A characterization of patients with low soluble urokinase plasminogen activator receptor who died within 90 days of hospital discharge.

Soluble urokinase plasminogen activator receptor (suPAR) is a marker of systemic chronic inflammation. Elevated suPAR levels are associated with adverse clinical outcomes, but a small subset of patients with low suPAR also experience poor outcomes. Therefore, we aimed to characterize patients presenting to the emergency department with low suPAR (<3 ng/mL) who died within 90 days after discharge in a registry-based study. Compared to patients with low suPAR who survived (n = 15 122), those who died within 90 days (n = 87) had higher age (75.4 years), higher medication use (7.0; 71.3% with polypharmacy) and more blood tests outside reference intervals (5.0) (including C-reactive protein, neutrophils and albumin), and the most common diagnoses were chronic pulmonary disease (27.6%), cerebrovascular disease (18.4%) and dementia (11.5%). Patients with low suPAR were more morbid than what was reflected by suPAR alone. Future studies must determine which factors that contribute the most to potential algorithms when stratifying patients based on their risk of adverse clinical outcomes. These data indicate that inclusion of medication data could be relevant.

Growth differentiation factor 15 (GDF15) levels are associated with malnutrition in acutely admitted older adults.

BACKGROUND AND AIMS: The aging process is often accompanied by high risk of malnutrition and elevated levels of growth differentiation factor 15 (GDF15). GDF15 is an increasingly recognized biomarker for regulation of metabolism, but few studies have investigated the connection between GDF15 and malnutrition in older age and how it relates to other features of aging such as decreased appetite and physical function. Therefore, we investigated the associations between GDF15 levels and nutritional status, appetite, and physical function in acutely admitted older adults. METHODS: Plasma GDF15 levels were measured using immunoassays in 302 older adults (≥65 years) admitted to the emergency department (ED). Nutritional status was evaluated with the Mini Nutritional Assessment Short-Form (MNA®-SF), appetite was evaluated with the Simplified Nutritional Appetite Questionnaire (SNAQ), and physical function was evaluated with handgrip strength (HGS), 30-s chair stand test (30s-RSS), and gait speed (GS). Associations between GDF15 and each outcome was determined by logistic regression adjusted for age, sex, and C-reactive protein (CRP). RESULTS: Each doubling in plasma GDF15 level was associated with an adjusted odds ratio (OR) (95% confidence interval) of 1.59 (1.10-2.29, P = 0.01) for risk of malnutrition compared to normal nutrition and 1.19 (0.85-1.69, P = 0.3)) for malnutrition compared to risk of malnutrition. Each doubling in GDF15 was associated with an adjusted OR of 1.63 (1.21-2.23)) for having poor appetite, 1.46 (1.07-1.99) for having low HGS, 1.74 (1.23-2.51) for having low 30s-RSS, and 1.99 (1.39-2.94) for having low GS. CONCLUSION: Among older adults admitted to the ED, higher GDF15 levels were significantly associated with malnutrition, poor appetite, and low physical function independent of age, sex, and CRP.

A registry-based study on universal screening for defective mismatch repair in colorectal cancer in Denmark highlights disparities in screening uptake and counselling referrals.

Universal screening for defective mismatch repair (dMMR) in colorectal cancer utilizes immunohistochemical staining for MLH1, MSH2, MSH6 and PSM2. Additionally, BRAF V600E mutations status and MLH1 hypermethylation should be performed to distinguish germline and somatic dMMR alterations. A decade of Danish population-based registries has been analysed regarding screening uptake, detection rate and referral to genetic counselling. MMR testing was performed in 71·8% (N = 34,664) of newly diagnosed colorectal cancers with an increasing trend to 88·8% coverage in the study's final year. The likelihood of undergoing MMR testing was reduced in males with 2% (95% CI 0·4-2·7, p = 0·008), with 4·1% in patients above age 70 years (95% CI 1·5-6·6, p = 0·003) compared in patients below age 51 years, with 16·3% in rectal cancers (95% CI 15·1-17·6, p < 0·001) and 1·4% left-sided colon cancers (95% CI 0·1-1·7, p = 0·03) compared to right-sided colon cancers. Tumour stage II and III increased the likelihood of being tested, with 3·7% for stage II (95% CI 2·2-5·6, p < 0·001) and 3·3% for stage III tumours (95% CI 1·8-4·8, p < 0·001) compared to stage I tumours, whereas the likelihood for stage IV tumours is reduced by 35·7% (95% CI 34·2-37·2, p < 0·001). Test rates significantly differed between the Danish health care regions. dMMR was identified in 15·1% (95% CI 14·8-15·6, p < 0·001) cases with somatic MMR inactivation in 6·7% of the cases. 8·3% tumours showed hereditary dMMR expression patterns, and 20·0% of those were referred to genetic counselling. Despite the high uptake rates, we found disparities between patient groups and missed opportunities for genetic diagnostics.

How do oilcloth sessions work? A realist evaluation approach to exploring ripple effects in an implementation strategy.

PURPOSE: To explore the mechanisms of the implementation strategy, "oilcloth sessions" and understand and explain the ripple effects of oilcloth sessions as a strategy to implement a new emergency department. DESIGN/METHODOLOGY/APPROACH: A qualitative design was used whereby data were collected using field notes from an ethnographic study of the oilcloth sessions and follow-up semi-structured interviews with staff, managers and key employees who participated in the oilcloth sessions. The data analysis was inspired by the realist evaluation approach of generative causality proposed by Pawson and Tilley. FINDINGS: The primary ripple effect was that the oilcloth sessions were used for different purposes than the proposed program theory, including being used as: (1) a stage, (2) a battlefield, (3) a space for imagination and (4) a strategic management tool influencing the implementation outcomes. The results bring essential knowledge that may help to explain why and how a well-defined implementation strategy has unplanned outcomes. ORIGINALITY/VALUE: Unintended outcomes of implementation strategies are an underexplored issue. This study may help implementation researchers rethink the activities required to reduce unintended negative outcomes or explore potential unplanned outcomes and, in this way, hinder or enhance outcomes, effectiveness and sustainability. Future studies within implementation research should incorporate attention to unintended outcomes to fully understand the impact of implementation strategies.

Effectiveness of a multidisciplinary and transitional nutritional intervention compared with standard care on health-related quality of life among acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition: A randomized controlled trial.

BACKGROUND & AIM: Malnutrition, risk of malnutrition, and risk factors for malnutrition are prevalent among acutely admitted medical patients aged ≥65 years and have significant health-related consequences. Consequently, we aimed to investigate the effectiveness of a multidisciplinary and transitional nutritional intervention on health-related quality of life compared with standard care. METHODS: The study was a block randomized, observer-blinded clinical trial with two parallel arms. The Intervention Group was offered a multidisciplinary transitional nutritional intervention consisting of dietary counselling and six sub-interventions targeting individually assessed risk factors for malnutrition, while the Control Group received standard care. The inclusion criteria were a Mini Nutritional Assessment Short-Form score ≤11, age ≥65 years, and an acute admittance to the Emergency Department. Outcomes were assessed on admission and 8 and 16 weeks after hospital discharge. The primary outcome was the difference between groups in change in health-related quality of life (assessed by the EuroQol-5D-5L) from baseline to 16 weeks after discharge. The secondary outcomes were difference in intake of energy and protein, well-being, muscle strength, and body weight at all timepoints. RESULTS: From October 2018 to April 2021, 130 participants were included. Sixteen weeks after discharge, 29% in the Intervention Group and 19% in the Control Group were lost to follow-up. Compliance varied between the sub-interventions targeting nutritional risk factors and was generally low after discharge, ranging from 0 to 61%. No difference was found between groups on change in health-related quality of life or on well-being, muscle strength, and body weight at any timepoint, neither using the intention-to-treat analysis nor the per-protocol analysis. The protein intake was higher in the Intervention Group during hospitalization (1.1 (Standard Deviation (SD) 0.4) vs 0.8 (SD 0.5) g/kg/day, p = 0.0092) and 8 weeks after discharge (1.2 (SD 0.5) vs 0.9 (0.4) g/kg/day, p = 0.0025). The percentual intake of calculated protein requirements (82% (SD 24) vs 61% (SD 32), p = 0.0021), but not of calculated energy requirements (89% (SD 23) vs 80% (SD 37), p = 0.2), was higher in the Intervention Group than in the Control Group during hospitalization. Additionally, the Intervention Group had a significantly higher percentual intake of calculated protein requirements (94% (SD 41) vs 74% (SD 30), p = 0.015) and calculated energy requirements (115% (SD 37) vs 94% (SD 31), p = 0.0070) 8 weeks after discharge. The intake of energy and protein was comparable between the groups 16 weeks after discharge. CONCLUSION: We found no effect of a multidisciplinary and transitional nutritional intervention for acutely admitted medical patients aged ≥65 years with malnutrition or risk of malnutrition on our primary outcome, health-related quality of life 16 weeks after discharge. Nor did the intervention affect the secondary outcomes, well-being, muscle strength, and body weight from admission to 8 or 16 weeks after discharge. However, the intervention improved energy and protein intake during hospitalization and 8 weeks after discharge. Low compliance with the intervention after discharge may have compromised the effect of the intervention. The study is registered at ClinicalTrials.gov (identifier: NCT03741283).

Correction: Longitudinal models for the progression of disease portfolios in a nationwide chronic heart disease population.

[This corrects the article DOI: 10.1371/journal.pone.0284496.].

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".

Development and validation of prognostic machine learning models for short- and long-term mortality among acutely admitted patients based on blood tests.

Several scores predicting mortality at the emergency department have been developed. However, all with shortcomings either simple and applicable in a clinical setting, with poor performance, or advanced, with high performance, but clinically difficult to implement. This study aimed to explore if machine learning algorithms could predict all-cause short- and long-term mortality based on the routine blood test collected at admission. METHODS: We analyzed data from a retrospective cohort study, including patients > 18 years admitted to the Emergency Department (ED) of Copenhagen University Hospital Hvidovre, Denmark between November 2013 and March 2017. The primary outcomes were 3-, 10-, 30-, and 365-day mortality after admission. PyCaret, an automated machine learning library, was used to evaluate the predictive performance of fifteen machine learning algorithms using the area under the receiver operating characteristic curve (AUC). RESULTS: Data from 48,841 admissions were analyzed, of these 34,190 (70%) were randomly divided into training data, and 14,651 (30%) were in test data. Eight machine learning algorithms achieved very good to excellent results of AUC on test data in a of range 0.85-0.93. In prediction of short-term mortality, lactate dehydrogenase (LDH), leukocyte counts and differentials, Blood urea nitrogen (BUN) and mean corpuscular hemoglobin concentration (MCHC) were the best predictors, whereas prediction of long-term mortality was favored by age, LDH, soluble urokinase plasminogen activator receptor (suPAR), albumin, and blood urea nitrogen (BUN). CONCLUSION: The findings suggest that measures of biomarkers taken from one blood sample during admission to the ED can identify patients at high risk of short-and long-term mortality following emergency admissions.

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.

Associations between alcohol intake and hospital contacts due to alcohol and unintentional injuries in 71,025 Danish adolescents - a prospective cohort study.

Background: Alcohol is a leading risk factor to adolescent health. However, it is unclear how associations between alcohol intake and injuries are shaped. We investigated the dose-response relationship between alcohol intake and risk of hospital contacts due to alcohol and unintentional injuries in adolescents. Methods: We conducted a prospective cohort study including 71,025 Danish students aged 15-24 years, followed up for five years from 2014 to 2019. The main outcome measures were hospital contacts due to alcohol and unintentional injuries (all injuries and head injuries), obtained from hospital registers. Findings: Approximately 90% of males and females reported drinking alcohol, and the median intake among those was 11 drinks/week in males and 8 drinks/week in females. During five years of follow-up, 1.3% had an alcohol-attributable hospital contact, the majority of which were due to acute intoxication (70%). Alcohol-attributable hospital contacts were equally frequent in males and females and between age groups (15-17-year-olds vs 18-24-year-olds). Compared with never drinking, the adjusted incidence rate ratios for weekly intake of <7, 7-13, 14-20, 21-27, and >27 drinks/week were 1.70 (95% confidence interval 1.23-2.34), 1.77 (1.27-2.46), 1.91 (1.35-2.70), 2.34 (1.59-3.46), and 3.25 (2.27-4.64) for having an alcohol-attributable hospital contact within five years of follow-up. Restricting follow-up to one year more than doubled risk estimates. During the five years of follow-up, 27% incurred an unintentional injury. The most frequent types of injury were to the wrist or hand (27.6%), ankle or foot (25.2%), or head (12.4%). Injuries were more frequent among males (first-time incidence rate 110 per 1000 person-years) compared to females (82 per 1000 person-years), with no differences between age groups. Compared with never drinking, the adjusted incidence rate ratios for weekly intake of <7, 7-13, 14-20, 21-27, and >27 drinks were 1.09 (1.03-1.15), 1.14 (1.07-1.20), 1.25 (1.17-1.33), 1.38 (1.28-1.49), and 1.58 (1.47-1.69) for having a hospital contact for any type of unintentional injury within five years of follow-up. Results for the one-year follow-up period were comparable. Separate analysis for head injuries showed similar results as the analysis on all injuries. Results were generally similar in males and females. Interpretation: Adolescents' drinking is associated with a higher risk of acute harm in terms of hospital contacts due to alcohol and unintentional injuries in a dose-response relationship. Thus, increased risk was apparent in those with low alcohol intake, suggesting a need for awareness of and initiatives to prevent youth drinking. Furthermore, initiatives should include a strengthened focus on people younger than 18 years. Funding: This study was funded by the Tryg Foundation (ID: 153539) and The Helse Foundation (21-B-0359).

Soluble Urokinase-Type Plasminogen Activator Receptor in Comatose Survivors After Out-of-Hospital Cardiac Arrest Treated with Targeted Temperature Management.

Exposure to whole-body ischemia/reperfusion after out-of-hospital cardiac arrest (OHCA) triggers a systemic inflammatory response where soluble urokinase plasminogen activator receptor (suPAR) is released. This study investigated serial levels of suPAR in differentiated target temperature management and the associations with mortality and 6-month neurological outcome. This is a single-center substudy of the randomized Targeted Temperature Management (TTM) for 24-hour versus 48-hour trial. In this analysis, we included 82 patients and measured serial levels of suPAR at 24, 48, and 72 hours after achievement of target temperature (32-34°C). We assessed all-cause mortality and neurological function evaluated by the Cerebral Performance Categories (CPC) at 6 months after OHCA. Levels of suPAR between TTH groups were evaluated in repeated measures mixed models. Mortality was assessed by the Kaplan-Meier method and serial measurements of suPAR (log2 transformed) were investigated by Cox proportional-hazards models. Good neurological outcome at 6 months was assessed by logistic regression analyses. Levels of suPAR were significantly different between TTH groups (pinteraction = 0.04) with the highest difference at 48 hours, 4.7 ng/mL (95% CI: 4.1-5.4 ng/mL) in the TTH24 group compared to 2.8 ng/mL (95% CI: 2.2-3.5 ng/mL) in the TTH48 group, p < 0.0001. Levels of suPAR above the median value were significantly associated with increased all-cause mortality at any time point (plog-rank<0.05). The interaction of suPAR levels and TTH group was not significant (pinteraction = NS). A twofold increase in levels of suPAR was significantly associated with a decreased odds ratio of a good neurological outcome in both unadjusted and adjusted analyses without interaction of TTH group (pinteraction = NS). Prolonged TTM of 48 hours versus 24 hours was associated with lower levels of suPAR. High levels of suPAR were associated with increased mortality and lower odds for good neurological outcome at 6 months with no significant interaction of TTH group.

Acceptability Among Frontline Staff Toward Distributing an Anonymous Alcohol Survey in Emergency Departments: A Mixed Methods Study.

ABSTRACT: Emergency departments (EDs) serve as the front line when patients encounter the hospital system. Limited data are available of patients' alcohol habits collected during Danish ED visits, and no studies have, to our knowledge, examined frontline staffs' (registered nurses and medical secretaries) acceptability to deliver anonymous alcohol surveys to patients. We aimed at examining the proportion of survey respondents and the prevalence of patients' alcohol habits and also exploring frontline staff acceptability of the distribution of an anonymous survey regarding patients' alcohol habits in EDs. Intendedly, all eligible patients ≥18 years old entering two EDs in March 2019 should receive a survey based on the Alcohol Use Disorder Identification Test. The study was an explanatory, sequential, mixed methods design, and results were analyzed with descriptive statistics and a deductive content analysis based on the theoretical framework of acceptability. In total, 15% (n = 1,305) of the total 8,679 patients in the EDs returned the survey. Qualitative analysis of interviews (n = 31) with staff showed that they had been reluctant to distribute the survey primarily because of ethical concerns of anonymity, freedom of choice, and being nonjudgmental toward patients. Hence, patients with no obvious alcohol problems were more likely to receive the survey. Still, we found that 23% of the respondents had an Alcohol Use Disorder Identification Test score ≥ 8. Results indicate that frontline staffs' recognition of patients' alcohol use is inadequate, and findings show a low degree of acceptability among staff to deliver an anonymous survey, which is in line with earlier described barriers toward screening activities in EDs.

Alcohol Intake and Academic Performance and Dropout in High School: A Prospective Cohort Study in 65,233 Adolescents.

PURPOSE: During the teenage years, many adolescents start drinking alcohol, and binge drinking is prevalent. We investigated the relationship between alcohol intake and academic performance. METHODS: We conducted a longitudinal cohort study by combining data from the Danish National Youth Study on 65,233 high school students aged 15-20 years, with information on dropout and grade point average. We assessed associations between alcohol intake and academic performance using multilevel Poisson regression and linear regression, accounting for dependency between students from the same school and class. RESULTS: The average alcohol intake was 10 drinks per week, and 43.6% engaged in binge drinking 3+ times per month. During follow-up, 9.8% of the boys and 6.7% of the girls dropped out. The incidence rate ratio was higher in never drinkers, frequent binge drinkers, and those with a high weekly alcohol intake as compared to those with a low intake. For example, the incidence rate ratio was 1.47 (95% confidence level: 1.24, 1.76) in girls who drank 21-27 drinks per week and 1.29 (95% confidence level: 1.13, 1.48) in girls who never drank as compared to those who drank <7 drinks per week. Alcohol associated with a lower grade point average over the entire span of intake in a dose-dependent manner, and similarly so in boys and girls. Findings were consistent in strata of socioeconomy and individual academic ambition. DISCUSSION: Alcohol intake has implications for academic performance and poses a threat for the prospects of the individual as well as society. Policies and interventions aimed at lowering the intake among high school students are warranted.

Biomarkers and the post-thrombotic syndrome: A systematic review of biomarkers associated with the occurrence of the post-thrombotic syndrome after lower extremity deep venous thrombosis.

INTRODUCTION: Post-thrombotic syndrome (PTS) is a frequent chronic complication of deep venous thrombosis (DVT). Biomarkers are potentially valuable clinical tools for handling PTS. The purpose of this review was to examine which biomarkers are associated with the development of PTS in adults with lower extremity DVT. METHODS: We performed a systematic review of all English language prospective studies of biomarkers and PTS published in PubMed and EMBASE. Studies were included if diagnosing DVT by diagnostic imaging and assessing PTS by clinical scales, for example, the Villalta scale. Biomarkers of thrombophilia and pathological clot properties were not assessed. Data was reported qualitatively. RESULTS: 15 prospective studies were included. Studies varied widely in study design and methods of data analysis. Forty-six different biomarkers were examined, with seven being measured in two or more studies. The most frequently studied biomarkers were D-dimer, CRP, and IL-6. Associations between PTS and D-dimer were predominantly significant, while results on CRP and IL-6 were inconsistent. ICAM-1 was consistently associated with PTS in all studies and at all timepoints. IL-10 was significantly related to PTS development in the largest study and at all time points. Adiponectin, tPA, HRG and TAFI, MMP-1 and -8, and TIMP-1 and -2 were significantly associated with PTS in single studies. CONCLUSION: (1) Further research on biomarkers and PTS is clearly warranted. (2) Significant differences in study designs made it difficult to draw reliable conclusions regarding individual biomarkers. We suggest the implementation of a standardized framework for the study of biomarkers and PTS, to make comparison of future studies more feasible. (3) D-dimer, ICAM-1, IL-10, MMP-1 and 8, TIMP-1, TIMP-2, and adiponectin are clinical biomarkers of particular interest to include in future studies of PTS. Large scale systemic quantitative proteomic analyses of DVT patients could help identify novel biomarkers of interest in PTS-patients.

Acceptability of restrictions in the COVID-19 pandemic: a population-based survey in Denmark and Sweden.

Introduction: Denmark and Sweden initially adopted different responses to the COVID-19 pandemic although the two countries share many characteristics. Denmark responded swiftly with many mandatory restrictions. In contrast, Sweden relied on voluntary restrictions and a more "relaxed" response during the first wave of the pandemic. However, increased rates of COVID-19 cases led to a new approach that involved many more mandatory restrictions, thus making Sweden's response similar to Denmark's in the second wave of the pandemic. Aim: The aim was to investigate and compare the extent to which the populations in Denmark and Sweden considered the COVID-19 restrictions to be acceptable during the first two waves of the pandemic. The study also aimed to identify the characteristics of those who were least accepting of the restrictions in the two countries. Materials and methods: Cross-sectional surveys were conducted in Denmark and Sweden in 2021. The study population was sampled from nationally representative web panels in the two countries, consisting of 2,619 individuals from Denmark and 2,633 from Sweden. The questionnaire captured key socio-demographic characteristics. Acceptability was operationalized based on a theoretical framework consisting of seven constructs and one overarching construct. Results: The respondents' age and gender patterns were similar in the two countries. The proportion of respondents in Denmark who agreed with the statements ("agree" alternative) that captured various acceptability constructs was generally higher for the first wave than the second wave of the pandemic. The opposite pattern was seen for Sweden. In Denmark, 66% in the first wave and 50% in the second wave were accepting of the restrictions. The corresponding figures for Sweden was 42% (first wave) and 47% (second wave). Low acceptance of the restrictions, defined as the 25% with the lowest total score on the seven acceptability statements, was associated with younger age, male gender and lower education levels. Conclusion: Respondents in Sweden were more accepting of the restrictions in the second wave, when the country used many mandatory restrictions. In contrast, respondents in Denmark were more accepting of the restrictions in the first wave than in the second wave, implying an increased weariness to comply with the restrictions over time. There were considerable socio-demographic differences between those who expressed low acceptance of the restrictions and the others in both countries, suggesting the importance of tailoring communication about the pandemic to different segments of the population.

Socioeconomic inequalities in alcohol-related harm in adolescents: a prospective cohort study of 68,299 Danish 15-19-year-olds.

Background: Evidence shows that similar levels of alcohol consumption lead to greater harm in adults with low socioeconomic position (SEP) compared to high SEP. We investigated if SEP is associated with alcohol-related hospital contacts in adolescents, and whether differences in risk can be explained by differences in levels of alcohol consumption, drinking pattern, and substance use. Methods: This is a prospective cohort study of 68,299 participants aged 15-19 years old from the Danish National Youth Cohort 2014. SEP was operationalised as parent educational level, family income and perceived financial strain in the family. Data were linked to national registers and participants were followed up for five years from 2014 to 2019. Outcomes were hospital contacts due to alcohol. Multilevel Poisson regression was used to estimate incidence rates (IR) and incidence rate ratios (IRR). Findings: During 280,010 person years of follow-up, 872 participants had an alcohol-attributable hospital contact; intoxications (n = 778, 89%) were the most common diagnosis. Low as compared to high SEP was associated with higher IRR of alcohol-attributable hospital contacts for all three SEP measures. The adjusted IRR of harm was 1.73 (95% CI: 1.29-2.33) for elementary school as the highest parent education compared to longer parent education and 1.57 (95% CI: 1.30-1.89) for family financial strain compared to those without financial strain. Adjustment for weekly alcohol intake, drinking pattern and substance use did not substantially change results. Cubic spline analysis of the association between family income and alcohol-attributable hospital contacts revealed a dose-response relationship with decreasing risk of alcohol-related harm with higher income. Interpretation: Our findings suggested that alcohol-related harm is more common in socioeconomically disadvantaged adolescents despite similar levels of alcohol consumption, regardless of differences in drinking pattern or substance use. Future preventive strategies should prioritise young adolescents, including those who are most disadvantaged. Funding: Tryg Foundation (ID: 153539).

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.

Mismatch repair deficiency testing in Lynch syndrome-associated urothelial tumors.

Introduction: Lynch syndrome-associated cancer develops due to germline pathogenic variants in one of the mismatch repair (MMR) genes, MLH1, MSH2, MSH6 or PMS2. Somatic second hits in tumors cause MMR deficiency, testing for which is used to screen for Lynch syndrome in colorectal cancer and to guide selection for immunotherapy. Both MMR protein immunohistochemistry and microsatellite instability (MSI) analysis can be used. However, concordance between methods can vary for different tumor types. Therefore, we aimed to compare methods of MMR deficiency testing in Lynch syndrome-associated urothelial cancers. Methods: Ninety-seven urothelial (61 upper tract and 28 bladder) tumors diagnosed from 1980 to 2017 in carriers of Lynch syndrome-associated pathogenic MMR variants and their first-degree relatives (FDR) were analyzed by MMR protein immunohistochemistry, the MSI Analysis System v1.2 (Promega), and an amplicon sequencing-based MSI assay. Two sets of MSI markers were used in sequencing-based MSI analysis: a panel of 24 and 54 markers developed for colorectal cancer and blood MSI analysis, respectively. Results: Among the 97 urothelial tumors, 86 (88.7%) showed immunohistochemical MMR loss and 68 were successfully analyzed by the Promega MSI assay, of which 48 (70.6%) were MSI-high and 20 (29.4%) were MSI-low/microsatellite stable. Seventy-two samples had sufficient DNA for the sequencing-based MSI assay, of which 55 (76.4%) and 61 (84.7%) scored as MSI-high using the 24-marker and 54-marker panels, respectively. The concordance between the MSI assays and immunohistochemistry was 70.6% (p = 0.003), 87.5% (p = 0.039), and 90.3% (p = 1.00) for the Promega assay, the 24-marker assay, and the 54-marker assay, respectively. Of the 11 tumors with retained MMR protein expression, four were MSI-low/MSI-high or MSI-high by the Promega assay or one of the sequencing-based assays. Conclusion: Our results show that Lynch syndrome-associated urothelial cancers frequently had loss of MMR protein expression. The Promega MSI assay was significantly less sensitive, but the 54-marker sequencing-based MSI analysis showed no significant difference compared to immunohistochemistry. Data from this study alongside previous studies, suggest that universal MMR deficiency testing of newly diagnosed urothelial cancers, using immunohistochemistry and/or sequencing-based MSI analysis of sensitive markers, offer a potentially useful approach to identification of Lynch syndrome cases.