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Min Kyu Park,1 Sook Joung Lee,2 Sang Beom Kim,3 Kyeong Woo Lee,3 Hye-Jeong Lee,4 Eun Young Han,5 Bo Ryun Kim5 1Department of Pharmacology and Clinical Pharmacology, Dong-A University College of Medicine and Hospital, Busan, Republic of Korea; 2Department of Physical Medicine and Rehabilitation, Catholic University of Korea, Daejeon St Mary’s Hospital, Daejeon, Republic of Korea; 3Department of Physical Medicine and Rehabilitation, Dong-A University College of Medicine, Dong-A University Hospital, Busan, Republic of Korea; 4Department of Pharmacology, College of Medicine, Dong-A University, Busan, Republic of Korea; 5Department of Rehabilitation Medicine, Jeju National University School of Medicine, Jeju National University Hospital, Jeju, Republic of Korea Background: Cervical compressive myelopathy (CCM) is a progressive, degenerative spine disease and the most common cause of spinal cord dysfunction in older individuals. Current clinical guidelines for spinal surgery recommend multimodal intraoperative monitoring (IOM) during spinal surgery as a reliable and valid diagnostic adjunct to assess spinal cord integrity. The aim of this study was to evaluate the effect of positive changes during IOM on the functional status in patients with CCM.Methods: Patients who underwent spinal surgery with IOM due to CCM were enrolled. During the surgery, patients underwent IOM using motor evoked potential (MEP) and somatosensory evoked potential (SEP). MEP and SEP were checked before and immediately after decompression. A decrease in latency >10% or an increase in amplitude >50% was regarded as a “positive changes”. Subjects were divided according to the presence of positive changes. Motor scores of American Spinal Injury Association (ASIA) impairment scale and Korean version of Modified Barthel Index (K-MBI) were evaluated before and after operation.Results: Twenty-nine patients underwent spinal surgery due to CCM. Eleven patients showed positive changes in MEP during IOM. When the two groups were compared, improvement rate in the ASIA motor score and K-MBI were significantly higher in patients with positive changes than in patients without positive changes at 1 month after surgery. However, 6 months after surgery, there were no significance differences between the groups. Regardless of positive change, nearly all patients suffered from neuropathic pain after operation.Conclusion: Positive changes in MEP during IOM may affect functional improvement 1 month after operation and early discharge without significant complications in CCM patients. However, they do not affect the neuropathic pain and long-term functional outcome. Thus, tailored proper management is needed to achieve maximal functional recovery in each patient after cervical spinal decompression surgery. Keywords: cervical myelopathy, degenerative disorder, intraoperative monitoring, function, positive change

Abstract NADH and NAD+ act as electron donors and acceptors and NAD+ was shown to stimulate mitochondrial biogenesis and metabolic health. We here develop a non-invasive Phosphorous Magnetic Resonance Spectroscopy (31P-MRS) method to quantify these metabolites in human skeletal muscle on a clinical 3 T MRI scanner. This new MR-sequence enables NADH and NAD+ quantification by suppressing α-ATP signal, normally overlapping with NADH and NAD+. The sequence is based on a double spin echo in combination with a modified z-Filter achieving strong α-ATP suppression with little effect on NAD+ and NADH. Here we test and validate it in phantoms and in humans by measuring reproducibility and detecting a physiological decrease in NAD+ and increase in NADH induced by ischemia. Furthermore, the 31P-MRS outcomes are compared to analysis in biopsies. Additionally, we show higher NAD+ and lower NADH content in physically active older adults compared to sedentary individuals, reflecting increased metabolic health.

Abstract Robust data privacy regulations hinder the exchange of healthcare data among institutions, crucial for global insights and developing generalised clinical models. Federated learning (FL) is ideal for training global models using datasets from different institutions without compromising privacy. However, disparities in electronic healthcare records (EHRs) lead to inconsistencies in ML-ready data views, making FL challenging without extensive preprocessing and information loss. These differences arise from variations in services, care standards, and record-keeping practices. This paper addresses data view heterogeneity by introducing a knowledge abstraction and filtering-based FL framework that allows FL over heterogeneous data views without manual alignment or information loss. The knowledge abstraction and filtering mechanism maps raw input representations to a unified, semantically rich shared space for effective global model training. Experiments on three healthcare datasets demonstrate the framework’s effectiveness in overcoming data view heterogeneity and facilitating information sharing in a federated setup.

Abstract Childhood apraxia of speech (CAS) is a severe and rare form of speech sound disorder (SSD). CAS is typically sporadic, but may segregate in families with broader speech and language deficits. We hypothesize that genetic changes may be involved in the etiology of CAS. We conduct whole-genome sequencing in 27 families with CAS, 101 individuals in all. We identify 17 genomic regions including 19 unique copy number variants (CNVs). Three variants are shared across families, but the rest are unique; three events are de novo. In four families, siblings with milder phenotypes co-inherited the same CNVs, demonstrating variable expressivity. We independently validate eight CNVs using microarray technology and find many of these CNVs are present in children with milder forms of SSD. Bioinformatic investigation reveal four CNVs with substantial functional consequences (cytobands 2q24.3, 6p12.3-6p12.2, 11q23.2-11q23.3, and 16p11.2). These discoveries show that CNVs are a heterogeneous, but prevalent, cause of CAS.

Abstract Drug sensitivity prediction models can aid in personalising cancer therapy, biomarker discovery, and drug design. Such models require survival data from randomised controlled trials which can be time consuming and expensive. In this proof-of-concept study, we demonstrate for the first time that deep learning can link histological patterns in whole slide images (WSIs) of Haematoxylin & Eosin (H&E) stained breast cancer sections with drug sensitivities inferred from cell lines. We employ patient-wise drug sensitivities imputed from gene expression-based mapping of drug effects on cancer cell lines to train a deep learning model that predicts patients’ sensitivity to multiple drugs from WSIs. We show that it is possible to use routine WSIs to predict the drug sensitivity profile of a cancer patient for a number of approved and experimental drugs. We also show that the proposed approach can identify cellular and histological patterns associated with drug sensitivity profiles of cancer patients.

Silicon oxide (SiOx) coatings are attracting significant attention and are widely used in industrial applications. They can be prepared by plasma-assisted chemical vapor deposition (PACVD). PACVD at atmospheric pressure (AP-PACVD) is often employed to synthesize SiOx coatings, but it has generally not been scaled up to an industrially viable level. In the present work, a SiOx coating was continuously deposited onto a polyethylene terephthalate film using industrial-scale roll-to-roll type AP-PACVD. 1,1,3,3-Tetramethyldisiloxane (TMDSO) and tetraethoxysilane (TEOS) were selected as precursors. The elemental compositions and chemical structures of the SiOx coatings were characterized, and oxygen and water-vapor transmission rates were measured. The SiOx coating using TEOS exhibited better barrier properties than that using TMDSO, corresponding to the high oxygen content, high SiO2 content, and high siloxane network content in the SiOx coating.

Introduction Waste in medical research is a relatively well-known issue. However, only a few initiatives exist to address this issue. Lean Management methods (Lean) were developed in industrial manufacturing and later applied within healthcare improvement. Overall, the results from studies of the application of Lean to healthcare appear to be positive in terms of greater efficiency regarding treatment outcomes and patient care. Nevertheless, the application of Lean to improve research processes is not well studied and, given that research alongside clinical practice and experiential knowledge provides the foundation for the treatment and care of patients, it is paramount to identify approaches and review the degree to which they increase efficiency within research procedures. Therefore, this review will scope the landscape of studies that investigated Lean and how to implement Lean in research processes, particularly regarding healthcare research.Methods and analysis Our approach follows the methodological framework of Arksey and O’Malley for conducting scoping reviews (PRISMA-ScR). The search strategy for this scoping review was developed using the PCC model. We will identify the relevant literature by searching four search databases: Scopus, Web of Science, Academic Search Premier and Business Source Complete. Next, we will use citation pearl growing to identify all relevant published literature. The data charting process will follow the PRISMA-ScR checklist and will be organised using NVivo. We will generate qualitative and quantitative assessments of the extracted data by using NVivo, RStudio and Excel. We will follow the PRISMA-ScR guideline when reporting the results.Ethics and dissemination The review will comprise existing published studies and no primary data will be collected. Our findings will be shared through open access peer-reviewed journals, national and international conferences and emails to all relevant collaborative relationships. We plan to disseminate our findings via academic social media platforms, newspaper articles and blogposts.

Abstract Background Since 2007 all pregnant women in the Netherlands are offered the second-trimester anomaly scan (SAS) in a nationwide prenatal screening program. This study aims to assess the level of informed choice of women opting for the SAS and to evaluate the presence of routinization 16 years after its implementation. It further explores decisional conflict and women’s decision making. Methods This prospective national survey study consisted of an online questionnaire which was completed after prenatal counseling and before undergoing the SAS. Informed choice was measured by the adapted multidimensional measure of informed choice (MMIC) and was defined in case women were classified as value-consistent, if their decision for the SAS was deliberated and made with sufficient knowledge. Results A total of 894/1167 (76.6%) women completed the questionnaire. Overall, 54.8% made an informed choice, 89.6% had good knowledge, 59.8% had deliberated their choice and 92.7% held a positive attitude towards the SAS. Women with low educational attainment (p=0.004) or respondents of non-Western descent (p=0.038) were less likely to make an informed choice. Decisional conflict was low, with a significantly lower decisional conflict score in women that made an informed choice (p

Abstract Introduction A substantial proportion of patients with bipolar disorder experience daily subsyndromal mood swings, and the term “mood instability” reflecting the variability in mood seems associated with poor prognostic factors, including impaired functioning, and increased risk of hospitalization and relapse. During the last decade, we have developed and tested a smartphone-based system for monitoring bipolar disorder. The present SmartBipolar randomized controlled trial (RCT) aims to investigate whether (1) daily smartphone-based outpatient monitoring and treatment including clinical feedback versus (2) daily smartphone-based monitoring without clinical feedback or (3) daily smartphone-based mood monitoring only improves mood instability and other clinically relevant patient-related outcomes in patients with bipolar disorder. Methods and analysis The SmartBipolar trial is a pragmatic randomized controlled parallel-group trial. Patients with bipolar disorder are invited to participate as part of their specialized outpatient treatment for patients with bipolar disorder in Mental Health Services in the Capital Region of Denmark. The included patients will be randomized to (1) daily smartphone-based monitoring and treatment including a clinical feedback loop (intervention group) or (2) daily smartphone-based monitoring without a clinical feedback loop (control group) or (3) daily smartphone-based mood monitoring only (control group). All patients receive specialized outpatient treatment for bipolar disorder in the Mental Health Services in the Capital Region of Denmark. The trial started in March 2021 and has currently included 150 patients. The outcomes are (1) mood instability (primary), (2) quality of life, self-rated depressive symptoms, self-rated manic symptoms, perceived stress, satisfaction with care, cumulated number and duration of psychiatric hospitalizations, and medication (secondary), and (3) smartphone-based measures per month of stress, anxiety, irritability, activity, and sleep as well as the percentage of days with presence of mixed mood, days with adherence to medication and adherence to smartphone-based self-monitoring. A total of 201 patients with bipolar disorder will be included in the SmartBipolar trial. Ethics and dissemination The SmartBipolar trial is funded by the Capital Region of Denmark and the Independent Research Fund Denmark. Ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248) as well as data permission (journal number: P-2019–809). The results will be published in peer-reviewed academic journals, presented at scientific meetings, and disseminated to patients’ organizations and media outlets. Trial registration Trial registration number: NCT04230421. Date March 1, 2021. Version 1.

Abstract Polymorphism of the CYP2D6 gene leads to substantial interindividual variability in CYP2D6 enzyme activity. Despite improvements in prediction of CYP2D6 activity based on genotype information, large interindividual variability within CYP2D6 genotypes remains and ethnicity could be a contributing factor. The aim of this study was to investigate interethnic differences in CYP2D6 activity using clinical datasets of three CYP2D6 substrates: (i) brexpiprazole (N = 476), (ii) tedatioxetine (N = 500), and (iii) vortioxetine (N = 1073). The CYP2D6 activity of all individuals in the dataset was estimated through population pharmacokinetic analyses as previously reported. Individuals were assigned a CYP2D6 phenotype and CYP2D6 genotype group based on their CYP2D6 genotype and interethnic differences were investigated within each group. Among individuals categorized as CYP2D6 normal metabolizers, African Americans had a lower CYP2D6 activity compared to Asians (p

Conservation translocations are an important tool in the prevention of species loss, but the translocation process is associated with numerous stressors. Non-invasively monitoring stress physiology via faecal glucocorticoid metabolites (FGMs) can provide valuable insights into factors impacting translocation success and how to mitigate negative impacts. After validating an assay to measure FGMs in greater stick-nest rats (Leporillus conditor), we examined whether translocation caused a predictable change in physiology. We compared longer-term (one to five months post-translocation) physiological responses across three source populations (remnant-wild, reintroduced-wild, captive-bred), and investigated effects of body condition and sex on FGMs. Notably, FGMs of the remnant-wild population did not significantly change post-translocation, while the reintroduced-wild population exhibited a significant decrease and the captive-bred population a significant increase. Individuals in lower body condition had the highest FGMs in both wild-type populations, whereas the captive-bred population showed the opposite relationship. There was no difference in FGMs between the sexes. Our work highlights that physiological responses after translocation may not be uniform and source population history is an important factor to be considered, emphasizing the need for novel ideas that facilitate successful adaptation. By better understanding how species and individuals respond to translocation, we can improve translocation outcomes.

Abstract Cardiac energy status, measured as phosphocreatine (PCr)/adenosine triphosphate (ATP) ratio with 31P-Magnetic Resonance Spectroscopy (31P-MRS) in vivo, is a prognostic factor in heart failure and is lowered in cardiometabolic disease. It has been suggested that, as oxidative phosphorylation is the major contributor to ATP synthesis, PCr/ATP ratio might be a reflection of cardiac mitochondrial function. The objective of the study was to investigate whether PCr/ATP ratios can be used as in vivo marker for cardiac mitochondrial function. We enrolled thirty-eight patients scheduled for open-heart surgery in this study. Cardiac 31P-MRS was performed before surgery. Tissue from the right atrial appendage was obtained during surgery for high-resolution respirometry for the assessment of mitochondrial function. There was no correlation between the PCr/ATP ratio and ADP-stimulated respiration rates (octanoylcarnitine R2

OBJECTIVES/GOALS: The Community Research Liaison Model (CRLM) is a novel model to facilitate community engaged research (CEnR) and community–academic research partnerships focused on health priorities identified by the community. We describe the CRLM development process and how it is operationalized today. METHODS/STUDY POPULATION: The CRLM, informed by the Principles of Community Engagement, builds trust among rural communities and expands capacity for community and investigator-initiated research. We followed a multi-phase process to design and implement a community engagement model that could be replicated. The resulting CRLM moves community–academic research collaborations from objectives to outputs using a conceptual framework that specifies our guiding principles, objectives, and actions to facilitate the objectives (i.e., capacity, motivations, and partners), and outputs. RESULTS/ANTICIPATED RESULTS: The CRLM has been fully implemented across Oregon. Six Community Research Liaisons collectively support 18 predominantly rural Oregon counties. Since 2017, the liaison team has engaged with communities on nearly 300 community projects. The CRLM has been successful in facilitating CEnR and community–academic research partnerships. The model has always existed on a dynamic foundation and continues to be responsive to the lessons learned by the community and researchers. The model is expanding across Oregon as an equitable approach to addressing health disparities across the state. DISCUSSION/SIGNIFICANCE: Our CRLM is based on the idea that community partnerships build research capacity at the community level and are the backbone for pursuing equitable solutions and better health for communities we serve. Our model is unique in its use of CRLs to facilitate community–academic partnerships; this model has brought successes and challenges over the years.

Meeting the increasing consumer and market expectations for sustainably produced beef requires measurement and demonstration of the producers’ sustainability practices. Typically, demonstration of sustainable production relies on time consuming and costly on-ground audits. Online tools using combinations of remotely sensed data and other information sources could offer a cost-effective alternative. However, there are also concerns about the merits and risks of such tools. This paper presents a case of the development process of an online platform for Australian beef producers to demonstrate their sustainable production practices, connected with learning opportunities for continual improvement of their sustainability performance. The project is led by an innovative cross-sectoral collaboration of beef industry, non-government organisation and university partners. Our approach combines producer and market perspectives; focusing on the “value proposition” of the proposed technology for producers, and value chains’ priorities in sustainability markets and in having the ability to demonstrate sustainability in a cost-effective manner. The development process adopted co-design at three levels: (1) the “Consortium” of project partners (2) collaborative co-design through small online groups with producers and value chain representatives; and (3) consultative co-design through producer testing of the platform as it is built by software developers. The design process focused on five themes: tree cover, ground cover, biodiversity stewardship, carbon balance, and drought resilience. We present the main platform design characteristics sought by the co-design groups, and the indicators and measures they considered important for each of the five themes. We then discuss a set of key issues and their implications for technology development, according to a framework expressing interactions between people and their properties, processes and technology. This case shows the importance of taking a “demand-led” rather than a “supply-driven” approach, for the best possible fit of new technology to its users. Since co-design is more often consultative than treating users as equals or leaders in a technology design process, our case highlights the desirability of a fully collaborative approach to co-design.

Summary: Limited access to diagnostic tests for liver fibrosis remains one of the main reasons for late diagnosis, especially in rural and remote communities. Saliva diagnostics is accessible with excellent patient compliance. The aim of this study was to develop a saliva-based diagnostic tool for liver fibrosis/cirrhosis. Salivary concentrations of hyaluronic acid (HA), tissue inhibitor of metalloproteinase-1 (TIMP-1), and α-2-macroglobulin (A2MG) were significantly increased (p

Background: A key hallmark of aging is the progressive loss of skeletal muscle mass. Due to limitations of the various methods typically applied to assess muscle mass, only limited information is available on age-related differences between various muscle groups. This study assessed differences in individual lower body muscle group volumes between healthy young and older males. Methods: Lower body muscle mass assessments were performed in 10 young (age: 27 ± 4 y) and 10 older (age: 71 ± 6 y) healthy, male adults using Dual-energy X-ray Absorptiometry (DXA), single slice (thigh) Computed Tomography (CT), as well as Magnetic Resonance Imaging (MRI). Muscle volumes of all individual muscle groups in the lower body were assessed by MRI. Results: Leg lean mass, as assessed with DXA, was not significantly different between older (9.2 ± 1.0 kg) and young (10.5 ± 2.0 kg) men (P = 0.075). Thigh muscle cross-sectional area, as assessed with CT, was significantly lower (by 13 %) in the older (137 ± 17 cm2) compared to young (157 ± 24 cm2) participants (P = 0.044). MRI-derived lower body muscle volume was also significantly lower (by 20 %) in older (6.7 ± 0.9 L) compared to young (8.3 ± 1.3 L) men (P = 0.005). This was primarily attributed to substantial differences in thigh (24 %), rather than lower leg (12 %) and pelvis (15 %) muscle volume in the older vs the young. Thigh muscle volume averaged 3.4 ± 0.5 L in older and 4.5 ± 0.7 L in young men (P = 0.001). Of all thigh muscle groups, the quadriceps femoris showed the most profound difference (30 %) between young (2.3 ± 0.4 L) and older (1.6 ± 0.2 L) men (P

Abstract Background There is no clear explanation for the large variation in threshold levels among peanut‐allergic children. We hypothesized that diet composition can partly explain this variation in thresholds, as nutrients and foods influence the intestinal barrier function and microbiota. Aim to explore the relationship between the threshold levels for peanut and nutritional intake and gut microbial composition in peanut‐allergic children. Methods In this explorative cross‐sectional study the cumulative threshold levels for peanut were determined by oral food challenge tests. Data on nutrients and foods consumed were obtained from 3‐day food diaries. Microbial composition of faeces and saliva were determined by molecular microbiota detection technique. Multivariable linear regression analysis and multiple logistic regression were used to explore the associations, adjusted for energy and senitization. Results Sixty‐five children were included, of whom 32 (49%) (median age 50 months, IQR 28.0–96.5) had a positive oral food challenge. Significant positive associations were found between the intake of total carbohydrates, vitamin A and cumulative threshold levels for peanut, while significant negative associations were found for long‐chain polyunsaturated fatty acids, linoleic acid and omega‐6 fatty acids. No associations were found between threshold levels and microbial composition of faeces and saliva. However, a significant higher abundance of Proteobacteria and Bacteroidetes in saliva (p = 0.011 and 0.04, respectively) and of Proteobacteria in faeces (p = 0.003) were found in children with a positive peanut challenge compared to children with a negative peanut challenge. Conclusion As a novel concept, this study showed that dietary composition is related to threshold levels for peanut.

Summary: Replenishing nicotinamide adenine dinucleotide (NAD) via supplementation of nicotinamide riboside (NR) has been shown to confer neuroprotective effects in models of aging and neurodegenerative diseases, including Parkinson’s disease (PD). Although generally considered safe, concerns have been raised that NR supplementation could impact methylation dependent reactions, including DNA methylation, because of increased production and methylation dependent breakdown of nicotinamide (NAM). We investigated the effect of NR supplementation on DNA methylation in a double blinded, placebo-controlled trial of 29 human subjects with PD, in blood cells and muscle tissue. Our results show that NR had no impact on DNA methylation homeostasis, including individuals with common pathogenic mutations in the MTHFR gene known to affect one-carbon metabolism. Pathway and methylation variance analyses indicate that there might be minor regulatory responses to NR. We conclude that short-term therapy with high-dose NR for up to 30 days has no deleterious impact on methylation homeostasis.

The Community Research Liaison Model (CRLM) is a novel model to facilitate community-engaged research (CEnR) and community–academic research partnerships focused on health priorities identified by the community. This model, informed by the Principles of Community Engagement, builds trust among rural communities and expands capacity for community and investigator-initiated research. We describe the CRLM development process and how it is operationalized today. We followed a multi-phase process to design and implement a community engagement model that could be replicated. The resulting CRLM moves community–academic research collaborations from objectives to outputs using a conceptual framework that specifies our guiding principles, objectives, and actions to facilitate the objectives (i.e., capacity, motivations, and partners), and outputs. The CRLM has been fully implemented across Oregon. Six Community Research Liaisons collectively support 18 predominantly rural Oregon counties. Since 2017, the liaison team has engaged with communities on nearly 300 community projects. The CRLM has been successful in facilitating CEnR and community–academic research partnerships. The model has always existed on a dynamic foundation and continues to be responsive to the lessons learned by the community and researchers. The model is expanding across Oregon as an equitable approach to addressing health disparities across the state.

Introduction Mesothelioma is a key asbestos-related disease (ARD) but can be difficult to diagnose. Countries presumably ban asbestos to reduce future ARD burdens, but it is unknown if countries ban asbestos as a consequence of ARD burdens. We assessed if and to what extent mesothelioma burden has an impact on a country banning asbestos and obtaining targets for preventative strategies.Methods We analysed the status of asbestos ban and mesothelioma burden during 1990–2019 in 198 countries. We assessed mesothelioma burden by age-adjusted mortality rates (MRs) estimated by the Global Burden of Disease Study (GBD) and mesothelioma identification by the WHO mortality database. For GBD-estimated mesothelioma MR, the pre-ban period in the asbestos-banned countries was compared with the 1990–2019 period in the not-banned countries. For mesothelioma identification, the 1990–2019 period was applied to both banned and not-banned countries.Results The association of mesothelioma MR with ban status increased as the ban year approached. Logistic regression analyses showed that the odds of a country banning asbestos increased 14.1-fold (95% CI 5.3 to 37.9) for mesothelioma identification combined with a 26% (12% to 42%) increase per unit increase of mesothelioma MR (one death per million per year) during the period 1–5 year before ban (model p

Abstract The aim of the study was to investigate if there is a clinically relevant drug interaction between metformin and codeine. Volunteers were randomized to receive on four separate occasions: (A) orally administered metformin (1 g), (B) intravenously administered metformin (0.5 g), (C) five doses of tablet codeine 25 mg; the last dose was administered together with oral metformin (1 g), and (D) five doses of tablet codeine 25 mg; the last dose was administered together with metformin (0.5 g) intravenously. Blood samples were drawn for 24 h after administration of metformin, and for 6 h after administration of codeine and analyzed using liquid chromatography and tandem mass spectrometry. Healthy volunteers genotyped as CYP2D6 normal metabolizers (*1/*1) without known reduced function variants in the OCT1 gene (rs12208357, rs34130495, rs34059508, and rs72552763) were invited. The median absorption fraction of metformin was 0.31 and was not influenced by codeine intake. The median time to maximum concentration (Tmax) after oral intake of metformin was 2 h without, and 3 h with codeine (p = 0.06). The geometric mean ratios of the areas under the plasma concentration time‐curve (AUCs) for morphine and its metabolites M3G and M6G for oral intake of metformin‐to‐no metformin were 1.21, 1.31, and 1.27, respectively, and for i.v. metformin‐to‐no metformin 1.28, 1.34, and 1.30, respectively. Concomitant oral and i.v. metformin increased the plasma levels of morphine, M3G and M6G. These small pharmacokinetic changes may well contribute to an increased risk of early discontinuation of metformin. Hence, a clinically relevant drug‐drug interaction between metformin and codeine seems plausible.

Abstract The cytochrome P450 (CYP) 2D6 enzyme exhibits large interindividual differences in metabolic activity. Patients are commonly assigned a CYP2D6 phenotype based on their CYP2D6 genotype, but there is a lack of consensus on how to translate genotypes into phenotypes, causing inconsistency in genotype‐based dose recommendations. The aim of this study was to quantify and compare the impact of different CYP2D6 genotypes and alleles on CYP2D6 metabolism using a large clinical data set. A population pharmacokinetic (popPK) model of tedatioxetine and its CYP2D6‐dependent metabolite was developed based on pharmacokinetic data from 578 subjects. The CYP2D6‐mediated metabolism was quantified for each subject based on estimates from the final popPK model, and CYP2D6 activity scores were calculated for each allele using multiple linear regression. The activity scores estimated for the decreased function alleles were 0.46 (CYP2D6*9), 0.34 (CYP2D6*10), 0.01 (CYP2D6*17), 0.65 (CYP2D6*29), and 0.21 (CYP2D6*41). The CYP2D6*17 and CYP2D6*41 alleles were thus associated with the lowest CYP2D6 activity, although only the difference to the CYP2D6*9 allele was shown to be statistically significant (p = 0.02 and p = 0.05, respectively). The study provides new in vivo evidence of the enzyme function of different CYP2D6 genotypes and alleles. Our findings suggest that the activity score assigned to CYP2D6*41 should be revisited, whereas CYP2D6*17 appears to exhibit substrate‐specific behavior. Further studies are needed to confirm the findings and to improve the understanding of CYP2D6 genotype–phenotype relationships across substrates.

Our home health (HH) division has collected Home Health Care CAHPS® Survey (HHCAHPS) data since 2011. To date, HH providers have not met performance thresholds related to patient experience. This study aimed to explore HHCAHPS composite measures and specific questions to predict 1) overall rating of care provided by the agency (Care Rating) and 2) willingness to recommend home health agency to family and friends (Recommend Agency). We also explored survey comments to identify specific themes related to positive and negative patient experiences. Logistic regression (N = 7 268) revealed being treated with courtesy and respect, and providers being informed and up to date about care were the 2 most impactful factors of Care Rating. The top 2 most impactful factors for Recommend Agency were problem-free care and providers being informed and up to date about care. Thematic analyses revealed negative patient experiences were described as staff being rude, unhelpful services, and disregarding the patients’ time and schedules. Positive patient experiences were described when patients believed HH services improved their health; quality and professional services were provided by knowledgeable HH providers; and HH providers respected them, their time, and their homes. Our findings suggest that HH agencies must improve interpersonal relationships, provider communication, and clinical skills and knowledge to provide the highest quality of service with the utmost courtesy, respect, and trust; specifically, within the context of elderly adults’ desire for independence and to remain in their homes. Experience Framework This article is associated with the Policy & Measurement lens of The Beryl Institute Experience Framework. (https://www.theberylinstitute.org/ExperienceFramework). Access other PXJ articles related to this lens. Access other resources related to this lens.

This article examines voluntary refugee aid from 2015 to 2020, investigating the extent to which volunteers and refugee aid recipients have related their perceptions and emotional interpretations to the welcoming discourse and the local organisation of voluntary refugee aid. The analysis was based on contrasting sample of interviews and newspaper articles and includes a comparison of the politicised metropolitan refugee aid in Berlin with traditional charity-based aid in Braunschweig. It becomes evident that the emotional perceptions of volunteers differ depending on their reason for helping and their previous experiences. In addition, the article suggests that the recipients of refugee aid, most notably shortly after their arrival, do not refer to the welcoming discourse but instead to their own experiences or those of their acquaintances. Combining the concepts of governmentality and performativity, I use a critical perspective on power and add an affect-theoretical level in the sense of immersive power. This theoretical view raises awareness of the significance of affects and emotions in voluntary refugee aid. Overall, the stance of the article shifts. It sees refugees not only as persons in need of help but contrasts this image with the potential they offer. It takes a critical look at the last five years of voluntary refugee aid and considers the implications for voluntary refugee aid if, indeed, emotions are as significant as they appear in the article. * This article belongs to a special issue on "Refugee Migration to Europe – Challenges and Potentials for Cities and Regions".

BackgroundDuring the COVID-19 pandemic, several home monitoring programs have described the success of reducing hospital admissions, but only a few studies have investigated the experiences of patients and health care professionals. ObjectiveThe objective of our study was to determine patients’ and health care professionals’ experiences and satisfaction with employing the COVID-box. MethodsIn this single-center, retrospective, observational study, patients and health care professionals were asked to anonymously fill out multiple-choice questionnaires with questions on a 5-point or 10-point Likert scale. The themes addressed by patients were the sense of reassurance and safety, experiences with teleconsultations, their appreciation for staying at home, and the instructions for using the COVID-box. The themes addressed by health care professionals who treated patients with the COVID-box were the characteristics of the COVID-box, the technical support service and general satisfaction, and their expectations and support for this telemonitoring concept. Scores were interpreted as insufficient (≤2 or ≤5, respectively), sufficient (3 or 6-7, respectively), or good (≥4 or ≥8, respectively) on a 5-point or 10-point Likert scale. ResultsA total of 117 patients and 25 health care professionals filled out the questionnaires. The median score was 4 (IQR 4-5) for the sense of safety, the appreciation for staying at home, and experiences with teleconsultations, with good scores from 76.5% (88/115), 86% (56/65), and 83.6% (92/110) of the patients, respectively. Further, 74.4% (87/117) of the patients scored the home monitoring program with a score of ≥8. Health care professionals scored the COVID-box with a minimum median score of 7 (IQR 7-10) on a 10-point scale for all domains (ie, the characteristics of the COVID-box and the technical support service and general satisfaction). For the sense of safety, user-friendliness, and additional value of the COVID-box, the median scores were 8 (IQR 8-10), 8 (IQR 7-9), and 10 (IQR 8-10), respectively, with good scores from 86% (19/22), 75% (15/20), and 96% (24/25) of the health care professionals, respectively. All health care professionals (25/25, 100%) gave a score of ≥8 for supporting this home monitoring concept, with a median score of 10 (IQR 10-10). ConclusionsThe positive experiences and satisfaction of involved users are key factors for the successful implementation of a novel eHealth solution. In our study, patients, as well as health care professionals, were highly satisfied with the use of the home monitoring program—the COVID-box project. Remote home monitoring may be an effective approach in cases of increased demand for hospital care and high pressure on health care systems.

Background: Pharyngitis is 1 of the most common conditions leading to inappropriate antibiotic prescriptions. When personal protective equipment (PPE) was at first constrained during the COVID-19 pandemic, Intermountain Healthcare recommended limiting rapid group A streptococcal pharyngitis (GAS) testing in urgent-care clinics to preserve PPE. Notably, the percentage of pharyngitis encounters prescribed an antibiotic and that underwent GAS testing is a key Healthcare Effectiveness Data and Information Set (HEDIS) measure. We have described our experience with urgent-care pharyngitis encounters and the impact of temporarily reducing GAS testing on antibiotic prescribing before and during the COVID19 pandemic. Method: We identified all urgent care encounters between July 2018 and August 2021 associated with a primary diagnosis of pharyngitis using ICD-10 CM codes and a validated methodology. Pharyngitis encounters were assessed for antibiotic prescriptions ordered through the electronic health record (EHR) and the use of point-of-care rapid GAS tests. Pharyngitis encounters were analyzed monthly. We assessed the percentage of encounters associated with an antibiotic prescription regardless of testing and the percentage of encounters associated with an antibiotic prescription when a GAS test was or was not performed. We examined 3 periods relating to COVID-19 and GAS testing recommendations: the prepandemic period (July 2018–March 2020), the pandemic onset period (April 2020–June 2020), and the pandemic period (July 2020–August 2021). Results: Prior to the pandemic, the monthly percentage of pharyngitis encounters for which rapid GAS testing was performed was nearly 90% (Fig. 1). The average monthly percentage of urgent-care pharyngitis encounters prescribed an antibiotic was 38.9%, and the average percentage of monthly pharyngitis encounters prescribed an antibiotic that also underwent GAS testing was 90.4%. This HEDIS measure declined from 90.4% during the prepandemic period to 29.8% in the pandemic onset period when GAS testing was limited. Following resumption of routine testing practices the monthly percentage of urgent-care pharyngitis encounters for which rapid GAS testing was performed returned to levels ≥80% by July 2020 (Fig. 1). The average percentage of monthly pharyngitis encounters prescribed an antibiotic that also underwent GAS testing rose to 87.3% during this period. Conclusions: Limited PPE in our urgent care centers during the initial months of the COVID-19 pandemic was associated with a mandated substantial decline in rapid GAS testing. As testing volume decreased, we noted a simultaneous relative increase of >30% in antibiotic prescribing for pharyngitis. These findings suggest that rapid streptococcal testing promotes appropriate antibiotic prescribing.

Introduction: Necrotising otitis externa (NOE) requires a high index of clinical suspicion in patients who use off-label cotton buds or Q-tips in the external auditory canal (EAC). Methods: A case series of 2 patients who presented to the emergency department with a 2-month history of worsening unilateral otalgia and aural fullness on a background of cotton bud use. Results: A combination of clinical, radiological, laboratory and examination under anaesthesia (EUA) findings confirmed the diagnosis of NOE with temporal bone osteomyelitis. Removal of the cotton bud FB from the EAC was followed by intravenous and topical quinolone antibiotics for 6 weeks. One patient required a SOMI (sternal occipital mandibular immobiliser) brace for atlantoaxial instability due to the extent of disease. Conclusion: NOE requires a high index of clinical suspicion in patients who use off-label cotton buds or Q-tips in the EAC.

While coffee and tea consumption has been associated with risk of diseases, their mechanisms of action remain elusive. Here the authors present a large EWAS on coffee and tea consumption in cohorts of European and African-American ancestries, finding that coffee consumption is associated with differential DNA methylation levels at multiple CpGs.

This study examined and mapped the extent to which gender became incorporated into the intersecting research fields of communications, film, and media studies. A total of 8054 academic publications from these disciplines, indexed in the Web of Science between 1975 and 2022 (ndocs = 8054), were extracted to create two types of bibliometric maps: (a) an author co-citation map, and (b) a co-occurrence map of key terms (taken from keyword lists, titles, and abstracts of publications). Our results revealed a pattern of seven distinct clusters of 995 authors (nauthors = 995) in the field. Additional research is needed to analyze the internal structure of these seven clusters, and label them accordingly. The key terms in the same authors’ works, however, show a distinctively different pattern, namely a divided, dichotomous, polarized structure (nterms = 720). Judging from this, we hypothesize that gender is discussed in two main ways: either as a critical concept concerning discourses, representations, and other social and cultural constructs, or as a variable in more formal sociological and psychological research designs. The conceptual framework and results of the present study lay the foundation for further research regarding the diverse academic agendas of the seven author clusters, the split nature of their discursive communities, as well as the key difference between the two patterns.

Abstract Background Despite the recommendation of European Working Group on Sarcopenia in Older People 2 (EWGSOP2) consensus statement not to exclude patients younger than 65 years, the prevalence of sarcopenia has not been investigated in younger post‐acute inpatient rehabilitation population. The objectives of this study were to: i) estimate the prevalence of sarcopenia in post‐acute inpatient rehabilitation population; ii) compare the prevalence of sarcopenia in patients above and below 65 years. Methods This cross‐sectional observational study recruited adult patients admitted to an inpatient rehabilitation unit at a metropolitan tertiary referral hospital in Melbourne, Australia. Participants' sarcopenia status was determined using the EWGSOP2 algorithm based on grip strength and muscle mass. Results Between November 2016 and January 2019, 203 participants were enrolled. Participants' broad diagnostic streams included musculoskeletal, neurologic, spinal, cardiac, amputee, and deconditioning. The overall prevalence of sarcopenia was 18% [95% confidence interval (CI) 13% to 24%]. The prevalence of sarcopenia in patients younger than 65 was 14% (95% CI 8% to 22%), and the prevalence in patients 65 and older was 23% (95% CI 15% to 32%), risk difference of 9% (95% CI: −1.2% to 20%; P = 0.1). With incorporation of these results into the most recent meta‐analysis of sarcopenia in inpatient rehabilitation, the mean pooled prevalence of sarcopenia was 47% (95% CI 23% to 71%). Stratified by age, patients with sarcopenia had significantly longer preceding length of stay in the acute hospital (P = 0.015). Conclusions The overall estimated prevalence of sarcopenia in patients admitted to inpatient rehabilitation was 18%, and the estimated prevalence of sarcopenia in patients younger than 65 was 14%.

Abstract Background Medicines are one of the most common healthcare interventions, yet evidence shows patients often do not receive the information they want about their medicines. This affects their adherence and healthcare engagement. There is limited research exploring what information patients want about their medicines, from whom and in what format. The aim of this study was to determine the medicines information needs of patients admitted to the general medical service of a large New Zealand (NZ) hospital, and identify the barriers and enablers to meeting these needs. Methods A descriptive exploratory approach using semi-structured interviews was used to understand the needs and preferences of patients for information about their regular medicines and the barriers and facilitators to obtaining this information. Patients admitted to a general medical ward at a large NZ hospital, aged 18 years and over, prescribed one or more regular medicines, and self-managing their own medicines prior to hospitalisation were included. Semi-structured interviews were conducted with each participant (n = 30) and transcribed, then analysed using a general inductive thematic analysis approach. Results Five overarching themes captured the medicines information needs of patients: (1) autonomy; (2) fostering relationships; (3) access; (4) communication; and (5) minimal information needs. Patients desired information to facilitate their decision-making and self-management of their health. Support people, written information, and having good relationships with health providers enabled this. Having access to information at the right time, communicated in a clear and consistent way with opportunities for follow-up, was important. A significant portion of participants were satisfied with receiving minimal information and had no expectations of needing more medicines information. Conclusions Although patients’ medicines information needs varied between individuals, the importance of receiving information in an accessible, timely manner, and having good relationships with health providers, were common to most. Considering these needs is important to optimise information delivery in general medical patients.

Abstract Introduction: The NIH Inclusion Across the Lifespan policy has implications for increasing older adult (OA) participation in research. This study aimed to understand influential factors and facilitators to rural OA research participation. Methods: Thirty-seven rural adults aged ≥66 years participated in focus groups in community centers in four Oregon “non-metro” counties. Transcribed discussions were coded using open-axial coding by an interdisciplinary analytical team. Results: Ages were 66–96 (mean 82.2) years. Majority were women (64%) and white (86%). Primary, interrelated discussion themes were Motivation and Facilitators, Perceptions of Research, and Barriers to Research Participation. Participants were motivated to engage in research because they believed research had implications for improved longevity and quality of life and potentially benefited future generations. Motivational factors influencing participation included self-benefit and improving others’ lives, opportunities to socialize and learn about current research, research transparency (funding, time commitment, and requirements), and financial compensation. Perceptions influencing trustworthiness in research included funding source (industry/non-industry) and familiarity with the research institution. Barriers to research participation included transportation and concern about privacy and confidentiality. Suggestions for making research participation easier included researchers coming to rural communities and meeting participants in places where OAs gather and providing transportation and hotel accommodations. Conclusion: Lessons learned offer practical guidance for research teams as they address the new NIH Inclusion Across the Lifespan policy. Including OAs in research in ways that motivate and facilitate participation will be critical for a robust representation across the lifespan and in tailoring treatments to the specific needs of this population.

Deep learning and, specifically, convoltional neural networks (CNN) represent a class of powerful models that facilitate the understanding of many problems in computer vision. When combined with a reasonable amount of data, CNNs can outperform traditional models for many tasks, including image classification. In this work, we utilize these powerful tools with imagery data collected through Google Street View images to perform virtual audits of neighborhood characteristics. We further investigate different architectures for chronic disease prevalence regression through networks that are applied to sets of images rather than single images. We show quantitative results and demonstrate that our proposed architectures outperform the traditional regression approaches.

This work is concerned with damage detection in a commercial 52-meter wind turbine blade during fatigue testing. Different artificial damages are introduced in the blade in the form of laminate cracks. The lengths of the damages are increased manually, and they all eventually propagate and develop into delaminations during fatigue loading. Strain gauges, acoustic emission sensors, distributed accelerometers, and an active vibration monitoring system are used to track different physical responses in healthy and damaged states of the blade. Based on the recorded data, opportunities and limitations of the different sensing systems for blade structural health monitoring are investigated.

Metastasis to the ovary from a bladder primary is extremely rare with limited case reports. The most common primary sites arise from stomach, colon or renal origin and usually occur from 40 years of age onwards. We report a case of an 18-year old woman with a right sided Krukenberg tumour from a bladder primary. This patient is much younger than any other case report of Krukenberg tumour and reiterates the need for early excision of urachal masses in all age groups.

Objective: To investigate the association between sarcopenia and functional improvement in patients older and younger than 65 years upon completion of an inpatient rehabilitation program.Design: Prospective cohort study.Participants: Adult consecutive patients who completed the inpatient rehabilitation program at a metropolitan tertiary referral hospital general inpatient rehabilitation unit.Methods: Sarcopenia status was determined using the European Working Group on Sarcopenia in Older People 2 algorithm, using muscle mass measured by BioImpedance Analysis and grip strength. Progress in rehabilitation was measured using change in the Functional Independence Measure and Goal Attainment Scaling score. To investigate the age group by sarcopenia status interaction we used quantile regression models with bootstrapped standard error estimation for functional improvement and linear regression model with robust standard error estimation for GAS score.Results: 257 participants [128 (50%) male, median age 63 years (IQR: 52–72)], 33(13%) with sarcopenia, completed inpatient rehabilitation [median length of stay 16 days (IQR: 11–27.5)]. Participants' median Functional Independence Measure change was 24 (IQR 15–33.5) and mean total Goal Attainment Scaling score was 57.6 (SD 10.2). Adjusting for admission Functional Independence Measure score, the median difference in Functional Independence Measure change between participants with and without sarcopenia was: −4.3 (95% CI: −10.6, 1.9); p = 0.17 in participants 65 years and younger, and 4.6 (95% CI: 1.0, 8.2); p = 0.01 in participants older than 65; age-by-sarcopenia interaction p = 0.02.Conclusions: Unlike younger people, older people with sarcopenia have greater functional improvement in inpatient rehabilitation than those without sarcopenia.

Introduction Despite current available treatment patients with bipolar disorder often experience relapses and decreased overall functioning. Furthermore, patients with bipolar disorder are often not treated medically or psychologically according to guidelines and recommendations. A Clinical Academic Group is a new treatment initiative bringing together clinical services, research, education and training to offer care and treatment that is based on reliable evidence backed up by research. The present Clinical Academic Group for bipolar disorder (the CAG Bipolar) randomised controlled trial (RCT) aims for the first time to investigate whether specialised outpatient treatment in CAG Bipolar versus generalised community-based treatment improves patient outcomes and clinician’s satisfaction with care in patients with bipolar disorder.Methods and analysis The CAG Bipolar trial is a pragmatic randomised controlled parallel-group trial undertaken in the Capital Region of Denmark covering a catchment area of 1.85 million people. Patients with bipolar disorder are invited to participate as part of their outpatient treatment in the Mental Health Services. The included patients will be randomised to (1) specialised outpatient treatment in the CAG Bipolar (intervention group) or (2) generalised community-based outpatient treatment (control group). The trial started 13 January 2020 and has currently included more than 600 patients. The outcomes are (1) psychiatric hospitalisations and cumulated number and duration of psychiatric hospitalisations (primary), and (2) self-rated depressive symptoms, self-rated manic symptoms, quality of life, perceived stress, satisfaction with care, use of medication and the clinicians’ satisfaction with their care (secondary). A total of 1000 patients with bipolar disorder will be included.Ethics and dissemination The CAG Bipolar RCT is funded by the Capital Region of Denmark and ethical approval has been obtained from the Regional Ethical Committee in The Capital Region of Denmark (H-19067248). Results will be published in peer-reviewed academic journals, presented at scientific meetings and disseminated to patient organisations and media outlets.Trial registration number NCT04229875.

Summary: The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women. Key Words: breastfeeding, immune activation, peripartum cardiomyopathy

A recent study proposed new TNM groupings for better survival discrimination among stage groups for medullary thyroid carcinoma (MTC) and validated these groupings in a population-based cohort in the United States. However, it is unknown how well the groupings perform in populations outside the United States. Consequently, we conducted the first population-based study aiming to evaluate if the recently proposed TNM groupings provide better survival discrimination than the current American Joint Committee on Cancer (AJCC) TNM staging system (seventh and eighth edition) in a nationwide MTC cohort outside the United States. This retrospective cohort study included 191 patients identified from the nationwide Danish MTC cohort between 1997 and 2014. In multivariate analysis, hazard ratios for overall survival under the current AJCC TNM staging system vs the proposed TNM groupings with stage I as reference were 1.32 (95% CI: 0.38–4.57) vs 3.04 (95% CI: 1.38–6.67) for stage II, 2.06 (95% CI: 0.45–9.39) vs 3.59 (95% CI: 1.61–8.03) for stage III and 5.87 (95% CI: 2.02–17.01) vs 59.26 (20.53–171.02) for stage IV. The newly proposed TNM groupings appear to provide better survival discrimination in the nationwide Danish MTC cohort than the current AJCC TNM staging. Adaption of the proposed TNM groupings by the current AJCC TNM staging system may potentially improve accurateness in survival discrimination. However, before such an adaption further population-based studies securing external validity are needed.