 7 affected males from 5 unrelated families were hemizygous for the ZRSR2 variant NM_005089.4:c.1207_1208del NP_005080.1:p.(Arg403GlyfsTer24), either occurring de novo or inherited in an X-linked recessive pattern. ZRSR2, located on chromosome Xp22.2, encodes a splicing factor of the minor spliceosome complex, which recognizes minor introns, representing 0.35% of human introns. Patient samples showed significant enrichment of minor intron retention. Among differentially spliced targets are ciliopathy-related genes, such as TMEM107 and CIBAR1. Primary fibroblasts containing the NM_005089.4:c.1207_1208del ZRSR2 variant had abnormally elongated cilia, confirming an association between defective U12-type intron splicing, OFD and abnormal primary cilia formation. CONCLUSION: We introduce a novel type of OFD associated with elongated cilia and differential splicing of minor intron-containing genes due to germline variation in ZRSR2.

Does a Soft Actuated Back Exosuit Influence Multimodal Physiological Measurements and User Perception During an Industry Inspired Task?

Back support soft exosuits are promising solutions to reduce risk of musculoskeletal injuries at workplaces resulting from physically demanding and repetitive lifting tasks. Design of novel active exosuits address the impact on the muscle activity and metabolic costs but do not consider other critical aspects such as comfort and user perception during the intended tasks. Thus, in this study, we describe a novel soft active exosuit in line with its impact on physiological and subjective measures during lifting. We tested four healthy participants who performed repetitive lifting tasks with and without this exosuit. The exosuit provided assistance proportional to the lumbar flexion angle measured using an inertial measurement unit. We measured the participant's multimodal physiological measures including surface electromyography, metabolic cost, heart rate, and skin temperature. We also measured subjective scores on user exertion, task load, and device acceptability. All participants perceived a reduction in task load when using the exosuit. Three participants showed reduction of muscle activity for the erector spinae muscles. The metabolic costs and heart rate reserve reduced for two participants, with similar trends for skin temperature. For future development of workplace exosuits, we recommend incorporating assessments of both physiological and subjective measures, considering the user-dependent response to the exosuit.

The Dynamic Adoption Journey: A Typology for Users and Non-Users of Occupational Exoskeletons.

Various barriers prevent the adoption of occupational exoskeletons. It is therefore important to understand why some people are willing to use occupational exoskeletons, while others are not. To identify why people use or do not use exoskeletons, we created a typology describing different types of users and non-users. These types were created based on existing literature on internet adoption and social robots. Next, literature and empirical data were used to identify reasons why some people use exoskeletons and others do not use them (yet). The typology includes users with pain and users without work-related musculoskeletal disorders, but also non-users: resisters, rejecters, discontinuers, excluded or expelled non-users. It can be used by companies interested in implementing exoskeletons to identify possible early adopters. For exoskeleton designers, it can be used as a tool to identify non-users and focus on design strategies to enable non-users to become users (such as making exoskeletons that would fit people with a wide range of body shapes). Future research can use these types to identify users and non-users in field trials or pilot projects.

Exploring technology acceptance of head-mounted device-based augmented reality surgical navigation in orthopaedic surgery.

BACKGROUND: This study used the Unified Theory of Acceptance and Use of Technology (UTAUT) to investigate the acceptance of HMD-based AR surgical navigation. METHODS: An experiment was conducted in which participants drilled 12 predefined holes using freehand drilling, proprioceptive control, and AR assistance. Technology acceptance was assessed through a survey and non-participant observations. RESULTS: Participants' intention to use AR correlated (p < 0.05) with social influence (Spearman's rho (rs) = 0.599), perceived performance improvement (rs = 0.592) and attitude towards AR (rs = 0.542). CONCLUSIONS: While most participants acknowledged the potential of AR, they also highlighted persistent barriers to adoption, such as issues related to user-friendliness, time efficiency and device discomfort. To overcome these challenges, future AR surgical navigation systems should focus on enhancing surgical performance while minimising disruptions to workflows and operating times. Engaging orthopaedic surgeons in the development process can facilitate the creation of tailored solutions and accelerate adoption.

Interdisciplinary evaluation of a robot physically collaborating with workers.

Collaborative Robots-CoBots-are emerging as a promising technological aid for workers. To date, most CoBots merely share their workspace or collaborate without contact, with their human partners. We claim that robots would be much more beneficial if they physically collaborated with the worker, on high payload tasks. To move high payloads, while remaining safe, the robot should use two or more lightweight arms. In this work, we address the following question: to what extent can robots help workers in physical human-robot collaboration tasks? To find an answer, we have gathered an interdisciplinary group, spanning from an industrial end user to cognitive ergonomists, and including biomechanicians and roboticists. We drew inspiration from an industrial process realized repetitively by workers of the SME HANKAMP (Netherlands). Eleven participants replicated the process, without and with the help of a robot. During the task, we monitored the participants' biomechanical activity. After the task, the participants completed a survey with usability and acceptability measures; seven workers of the SME completed the same survey. The results of our research are the following. First, by applying-for the first time in collaborative robotics-Potvin's method, we show that the robot substantially reduces the participants' muscular effort. Second: we design and present an unprecedented method for measuring the robot reliability and reproducibility in collaborative scenarios. Third: by correlating the worker's effort with the power measured by the robot, we show that the two agents act in energetic synergy. Fourth: the participant's increasing level of experience with robots shifts his/her focus from the robot's overall functionality towards finer expectations. Last but not least: workers and participants are willing to work with the robot and think it is useful.

Human cell-based in vitro systems to assess respiratory toxicity: a case study using silanes.

Inhalation is a major route by which human exposure to substances can occur. Resources have therefore been dedicated to optimize human-relevant in vitro approaches that can accurately and efficiently predict the toxicity of inhaled chemicals for robust risk assessment and management. In this study-the IN vitro Systems to PredIct REspiratory toxicity Initiative-2 cell-based systems were used to predict the ability of chemicals to cause portal-of-entry effects on the human respiratory tract. A human bronchial epithelial cell line (BEAS-2B) and a reconstructed human tissue model (MucilAir, Epithelix) were exposed to triethoxysilane (TES) and trimethoxysilane (TMS) as vapor (mixed with N2 gas) at the air-liquid interface. Cell viability, cytotoxicity, and secretion of inflammatory markers were assessed in both cell systems and, for MucilAir tissues, morphology, barrier integrity, cilia beating frequency, and recovery after 7 days were also examined. The results show that both cell systems provide valuable information; the BEAS-2B cells were more sensitive in terms of cell viability and inflammatory markers, whereas MucilAir tissues allowed for the assessment of additional cellular effects and time points. As a proof of concept, the data were also used to calculate human equivalent concentrations. As expected, based on chemical properties and existing data, the silanes demonstrated toxicity in both systems with TMS being generally more toxic than TES. Overall, the results demonstrate that these in vitro test systems can provide valuable information relevant to predicting the likelihood of toxicity following inhalation exposure to chemicals in humans.

The association of hypoglycemia with outcome of critically ill children in relation to nutritional and blood glucose control strategies.

BACKGROUND: Withholding parenteral nutrition (PN) until one week after PICU admission facilitated recovery from critical illness and protected against emotional and behavioral problems 4 years later. However, the intervention increased the risk of hypoglycemia, which may have counteracted part of the benefit. Previously, hypoglycemia occurring under tight glucose control in critically ill children receiving early PN did not associate with long-term harm. We investigated whether hypoglycemia in PICU differentially associates with outcome in the context of withholding early PN, and whether any potential association with outcome may depend on the applied glucose control protocol. METHODS: In this secondary analysis of the multicenter PEPaNIC RCT, we studied whether hypoglycemia in PICU associated with mortality (N = 1440) and 4-years neurodevelopmental outcome (N = 674) through univariable comparison and multivariable regression analyses adjusting for potential confounders. In patients with available blood samples (N = 556), multivariable models were additionally adjusted for baseline serum NSE and S100B concentrations as biomarkers of neuronal, respectively, astrocytic damage. To study whether an association of hypoglycemia with outcome may be affected by the nutritional strategy or center-specific glucose control protocol, we further adjusted the models for the interaction between hypoglycemia and the randomized nutritional strategy, respectively, treatment center. In sensitivity analyses, we studied whether any association with outcome was different in patients with iatrogenic or spontaneous/recurrent hypoglycemia. RESULTS: Hypoglycemia univariably associated with higher mortality in PICU, at 90 days and 4 years after randomization, but not when adjusted for risk factors. After 4 years, critically ill children with hypoglycemia scored significantly worse for certain parent/caregiver-reported executive functions (working memory, planning and organization, metacognition) than patients without hypoglycemia, also when adjusted for risk factors including baseline NSE and S100B. Further adjustment for the interaction of hypoglycemia with the randomized intervention or treatment center revealed a potential interaction, whereby tight glucose control and withholding early PN may be protective. Impaired executive functions were most pronounced in patients with spontaneous or recurrent hypoglycemia. CONCLUSION: Critically ill children exposed to hypoglycemia in PICU were at higher risk of impaired executive functions after 4 years, especially in cases of spontaneous/recurrent hypoglycemia.

The role of phone-based triage nurses in supporting older adults with multimorbidity to digitally self-manage - Findings from the ProACT proof-of-concept study.

Background: Achieving patient-centred care necessitates supporting individuals to have more involvement in the self-management of their care. Digital health technologies are widely recognised as a solution to empower more effective self-management. However, given the complexity of multiple chronic condition (multimorbidity) management, coupled with changes that occur as part of the normal ageing process, human support alongside digital self-management is often necessary for older people with multimorbidity (PwM) to sustain successful self-management. Methods: The aim of the study was to explore the role played by a clinical, nurse-led telephone triage service in responding to alerts generated by older adults using a digital health platform, ProACT, to self-manage multiple chronic conditions over a period of 1 year. Semi-structured interviews with participants with multimorbidity were carried out across four time points during the trial, while interviews and focus groups were conducted with triage nurses at the end of the trial. Thematic analysis was conducted on the resulting transcripts. Results: Themes found in the data include the work of triage nurses; the benefits of triage support; tensions such as anxiety due to patient monitoring; and the relationship between triage nurses and participants. Discussion: This work contributes to an understanding of how older adults with multimorbidity and triage nurses collaborate in multiple chronic disease self-management. Findings are discussed within the context of Hudon et al.'s patient-centred care framework and indicate that patient-centred care was achieved, with both PwM and triage participants reporting positive experiences, relationships and several benefits of the triage support alongside digital self-management.

Impact of critical illness and withholding of early parenteral nutrition in the pediatric intensive care unit on long-term physical performance of children: a 4-year follow-up of the PEPaNIC randomized controlled trial.

BACKGROUND: Many critically ill children face long-term developmental impairments. The PEPaNIC trial attributed part of the problems at the level of neurocognitive and emotional/behavioral development to early use of parenteral nutrition (early-PN) in the PICU, as compared with withholding it for 1 week (late-PN). Insight in long-term daily life physical functional capacity after critical illness is limited. Also, whether timing of initiating PN affects long-term physical function of these children remained unknown. METHODS: This preplanned follow-up study of the multicenter PEPaNIC randomized controlled trial subjected 521 former critically ill children (253 early-PN, 268 late-PN) to quantitative physical function tests 4 years after PICU admission in Leuven or Rotterdam, in comparison with 346 age- and sex-matched healthy children. Tests included handgrip strength measurement, timed up-and-go test, 6-min walk test, and evaluation of everyday overall physical activity with an accelerometer. We compared these functional measures for the former critically ill and healthy children and for former critically ill children randomized to late-PN versus early-PN, with multivariable linear or logistic regression analyses adjusting for risk factors. RESULTS: As compared with healthy children, former critically ill children showed less handgrip strength (p < 0.0001), completed the timed up-and-go test more slowly (p < 0.0001), walked a shorter distance in 6 min (p < 0.0001) during which they experienced a larger drop in peripheral oxygen saturation (p ≤ 0.026), showed a lower energy expenditure (p ≤ 0.024), performed more light and less moderate physical activity (p ≤ 0.047), and walked fewer steps per day (p = 0.0074). Late-PN as compared with early-PN did not significantly affect these outcomes. CONCLUSIONS: Four years after PICU admission, former critically ill children showed worse physical performance as compared with healthy children, without impact of timing of supplemental PN in the PICU. This study provides further support for de-implementing the early use of PN in the PICU. Trial registration ClinicalTrials.gov, NCT01536275 ; registered on February 22, 2012.

An industrial exoskeleton user acceptance framework based on a literature review of empirical studies.

Studying the acceptance of exoskeletons in industry has gained increased attention. Exoskeletons (wearable support devices) are envisioned to alleviate heavy work. Examining what factors influence the use of exoskeletons is important, because influencing these factors could positively contribute to the adoption of industrial exoskeletons. The factors identified in this paper have been systematically derived from empirical research with (potential future) end users, most of whom have tried on an exoskeleton. Our framework with factors influencing the acceptance of industrial exoskeletons can be used during the (ideally iterative) design, (re)development and evaluation phase of new or existing exoskeletons. This could improve the quality of exoskeletons since this allows designers to already consider acceptance factors early in the design process instead of finding out what is important late in the design process during (field) testing. In turn, this might accelerate the adoption of exoskeletons. Also, our framework can be used to study the ongoing introduction of exoskeletons at work since it also addresses policy decisions companies interested in implementing exoskeletons should consider.

Characterising extracellular vesicles from individual low volume cerebrospinal fluid samples, isolated by SmartSEC.

Extracellular vesicles (EVs) are suggested to have a role in the progression of neurodegeneration, and are able to transmit pathological proteins from one cell to another. One of the biofluids from which EVs can be isolated is cerebrospinal fluid (CSF). However, so far, few studies have been performed on small volumes of CSF. Since pooling of patient samples possibly leads to the loss of essential individual patient information, and CSF samples are precious, it is important to have efficient techniques for the isolation of EVs from smaller volumes. In this study, the SmartSEC HT isolation kit from System Biosciences has been evaluated for this purpose. The SmartSEC HT isolation kit was used for isolation of EVs from 500 µL starting volumes of CSF, resulting in two possible EV fractions of 500 µL. Both fractions were characterised and compared to one another using a whole range of characterisation techniques. Results indicated the presence of EVs in both fractions, albeit fraction 1 showed more reproducible results over the different characterisation methods. For example, CMG (CellMask Green membrane stain) fluorescence nanotracking analysis (NTA), ExoView, and the particles/µg ratio demonstrated a clear difference between fraction 1 and 2, where fraction 1 came out as the one where most EVs were eluted with the least contamination. In the other methods, this difference was less noticeable. We successfully performed complementary characterisation tests using only 500 µL of CSF starting volume, and, conclude that fraction 1 consisted of sufficiently pure EVs for further biomarker studies. This means that future EV extractions may be based upon smaller CSF quantities, such as from individual patients. In that way, patient samples do not have to be pooled and individual patient information can be included in forthcoming studies, potentially linking EV content, size and distribution to individualised neurological diagnoses.

A Digital Platform to Support Self-management of Multiple Chronic Conditions (ProACT): Findings in Relation to Engagement During a One-Year Proof-of-Concept Trial.

BACKGROUND: Populations globally are ageing, resulting in higher incidence rates of chronic diseases. Digital health platforms, designed to support those with chronic conditions to self-manage at home, offer a promising solution to help people monitor their conditions and lifestyle, maintain good health, and reduce unscheduled clinical visits. However, despite high prevalence rates of multimorbidity or multiple chronic conditions, most platforms tend to focus on a single disease. A further challenge is that despite the importance of users actively engaging with such systems, little research has explored engagement. OBJECTIVE: The objectives of this study are to design and develop a digital health platform, ProACT, for facilitating older adults self-managing multimorbidity, with support from their care network, and evaluate end user engagement and experiences with this platform through a 12-month trial. METHODS: The ProACT digital health platform is presented in this paper. The platform was evaluated in a year-long proof-of-concept action research trial with 120 older persons with multimorbidity in Ireland and Belgium. Alongside the technology, participants had access to a clinical triage service responding to symptom alerts and a technical helpdesk. Interactions with the platform during the trial were logged to determine engagement. Semistructured interviews were conducted with participants and analyzed using inductive thematic analysis, whereas usability and user burden were examined using validated questionnaires. RESULTS: This paper presents the ProACT platform and its components, along with findings on engagement with the platform and its usability. Of the 120 participants who participated, 24 (20%) withdrew before the end of the study, whereas 3 (2.5%) died. The remaining 93 participants actively used the platform until the end of the trial, on average, taking 2 or 3 health readings daily over the course of the trial in Ireland and Belgium, respectively. The participants reported ProACT to be usable and of low burden. Findings from interviews revealed that participants experienced multiple benefits as a result of using ProACT, including improved self-management, health, and well-being and support from the triage service. For those who withdrew, barriers to engagement were poor health and frustration when technology, in particular sensing devices, did not work as expected. CONCLUSIONS: This is the first study to present findings from a longitudinal study of older adults using digital health technology to self-manage multimorbidity. Our findings show that older adults sustained engagement with the technology and found it usable. Potential reasons for these results include a strong focus on user-centered design and engagement throughout the project lifecycle, resulting in a platform that meets user needs, as well as the integration of behavior change techniques and personal analytics into the platform. The provision of triage and technical support services alongside the platform during the trial were also important facilitators of engagement. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR2-10.2196/22125.

A Digital Health Platform for Integrated and Proactive Patient-Centered Multimorbidity Self-management and Care (ProACT): Protocol for an Action Research Proof-of-Concept Trial.

BACKGROUND: Multimorbidity is defined as the presence of two or more chronic diseases and associated comorbidities. There is a need to improve best practices around the provision of well-coordinated, person-centered care for persons with multimorbidities. Present health systems across the European Union (EU) focus on supporting a single-disease framework of care; the primary challenge is to create a patient-centric, integrated care ecosystem to understand and manage multimorbidity. ProACT is a large-scale project funded by the European Commission under the Horizon 2020 programme, that involved the design, development, and evaluation of a digital health platform to improve and advance home-based integrated care, and supported self-management, for older adults (aged ≥65 years) living with multimorbidity. OBJECTIVE: This paper describes the trial implementation protocol of a proof-of-concept digital health platform (ProACT) in 2 EU member states (Ireland and Belgium) to support older persons with multimorbidities self-managing at home, supported by their care network (CN). METHODS: Research was conducted across 2 EU member states, Ireland and Belgium. A 12-month action research trial design, divided into 3 evaluation cycles and lasting 3 months each, with a reflective redesign and development phase of 1 month after cycles 1 and 2 was conducted. Participants were 120 (60/120, 50% in Ireland and 60/120, 50% in Belgium) older persons with multimorbidities diagnosed with two or more of the following chronic conditions: diabetes, chronic obstructive pulmonary disease, chronic heart failure, and cardiovascular diseases. With permission from persons with multimorbidities, members of their CN were invited to participate in the study. Persons with multimorbidities were provided with ProACT technologies (tablet, devices, or sensors) to support them in self-managing their conditions. CN members also received access to an app to remotely support their persons with multimorbidity. Qualitative and quantitative feedback and evaluation data from persons with multimorbidity and CN participants were collected across four time points: baseline (T1), at the end of each 3-month action research cycle (T2 and T3), and in a final posttrial interview (T4). Thematic analysis was used to analyze the qualitative interview data. Quantitative data were analyzed via platform use statistics (to assess engagement) and standardized questionnaires (using descriptive and inferential statistics). This study is approved by the ethics committees of Ireland and Belgium. RESULTS: The trial implementation phase for this 44-month (2016-2019) funded study was April 2018 to June 2019. The trial outcomes are at various stages of publication since 2021. CONCLUSIONS: ProACT aims to co-design and develop a digital intervention with persons with multimorbidities and their CN, incorporating clinical guidelines with the state of the art in human-computer interaction, behavioral science, health psychology, and data analytic methods to deliver a digital health platform to advance self-management of multimorbidity at home, as part of a proactive, integrated model of supported person-centered care. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): RR1-10.2196/22125.

The effect of augmented reality on the accuracy and learning curve of external ventricular drain placement.

OBJECTIVE: The traditional freehand technique for external ventricular drain (EVD) placement is most frequently used, but remains the primary risk factor for inaccurate drain placement. As this procedure could benefit from image guidance, the authors set forth to demonstrate the impact of augmented-reality (AR) assistance on the accuracy and learning curve of EVD placement compared with the freehand technique. METHODS: Sixteen medical students performed a total of 128 EVD placements on a custom-made phantom head, both before and after receiving a standardized training session. They were guided by either the freehand technique or by AR, which provided an anatomical overlay and tailored guidance for EVD placement through inside-out infrared tracking. The outcome was quantified by the metric accuracy of EVD placement as well as by its clinical quality. RESULTS: The mean target error was significantly impacted by either AR (p = 0.003) or training (p = 0.02) in a direct comparison with the untrained freehand performance. Both untrained (11.9 ± 4.5 mm) and trained (12.2 ± 4.7 mm) AR performances were significantly better than the untrained freehand performance (19.9 ± 4.2 mm), which improved after training (13.5 ± 4.7 mm). The quality of EVD placement as assessed by the modified Kakarla scale (mKS) was significantly impacted by AR guidance (p = 0.005) but not by training (p = 0.07). Both untrained and trained AR performances (59.4% mKS grade 1 for both) were significantly better than the untrained freehand performance (25.0% mKS grade 1). Spatial aptitude testing revealed a correlation between perceptual ability and untrained AR-guided performance (r = 0.63). CONCLUSIONS: Compared with the freehand technique, AR guidance for EVD placement yielded a higher outcome accuracy and quality for procedure novices. With AR, untrained individuals performed as well as trained individuals, which indicates that AR guidance not only improved performance but also positively impacted the learning curve. Future efforts will focus on the translation and evaluation of AR for EVD placement in the clinical setting.