How nurses use National Early Warning Score and Individual Early Warning Score to support their patient risk assessment practice: A fieldwork study.

AIM: To explore and describe how the National Early Warning Score (NEWS) and Individual Early Warning Score (I-EWS) are used and how they support nurses' patient risk assessment practice. DESIGN: A qualitative observational fieldwork study drawing on ethnographical principles was performed in six hospitals in two regions of Denmark in 2019. METHODS: Data were generated from participant observations and informal interviews with 32 nurses across 15 different wards in the hospitals. A total of 180 h of participant observation was performed. The observations lasted between 1.5 and 8 h and were conducted during day or evening shifts. RESULTS: NEWS and I-EWS supported nurses' observations of patients, providing useful knowledge for planning patient care, and prompting critical thinking. However, the risk assessment task was sometimes delegated to less experienced staff members, such as nursing students and healthcare assistants. The Early Warning Score (EWS) systems were often adapted by nurses according to contextual aspects, such as the culture of the speciality in which the nurses worked and their levels of competency. In some situations, I-EWS had the effect of enhancing nurse autonomy and responsibility for decision-making in relation to patient care. CONCLUSIONS: EWS systems support nurses' patient risk assessment practice, providing useful information. I-EWS makes it easier to factor the heterogeneity of patients and the clinical situation into the risk assessments. The delegation of risk assessment to other, less experienced staff members pose a risk to patient safety, which needs to be addressed in the ongoing debate regarding the shortage of nurses. IMPACT: The findings of this study can help ward nurses, hospital managers and policymakers to develop and improve strategies for improved person-centred nursing care.

SARS-CoV-2 antibody prevalence among homeless people and shelter workers in Denmark: a nationwide cross-sectional study.

BACKGROUND: People experiencing homelessness (PEH) and associated shelter workers may be at higher risk of infection with "Severe acute respiratory syndrome coronavirus 2" (SARS-CoV-2). The aim of this study was to determine the prevalence of SARS-CoV-2 among PEH and shelter workers in Denmark. DESIGN AND METHODS: In November 2020, we conducted a nationwide cross-sectional seroprevalence study among PEH and shelter workers at 21 recruitment sites in Denmark. The assessment included a point-of-care test for antibodies against SARS-CoV-2, followed by a questionnaire. The seroprevalence was compared to that of geographically matched blood donors considered as a proxy for the background population, tested using a total Ig ELISA assay. RESULTS: We included 827 participants in the study, of whom 819 provided their SARS-CoV-2 antibody results. Of those, 628 were PEH (median age 50.8 (IQR 40.9-59.1) years, 35.5% female) and 191 were shelter workers (median age 46.6 (IQR 36.1-55.0) years and 74.5% female). The overall seroprevalence was 6.7% and was similar among PEH and shelter workers (6.8% vs 6.3%, p = 0.87); and 12.2% among all participants who engaged in sex work. The overall participant seroprevalence was significantly higher than that of the background population (2.9%, p < 0.001). When combining all participants who reported sex work or were recruited at designated safe havens, we found a significantly increased risk of seropositivity compared to other participants (OR 2.23, 95%CI 1.06-4.43, p = 0.02). Seropositive and seronegative participants reported a similar presence of at least one SARS-CoV-2 associated symptom (49% and 54%, respectively). INTERPRETATIONS: The prevalence of SARS-CoV-2 antibodies was more than twice as high among PEH and associated shelter workers, compared to the background population. These results could be taken into consideration when deciding in which phase PEH are eligible for a vaccine, as part of the Danish national SARS-CoV-2 vaccination program rollout. FUNDING: TrygFonden and HelseFonden.

Clinical assessment as a part of an early warning score-a Danish cluster-randomised, multicentre study of an individual early warning score.

BACKGROUND: The clinical benefit of Early Warning Scores (EWSs) is undocumented. Nursing staff's clinical assessment might improve the prediction of outcome and allow more efficient use of resources. We aimed to investigate whether the combination of clinical assessment and EWS would reduce the number of routine measurements without increasing mortality. METHODS: We did a cluster-randomised, crossover, non-inferiority study at eight hospitals in Denmark. Patients aged 18 years or older, admitted for more than 24 h were included. Admissions to paediatric or obstetric wards were excluded. The participating hospitals were randomly assigned 1:1 to start as either intervention or control with subsequent crossover. Primary outcomes were 30-day all-cause mortality (non-inferiority margin=0·5%) and average number of EWS per day per patient. The intervention was implementation of the Individual EWS (I-EWS), in which nursing staff can adjust the calculated score on the basis of their clinical assessment of the patient. I-EWS was compared with the National Early Warning Score (NEWS). The study is registered at ClinicalTrials.gov, NCT03690128 and is complete. FINDINGS: Unique admissions longer than 24 h were included from Oct 15, 2018 to Sept 30, 2019. Of 90 964 patients assessed, n=46 470 were assigned to the I-EWS group and n=44 494 to the NEWS group. Mortality within 30 days was 4·6% for the I-EWS group, and 4·3% for the NEWS group (adjusted odds ratio 1·05 [95% CI 0·99-1·12], p=0·12). In subgroup analyses I-EWS showed increased 30-day mortality for hospitals that did I-EWS in fall-winter, which was probably due to seasonality, and within patients admitted in a surgical specialty. Overall risk difference was 0·22% (95% CI -0·04 to 0·48) meaning that the non-inferiority criteria were met. The average number of scorings per patient per day was reduced from 3·14 to 3·10 (ie, a relative reduction of 0·64% [95% CI -0·16 to -1·11], p=0·0084) in the I-EWS group. INTERPRETATION: Including clinical assessment in I-EWS was feasible and overall non-inferior to the widely implemented NEWS in terms of all-cause mortality at 30 days, and the number of routine measurements was minimally reduced. However I-EWS should be used with caution in surgical patients. FUNDING: Capital Region Research Foundation, Gangsted Foundation, Candys Foundation, Herlev-Gentofte Hospital Research Foundation, Laerdal Foundation, and The Foundation of Director Boennelycke and wife.

Anti-SARS-CoV-2 Seropositivity Among Medical Students in Copenhagen.

BACKGROUND: Health care workers are at a higher risk of getting infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) than the general population. Knowledge about medical students' exposure to SARS-CoV-2 is lacking. Thus, we measured the prevalence of SARS-CoV-2 antibodies in a cohort of Danish medical students. METHODS: We invited all medical students at the University of Copenhagen (UCPH) to participate. Students underwent venous blood sampling and a questionnaire about work-life behaviors possibly associated with SARS-CoV-2 exposure and coronavirus disease 2019 (COVID-19) symptoms. Samples were analyzed for total immunoglobulin G (IgG) antibodies against SARS-CoV-2, and seropositive samples were screened for IgG, immunoglobulin M, and immunoglobulin A antibodies. We determined associations between seropositivity and clinical and social activities and self-reported symptoms. RESULTS: Between October 19 and 26, 1120 students participated in the questionnaire and 1096 were included. Of all included, 379 (34.58%) were seropositive. Seropositivity was associated with attendance at 2 parties at UCPH, on February 29 and March 6, 2020 (odds ratio [OR], 5.96; 95% CI, 4.34-8.24; P < .001). Four hundred sixty-one students (42.06%) worked with COVID-19 patients, which was significantly associated with seropositivity (OR, 1.38; 95% CI, 1.03-1.85; P = .033). The symptom most associated with seropositivity was loss of smell and/or taste (n = 183 of all, 31.35%; OR, 24.48; 95% CI, 15.49-40.60; P < .001). Bachelor's students were significantly more likely to be seropositive than Master's students (42.28% vs 16.87%; P < .001). CONCLUSIONS: Medical students have the highest reported seropositivity in the Danish health care system. In this cohort of students at UCPH, seropositivity was associated with social behavior markers and, to a lesser extent, with self-reported contact with SARS-CoV-2-infected patients.

Nurses' Experiences and Perceptions of two Early Warning Score systems to Identify Patient Deterioration-A Focus Group Study.

AIMS: To explore Registered Nurses' experiences and perceptions with National Early Warning Score and Individual Early Warning Score to identify patient deterioration. DESIGN: A qualitative exploratory design. METHODS: Six focus groups were conducted at six Danish hospitals from February to June 2019. Registered Nurses from both medical, surgical and emergency departments participated. The focus groups were analysed using content analysis. RESULTS: One theme and four categories were identified. Theme: Meaningful in identifying patient deterioration but causing frustration due to lack of flexibility. Categories: (a) Inter-professional collaboration strengthened through the use of Early Warning Score systems, (b) Enhanced professional development and communication among nurses when using Early Warning Score systems, (c) Detecting patient deterioration by integrating nurses' clinical gaze with Early Warning Score systems and (d) Modification and fear of making mistakes when using Early Warning Score systems.

Comparison of 16 Serological SARS-CoV-2 Immunoassays in 16 Clinical Laboratories.

Serological assays for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are needed to support clinical diagnosis and epidemiological investigations. Recently, assays for large-scale detection of total antibodies (Ab), immunoglobulin G (IgG), and IgM against SARS-CoV-2 antigens have been developed, but there are limited data on the diagnostic accuracy of these assays. This study was a Danish national collaboration and evaluated 15 commercial and one in-house anti-SARS-CoV-2 assays in 16 laboratories. Sensitivity was evaluated using 150 samples from individuals with asymptomatic, mild, or moderate COVID-19, nonhospitalized or hospitalized, confirmed by nucleic acid amplification tests (NAAT); samples were collected 13 to 73 days either from symptom onset or from positive NAAT (patients without symptoms). Specificity and cross-reactivity were evaluated in samples collected prior to the SARS-CoV-2 epidemic from >586 blood donors and patients with autoimmune diseases, cytomegalovirus or Epstein-Barr virus infections, and acute viral infections. A specificity of ≥99% was achieved by all total-Ab and IgG assays except one, DiaSorin Liaison XL IgG (97.2%). Sensitivities in descending order were Wantai ELISA total Ab (96.7%), CUH-NOVO in-house ELISA total Ab (96.0%), Ortho Vitros total Ab (95.3%), YHLO iFlash IgG (94.0%), Ortho Vitros IgG (93.3%), Siemens Atellica total Ab (93.2%), Roche Elecsys total Ab (92.7%), Abbott Architect IgG (90.0%), Abbott Alinity IgG (median 88.0%), DiaSorin Liaison XL IgG (median 84.6%), Siemens Vista total Ab (81.0%), Euroimmun/ELISA IgG (78.0%), and Snibe Maglumi IgG (median 78.0%). However, confidence intervals overlapped for several assays. The IgM results were variable, with the Wantai IgM ELISA showing the highest sensitivity (82.7%) and specificity (99%). The rate of seropositivity increased with time from symptom onset and symptom severity.

Effectiveness of Adding a Mask Recommendation to Other Public Health Measures to Prevent SARS-CoV-2 Infection in Danish Mask Wearers : A Randomized Controlled Trial.

BACKGROUND: Observational evidence suggests that mask wearing mitigates transmission of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). It is uncertain if this observed association arises through protection of uninfected wearers (protective effect), via reduced transmission from infected mask wearers (source control), or both. OBJECTIVE: To assess whether recommending surgical mask use outside the home reduces wearers' risk for SARS-CoV-2 infection in a setting where masks were uncommon and not among recommended public health measures. DESIGN: Randomized controlled trial (DANMASK-19 [Danish Study to Assess Face Masks for the Protection Against COVID-19 Infection]). (ClinicalTrials.gov: NCT04337541). SETTING: Denmark, April and May 2020. PARTICIPANTS: Adults spending more than 3 hours per day outside the home without occupational mask use. INTERVENTION: Encouragement to follow social distancing measures for coronavirus disease 2019, plus either no mask recommendation or a recommendation to wear a mask when outside the home among other persons together with a supply of 50 surgical masks and instructions for proper use. MEASUREMENTS: The primary outcome was SARS-CoV-2 infection in the mask wearer at 1 month by antibody testing, polymerase chain reaction (PCR), or hospital diagnosis. The secondary outcome was PCR positivity for other respiratory viruses. RESULTS: A total of 3030 participants were randomly assigned to the recommendation to wear masks, and 2994 were assigned to control; 4862 completed the study. Infection with SARS-CoV-2 occurred in 42 participants recommended masks (1.8%) and 53 control participants (2.1%). The between-group difference was -0.3 percentage point (95% CI, -1.2 to 0.4 percentage point; P = 0.38) (odds ratio, 0.82 [CI, 0.54 to 1.23]; P = 0.33). Multiple imputation accounting for loss to follow-up yielded similar results. Although the difference observed was not statistically significant, the 95% CIs are compatible with a 46% reduction to a 23% increase in infection. LIMITATION: Inconclusive results, missing data, variable adherence, patient-reported findings on home tests, no blinding, and no assessment of whether masks could decrease disease transmission from mask wearers to others. CONCLUSION: The recommendation to wear surgical masks to supplement other public health measures did not reduce the SARS-CoV-2 infection rate among wearers by more than 50% in a community with modest infection rates, some degree of social distancing, and uncommon general mask use. The data were compatible with lesser degrees of self-protection. PRIMARY FUNDING SOURCE: The Salling Foundations.

Risk of COVID-19 in health-care workers in Denmark: an observational cohort study.

BACKGROUND: Health-care workers are thought to be highly exposed to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We aimed to investigate the prevalence of antibodies against SARS-CoV-2 in health-care workers and the proportion of seroconverted health-care workers with previous symptoms of COVID-19. METHODS: In this observational cohort study, screening was offered to health-care workers in the Capital Region of Denmark, including medical, nursing, and other students who were associated with hospitals in the region. Screening included point-of-care tests for IgM and IgG antibodies against SARS-CoV-2. Test results and participant characteristics were recorded. Results were compared with findings in blood donors in the Capital Region in the study period. FINDINGS: Between April 15 and April 23, 2020, we screened 29 295 health-care workers, of whom 28 792 (98·28%) provided their test results. We identified 1163 (4·04% [95% CI 3·82-4·27]) seropositive health-care workers. Seroprevalence was higher in health-care workers than in blood donors (142 [3·04%] of 4672; risk ratio [RR] 1·33 [95% CI 1·12-1·58]; p<0·001). Seroprevalence was higher in male health-care workers (331 [5·45%] of 6077) than in female health-care workers (832 [3·66%] of 22 715; RR 1·49 [1·31-1·68]; p<0·001). Frontline health-care workers working in hospitals had a significantly higher seroprevalence (779 [4·55%] of 16 356) than health-care workers in other settings (384 [3·29%] of 11 657; RR 1·38 [1·22-1·56]; p<0·001). Health-care workers working on dedicated COVID-19 wards (95 [7·19%] of 1321) had a significantly higher seroprevalence than other frontline health-care workers working in hospitals (696 [4·35%] of 15 983; RR 1·65 [1·34-2·03]; p<0·001). 622 [53·5%] of 1163 seropositive participants reported symptoms attributable to SARS-CoV-2. Loss of taste or smell was the symptom that was most strongly associated with seropositivity (377 [32·39%] of 1164 participants with this symptom were seropositive vs 786 [2·84%] of 27 628 without this symptom; RR 11·38 [10·22-12·68]). The study is registered at ClinicalTrials.gov, NCT04346186. INTERPRETATION: The prevalence of health-care workers with antibodies against SARS-CoV-2 was low but higher than in blood donors. The risk of SARS-CoV-2 infection in health-care workers was related to exposure to infected patients. More than half of seropositive health-care workers reported symptoms attributable to COVID-19. FUNDING: Lundbeck Foundation.

Adjusting Early Warning Score by clinical assessment: a study protocol for a Danish cluster-randomised, multicentre study of an Individual Early Warning Score (I-EWS).

INTRODUCTION: Track and trigger systems (TTSs) based on vital signs are implemented in hospitals worldwide to identify patients with clinical deterioration. TTSs may provide prognostic information but do not actively include clinical assessment, and their impact on severe adverse events remain uncertain. The demand for prospective, multicentre studies to demonstrate the effectiveness of TTSs has grown the last decade. Individual Early Warning Score (I-EWS) is a newly developed TTS with an aggregated score based on vital signs that can be adjusted according to the clinical assessment of the patient. The objective is to compare I-EWS with the existing National Early Warning Score (NEWS) algorithm regarding clinical outcomes and use of resources. METHOD AND ANALYSIS: In a prospective, multicentre, cluster-randomised, crossover, non-inferiority study. Eight hospitals are randomised to use either NEWS in combination with the Capital Region of Denmark NEWS Override System (CROS) or implement I-EWS for 6.5 months, followed by a crossover. Based on their clinical assessment, the nursing staff can adjust the aggregated score with a maximum of -4 or +6 points. We expect to include 150 000 unique patients. The primary endpoint is all-cause mortality at 30 days. Coprimary endpoint is the average number of times per day a patient is NEWS/I-EWS-scored, and secondary outcomes are all-cause mortality at 48 hours and at 7 days as well as length of stay. ETHICS AND DISSEMINATION: The study was presented for the Regional Ethics committee who decided that no formal approval was needed according to Danish law (J.no. 1701733). The I-EWS study is a large prospective, randomised multicentre study that investigates the effect of integrating a clinical assessment performed by the nursing staff in a TTS, in a head-to-head comparison with the internationally used NEWS with the opportunity to use CROS. TRIAL REGISTRATION NUMBER: NCT03690128.

Case of Acute Graft Failure during Suspected Humoral Rejection with Preserved Ejection Fraction, but Severely Reduced Longitudinal Deformation Detected by 2D-Speckle Tracking.

This case displays limited utility of left ventricular ejection fraction to detect acute graft failure due to microvascular vasculopathy and suspected humoral rejection. Despite severe and progressive graft failure, clinically and by right heart catheterizations, left ventricular ejection fraction remained unchanged, indicating need of more reliable noninvasive methods for graft function surveillance. Global longitudinal strain relates to clinical heart failure, filling pressure, and cardiac index during suspected humoral rejection and microvascular dysfunction in this HTX patient. We suggest routine monitoring of graft function by global longitudinal strain as supplement to routine left ventricular ejection fraction and diastolic Doppler measurements.

The calcineurin activity profiles of cyclosporin and tacrolimus are different in stable renal transplant patients.

Cyclosporin and tacrolimus remain the cornerstone immunosuppressive drugs in organ transplantation. Dosing and monitoring these drugs is based on pharmacokinetic protocols, but measuring a pharmacodynamic parameter, calcineurin phosphatase (CaN) activity, could be a valuable supplement in determining optimal doses. Forty stable renal transplant patients were investigated three times in a 6-month period. Blood samples were drawn at 0, 1, 2, 3 and 4 h after oral intake of tacrolimus (FK) or cyclosporin at days 1 and 180. At day 90, one blood sample at trough level (FK) or C2 level (cyclosporin A, CsA) was drawn. CaN activity was determined in whole blood as the release of 32P from a phosphorylated peptide. Activity of the 32P was quantitated by liquid scintillation and results converted to Units CaN, utilizing a calibration curve with CaN. We demonstrated that calcineurin activity profiles at days 1 and 180 were the same for both drugs. Furthermore, we found that patients treated with tacrolimus or cyclosporin displayed different calcineurin activity profiles. We found that cyclosporin displayed greater calcineurin inhibition than tacrolimus. We have demonstrated that the two drugs exert significantly different effects on calcineurin activity in renal transplant patients with stable, well-functioning grafts and that tacrolimus-treated patients can maintain good, stable graft function with minimal CaN inhibition.

Validation of the calcineurin phosphatase assay.

BACKGROUND: The calcineurin inhibitors cyclosporine and tacrolimus are used as primary immunosuppressive drugs in transplant patients. Measuring calcineurin phosphatase (CaN) activity is a proposed pharmacodynamic approach to optimize dosing of these drugs. METHODS: Whole blood samples were obtained from 10 patients treated with calcineurin inhibitors and 20 healthy volunteers and frozen at -80 degrees C. CaN activity was measured by its ability to dephosphorylate a 19-amino acid peptide previously phosphorylated with [gamma-(32)P]ATP. Radioactivity was quantified by liquid scintillation, and results were converted from cpm to U of CaN. Validation of the assay included enzyme kinetics, linearity, precision (at low and normal CaN activities), analytical recovery, and limit of detection. RESULTS: The enzyme followed simple Michaelis-Menten-type kinetics: V(max) was estimated as 240 nmol (32)P x L(-1) x min(-1) and K(m) as 70 micromol/L. The assay was linear within the concentration range examined. Analytical recovery varied from 68% to 72%. The total analytical SD was 0.059 and 0.053 U of CaN for high and low CaN activity, respectively. The within-day SD for high and low activity was 0.032 and 0.039 U of CaN, respectively. The limit of detection was 0.04 U of CaN, which is far below the values measured in patients treated with CaN inhibitors. CONCLUSIONS: In addition to the pharmacokinetic monitoring applied today, the CaN assay can be used to monitor patients treated with calcineurin inhibitors, hopefully leading to prolonged graft survival.

Blood tacrolimus levels and calcineurin phosphatase activity early after renal transplantation.

The toxicity of tacrolimus (FK) despite therapeutic levels (trough) has led us to investigate its relationship with the inhibition of calcineurin (CaN) in recently transplanted renal patients. Twenty-one patients taking FK had blood drawn on day 3 and 14 at 0,1,2,3,4 and 6h. CaN activity was measured by its ability to cleave 32P from a previously radiolabeled phosphorylated 19-amino acid peptide. Radioactivity was quantitated and results were converted to units CaN. FK concentration was measured simultaneously. Maximal suppression of CaN occurred after 2h on both days. Unlike FK levels, CaN activity returned to predose levels by 6h. Comparing mean CaN activity at time 0 with each subsequent time showed statistical significance at hours 1, 2 and 3 on each day. Comparing mean FK concentrations, similarly, revealed statistical significance at all hours. Area under CaN activity curve (AUCCaN) vs. mean FK levels failed to show significance. However, comparing AUCCaN with mean CaN activity was significant throughout. CaN capacity at time 0 and 6h (day 14) resulted in the best estimate of CaN inhibition. Prior to steady-state (day 3), the best estimate occurred at 2h. No single FK concentration seemed to be a reliable indicator of CaN inhibition.