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Abstract Objective To explore the extent of use and perceived effectiveness of using a medication lubricant that is specifically designed to help people who struggle to swallow their solid medications whole. Method Health care workers of varying professional levels in aged care facilities (ACFs) across Australia who are involved in medication administration were invited to participate in a structured online survey. Results Of the 355 health care workers who completed the survey, 48% had used the medication lubricant to aid administration of whole and/or crushed solid oral dosage forms, and of these 89% agreed with the statement that “it is effective method to facilitate medication swallowing in residents.” The main benefits of using the medication lubricant were considered to be easier medication administration to residents (49%), reduction in need for crushing of medications (34%), and better adherence with medications (33%). Conclusions This study showed that using a medication lubricant for aged care residents may facilitate the process of medication administration for health care workers, which they perceive to improve residents' adherence with medications. Serious complications associated with solid dosage form modification may also be decreased by using a medication lubricant, as the need for modifying medications is reduced. Therapeutic Goods Administration (TGA)‐approved medication lubricants could therefore be a valuable tool to aid the medication administration for patients who have difficulties swallowing medications. Future research may consider the clinical efficacy and acceptability of medication lubricants specifically for people with swallowing difficulties.

The effect of climate change on rockfalls in the German low mountain regions is investigated following two different approaches. The first approach uses a logistic regression model that describes the combined effect of precipitation, freeze–thaw cycles, and fissure water on rockfall probability. The climate change signal for the past 6 decades is analysed by applying the model to meteorological observations. The possible effect of climate change until the end of the century is explored by applying the statistical model to the output of a multi-model ensemble of 23 regional climate scenario simulations. It is found that the number of days per year exhibiting an above-average probability for rockfalls has mostly been decreasing during the last few decades. Statistical significance is, however, present at only a few sites. A robust and statistically significant decrease can be seen in the Representative Concentration Pathway (RCP) climate scenario 8.5 (RCP8.5) simulations for Germany and neighbouring regions, locally falling below −10 % when comparing the last 30 years of the 20th century to the last 30 years of the 21st century. The most important factor determining the projected decrease in rockfall probability is a reduction in the number of freeze–thaw cycles expected under future climate conditions. For the second approach four large-scale meteorological patterns that are associated with enhanced rockfall probability are identified from reanalysis data. The frequency of all four patterns exhibits a seasonal cycle that maximises in the cold half of the year (winter and spring). Trends in the number of days that can be assigned to these patterns are determined both in meteorological reanalysis data and in climate simulations. In the reanalysis no statistically significant trend is found. For the future scenario simulations all climate models show a statistically significant decrease in the number of rockfall-promoting weather situations.

Swallowing oral solid dosage forms is challenging for those who have medication swallowing difficulties, including patients with dysphagia. One option is to mix the drug (whole or crushed) with a thick vehicle (medication lubricant). Previous in vitro studies consistently suggest that thick vehicles could impact the dissolution of solid dosage forms, potentially influencing their therapeutic effectiveness, but do not account for changes that happen during oral processing and swallowing. This study aims to investigate the potential impact of medication lubricants on drug release and examine the effect of oral processing. In vitro dissolution of whole and crushed paracetamol tablets mixed with five commercially available medication lubricants (two IDDSI level 2, two IDDSI level 3, and one IDDSI level 4) were tested with and without oral processing; a medication lubricant with/without paracetamol was placed in the mouth (five healthy volunteers), prepared for swallowing, but then expectorated and assessed for physical characteristics and drug release. Medication lubricants, both alone and mixed with crushed paracetamol tablets, showed a significant decrease in viscosity after oral processing. Without oral processing, IDDSI level 3 and 4 lubricants significantly delayed the dissolution of paracetamol tablets. After oral processing, particularly with crushed tablets, there was a substantial increase in the dissolution rate. These findings suggest that dissolution testing overestimates the impact of medication lubricants on drug dissolution. Therefore, using in vitro dissolution tests to predict the dissolution rate of medications mixed with thick vehicles is discouraged. It is essential to consider ways to incorporate the effects of the oral environment and oral processing on thick vehicles used for oral medication administration.

A rockfall dataset for Germany is analysed with the objective of identifying the meteorological and hydrological (pre-)conditions that change the probability for such events in central Europe. The factors investigated in the analysis are precipitation amount and intensity, freeze–thaw cycles, and subsurface moisture. As there is no suitable observational dataset for all relevant subsurface moisture types (e.g. water in rock pores and cleft water) available, simulated soil moisture and a proxy for pore water are tested as substitutes. The potential triggering factors were analysed both for the day of the event and for the days leading up to it. A logistic regression model was built, which considers individual potential triggering factors and their interactions. It is found that the most important factor influencing rockfall probability in the research area is the precipitation amount at the day of the event, but the water content of the ground on that day and freeze–thaw cycles in the days prior to the event also influence the hazard probability. Comparing simulated soil moisture and the pore-water proxy as predictors for rockfall reveals that the proxy, calculated as accumulated precipitation minus potential evaporation, performs slightly better in the statistical model. Using the statistical model, the effects of meteorological conditions on rockfall probability in German low mountain ranges can be quantified. The model suggests that precipitation is most efficient when the pore-water content of the ground is high. An increase in daily precipitation from its local 50th percentile to its 90th percentile approximately doubles the probability for a rockfall event under median pore-water conditions. When the pore-water proxy is at its 95th percentile, the same increase in precipitation leads to a 4-fold increase in rockfall probability. The occurrence of a freeze–thaw cycle in the preceding days increases the rockfall hazard by about 50 %. The most critical combination can therefore be expected in winter and at the beginning of spring after a freeze–thaw transition, which is followed by a day with high precipitation amounts and takes place in a region preconditioned by a high level of subsurface moisture.

Rapidly evolving floods are rare but powerful drivers of landscape reorganisation that have severe and long-lasting impacts on both the functions of a landscape’s subsystems and the affected society. The July 2021 flood that particularly hit several river catchments of the Eifel region in western Germany and Belgium was a drastic example. While media and scientists highlighted the meteorological and hydrological aspects of this flood, it was not just the rising water levels in the main valleys that posed a hazard, caused damage, and drove environmental reorganisation. Instead, the concurrent coupling of landscape elements and the wood, sediment, and debris carried by the fast-flowing water made this flood so devastating and difficult to predict. Because more intense floods are able to interact with more landscape components, they at times reveal rare non-linear feedbacks, which may be hidden during smaller events due to their high thresholds of initiation. Here, we briefly review the boundary conditions of the 14–15 July 2021 flood and discuss the emerging features that made this event different from previous floods. We identify hillslope processes, aspects of debris mobilisation, the legacy of sustained human land use, and emerging process connections and feedbacks as critical non-hydrological dimensions of the flood. With this landscape scale perspective, we develop requirements for improved future event anticipation, mitigation, and fundamental system understanding.

Instructors and researchers often use research-based assessments to identify the impact of instructional activities. These investigations often focus on issues of diversity, equity, and inclusions by comparing outcomes across social identity groups (e.g., gender, race, and class). Comparisons across groups assume the assessments measure the same factors in the same way across social identity groups. Very few research-based assessments, however, have validation evidence to support this assumption. Measurement invariance testing provides validity evidence that an assessment measures latent factors (e.g., Newtonian thinking or physics identity) equivalently across groups. We examined the measurement invariance of the Eaton and Willoughby five (EW5) factor model on the Force Concept Inventory. We found evidence for measurement invariance across the intersections of gender (men and women) and race or ethnicity (Asian, Black, Hispanic, White, and White Hispanic). These results indicate that performance differences across the five factors can further understanding of equity in physics courses. Without measurement invariance, such work could produce misleading results that undermine efforts to support equity in physics courses.

We present an acute manifestation of mesenteric lymphangioma in a 1-Year-Old Girl. Lymphangiomas (LA) comprise a considerable group of different benign vascular malformations of the lymphatic system and account for about 6% of all benign pediatric tumors. About 5% of LA present intraabdominally as mesenteric LA. Diagnosis of this disease can be initially difficult, but the use of ultrasound allows for a quick diagnosis. Although the tumor is benign, it can lead to an acute abdomen requiring emergency surgery.

Introduction: The decision to deprescribe medications used for both disease prevention and symptom control (dual-purpose medications or DPMs) is often challenging for clinicians. We aim to establish the impact of deprescribing DPMs on patient-related outcomes for older adults near end-of-life (EOL). Methods: This systematic review was conducted according to the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guideline. Literature was searched on PubMed, EMBASE, CINAHL, PsycINFO and Google Scholar until December 2019 for studies on deprescribing intervention with a control group (with or without randomisation); targeting ⩾65-year olds, at EOL, with at least one life-limiting illness and at least one potentially inappropriate DPM. We were interested in any patient-related outcomes. Studies with similar outcome assessment criteria were subjected to meta-analysis and narrative synthesis otherwise. The risk of bias was assessed using Cochrane Risk of Bias and ROBINS-I tools for randomised controlled trials (RCTs) and quasi-experimental non-randomised controlled studies, respectively. Results: Five studies covering 689 participants with mean age 81.6–85.7 years, the majority (74.6–100%) with dementia were included. The risk of bias was moderate to low. The deprescribing of DPMs lowered the risk of mortality (risk ratio (RR) = 0.59, 95% confidence interval (CI) = 0.44–0.79) and referral to acute care facilities (RR = 0.40, 95% CI = 0.22–0.73), but did not have a significant impact on the risk of falls, non-vertebral fracture, emergency presentation, unplanned hospital admission, or general practitioner visits. No significant difference was observed in the quality of life, physical and cognitive functions between the intervention and control groups. Conclusion: There is some evidence that deprescribing of DPMs for older adults near the EOL can lower the risk of mortality and referral to acute care facilities, but there are insufficient good-quality studies powered to confirm a benefit in terms of quality of life, physical or cognitive function, health service utilisation and adverse events. Plain Language Summary What is the health impact of withdrawal or dose reduction of medication used for disease prevention and symptom control in older adults near end-of-life? Introduction: Older adults (aged ⩾ 65 years) with advanced diseases such as cancer, dementia, and organ failure tend to have a limited life expectancy. With the progression of these diseases towards the end-of-life, the intensity for day-to-day supportive care becomes increasingly necessary. The use of medications for symptom management is a critical part of such care, but the use of medications for long-term disease prevention can become irrelevant due to the already shortened life expectancy and may become harmful due to alterations in physiology and pharmacology associated with age and frailty. This necessitates the withdrawal or dose reduction of inappropriate medications, the process called deprescribing. The decision to deprescribe medications used for both disease prevention and symptom control (DPMs) in this population is often challenging for clinicians. In this context, whether deprescribing of DPMs can improve patient-related health outcomes is unknown. Methods: Evidence from the literature was reviewed and analysed, and the quality of studies was assessed. Five studies were identified, which had 689 participants with an average age above 80 years and mostly suffering from dementia. Results: The analysis of these studies showed deprescribing of DPMs lowered the risk of death and referral to acute care facilities at 12 months but had no significant impact on falls, non-vertebral fractures, emergency presentations, unplanned hospital admission, general practitioner visits, quality of life, physical and mental functions. Conclusion: In conclusion, there were insufficient numbers of high-quality studies powered to confirm whether deprescribing of DPMs reduces adverse events, health service use, or improves the quality of life or functioning in older adults near the end of life.

Background: The etiopathogenesis of appendicitis is still not fully understood. Few reports have researched the impact of weather as a cofactor for the development of appendicitis., Methods: To investigate the potential association between the development of appendicitis and exposure to ambient meteorological conditions, a retrospective case-crossover study was conducted. Publicly available meteorologic data were matched with those from 1343 patients aged ≤19 years with histologically confirmed acute (AA; n = 996) or perforated appendicitis (PA; n = 347) treated at our pediatric surgical hospital between October 2001 and October 2018., Results: A time-stratified conditional logistic regression analysis revealed increased odds ratios (ORs) for AA of 4-5% for each 1 hPa increase in vapor pressure during each 3-7 day cumulative moving averages (CMA) lag preceding appendectomy. This effect was stronger on stratification by age class >10 years (OR 1.05-1.08; 3-7-day CMA) and during spring (OR 1.08-1.09; 4-7-day CMA). Moreover, each 1% increase in relative humidity on the day of appendectomy was associated with a 2% decrease in the OR for PA, which was 4% during autumn under seasonal stratification., Conclusion: The role of meteorologic factors in the development of appendicitis remains largely unclear. In accordance with the literature, our results show that seasonal variations together with exposure to altered levels of humidity and vapor pressure may impact patients at different grades of appendiceal inflammation. Thus, transient fluctuations in meteorologic and seasonal variables may constitute cofactors that potentially influence the occurrence and course of pediatric appendicitis., Competing Interests: Declaration of Competing interest No financial or nonfinancial benefits have been received or will be received from any party related directly or indirectly to the subject of this article., (Copyright © 2024 Taiwan Pediatric Association. Published by Elsevier B.V. All rights reserved.)

Background: Pilonidal disease (PD) is an acquired condition related to hair-induced mechanical forces on the skin surface of the intergluteal cleft, with subsequent abscess formation with or without a concomitant draining sinus (pit). While surgical management currently is the mainstay of treatment, pilonidal disease laser treatment (PiLaT) has recently been recognized as a promising treatment option for non-inflammatory diseases. Nonetheless, there is a paucity of available data on adolescent pilonidal disease laser treatment (a-PiLaT)., Methods: We describe our preliminary experience with PiLaT performed in adolescents aged 10-17 years at our tertiary paediatric surgical hospital from 2019 to 2023. Data on perioperative characteristics and clinical outcomes at follow-up were retrospectively analysed., Results: A total of 17 consecutive patients (n = 12 female, 71%) underwent a-PiLaT. At the time of treatment, the patients' mean age and body mass index were 13.6 ± 1.6 years and 25.3 ± 5.6 kg m -2 , respectively. The mean operative time was 21.5 ± 10.4 min, whereas the mean follow-up period was 24.5 ± 16.8 months, with a complication rate of 24% (n = 4) and recurrence rate of 18% (n = 3). With respect to postsurgical scar assessment, the mean Patient and Observer Scar Assessment Scale scores (score range 6-60, with higher scores indicating worse outcome) were 14.2 ± 6.5 (patients' evaluation) and 11.4 ± 4.7 (observers' evaluation)., Conclusion: The a-PiLaT represents a novel approach for managing PD in adolescents. Our preliminary data on the outcomes of a small series of patients with pilonidal sinuses after a-PiLaT indicated complication and recurrence rates comparable to those reported in the literature for adults. This new minimally invasive technique has great potential and is therefore worthy of further research on a larger population., (© 2024. The Author(s).)

Despite its broad potential applications, substitution of carbon by transition metal atoms in graphene has so far been explored only to a limited extent. We report the realization of substitutional Mn doping of graphene to a record high atomic concentration of 0.5%, which was achieved using ultralow-energy ion implantation. By correlating the experimental data with the results of ab initio Born-Oppenheimer molecular dynamics calculations, we infer that direct substitution is the dominant mechanism of impurity incorporation. Thermal annealing in ultrahigh vacuum provides efficient removal of surface contaminants and additional implantation-induced disorder, resulting in Mn-doped graphene that, aside from the substitutional Mn impurities, is essentially as clean and defect-free as the as-grown layer. We further show that the Dirac character of graphene is preserved upon substitutional Mn doping, even in this high concentration regime, making this system ideal for studying the interaction between Dirac conduction electrons and localized magnetic moments. More generally, these results show that ultralow energy ion implantation can be used for controlled functionalization of graphene with substitutional transition-metal atoms, of relevance for a wide range of applications, from magnetism and spintronics to single-atom catalysis.

Objective: To investigate real-world effectiveness of tumor necrosis factor inhibitors (TNFi) in patients with axial spondyloarthritis (axSpA) and the association with (i) treatment line (second and third TNFi-series) and (ii) reason for withdrawal from the preceding TNFi [lack of efficacy (LOE) vs adverse events (AE)]., Methods: Prospectively collected routine care data from 12 European registries were pooled. Rates for 12-month drug retention and 6-month remission [Ankylosing Spondylitis Disease Activity Score C-reactive protein inactive disease (ASDAS-ID)] were assessed in second and third TNFi-series and stratified by withdrawal reason., Results: We included 8254 s and 2939 third TNFi-series; 12-month drug retention rates were similar (71%). Six-month ASDAS-ID rates were higher for the second (23%) than third TNFi (16%). Twelve-month drug retention rates for patients withdrawing from the preceding TNFi due to AE vs LOE were similar for the second (68% and 67%) and third TNFi (both 68%), while for the second TNFi, rates were lower in primary than secondary non-responders (LOE <26 vs ≥26 weeks) (58% vs 71%, P < 0.001). Six-month ASDAS-ID rates for the second TNFi were higher if the withdrawal reason was AE (27%) vs LOE (17%), P < 0.001, while similar for the third TNFi (19% vs 13%, P = 0.20)., Conclusion: A similar proportion of axSpA patients remained on a second and third TNFi after one year, but with low remission rates for the third TNFi. Remission rates on the second TNFi (but not the third) were higher if the withdrawal reason from the preceding TNFi was AE vs LOE., (© The Author(s) 2023. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective. Perinatal asphyxia poses a significant risk to neonatal health, necessitating accurate fetal heart rate monitoring for effective detection and management. The current gold standard, cardiotocography, has inherent limitations, highlighting the need for alternative approaches. The emerging technology of non-invasive fetal electrocardiography shows promise as a new sensing technology for fetal cardiac activity, offering potential advancements in the detection and management of perinatal asphyxia. Although algorithms for fetal QRS detection have been developed in the past, only a few of them demonstrate accurate performance in the presence of noise and artifacts. Approach. In this work, we propose Power-MF , a new algorithm for fetal QRS detection combining power spectral density and matched filter techniques. We benchmark Power-MF against three open-source algorithms on two recently published datasets (Abdominal and Direct Fetal ECG Database: ADFECG, subsets B1 Pregnancy and B2 Labour; Non-invasive Multimodal Foetal ECG-Doppler Dataset for Antenatal Cardiology Research: NInFEA). Main results. Our results show that Power-MF outperforms state-of-the-art algorithms on ADFECG (B1 Pregnancy: 99.5% ± 0.5% F1-score, B2 Labour: 98.0% ± 3.0% F1-score) and on NInFEA in three of six electrode configurations by being more robust against noise. Significance. Through this work, we contribute to improving the accuracy and reliability of fetal cardiac monitoring, an essential step toward early detection of perinatal asphyxia with the long-term goal of reducing costs and making prenatal care more accessible., (Creative Commons Attribution license.)

Background: Digital assistive technologies (DATs) have emerged as promising tools to support the daily life of people with dementia (PWD). Current research tends to concentrate either on specific categories of DATs or provide a generic view. Therefore, it is of essence to provide a review of different kinds of DATs and how they contribute to improving quality of life (QOL) for PWD., Design: Scoping review using the framework proposed by Arksey and O'Malley and recommendations from Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews., Data Sources: Cochrane, Embase, PubMed, Scopus and Web of Science (January 2013 to May 2023)., Eligibility Criteria for Selecting Studies: Completed scientific literature with a primary focus on DATs for PWD, perspectives of caregivers, family members or healthcare workers in relation to a PWD, people living in diverse settings and all severities of dementia., Data Extraction and Synthesis: Screening and data extraction were conducted, followed by quantitative and qualitative analyses using thematic analysis principles and Digital Therapeutics Alliance categories for DAT grouping., Results: The literature search identified 6083 records, with 1056 duplicates. After screening, 4560 full texts were excluded, yielding 122 studies of different designs. The DATs were categorised into digital therapeutics (n=109), patient monitoring (n=30), digital diagnostics (n=2), care support (n=2) and health system clinical software (n=1). These categories were identified to impact various aspects of QOL: preserving autonomy, engagement, and social interaction, health monitoring and promotion, improving activities of daily living, improving cognition, maintaining dignity, managing behavioural and psychological symptoms of dementia and safety/surveillance., Conclusions: Various DATs offer extensive support, elevating the QOL of PWD. Digital therapeutics are predominantly used for ageing-in-place and independent living through assistance with daily tasks. Future research should focus on less-represented digital health technology categories, such as care support, health & wellness or software solutions. Observing ongoing DAT developments and their long-term effects on QOL remains essential., Competing Interests: Competing interests: MN and TK are affiliated with the Centre for Digital Health Interventions (CDHI), a joint initiative of the Institute for Implementation Science in Health Care, University of Zurich, the Department of Management, Technology, and Economics at ETH Zurich and the Institute of Technology Management and School of Medicine at the University of St. Gallen. CDHI is funded in part by CSS, a Swiss health insurer. TK is also a co-founder of Pathmate Technologies, a university spin-off company that creates and delivers digital clinical pathways. However, neither CSS nor Pathmate Technologies was involved in this research. All other authors declare no conflict of interest., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Identifying the microscopic nature of non-equilibrium energy transfer mechanisms among electronic, spin, and lattice degrees of freedom is central to understanding ultrafast phenomena such as manipulating magnetism on the femtosecond timescale. Here, we use time- and angle-resolved photoemission spectroscopy to go beyond the often-used ensemble-averaged view of non-equilibrium dynamics in terms of quasiparticle temperature evolutions. We show for ferromagnetic Ni that the non-equilibrium electron and spin dynamics display pronounced variations with electron momentum, whereas the magnetic exchange interaction remains isotropic. This highlights the influence of lattice-mediated scattering processes and opens a pathway toward unraveling the still elusive microscopic mechanism of spin-lattice angular momentum transfer.

Background: Treatment of persistent spinal pain syndrome (PSPS) is challenging. Chronic pain associated with PSPS can lead to an impaired ability to work., Objective: To obtain information on whether receiving a disability pension (DP) affects pain and pain treatments in retiring working-age PSPS patients. Neuropathic pain medication and antidepressant use were considered as an indicator of neuropathic pain., Methods: The study group comprised 129 consecutive PSPS patients with spinal cord stimulation (SCS) devices implanted at Kuopio University Hospital Neurosurgery between January 1, 1996, and December 31, 2014. Purchase data of gabapentinoids, tricyclic antidepressants, and serotonin-norepinephrine reuptake inhibitors from January 1995 to March 2016, as well as the data on working ability, were retrieved from national registries., Results: The data showed that 28 of 129 (21.7%) SCS permanent patients had a DP, and 27 had a sufficient follow-up time (two years before and one year after DP). Most patients (61%) used neuropathic pain medications during the follow-up, while 44% used antidepressants. Most patients (70%, n  = 19) retired because of dorsopathies. The dose of gabapentinoids started to increase before the DP; after the DP, the doses started to increase again after the decrease but remained at a lower level., Conclusions: Neuropathic pain medication and antidepressant use suggest that pain continues after the DP-that is, pensioners continue to experience inconvenient chronic pain. Resources for patient care are therefore needed after the DP. However, the DP reduces the dose increase of gabapentinoids; the dose is higher immediately before retirement than at the end of the follow-up., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2024 Hanna Kaijankoski et al.)

Background: Although digital maternity records (DMRs) have been evaluated in the past, no previous work investigated usability or acceptance through an observational usability study., Objective: The primary objective was to assess the usability and perception of a DMR smartphone app for pregnant women. The secondary objective was to assess personal preferences and habits related to online information searching, wearable data presentation and interpretation, at-home examination, and sharing data for research purposes during pregnancy., Methods: A DMR smartphone app was developed. Key features such as wearable device integration, study functionalities (eg, questionnaires), and common pregnancy app functionalities (eg, mood tracker) were included. Women who had previously given birth were invited to participate. Participants completed 10 tasks while asked to think aloud. Sessions were conducted via Zoom. Video, audio, and the shared screen were recorded for analysis. Task completion times, task success, errors, and self-reported (free text) feedback were evaluated. Usability was measured through the System Usability Scale (SUS) and User Experience Questionnaire (UEQ). Semistructured interviews were conducted to explore the secondary objective., Results: A total of 11 participants (mean age 34.6, SD 2.2 years) were included in the study. A mean SUS score of 79.09 (SD 18.38) was achieved. The app was rated "above average" in 4 of 6 UEQ categories. Sixteen unique features were requested. We found that 5 of 11 participants would only use wearables during pregnancy if requested to by their physician, while 10 of 11 stated they would share their data for research purposes., Conclusions: Pregnant women rely on their medical caregivers for advice, including on the use of mobile and ubiquitous health technology. Clear benefits must be communicated if issuing wearable devices to pregnant women. Participants that experienced pregnancy complications in the past were overall more open toward the use of wearable devices in pregnancy. Pregnant women have different opinions regarding access to, interpretation of, and reactions to alerts based on wearable data. Future work should investigate personalized concepts covering these aspects., (© Michael Nissen, Carlos A Perez, Katharina M Jaeger, Hannah Bleher, Madeleine Flaucher, Hanna Huebner, Nina Danzberger, Adriana Titzmann, Constanza A Pontones, Peter A Fasching, Matthias W Beckmann, Bjoern M Eskofier, Heike Leutheuser. Originally published in JMIR Pediatrics and Parenting (https://pediatrics.jmir.org).)

During pregnancy, almost all women experience pregnancy-related symptoms. The relationship between symptoms and their association with pregnancy outcomes is not well understood. Many pregnancy apps allow pregnant women to track their symptoms. To date, the resulting data are primarily used from a commercial rather than a scientific perspective. In this work, we aim to examine symptom occurrence, course, and their correlation throughout pregnancy. Self-reported app data of a pregnancy symptom tracker is used. In this context, we present methods to handle noisy real-world app data from commercial applications to understand the trajectory of user and patient-reported data. We report real-world evidence from patient-reported outcomes that exceeds previous works: 1,549,186 tracked symptoms from 183,732 users of a smartphone pregnancy app symptom tracker are analyzed. The majority of users track symptoms on a single day. These data are generalizable to those users who use the tracker for at least 5 months. Week-by-week symptom report data are presented for each symptom. There are few or conflicting reports in the literature on the course of diarrhea, fatigue, headache, heartburn, and sleep problems. A peak in fatigue in the first trimester, a peak in headache reports around gestation week 15, and a steady increase in the reports of sleeping difficulty throughout pregnancy are found. Our work highlights the potential of secondary use of industry data. It reveals and clarifies several previously unknown or disputed symptom trajectories and relationships. Collaboration between academia and industry can help generate new scientific knowledge., (© 2023. Springer Nature Limited.)

Breast cancer is affecting millions of people worldwide. If not appropriately handled, the side effects of different modalities of cancer treatment can negatively impact patients' quality of life and cause treatment interruptions. In recent years, mobile health (mHealth) interventions have shown promising opportunities to support breast cancer care. Numerous studies implemented mobile health interventions aiming to support patients with breast cancer, for example, through physical activity promotion or educational content. Nonetheless, current literature reveals that real-world evidence for the actual benefits remains unclear. In this systematic review, we focus on analyzing the methodology used in recent studies to determine the effects of mHealth applications and wearable devices on the outcome of patients with breast cancer. We followed the PRISMA guideline for the selection, analysis, and reporting of relevant studies found in the databases of Medline, Scopus, Web of Science, and Cochrane Library. A total of 276 unique records were identified, and 20 studies met the inclusion criteria. Study quality was assessed with the Effective Public Health Practice Project (EPHPP) Quality Assessment Tool for Quantitative Studies. While many of the studies used standardized questionnaires as patient-reported outcome measures, there was minimal use of objective measurements, such as activity sensors. Adoption, drop-out rates, and usage behavior of users of the mobile health intervention were often not reported. Future work should clearly define the focus and desired outcome of mHealth interventions and select outcome measures accordingly. Greater transparency facilitates the interpretation of results and conclusions about the real-world evidence of mobile health in breast cancer care., (© The Author(s) 2023. Published by Oxford University Press.)

Background: Thrombosis with thrombocytopenia syndrome (TTS) associated with viral vector COVID-19 vaccines, including ChAdOx1-S (AstraZeneca AZD1222) vaccine, can result in significant morbidity and mortality. We report the clinicopathological features of TTS following ChAdOx1-S vaccination and summarise the case outcomes in Australia., Methods: In this cohort study, patients diagnosed with TTS in Australia between 23 March and 31 December 2021 were identified according to predefined criteria. Cases were included if they met the Therapeutic Goods Administration (TGA) probable and confirmed case definitions and were reclassified using Centres for Disease Control and Prevention (CDC) definition for analysis. Data were collected on patient baseline characteristics, clinicopathological features, risk factors, treatment and outcomes., Findings: A total of 170 TTS cases were identified, with most occurring after the first dose (87%) of ChAdOx1-S. The median time to symptom onset after vaccination and symptom onset to admission was 11 and 2 days respectively. The median age of cases was 66 years (interquartile range 55-74). All except two patients received therapeutic anticoagulation and 66% received intravenous immunoglobulin. Overall, 85.3% of cases were discharged home after a median hospitalisation of 6 days, 9.4% required ongoing rehabilitation and 5.3% died. Eight deaths were related to TTS, with another dying from an unrelated condition while receiving treatment for TTS. Deaths occurred more commonly in those classified as Tier 1 according to the CDC definition and were associated with more severe thrombocytopenia and disease-related haemorrhage., Interpretation: TTS, while rare, can be severe and have catastrophic outcomes in some individuals. In Australia, the mortality rate was low compared to that reported in other high-income countries. Almost all received therapeutic anticoagulation with no bleeding complications and were successfully discharged. This emphasises the importance of community education and an established pathway for early recognition, diagnosis and treatment of TTS., Funding: Australian Commonwealth Department of Health and Aged Care. H.A Tran, N. Wood, J. Buttery, N.W. Crawford, S.D. Chunilal, V.M. Chen are supported by Medical Research Future Funds (MRFF) grant ID 2015305., Competing Interests: HT acknowledged grants/contracts with the National Health and Medical Research Council (NHMRC) MRFF; NCr with Serious Adverse Events Following Vaccination in the Community (SAEFVIC); KM, NW with the Australian Government Department of Health, Australian Government Department of Foreign Affairs and Trade, NSW Department of Health, NHMRC, WHO and Gavi the Vaccine Alliance. CP disclosed support for the present manuscript through funding from the National Centre for Immunisation Research and Surveillance; KM, NW through the Australian Government Department of Health and NHMRC. KM declared payment for expert testimony and participation on a Data Safety Monitoring Board or Advisory Board., (© 2023 The Author(s).)

Smartphones enable and facilitate biomedical studies as they allow the recording of various biomedical signals, including photoplethysmograms (PPG). However, user engagement rates in mobile health studies are reduced when an application (app) needs to be installed. This could be alleviated by using installation-free web apps. We evaluate the feasibility of browser-based PPG recording, conducting the first usability study on smartphone-based PPG. We present an at-home study using a web app and library for PPG recording using the rear camera and flash. The underlying library is freely made available to researchers. 25 Android users participated, using their own smartphones. The study consisted of a demographic and anamnestic questionnaire, the signal recording itself (60 s), and a consecutive usability questionnaire. After filtering, heart rate was extracted (14/17 successful), signal-to-noise ratios assessed (0.64 ± 0.50 dB, mean ± standard deviation), and quality was visually inspected (12/17 usable for diagnosis). Recording was not supported in 9 cases. This was due to the browser's insufficient support for the flash light API. The app received a System Usability Scale score of 82 ± 9, which is above the 90th percentile. Overall, browser flash light support is the main limiting factor for broad device support. Thus, browser-based PPG is not yet widely applicable, although most participants feel comfortable with the recording itself. The utilization of the user-facing camera might represent a more promising approach. This study contributes to the development of low-barrier, user-friendly, installation-free smartphone signal acquisition. This enables profound, comprehensive data collection for research and clinical practice.Clinical relevance- WebPPG offers low-barrier remote diagnostic capabilities without the need for app installation.

Study Objective: Ovarian torsion (OT) in pediatric age is a challenging condition to diagnose and treat. To date, there is still no clear consensus about its management. Our aim was to assess some possible associated factors that can help surgeons in decision-making., Design: We conducted a retrospective multicentric study of pediatric OT surgically treated between 2010 and 2020 in six Italian and German institutions, comparing our findings with a literature review of the last 10 years (2010-2020)., Participants: Patients aged 0-18 years with a diagnosis of OT intraoperatively confirmed and surgically treated at the involved institutions., Results: Ninety-seven patients with a mean age at diagnosis of 8.37 years were enrolled in the study. Severe abdominal pain was present in 82 patients (84.5%). Eighty children (82.5%) presented an enlarged ovary with an US diameter > 5 cm and only 32 (40%) of them underwent conservative surgery. A laparoscopic approach was performed in 60 cases (61.9%) although in 15 (15.5%) conversion to open surgery was deemed necessary. A functional cyst was present in 49 patients (50.5%) while 11 children (11.3%) suffered from OT on a normal ovary., Conclusions: Our results showed that a post-menarchal age (p = .001), a pre-operative US ovarian size < 5 cm, (p = .001), the presence of severe abdominal pain (p = .002), a laparoscopic approach (p < .001), and the presence of a functional cyst (p = .002) were significantly associated with conservative surgery., (© 2022. The Author(s).)

Ultrasound examinations during pregnancy can detect abnormal fetal development, which is a leading cause of perinatal mortality. In multiple pregnancies, the position of the fetuses may change between examinations. The individual fetus cannot be clearly identified. Fetal re-identification may improve diagnostic capabilities by tracing individual fetal changes. This work evaluates the feasibility of fetal re-identification on FETAL&#95;PLANES&#95;DB, a publicly available dataset of singleton pregnancy ultrasound images. Five dataset subsets with 6,491 images from 1,088 pregnant women and two re-identification frameworks (Torchreid, FastReID) are evaluated. FastReID achieves a mean average precision of 68.77% (68.42%) and mean precision at rank 10 score of 89.60% (95.55%) when trained on images showing the fetal brain (abdomen). Visualization with gradient-weighted class activation mapping shows that the classifiers appear to rely on anatomical features. We conclude that fetal re-identification in ultrasound images may be feasible. However, more work on additional datasets, including images from multiple pregnancies and several subsequent examinations, is required to ensure and investigate performance stability and explainability.Clinical relevance- To date, fetuses in multiple pregnancies cannot be distinguished between ultrasound examinations. This work provides the first evidence for feasibility of fetal re-identification in pregnancy ultrasound images. This may improve diagnostic capabilities in clinical practice in the future, such as longitudinal analysis of fetal changes or abnormalities.

Motivation: Recent advances in spatial proteomics technologies have enabled the profiling of dozens of proteins in thousands of single cells in situ. This has created the opportunity to move beyond quantifying the composition of cell types in tissue, and instead probe the spatial relationships between cells. However, most current methods for clustering data from these assays only consider the expression values of cells and ignore the spatial context. Furthermore, existing approaches do not account for prior information about the expected cell populations in a sample., Results: To address these shortcomings, we developed SpatialSort, a spatially aware Bayesian clustering approach that allows for the incorporation of prior biological knowledge. Our method is able to account for the affinities of cells of different types to neighbour in space, and by incorporating prior information about expected cell populations, it is able to simultaneously improve clustering accuracy and perform automated annotation of clusters. Using synthetic and real data, we show that by using spatial and prior information SpatialSort improves clustering accuracy. We also demonstrate how SpatialSort can perform label transfer between spatial and nonspatial modalities through the analysis of a real world diffuse large B-cell lymphoma dataset., Availability and Implementation: Source code is available on Github at: https://github.com/Roth-Lab/SpatialSort., (© The Author(s) 2023. Published by Oxford University Press.)

Background and Objectives: Mobile and remote ultrasound devices are becoming increasingly available. The benefits and possible risks of self-guided ultrasound examinations conducted by pregnant women at home have not yet been well explored. This study investigated aspects of feasibility and acceptance, as well as the success rates of such examinations., Methods: In this prospective, single-center, interventional study, forty-six women with singleton pregnancies between 17 + 0 and 29 + 6 weeks of gestation were included in two cohorts, using two different mobile ultrasound systems. The participants examined the fetal heartbeat, fetal profile and amniotic fluid. Aspects of feasibility and acceptance were evaluated using a questionnaire. Success rates in relation to image and video quality were evaluated by healthcare professionals., Results: Two thirds of the women were able to imagine performing the self-guided examination at home, but 87.0% would prefer live support by a professional. Concerns about their own safety and that of the child were expressed by 23.9% of the women. Success rates for locating the target structure were 52.2% for videos of the fetal heartbeat, 52.2% for videos of the amniotic fluid in all four quadrants and 17.9% for videos of the fetal profile., Conclusion: These results show wide acceptance of self-examination using mobile systems for fetal ultrasonography during pregnancy. Image quality was adequate for assessing the amniotic fluid and fetal heartbeat in most participants. Further studies are needed to determine whether ultrasound self-examinations can be implemented in prenatal care and how this would affect the fetomaternal outcome.

Accurate characterization of diffusing nanoscale species is increasingly important for revealing processes at the nanoscale, with fiber-assisted nanoparticle-tracking-analysis representing a new and promising approach in this field. In this work, we uncover the potential of this approach for the characterization of very small nanoparticles (<20 nm) through experimental studies, statistical analysis and the employment of a sophisticated fiber and chip design. The central results is the characterization of diffusing nanoparticles as small as 9 nm with record-high precision, corresponding to the smallest diameter yet determined for an individual nanoparticle with nanoparticle-tracking-analysis using elastic light scattering alone. Here, the detectable scattering cross-section is limited only by the background scattering of the ultrapure water, thus reaching the fundamental limit of Nanoparticle-Tracking-Analysis in general. The obtained results outperform other realizations and allow access to previously difficult to address application fields such as understanding nanoparticle growth or control of pharmaceuticals., (© 2023. The Author(s).)

Background: After enterostomy creation, the distal bowel to the ostomy is excluded from the physiologic passage of stool, nutrient uptake, and growth of this intestinal section. Those infants frequently require long-term parenteral nutrition, continued after enterostomy reversal due to the notable diameter discrepancy of the proximal and distal bowel. Previous studies have shown that mucous fistula refeeding (MFR) results in faster weight gain in infants. The aim of the randomized multicenter open-label controlled MUC ous FI stula RE feeding (" MUC-FIRE ") trial is to demonstrate that MFR between enterostomy creation and reversal reduces the time to full enteral feeds after enterostomy closure compared to controls, resulting in shorter hospital stay and less adverse effects of parenteral nutrition. Methods/Design: A total of 120 infants will be included in the MUC-FIRE trial. Following enterostomy creation, infants will be randomized to either an intervention or a non-intervention group.In the intervention group, perioperative MFR between enterostomy creation and reversal will be performed. The control group receives standard care without MFR.The primary efficacy endpoint of the study is the time to full enteral feeds. Secondary endpoints include first postoperative bowel movement after stoma reversal, postoperative weight gain, and days of postoperative parenteral nutrition. In addition adverse events will be analyzed., Discussion: The MUC-FIRE trial will be the first prospective randomized trial to investigate the benefits and disadvantages of MFR in infants. The results of the trial are expected to provide an evidence-based foundation for guidelines in pediatric surgical centers worldwide., Trial Registration: The trial has been registered at clinicaltrials.gov (number: NCT03469609, date of registration: March 19, 2018; last update: January 20, 2023, https://clinicaltrials.gov/ct2/show/NCT03469609?term=NCT03469609&draw=2&rank=1)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Objectives: Many axial spondylarthritis (axSpA) patients receive a conventional synthetic DMARD (csDMARD) in combination with a TNF inhibitor (TNFi). However, the value of this co-therapy remains unclear. The objectives were to describe the characteristics of axSpA patients initiating a first TNFi as monotherapy compared with co-therapy with csDMARD, to compare one-year TNFi retention and remission rates, and to explore the impact of peripheral arthritis., Methods: Data was collected from 13 European registries. One-year outcomes included TNFi retention and hazard ratios (HR) for discontinuation with 95% CIs. Logistic regression was performed with adjusted odds ratios (OR) of achieving remission (Ankylosing Spondylitis Disease Activity Score (ASDAS)-CRP < 1.3 and/or BASDAI < 2) and stratified by treatment. Inter-registry heterogeneity was assessed using random-effect meta-analyses, combined results were presented when heterogeneity was not significant. Peripheral arthritis was defined as ≥1 swollen joint at baseline (=TNFi start)., Results: Amongst 24 171 axSpA patients, 32% received csDMARD co-therapy (range across countries: 13.5% to 71.2%). The co-therapy group had more baseline peripheral arthritis and higher CRP than the monotherapy group. One-year TNFi-retention rates (95% CI): 79% (78, 79%) for TNFi monotherapy vs 82% (81, 83%) with co-therapy (P < 0.001). Remission was obtained in 20% on monotherapy and 22% on co-therapy (P < 0.001); adjusted OR of 1.16 (1.07, 1.25). Remission rates at 12 months were similar in patients with/without peripheral arthritis., Conclusion: This large European study of axial SpA patients showed similar one-year treatment outcomes for TNFi monotherapy and csDMARD co-therapy, although considerable heterogeneity across countries limited the identification of certain subgroups (e.g. peripheral arthritis) that may benefit from co-therapy., (© The Author(s) 2022. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Omphalocele represents a rare congenital abdominal wall defect. In giant omphalocele, due to the viscero-abdominal disproportion, gradual reintegration of eviscerated organs is often associated with medical challenges. We report our preliminary experience combining staged gravitational reduction with vacuum (VAC) therapy as a novel approach for treatment of giant omphalocele., Patients and Methods: Retrospective chart review of six patients (five females) born between September 2018 and May 2022 who underwent staged reduction of giant omphalocele in conjunction with VAC therapy was conducted. Treatment was performed at two German third-level Pediatric Surgery Departments. Biometric and periprocedural data were assessed. Main outcome measure was the feasibility of VAC therapy for giant omphalocele. Data are reported as median and interquartile range (Q1-Q3)., Results: Gestational age was 37 (37-38) weeks, and birth weight was 2700 (2500-3000) g. VAC dressing was changed every 3 (3-4) days until abdominal fascia closure at the age of 9 (3-13) days. Time to first/full oral feeds was 3 (1-5)/20 (12-24) days with a hospital stay of 22 (17-30) days. Follow-up was 8 (5-22) months and complications were of minor extent (none: n  = 2; Clavien-Dindo I: n  = 3; Clavien-Dindo II: n  = 1), comprising a delayed neo-umbilical cord rest separation ( n  = 2) and/or concomitant neo-umbilical site infection ( n  = 2) with no repeat surgery., Conclusion: In neonates with giant omphalocele, VAC constitutes a promising and technically feasible enhancement of the staged gravitational reduction method. This study shows evidence that VAC may accelerate restoration of the abdominal wall integrity in giant omphalocele, thus minimizing associated comorbidities inherent to a prolonged hospitalization., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 Nissen, Romanova, Weigl, Petrikowski, Alrefai and Hubertus.)

Follicular lymphoma (FL) is an indolent cancer of mature B-cells but with ongoing risk of transformation to more aggressive histology over time. Recurrent mutations associated with transformation have been identified; however, prognostic features that can be discerned at diagnosis could be clinically useful. We present here comprehensive profiling of both tumor and immune compartments in 155 diagnostic FL biopsies at single-cell resolution by mass cytometry. This revealed a diversity of phenotypes but included two recurrent patterns, one which closely resembles germinal center B-cells (GCB) and another which appears more related to memory B-cells (MB). GCB-type tumors are enriched for EZH2, TNFRSF14, and MEF2B mutations, while MB-type tumors contain increased follicular helper T-cells. MB-type and intratumoral phenotypic diversity are independently associated with increased risk of transformation, supporting biological relevance of these features. Notably, a reduced 26-marker panel retains sufficient information to allow phenotypic profiling of future cohorts by conventional flow cytometry., (© 2022. The Author(s).)

Background: Patients' knowledge was found to be a key contributor to the success of therapy. Many efforts have been made to educate patients in their disease. However, research found that many patients still lack knowledge regarding their disease. Integrating patient education into social media platforms can bring materials closer to recipients., Objective: The aim of this study is to test the effectiveness of patient education via Instagram., Methods: A randomized controlled trial was conducted to test the effectiveness of patient education via Instagram among patients with inflammatory bowel disease. Participants were recruited online from the open Instagram page of a patient organization. The intervention group was educated via Instagram for 5 weeks by the research team; the control group did not receive any educational intervention. The knowledge about their disease was measured pre- and postintervention using the Inflammatory Bowel Disease Knowledge questionnaire. Data were analyzed by comparing mean knowledge scores and by regression analysis. The trial was purely web based., Results: In total, 49 participants filled out both questionnaires. The intervention group included 25 participants, and the control group included 24 participants. The preintervention knowledge level of the intervention group was reflected as a score of 18.67 out of 24 points; this improved by 3 points to 21.67 postintervention. The postintervention difference between the control and intervention groups was 3.59 points and was statistically significant (t 32.88 =-4.56, 95% CI 1.98-5.19; P<.001). Results of the regression analysis, accounting for preintervention knowledge and group heterogeneity, indicated an increase of 3.33 points that was explained by the intervention (P<.001)., Conclusions: Patient education via Instagram is an effective way to increase disease-related knowledge. Future studies are needed to assess the effects in other conditions and to compare different means of patient education., Trial Registration: German Clinical Trials Register DRKS00022935; https://tinyurl.com/bed4bzvh., (©Dominik Blunck, Lena Kastner, Michael Nissen, Jacqueline Winkler. Originally published in the Journal of Medical Internet Research (https://www.jmir.org), 19.10.2022.)

Purpose: This study aims to elucidate the incidence of and independent risk factors for spinal cord stimulator implantations for patients who underwent lumbar spine surgery., Methods: The PERFormance, Effectiveness, and Cost of Treatment (PERFECT) episodes database, which was established for selected diseases and procedures in Finland, includes all patients who underwent lumbar spine surgery for degenerative spine conditions or spinal cord stimulation (SCS) in Finland from 1986 to 2018. The data on age, sex, hospital diagnoses, surgical procedures, and causes of death were imported from the Finnish national registers into the PERFECT database., Results: Between 1986 and 2018, 157,824 patients had their first lumbar spine procedure and for 1769 (1.1%) of them, a subsequent SCS procedure was observed during the follow-up. The cumulative incidence of SCS for persistent or recurrent pain after lumbar disk herniation, spinal stenosis, degenerative disk disease, and spondylolysis and spondylolisthesis surgery at 15 years was 1.2%, 1.0%, 2.7%, and 2.6% respectively. At 15 years, the cumulative incidence of SCS for persistent or recurrent pain after lumbar spine surgery after five or more lumbar spinal operations was 11.9%., Conclusion: Repeated surgery was the most prominent significant risk factor for SCS for persistent or recurrent pain after lumbar spine surgery. The risk of SCS for persistent or recurrent pain after lumbar spine surgery increases significantly along with the number of lumbar spine procedures. When considering repeated lumbar spine surgery, careful evaluation of treatment options should take place to ensure good patient outcomes., (© 2022. The Author(s).)

Immune checkpoint inhibitors (ICI) are used in the treatment of urothelial and renal cell cancers. While some patients may have exceptional responses, better predictive biomarkers are needed. We profiled the circulating immune compartment of patients receiving ICI to identify possible immune markers associated with immunotherapy response or resistance. Peripheral blood samples were collected prior to, and 3 weeks after initiation of ICI. Using mass cytometry, 26 distinct immune populations were identified. Responders to immune checkpoint inhibitors had higher frequencies of naïve CD4+ T-cells, and lower frequencies of CD161+ Th17 cells and CCR4+ Th2 cells. Non-responders had a higher frequency of circulating PD1+ T-cells at baseline; there was a subsequent decrease in frequency with exposure to ICI with a concomitant increase in Ki67 expression. Flow cytometry for cytokines and chemokine receptors showed that CD4+ T cells of non-responder patients expressed less CXCR4 and CCR7. In addition, their PD1- CD4+ T cells had higher TNFα and higher CCR4 expression, while their PD1+ CD4+ T cells had higher interferon γ and lower CCR4 expression. The role of γ/δ T-cells was also explored. In responders, these cells had higher levels of interferon γ, TNFα and CCR5. One patient with a complete response had markedly higher frequency of γ/δ T-cells at baseline, and an expansion of these cells after treatment. This case was analyzed using single-cell gene expression profiling. The bulk of the γ/δ T cells consisted of a single clone of Vγ9/Vδ2 cells both before and after expansion, although the expansion was polyclonal. Gene expression analysis showed that exposure to an ICI led to a more activated phenotype of the γ/δ T cells. In this study, the circulating immune compartment was shown to have potential for biomarker discovery. Its dynamic changes during treatment may be used to assess response before radiographic changes are apparent, and these changes may help us delineate mechanisms that underpin both response and resistance to ICI. It also hypothesizes a potential role for γ/δ T cells as effector cells in some cases., Competing Interests: Author J-ML received honoraria from Bayer, EMD Serono, Pfizer and Tersera. LN received honoraria from Pfizer, Ipsen, Bayer, Merck, Astra Zeneca and research support from Ipsen, Janssen, EMD Serono. KC received honoraria from Astellas, AstraZeneca, Daiichi Sankyo, Janssen, Merck, Novartis, Pfizer, Point Biopharma, Roche, Sanofi, and research support from Astellas, AstraZeneca, Janssen, Merck, Sanofi. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Lavoie, Baichoo, Chavez, Nappi, Khalaf, Kollmannsberger, Chi, Weng, Steidl, Eigl and Nissen.)

Accurate determination of the size distribution of nanoparticle ensembles remains a challenge in nanotechnology-related applications due to the limitations of established methods. Here, a microstructured fiber-assisted nanoparticle tracking analysis (FaNTA) realization is introduced that breaks existing limitations through the recording of exceptionally long trajectories of rapidly diffusing polydisperse nanoparticles, resulting in excellent sizing precision and unprecedented separation capabilities of bimodal nanoparticle mixtures. An effective-single-mode antiresonant-element fiber allows to efficiently confine nanoparticles in a light-guiding microchannel and individually track them over more than 1000 frames, while aberration-free imaging is experimentally confirmed by cross-correlation analysis. Unique features of the approach are (i) the highly precise determination of the size distribution of monodisperse nanoparticle ensembles (only 7% coefficient of variation) and (ii) the accurate characterization of individual components in a bimodal mixture with very close mean diameters, both experimentally demonstrated for polymer nanospheres. The outstanding performance of the FaNTA realization can be quantified by introducing a new model for the bimodal separation index. Since FaNTA is applicable to all types of nano-objects down to sub-20 nm diameters, the method will improve the precision standard of mono- and polydisperse nanoparticle samples such as nano-plastics or extracellular vesicles., (© 2022 The Authors. Small published by Wiley-VCH GmbH.)

Objectives: To investigate time trends in baseline characteristics and retention, remission and response rates in bio-naïve axial spondyloarthritis (axSpA) and psoriatic arthritis (PsA) patients initiating TNF inhibitor (TNFi) treatment., Methods: Prospectively collected data on bio-naïve axSpA and PsA patients from routine care in 15 European countries were pooled. Three cohorts were defined according to year of TNFi initiation: A (1999-2008), B (2009-2014) and C (2015-2018). Retention, remission and response rates were assessed at 6, 12 and 24 months., Results: In total, 27 149 axSpA and 17 446 PsA patients were included. Cohort A patients had longer disease duration compared with B and C. In axSpA, cohort A had the largest proportion of male and HLA-B27 positive patients. In PsA, baseline disease activity was highest in cohort A. Retention rates in axSpA/PsA were highest in cohort A and differed only slightly between B and C. For all cohorts, disease activity decreased markedly from 0 to 6 months. In axSpA, disease activity at 24 months was highest in cohort A, where also remission and response rates were lowest. In PsA, remission rates at 6 and 12 months tended to be lowest in cohort A. Response rates were at all time points comparable across cohorts, and less between-cohort disease activity differences were seen at 24 months., Conclusion: Our findings indicate that over the past decades, clinicians have implemented more aggressive treatment strategies in spondyloarthritis. This was illustrated by shorter disease duration at treatment initiation, decreased retention rates and higher remission rates during recent years., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Spinal cord stimulation (SCS) is an effective treatment for failed back surgery syndrome (FBSS). In patients with FBSS, opioids have often been initiated, even before SCS is trialed., Objective: We studied the effect of retirement on opioid use in patients with chronic pain after failed back surgery., Study Design: A retrospective study design., Setting: The study was conducted at Kuopio University Hospital., Methods: The study group consisted of all 230 patients with SCS trialed or implanted for FBSS at Kuopio University Hospital Neurosurgery from January 1, 1996 through December 31, 2014. All purchases of prescribed opioids and their daily defined doses, as well as data on working ability, were obtained from the Social Insurance Institution. Patients were divided into 3 groups: SCS trial only, SCS implanted permanently, and SCS implanted but later explanted. We analyzed the differences in opioid use among these groups 2 years before and 2 years after the start of their disability pension (DP)., Results: During the follow-up period, a total of 60 patients received a DP. One year before DP, the majority of patients used opioids (n = 43, 72%), and throughout the one-year follow-up after retirement, the number of users increased slightly (n = 46, 77%). In the permanently implanted SCS group, the number of strong opioid users decreased after retirement. Most patients used a moderate dose (0.1-10.5 morphine milligram equivalent/d). Retirement appeared to interrupt dose escalation in all groups, but doses increased further as the follow-up continued., Limitations: No structured questionnaires were used in this study. Also, many underlying factors contributing to chronic pain were missing., Conclusions: DP did not reduce the use of opioids in patients with FBSS. Opioid doses were lower and dose escalation less steep with continuous SCS therapy.

Competing Interests: Competing interests: None declared.

Automated Electrocardiogram (ECG) classification using deep neural networks requires large datasets annotated by medical professionals, which is time-consuming and expensive. This work examines ECG augmentation as a method for enriching existing datasets at low cost. First, we introduce three novel augmentations: Limb Electrode Move and Chest Electrode Move both simulate a minor electrode mislocation during signal measurement, and Heart Vector Transform generates an ECG by modeling a rotated main heart axis. These techniques are then combined with nine time series signal augmentations from literature. Evaluation was performed on ICBEB, PTB-XL Diagnostic, PTB-XL Rhythm, and PTB-XL Form datasets. Compared to models trained without data augmentation, area under the receiver operating characteristic curve (AUC) was increased by 3.5%, 1.7%, 1.4% and 3.5%, respectively. Our experiments demonstrated that data augmentation can improve deep learning performance in ECG classification. Analyses of the individual augmentation effects established the efficacy of the three proposed augmentations.