Opportunistic screening for COPD among socially marginalized patients.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is a common disease associated with premature death. Tobacco exposure is the main risk factor, but lower socioeconomic status, early life insults, and occupational exposures are also important risk factors. Socially marginalized people, facing homelessness, substance use disorder, and mental illness, are likely to have a higher risk of developing COPD, and, furthermore, experience barriers to healthcare access and consequently poorer outcomes. OBJECTIVE: This study aims to assess COPD prevalence and the impact of opportunistic screening among hospitalized patients who are in contact with hospital social nurses. These patients constitute a group of patients with a high prevalence of psychiatric and somatic diseases, substance use, low life expectancy, and are socially marginalized. METHODS: The present prospective longitudinal study includes a clinical examination at baseline. Participants will have spirometry done and be interviewed regarding risk factors, socioeconomic conditions, and respiratory symptoms. The 5-year follow-up assessment incorporates data from baseline and register data over the 5 years, including information on morbidity, use of COPD medication, hospital contacts, mortality, and socioeconomic factors. ANTICIPATED RESULTS: Referral for further diagnostic work-up and management after the screening, including COPD treatment and smoking cessation support, is expected to improve survival rates. The study is still enrolling patients. TRIAL REGISTRATION: The study is registered at ClinicalTrials.gov , NCT04754308 with study status: "enrolling".

Influences of specialty identity when implementing a new emergency department in Denmark: a qualitative study.

BACKGROUND: The Danish Health Authority recommended the implementation of new types of emergency departments. Organizational changes in the hospital sector challenged the role, identity, and autonomy of medical specialists. They tend to identify with their specialty, which can challenge successful implementation of change. However, investigations on specialty identity are rare in implementation science, and how the co-existence of different specialty identities influences the implementation of new emergency departments needs to be explored for the development of tailored implementation strategies. The aim of this study was to examine how medical specialty identity influences collaboration between physicians when implementing a new emergency department in Denmark. METHODS: Qualitative methods in the form of participants' observations at 13 oilcloth sessions (a micro-simulation method) were conducted followed up by 53 individual semi-structured interviews with participants from the oilcloth sessions. Out of the 53 interviews, 26 were conducted with specialists. Data from their interviews are included in this study. Data were analysed deductively inspired by Social Identity Theory. RESULTS: The analysis yielded three overarching themes: [1] ongoing creation and re-creation of specialty identity through boundary drawing; [2] social categorization and power relations; and [3] the patient as a boundary object. CONCLUSIONS: Specialty identity is an important determinant of collaboration among physicians when implementing a new emergency department. Specialty identity involves social categorization, which entails ongoing creation and re-creation of boundary drawing and exercising of power among the physicians. In some situations, the patient became a positive boundary object, increasing the possibility for a successful collaboration and supporting successful implementation, but direct expressions of boundaries and mistrust were evident. Both were manifested through a dominating power expressed through social categorization in the form of in- and out-groups and in an "us and them" discourse, which created distance and separation among physicians from different specialties. This distancing and separation became a barrier to the implementation of the new emergency department.

Performance of Panel-Estimated GFR Among Hospitalized Older Adults.

RATIONALE & OBJECTIVE: Older adults represent nearly half of all hospitalized patients and are vulnerable to inappropriate dosing of medications eliminated through the kidneys. However, few studies in this population have evaluated the performance of equations for estimating the glomerular filtration rate (GFR)-particularly those that incorporate multiple filtration markers. STUDY DESIGN: Cross-sectional diagnostic test substudy of a randomized clinical trial. SETTING & PARTICIPANTS: Adults≥65 years of age presenting to the emergency department of Copenhagen University Hospital Amager and Hvidovre in Hvidovre, Denmark, between October 2018 and April 2021. TESTS COMPARED: Measured GFR (mGFR) determined using 99mTc-DTPA plasma clearance compared with estimated GFR (eGFR) calculated using 6 different equations based on creatinine; 3 based on creatinine and cystatin C combined; and 2 based on panels of markers including creatinine, cystatin C, ß-trace protein (BTP) and/or ß2-microglobulin (B2M). OUTCOME: The performance of each eGFR equation compared with mGFR with respect to bias, relative bias, inaccuracy (1-P30), and root mean squared error (RMSE). RESULTS: We assessed eGFR performance for 106 patients (58% female, median age 78.3 years, median mGFR 62.9mL/min/1.73m2). Among the creatinine-based equations, the 2009 CKD-EPIcr equation yielded the smallest relative bias (+4.2%). Among the creatinine-cystatin C combination equations, the 2021 CKD-EPIcomb equation yielded the smallest relative bias (-3.4%), inaccuracy (3.8%), and RMSE (0.139). Compared with the 2021 CKD-EPIcomb, the CKD-EPIpanel equation yielded a smaller RMSE (0.136) but larger relative bias (-4.0%) and inaccuracy (5.7%). LIMITATIONS: Only White patients were included; only a subset of patients from the original clinical trial underwent GFR measurement; and filtration marker concentration can be affected by subclinical changes in volume status. CONCLUSIONS: The 2009 CKD-EPIcr, 2021 CKD-EPIcomb, and CKD-EPIpanel equations performed best and notably outperformed their respective full-age spectrum equations. The addition of cystatin C to creatinine-based equations improved performance, while the addition of BTP and/or B2M yielded minimal improvement. FUNDING: Grants from public sector industry (Amgros I/S) and government (Capital Region of Denmark). TRIAL REGISTRATION: Registered at ClinicalTrials.gov with registration number NCT03741283. PLAIN-LANGUAGE SUMMARY: Inaccurate kidney function assessment can lead to medication errors, a common cause of hospitalization and early readmission among older adults. Several novel methods have been developed to estimate kidney function based on a panel of kidney function markers that can be measured from a single blood sample. We evaluated the accuracy of these new methods (relative to a gold standard method) among 106 hospitalized older adults. We found that kidney function estimates combining 2 markers (creatinine and cystatin C) were highly accurate and noticeably more accurate than estimates based on creatinine alone. Estimates incorporating additional markers such as ß-trace protein and ß2-microglobulin did not further improve accuracy.

Estimated glomerular filtration rate based on creatinine, cystatin C, ß-trace protein and ß2 microglobulin in patients undergoing nontraumatic lower extremity amputation.

AIMS: The study's aim is to compare current and new equations for estimating glomerular filtration rate (GFR) based on creatinine, cystatin C, ß-trace protein (BTP) and ß2 microglobulin (B2M) among patients undergoing major amputation. METHODS: This is a secondary analysis of data from a prospective cohort study investigating patients undergoing nontraumatic lower extremity amputation. Estimated GFR (eGFR) was calculated using equations based on creatinine (eGFRcre[2009] and eGFRcre[2021]), cystatin C (eGFRcys), the combination of creatinine and cystatin C (eGFRcomb[2012] and eGFRcomb[2021]) or a panel of all 4 filtration markers (eGFRpanel). Primary outcome was changed in eGFR across amputation according to each equation. Two case studies of prior amputation with GFR measured by 99mTc-DTPA clearance are described to illustrate the relative accuracies of each eGFR equation. RESULTS: Analysis of the primary outcome included 29 patients (median age 75 years, 31% female). Amputation was associated with a significant decrease in creatinine concentration (-0.09 mg/dL, P = 0.004), corresponding to a significant increase in eGFRcre[2009] (+6.1 mL/min, P = 0.006) and eGFRcre[2021] (+6.3 mL/min, P = 0.006). Change across amputation was not significant for cystatin C, BTP, B2M or equations incorporating these markers (all P > 0.05). In both case studies, eGFRcre[2021] yielded the largest positive bias, eGFRcys yielded the largest negative bias and eGFRcomb[2012] and eGFRcomb[2021] yielded the smallest absolute bias. CONCLUSION: Creatinine-based estimates were substantially higher than cystatin C-based estimates before amputation and significantly increased across amputation. Estimates combining creatinine and cystatin were stable across amputation, while the addition of BTP and B2M is unlikely to be clinically relevant.

Shared and distinct factors underlying in-hospital mobility of older adults in Israel and Denmark (97/100).

BACKGROUND: Low in-hospital mobility is widely acknowledged as a major risk factor in acquiring hospital-associated disabilities. Various predictors of in-hospital low mobility have been suggested, among them older age, disabling admission diagnosis, poor cognitive and physical functioning, and pre-hospitalization mobility. However, the universalism of the phenomena is not well studied, as similar risk factors to low in-hospital mobility have not been tested. METHODS: The study was a secondary analysis of data on in-hospital mobility that investigated the relationship between in-hospital mobility and a set of similar risk factors in independently mobile prior to hospitalization older adults, hospitalized in acute care settings in Israel (N = 206) and Denmark (N = 113). In Israel, mobility was measured via ActiGraph GT9X and in Denmark by ActivPal3 for up to seven hospital days. RESULTS: Parallel multivariate analyses revealed that a higher level of community mobility prior to hospitalization and higher mobility ability status on admission were common predictors of a higher number of in-hospital steps, whereas the longer length of hospital stay was significantly correlated with a lower number of steps in both samples. The risk of malnutrition on admission was associated with a lower number of steps, but only in the Israeli sample. CONCLUSIONS: Despite different assessment methods, older adults' low in-hospital mobility has similar risk factors in Israel and Denmark. Pre-hospitalization and admission mobility ability are robust and constant risk factors across the two studies. This information can encourage the development of both international standard risk evaluations and tailored country-based approaches.

Effect of Influenza Vaccination on Risk of Coronavirus Disease 2019: A Prospective Cohort Study of 46†000 Healthcare Workers.

BACKGROUND: The purpose of this study was to assess whether influenza vaccination has an impact on the risk of coronavirus disease 2019 (COVID-19). METHODS: A cohort of 46 112 healthcare workers were tested for antibodies against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and filled in a survey on COVID-19 symptoms, hospitalization, and influenza vaccination. RESULTS: The risk ratio of hospitalization due to SARS-CoV-2 for influenza vaccinated compared with unvaccinated participants was 1.00 for the seasonal vaccination in 2019/2020 (confidence interval, .56-1.78, P = 1.00). Likewise, no clinical effect of influenza vaccination on development of antibodies against SARS-CoV-2 was found. CONCLUSIONS: The present findings indicate that influenza vaccination does not affect the risk of SARS-CoV-2 infection or COVID-19.

Using soluble urokinase plasminogen activator receptor to stratify patients for medication review in the emergency department.

AIMS: To investigate whether the association between levels of medication use (including polypharmacy and potentially inappropriate medications [PIMs]) and health outcomes such as readmission and mortality is dependent on baseline soluble urokinase plasminogen activator receptor (suPAR). METHODS: This registry-based cohort study included medical patients admitted to the emergency department at Copenhagen University Hospital Hvidovre, Denmark. Patients were grouped according to their admission suPAR levels: low (0-3 ng/mL), intermediate (3-6 ng/mL), or high (>6 ng/mL). Hyper-polypharmacy was defined as ≥10 prescribed medications. PIMs were identified based on the EU(7)-PIM list, and data on admissions and mortality were obtained from national registries. Risk of 90-day readmission and mortality was assessed by Cox regression analysis adjusted for sex, age and Charlson comorbidity index. Results were reported as hazard ratios within 90 days of index discharge. RESULTS: In total, 26 291 patients (median age 57.3 y; 52.7% female) were included. Risk of 90-day readmission and mortality increased significantly for patients with higher suPAR or higher number of medications. Among patients with low suPAR, patients with ≥10 prescribed medications had a hazard ratio of 2.41 (95% confidence interval = 2.09-2.78) for 90-day readmission and 8.46 (95% confidence interval = 2.53-28.28) for 90-day mortality compared to patients with 0 medications. Patients with high suPAR generally had high risk of readmission and mortality, and the impact of medication use was less pronounced in this group. Similar, but weaker, association patterns were observed between suPAR and PIMs. CONCLUSION: The association between levels of medication use and health outcomes is dependent on baseline suPAR.

Variations in physical activity and sedentary behavior during and after hospitalization in acutely admitted older medical patients: a longitudinal study.

BACKGROUND: Inactivity is frequent among older patients during hospitalization. It is unknown how patients' daily activity pattern (diurnal profile) vary between hospitalization and after discharge. This study aims to describe and compare the distribution of physical activity and sedentary behavior in acutely hospitalized older patients during hospitalization and after discharge. METHODS: We included data on 80 patients (+65 years) admitted with acute medical illness from the STAND-Cph trial. Physical activity and sedentary behavior were measured as daily number of steps, uptime (walking/standing) and sedentary behavior (lying/sitting) with an activity monitor (activPAL3, PAL Technologies Ltd). The patients wore the monitor for three periods of one week: during hospitalization, after discharge, and four weeks after discharge. RESULTS: The patients' median age was 80 years [IQR: 75;88], 68% were female and the median De Morton Mobility Index (DEMMI) was 57 [IQR: 48;67]. The daily median uptime was 1.7 h [IQR: 1;2.8] during hospitalization, 4.0 h [IQR: 2.7;5.4] after discharge and 4.0 h [IQR: 2.8;5.8] four weeks after discharge. The daily median number of steps was 728 [IQR: 176;2089], 2207 [IQR: 1433;3148], and 2622 [IQR: 1714;3865], respectively, and median daily sedentary behavior was 21.4 h (IQR: 20.7;22.4), 19.5 h (IQR: 18.1;21.0) and 19.6 h (IQR: 18.0;20.8), respectively. During hospitalization, a small activity peak was observed between 9-11 AM without any notable variation after. At discharge and four weeks after discharge, a peak in physical activity was seen between 9-12 AM and at 5 PM. CONCLUSION: Older hospitalized patients spend most of their time being sedentary with their highest activity between 9-11 AM. Daily activity doubles after discharge with one extra peak in the afternoon. Daily routines might be disrupted, and older patients have the potential to be more physically active during hospitalization. Interventions that encourage physical activity during hospitalization are warranted.

Co-designing implementation strategies for the WALK-Cph intervention in Denmark aimed at increasing mobility in acutely hospitalized older patients: a qualitative analysis of selected strategies and their justifications.

BACKGROUND: Selecting appropriate strategies to target barriers to implementing interventions represents a considerable challenge in implementation research and practice. The aim was to investigate what categories of implementation strategies were selected by health care practitioners and their managers in a co-design process and how they justified these strategies aimed at facilitating the implementation of the WALK-Cph intervention. METHODS: The study used a qualitative research design to explore what implementation strategies were selected and the justifications for selecting these strategies. Workshops were used because this qualitative method is particularly well suited for studying co-design processes that involve substantial attention to social interaction and the context. Data were 1) analyzed deductively based on the Proctor et al. taxonomy of implementation strategies, 2) categorized in accordance with the ERIC compilation of implementation strategies by Powell et al., and 3) analyzed to examine the justification for the selected strategies by the Proctor et al. framework for justifications of implementation strategies. RESULTS: Thirteen different types of implementation strategies were chosen across two hospitals. The deductive analysis showed that selection of implementation strategies was based on pragmatic and theoretical justifications. The contents of the two types of justifications were thematized into nine subthemes. CONCLUSION: This study contributes with knowledge about categories and justification of implementation strategies selected in a co-design process. In this study, implementation strategies were selected through pragmatic and theoretical justifications. This points to a challenge in balancing strategies based on practice-based and research-based knowledge and thereby selection of strategies with or without proven effectiveness.

Implementing a new emergency department: a qualitative study of health professionals' change responses and perceptions.

BACKGROUND: The aim of the study is two-fold. It explores how managers and key employees at the Emergency Department (ED) and specialist departments in a university hospital in the Capital Region of Denmark respond to the planned change to a new ED, and how they perceive the change involved in the implementation of the new ED. The study investigates what happens when health professionals are confronted with implementation of policy that changes their organization and everyday work lives. Few studies provide in-depth investigations of health professionals' reactions to the implementation of new EDs, and particularly how they influence the implementation of a nationwide organizational change framed within a political strategy. METHODS: The study used semi-structured individual interviews with 51 health professionals involved in implementation activities related to an organizational change of establishing a new ED with new patient pathways for acutely ill patients. The data was deductively analyzed using Leon Coetsee's theoretical framework of change responses, but the analysis also allowed for a more inductive reading of the material. RESULTS: Fourteen types of responses to establishing a new ED were identified and mapped onto six of the seven overall change responses in Coetsee's framework. The participants perceived the change as particularly three changes. Firstly, they wished to create the best possible acute patient pathway in relation to their specialty. Whether the planned new ED would redeem this was disputed. Secondly, participants perceived the change as relocation to a new building, which both posed potentials and worries. Thirdly, both hopeful and frustrated statements were given about the newly established medical specialty of emergency medicine (EM), which was connected to the success of the new ED. CONCLUSIONS: The study showcases how implementation processes within health care are not straightforward and that it is not only the content of the implementation that determines the success of the implementation and its outcomes but also how these are perceived by managers and employees responsible for the process and their context. In this way, managers must recognize that it cannot be pre-determined how implementation will proceed, which necessitates fluid implementation plans and demands implementation managements skills.

Oilcloth sessions as an implementation strategy: a qualitative study in Denmark.

BACKGROUND: The aim of this study was to explore healthcare professionals, managers, and other key employees' experiences of oilcloth sessions as a strategy when implementing new emergency departments in Denmark, based on their participations in these sessions. The study addresses the importance of securing alignment in implementation strategies. Too often, this does not get enough attention in the literature and in practice. In this study, alignment among components was achieved in an educational implementation strategy called oilcloth sessions. METHODS: The study is based on participants' observations of 13 oilcloth sessions and follow-up via 53 semi-structured interviews with the board of directors, managers, and key employees from the present emergency department and different specialty departments. Data were analysed deductively using Biggs and Tang's model of didactic alignment. RESULTS: The analysis showed the complexity of challenges when using oilcloth sessions as a strategy when implementing a new emergency department described in terms of three phases and nine main themes (a-i): the preparation phase: (a) preparing individually and collectively, (b) objectives, (c) involving participants, (d) selecting cases; the execution phase: (e) using materials, (f) facilitating the sessions, (g) temporal structures; evaluation: (h) following up on the sessions, (i) adapting to the context. CONCLUSIONS: This study shows that it is important to ensure alignment among elements in implementation strategies. Thus, oilcloth sessions with high alignment are useful if the challenges experienced are to be overcome and the strategy will be experienced as a useful way to support the implementation of a new emergency department from the participants' point of view. Bigg and Tang's didactic model is useful as an analytical framework to ensure alignment in implementation strategies in general.

Do glia provide the link between low-grade systemic inflammation and normal cognitive ageing? A 1 H magnetic resonance spectroscopy study at 7 tesla.

Low-grade systemic inflammation contributes to ageing-related cognitive decline, possibly by triggering a neuroinflammatory response through glial activation. Using proton magnetic resonance spectroscopy (1 H-MRS) at 7T in normal human individuals from 18 to 79 years in a cross-sectional study, we previously observed higher regional levels of myo-inositol (mIns), total creatine (tCr) and total choline (tCho) in older than younger age groups. Moreover, visuo-spatial working memory (vsWM) correlated negatively with tCr and tCho in anterior cingulate cortex (ACC) and mIns in hippocampus and thalamus. As mIns, tCr and tCho are higher in glia than neurons, this suggest a potential in vivo connection between cognitive ageing and higher regional levels of glia-related metabolites. In the present study, we tested whether these metabolic differences may be related to low-grade systemic inflammation. In the same individuals, plasma concentrations of the proinflammatory markers C-reactive protein (CRP), interleukin 8 (IL-8), and tumour necrosis factor α (TNF-α) were measured on the same day as 1 H-MRS assessments. We tested whether CRP, IL-8, and TNF-α concentrations correlated with the levels of glia-related metabolites. CRP and IL-8, but not TNF-α, were higher in older (69-79 years) than younger (18-26 years) individuals. CRP correlated positively with thalamic mIns and negatively with vsWM. IL-8 correlated positively with ACC tCho and hippocampal mIns, but not with vsWM. Mediation analysis revealed an indirect effect of IL-8 on vsWM via ACC tCho. Together, these findings corroborate the role of glial cells, perhaps via their role in neuroinflammation, as part of the neurobiological link between systemic inflammation and cognitive ageing.

Lynch syndrome-associated epithelial ovarian cancer and its immunological profile.

INTRODUCTION: Lynch syndrome is a multi-tumor syndrome characterized by mismatch repair deficiency (MMR-d), microsatellite instability (MSI), and increased tumor-infiltrating lymphocytes (TILs) making these tumors candidates for treatment with immune checkpoint inhibitors. However, response may depend on tumor-induced immune evasion mechanisms, e.g. loss of Beta-2-Microglobulin (B2M) or upregulation of programmed death protein ligand 1 (PD-L1). We investigated the immune response and B2M and PD-L1 expression in Lynch syndrome-associated ovarian cancers. METHODS: We successfully analyzed 30 Lynch syndrome-associated epithelial ovarian cancers collected through the Danish Hereditary Non-Polyposis Colorectal Cancer (HNPCC) register. MMR-d, MSI, immune response (CD3, CD8, and CD68), and immune evasion mechanisms (B2M and PD-L1) were investigated. Statistical associations between these markers were evaluated in addition to survival in relation to B2M/PD-L1. RESULTS: Of the 29 evaluable tumors, 27 were MMR-d (93.1%). Likewise of 26 evaluable tumors, 14 were MSI (53.8%). MMR-d/MMR-proficiency associated with MSI/MSS in 60.0%. Half of the ovarian tumors presented with high levels of TILs. Loss of B2M expression was observed in 46.7% of the tumors, while expression of PD-L1 was seen in 28.0% of the cases. There was no association between B2M/PD-L1 and MSI/TILs/survival. Loss of B2M was often seen in tumors with low TILs (p = 0.056 or p = 0.059 for CD3 and CD8 positive cells, respectively). CONCLUSION: MMR-d, MSI, and TILs are also seen in Lynch syndrome-associated ovarian cancers making these potential candidates for checkpoint-based immunotherapy. The clinical impact from immune evasion through loss of B2M needs to be investigated further in larger cohorts.

Mortality and major complications after emergency laparotomy: A pilot study of risk prediction model development by preoperative blood-based immune parameters.

BACKGROUND: Emergency laparotomy is associated with high risk of postoperative complications and mortality. Preoperative identification of patients at high risk of adverse outcome is important. The immune response to conditions requiring emergency laparotomy is not understood in detail. The present study describes preoperative blood-based immune profiles and their potential value in surgical risk assessment. METHOD: Patients (N = 100) referred for emergency laparotomy at Hvidovre Hospital were consecutively included from 3 June 2013-11 April 2014. All patients had blood samples collected before surgery and the immune parameters c-reactive protein (CRP), Interleukin-6 (IL-6), Interleukin-10 (IL-10), interferon-γ induced protein 10 kDa (IP-10), tumor necrosis factor α (TNF-α) and soluble urokinase plasminogen receptor activator (suPAR) were determined. Patients were stratified according to major postoperative complications (including death), 30- and 180-day mortality. Using logistic regression models and receiver operating characteristics curves the predictive ability of the immune parameters were estimated. RESULTS: Major complications were recorded in 45 (45.0%) of the patients, whereas 30-day and 180-day mortalities were 17 (17.0%) and 25 (25.0%), respectively. Concentrations of suPAR and TNF-α were associated with major complications while CRP, IL-6, suPAR and TNF-α were associated with mortality. Adding the combined immune parameters to a regression model including age, sex, American Society of Anesthesiologists physical status and Eastern Cooperative Oncology Group Performance Status significantly improved the predictive ability for major complications, 30-day mortality and 180-day mortality. CONCLUSION: In emergency laparotomy, preoperative blood-based immune parameters added predictive power to regression models and could be considered in risk prediction model development.

The effect of the employment of experienced physicians in the Emergency Department on quality of care and equality-a quasi-experimental retrospective cohort study.

BACKGROUND: Increasing acute admissions in Emergency Departments (EDs) negatively affect quality of care, safety and flow. Thus, the Danish Health Authorities recommend the presence of experienced physicians in the ED. In 2016, consultant-led triage and continuous presence of consultants were introduced at a larger ED in Copenhagen, Denmark. This study investigated whether the employment of consultants in a Danish ED affected the quality of care for acutely admitted medical patients in terms of length of admission, readmission and mortality, as well as socioeconomic equality in quality of care delivery. METHODS: Admission data were collected during two 7-month periods, one prior to and one after the organizational intervention, with 9869 adult medical patients admitted for up to 48 h in the ED. Linear regression and Cox proportional hazards regression analyses adjusted for age, sex, comorbidities, level of education and employment status were applied. RESULTS: Following the employment of consultants, an overall 11% increase in index-admissions was observed, and 90% of patients were discharged by a consultant with a reduced mean length of admission by 1.4 h (95% CI: 1.0-1.9). No change was found in in-hospital mortality, readmission or mortality within 90 days after discharge. No change in distribution of quality indicators across patients' socioeconomic status was found. CONCLUSIONS: Consultants in the ED was found to reduce length of hospitalization without a negative effect on the quality of care for ED-admitted medical patients in general or patients with lower socioeconomic status.

Adaptations and modifications to a co-designed intervention and its clinical implementation: a qualitative study in Denmark.

BACKGROUND: There is a long-standing debate in implementation research on whether adaptations to evidence-based interventions (EBIs) are desirable in health care. If an intervention is adapted and not delivered as conceived and planned, it is said to have low fidelity. The WALK-Cph project was developed based on the assumption that involving stakeholders in co-design processes would facilitate the fidelity of an intervention to increase the mobility of acutely admitted older medical patients and its implementation in two hospitals in Denmark. The purpose of this study is to describe and analyse adaptations and modifications that were made to the co-designed WALK-Cph intervention and its implementation. METHODS: This study used a qualitative design. An ethnographic field study was performed using participant observations, workshops and semi-structured interviews. Data were analysed twice using the Framework Method. The first analysis was based on the frameworks from Stirman, Moore and Proctor. The second analysis, a retrospective modifications analysis, was based on the Adaptation-Impact Framework. RESULTS: Many different types of adaptations and modifications were made to the WALK-Cph intervention and its implementation plan. Most of the modifications were made on the contents of the intervention. In total, 44 adaptations and modifications were made, of which 21 were planned (adaptations) and 23 were made haphazardly (modifications). Most of the content and context adaptations and modifications made on the intervention had a mixed result regarding enhanced fidelity. The retrospective modifications analysis showed that modifications were ongoing and both situationally and contextually shaped. CONCLUSIONS: Although an extensive co-design process was carried out to facilitate the fidelity of the WALK-Cph intervention, this study showed that many adaptations and modifications were still made to both the intervention and its implementation plan. It could indicate that the co-design process had a small effect or that adaptations and modifications are ongoing and both situationally and contextually shaped, which challenge the assumption and the desire to be able to plan and control changes.

Soluble Urokinase Receptor (SuPAR) in COVID-19-Related AKI.

BACKGROUND: AKI commonly occurs in patients with coronavirus disease 2019 (COVID-19). Its pathogenesis is poorly understood. The urokinase receptor system is a key regulator of the intersection between inflammation, immunity, and coagulation, and soluble urokinase plasminogen activator receptor (suPAR) has been identified as an immunologic risk factor for AKI. Whether suPAR is associated with COVID-19-related AKI is unknown. METHODS: In a multinational observational study of adult patients hospitalized for COVID-19, we measured suPAR levels in plasma samples from 352 adult patients that had been collected within 48 hours of admission. We examined the association between suPAR levels and incident in-hospital AKI. RESULTS: Of the 352 patients (57.4% were male, 13.9% were black, and mean age was 61 years), 91 (25.9%) developed AKI during their hospitalization, of whom 25 (27.4%) required dialysis. The median suPAR level was 5.61 ng/ml. AKI incidence rose with increasing suPAR tertiles, from a 6.0% incidence in patients with suPAR <4.60 ng/ml (first tertile) to a 45.8% incidence of AKI in patients with suPAR levels >6.86 ng/ml (third tertile). None of the patients with suPAR <4.60 ng/ml required dialysis during their hospitalization. In multivariable analysis, the highest suPAR tertile was associated with a 9.15-fold increase in the odds of AKI (95% confidence interval [95% CI], 3.64 to 22.93) and a 22.86-fold increase in the odds of requiring dialysis (95% CI, 2.77 to 188.75). The association was independent of inflammatory markers and persisted across subgroups. CONCLUSIONS: Admission suPAR levels in patients hospitalized for COVID-19 are predictive of in-hospital AKI and the need for dialysis. SuPAR may be a key component of the pathophysiology of AKI in COVID-19.

Soluble Urokinase Plasminogen Activator Receptor as a Decision Marker for Early Discharge of Patients with COVID-19 Symptoms in the Emergency Department.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (The Covid-19 pandemic) strains health care capacity. Better risk stratification, with discharge of patients with a predicted mild disease trajectory, can ease this burden. Elevated blood-soluble urokinase plasminogen activator receptor (suPAR) has previously been shown to be associated with risk of intubation in confirmed COVID-19 patients. OBJECTIVE: To evaluate whether point-of-care measures of suPAR in patients presenting to the emergency department (ED) with symptoms of COVID-19 can identify patients that can be safely discharged. METHODS: Observational cohort study including all patients in the ED with symptoms of COVID-19 from March 19 to April 3, 2020. SuPAR was measured at first presentation. Review of electronic patient records 14 days after admission was used to assess disease trajectory. Primary endpoints were mild, moderate, severe, or very severe trajectory. The predictive value of suPAR, National Early Warning Score (NEWS), C-reactive protein (CRP), and duration of symptoms was calculated using receiver operating characteristics (ROC). RESULTS: Of 386 patients, 171 (44%) had a mild disease trajectory, 79 (20%) a moderate, 63 (16%) a severe, and 73 (19%) a very severe disease trajectory. Low suPAR was a strong marker of mild disease trajectory. Results suggest a cut-off for discharge for suPAR < 2.0 ng/mL if suPAR is used as a single parameter, and <3.0 ng/mL when combined with NEWS ≤ 4 and CRP < 10 mg/L. CONCLUSION: suPAR is a potential biomarker for triage and safe early discharge of patients with COVID-19 symptoms in the ED. suPAR can be used even before SARS-CoV-2 status is known.

Alterations of monocyte NF-κB p65/RelA signaling in a cohort of older medical patients, age-matched controls, and healthy young adults.

BACKGROUND: Altered monocyte NF-κB signaling is a possible cause of inflammaging and driver of aging, however, evidence from human aging studies is sparse. We assessed monocyte NF-κB signaling across different aging trajectories by comparing healthy older adults to older adults with a recent emergency department (ED) admission and to young adults. METHODS: We used data from: 52 older (≥65 years) Patients collected upon ED admission and at follow-up 30-days after discharge; 52 age- and sex-matched Older Controls without recent hospitalization; and 60 healthy Young Controls (20-35 years). Using flow cytometry, we assessed basal NF-κB phosphorylation (pNF-κB p65/RelA; Ser529) and induction of pNF-κB following stimulation with LPS or TNF-α in monocytes. We assessed frailty (FI-OutRef), physical and cognitive function, and plasma levels of IL-6, IL-18, TNF-α, and soluble urokinase plasminogen activator receptor. RESULTS: Patients at follow-up were frailer, had higher levels of inflammatory markers and decreased physical and cognitive function than Older Controls. Patients at follow-up had higher basal pNF-κB levels than Older Controls (median fluorescence intensity (MFI): 125, IQR: 105-153 vs. MFI: 80, IQR: 71-90, p < 0.0001), and reduced pNF-κB induction in response to LPS (mean pNF-κB MFI fold change calculated as the log10 ratio of LPS-stimulation to the PBS-control: 0.10, 95% CI: 0.08 to 0.12 vs. 0.13, 95% CI: 0.10 to 0.15, p = 0.05) and TNF-α stimulation (0.02, 95% CI: - 0.00 to 0.05 vs. 0.10, 95% CI: 0.08 to 0.12, p < 0.0001). Older Controls had higher levels of inflammatory markers than Young Controls, but basal pNF-κB MFI did not differ between Older and Young Controls (MFI: 81, IQR: 70-86; p = 0.72). Older Controls had reduced pNF-κB induction in response to LPS and TNF-α compared to Young Controls (LPS: 0.40, 95% CI: 0.35 to 0.44, p < 0.0001; and TNF-α: 0.33, 95% CI: 0.27 to 0.40, p < 0.0001). In Older Controls, basal pNF-κB MFI was associated with FI-OutRef (p = 0.02). CONCLUSIONS: Increased basal pNF-κB activity in monocytes could be involved in the processes of frailty and accelerated aging. Furthermore, we show that monocyte NF-κB activation upon stimulation was impaired in frail older adults, which could result in reduced immune responses and vaccine effectiveness.

Effects of a highly controlled carbohydrate-reduced high-protein diet on markers of oxidatively generated nucleic acid modifications and inflammation in weight stable participants with type 2 diabetes; a randomized controlled trial.

Carbohydrate-restricted diets are increasingly recognized as options for dietary management of type 2 diabetes mellitus (T2DM). We investigated the effects of a carbohydrate-reduced high-protein (CRHP) and a conventional diabetes (CD) diet on oxidative stress and inflammation in weight stable individuals with T2DM. We hypothesized that the CRHP diet would improve markers of oxidatively generated RNA and DNA modifications as well as inflammatory parameters. Thirty participants with T2DM were randomized to 6 weeks of CRHP or CD dietary treatment (30/50 energy percentage (E%) carbohydrate, 30/17E% protein, 40/33E% fat), followed by a cross-over to the opposite diet for a subsequent 6-week period. All meals were provided during the study and body weight was controlled. Diurnal urine samples were collected after 4 weeks on each diet and oxidatively generated RNA and DNA modifications were measured as 8-oxo-7,8-dihydroguanosine (8-oxoGuo) and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), respectively. Fasting concentrations of soluble urokinase plasminogen activator receptor, high-sensitivity C-reactive protein, tumor necrosis factor alpha and interleukin-6 were measured before and after 6 weeks of interventions. Compared with the CD diet, the CRHP diet increased 24-hour urinary excretion of 8-oxoGuo by 9.3% (38.6 ± 12.6 vs. 35.3 ± 11.0 nmol/24 h, p = .03), whereas 8-oxodG did not differ between diets (24.0 ± 9.5 vs. 24.8 ± 11.1 nmol/24 h, p = .17). Changes in plasma inflammatory parameters did not differ between CRHP and CD diets, all p ≥ .2. The clinical implications of increased RNA oxidation following a CRHP diet as well as long-term effects of carbohydrate-restriction on markers of oxidatively generated nucleic acid modifications should be a field of future study.