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Prostate cancer (PCa) is a major public health concern for men globally and the most commonly diagnosed cancer among men in the European Union (EU). Despite large trials suggesting benefits from early detection of PCa, risks of overdiagnosis and overtreatment are evident. In 2022, the EU Commission proposed introducing prostate-specific antigen (PSA) testing for men in an organised setting, in combination with magnetic resonance imaging (MRI) scanning as a follow-up test to minimise these risks. PRostate cancer Awareness and Initiative for Screening Europe (PRAISE-U) is a pilot study evaluating the implementation of a risk-stratified population-based approach to PCa screening in Ireland, Lithuania, Poland, and two areas in Spain (Galicia and Manresa) for feasibility, efficacy, and cost effectiveness. As per the protocol designed for the pilots, men aged 50–69 yr residing within the catchment area of the study sites will be invited to participate. Those consenting to participate will undergo PSA testing, and men with PSA >3 ng/ml will undergo risk stratification before MRI and, if necessary, after MRI before undergoing biopsy. A collaborative user board comprising health care professionals, patients, and decision-makers will be formed to provide stakeholder input throughout the study. PRAISE-U will be evaluated on three major pillars: analysis of clinical and programme outcomes, psychosocial impact, and cost effectiveness. A set of key performance indicators (KPIs) has been developed to be piloted in the PRAISE-U pilot sites. The KPIs will serve to assess the performance and outcomes of risk-stratified PCa screening at each site. A REDCap database will be used to collect and manage pseudoanonymised data from the pilot sites. Ethics approval was obtained from each pilot site. The PRAISE-U pilot implementation is expected to commence in the 3rd quarter of 2024 for 12 mo and provide valuable data on the implementation outcomes of a risk-stratified screening approach across Europe. The findings is expected to inform the development of an optimised screening strategy with an acceptable benefit to harm ratio.

Summary: Here, we present a protocol for assessing metabolic activity of bacterial populations by measuring heat flow using isothermal calorimetry. We outline the steps for preparing the different growth models of Pseudomonas aeruginosa and performing continuous metabolic activity measurements in the calScreener. We detail simple principal component analysis to differentiate between metabolic states of different populations and probabilistic logistic classification to assess resemblance to wild-type bacteria. This protocol for fine-scale metabolic measurement can aid in understanding microbial physiology.For complete details on the use and execution of this protocol, please refer to Lichtenberg et al. (2022).1 : Publisher’s note: Undertaking any experimental protocol requires adherence to local institutional guidelines for laboratory safety and ethics.

Summary: Enterovirus A71 (EV-A71) causes hand, foot, and mouth disease outbreaks with neurological complications and deaths. We previously isolated an EV-A71 variant in the stool, cerebrospinal fluid, and blood of an immunocompromised patient who had a leucine-to-arginine substitution on the VP1 capsid protein, resulting in increased heparin sulfate binding. We show here that this mutation increases the virus’s pathogenicity in orally infected mice with depleted B cells, which mimics the patient’s immune status, and increases susceptibility to neutralizing antibodies. However, a double mutant with even greater heparin sulfate affinity is not pathogenic, suggesting that increased heparin sulfate affinity may trap virions in peripheral tissues and reduce neurovirulence. This research sheds light on the increased pathogenicity of variant with heparin sulfate (HS)-binding ability in individuals with decreased B cell immunity.

Summary: Background: Niemann-Pick disease type C (NPC) is a rare prematurely fatal lysosomal lipid storage disease with limited therapeutic options. The prominent neuropathological hallmarks include hypomyelination and cerebellar atrophy. We previously demonstrated the efficacy of recombinant human heat shock protein 70 (rhHSP70) in preclinical models of the disease. It reduced glycosphingolipid levels in the central nervous system (CNS), improving cerebellar myelination and improved behavioural phenotypes in Npc1nih (Npc1−/−) mice. Furthermore, treatment with arimoclomol, a well-characterised HSP amplifier, attenuated lysosomal storage in NPC patient fibroblasts and improved neurological symptoms in Npc1−/− mice. Taken together, these findings prompted the investigation of the effects of HSP amplification on CNS myelination. Methods: We administered bimoclomol daily or rhHSP70 6 times per week to Npc1−/− (BALB/cNctr-Npc1m1N/J, also named Npc1nih) mice by intraperitoneal injection from P7 through P34 to investigate the impact on CNS myelination. The Src-kinase inhibitor saracatinib was administered with/without bimoclomol twice daily to explore the contribution of Fyn kinase to bimoclomol's effects. Findings: Treatment with either bimoclomol or rhHSP70 improved myelination and increased the numbers of mature oligodendrocytes (OLs) as well as the ratio of active-to-inactive forms of phosphorylated Fyn kinase in the cerebellum of Npc1−/− mice. Additionally, treatment with bimoclomol preserved cerebellar weight, an effect that was abrogated when co-administered with saracatinib, an inhibitor of Fyn kinase. Bimoclomol-treated mice also exhibited increased numbers of immature OLs within the cortex. Interpretation: These data increase our understanding of the mechanisms by which HSP70 regulates myelination and provide further support for the clinical development of HSP-amplifying therapies in the treatment of NPC. Funding: Funding for this study was provided by Orphazyme A/S (Copenhagen, Denmark) and a Pathfinder Award from The Wellcome Trust.

Peer support is increasingly an integrated part of formalized mental health care, in which individuals with lived experiences of mental illness are employed as peer workers (PWs) to provide support to service users. While the supportive nature of peer support has been widely recognized in the mental health system, little is known about the everyday emotional management that such work requires. To address this gap, we examine the emotional mechanisms of mutuality embedded in peer support. Through an interactionist analysis of ethnographic data on peer work collected in three Danish mental health centers, we conceptualize the sense of mutuality as enactment, and analyze PWs’ emotion management in interactions with service users. Our analysis shows that PWs’ enactment of mutuality works on a continuum of loose and tight emotion management with different objects, strategies and levels of intensity. These findings show that the feeling of mutuality is an interactional accomplishment emerging through an interplay between PWs’ mutuality enactment and applied strategies of emotion management. This study highlights how PWs’ enactment of mutuality changes the mental health encounter, and contributes to the general discussion on the professionalization of peer work and experiential knowledge in medical institutions.

Objective: Heat Shock Proteins (HSPs) maintain cellular homeostasis under stress. HSP70 represents a major stress-inducible family member and has been identified as a druggable target in inherited cholesterol-sphingolipid storage diseases. We investigated if HSP70 modulates cholesterol accumulation in more common conditions related to atherogenesis. Methods: We studied the effects of recombinant HSP70 in cholesterol-laden primary macrophages from human blood donors and pharmacological HSP70 upregulation in high-cholesterol diet fed zebrafish. Results: Recombinant HSP70 facilitated cholesterol removal from primary human macrophage foam cells. RNA sequencing revealed that HSP70 induced a robust transcriptional re-programming, including upregulation of key targets of liver X receptors (LXR), master regulators of whole-body cholesterol removal. Mechanistically, HSP70 interacted with the macrophage LXRalpha promoter, increased LXRalpha and its target mRNAs, and led to elevated levels of key proteins facilitating cholesterol efflux, including ATP-binding cassette transporters A1 and G1. Pharmacological augmentation of endogenous HSP70 in high-cholesterol diet fed zebrafish activated LXR and its target mRNAs and reduced cholesterol storage at the whole organism level. Conclusion: These data demonstrate that HSP70 exerts a cholesterol lowering effect in primary human cells and animals and uncover a nuclear action of HSP70 in mediating cross-talk between HSP and LXR transcriptional regulation. Keywords: Cholesterol metabolism, Liver X receptor, Heat shock protein, Human macrophages, Transcriptional regulation

Background: Hepatitis E virus (HEV) genotype 3 is endemic in Europe, and the infection is mostly subclinical or acute and self-limiting. However, persistent infection is described among HIV-infected individuals. The prevalence of antibodies against HEV (anti-HEV) among HIV-infected persons varies geographically and is unknown in Denmark. Rates of co-infection with HEV among HIV-infected individuals in Denmark over three decades, from the early 1980s to 2013, were investigated. Methods: A total of 2506 HIV-infected persons were investigated from two cohorts followed at Hvidovre Hospital, Denmark. Blood samples were tested retrospectively for anti-HEV, including samples from 2216 persons who were enrolled in a prospective clinical cohort and followed between 1995 and 2013, as well as samples from 290 persons from a historical cohort followed between 1980 and 1994. For anti-HEV seroconverting individuals, serial samples were tested for HEV RNA. Factors associated with anti-HEV status were explored using multivariable logistic regression analysis. Results: The overall HEV seroprevalence rates were stable during the 1980s, 1990s, and 2000–2013 (23.1%, 22.9%, and 23.7%, respectively). In all decades, rates of anti-HEV increased with older age, and anti-HEV seropositivity was associated with older generations, HIV risk group, and geographic origin. Persistent HEV infection was not detected in any of 57 individuals with anti-HEV seroconversion. Conclusions: HEV seroprevalence rates were stable in HIV-infected individuals from the early 1980s to 2013. Rates increased with age. No evidence of persistent HEV infection was detected. Infection with HEV is frequent, but persistent HEV infection is rare among HIV-infected individuals. Keywords: Hepatitis E virus, HEV, Prevalence, HIV, Persistent HEV RNA

Aims: The primary aim of this study is to investigate whether out-of-hospital cardiac arrest (OHCA) survivors have lower levels of self-reported physical activity compared to a non-cardiac arrest (CA) control group who had acute myocardial infarction (MI). Additional aims are to explore potential predictors of physical inactivity (older age, female gender, problems with general physical function, global cognition, mental processing speed/attention, anxiety symptoms, depression symptoms, kinesiophobia, fatigue), and to investigate the relationship between self-reported and objectively measured physical activity among OHCA-survivors. Methods: The Targeted Hypothermia versus Targeted Normothermia after Out-of-Hospital Cardiac Arrest trial (TTM2-trial) collects information regarding age, gender, self-reported physical activity, general physical function, global cognition and mental processing speed/attention at 6 months after OHCA. In this TTM2-trial cross-sectional prospective sub-study, participants at selected sites are invited to an additional follow-up meeting within 4 weeks from the main study follow-up. At this meeting, information regarding anxiety symptoms, depression symptoms, kinesiophobia and fatigue is collected. The OHCA-survivors are then provided with an objective measure of physical activity, a hip-placed accelerometer, to wear for one week, together with a training diary. At the end of the week, participants are asked to once again answer two self-reported questions regarding physical activity for that specific week. MI-controls attend a single follow-up meeting and perform the same assessments as the OHCA-survivors, except from wearing the accelerometer. We aim to include 110 OHCA-survivors and 110 MI-controls in Sweden, Denmark and the United Kingdom. Conclusion: The results from this sub-study will provide novel information about physical activity among OHCA-survivors. Trial registration: Registered at ClinicalTrials.gov: NCT03543332, date of registration June 1, 2018

Objective: To describe the clinical trial “Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest” (VAM-IHCA). Methods: The VAM-IHCA trial is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. The study drugs consist of 40 mg methylprednisolone and 20 IU of vasopressin given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).The primary outcome is return of spontaneous circulation and key secondary outcomes include survival and survival with a favorable neurological outcome at 30 days. 492 patients will be enrolled. The trial was registered at the EU Clinical Trials Register (EudraCT Number: 2017-004773-13) on Jan. 25, 2018 and ClinicalTrials.gov (Identifier: NCT03640949) on Aug. 21, 2018. Results: The trial started in October 2018 and the last patient is anticipated to be included in January 2021. The primary results will be reported after 3-months follow-up and are, therefore, anticipated in mid-2021. Conclusion: The current article describes the design of the VAM-IHCA trial. The results from this trial will help clarify whether the combination of vasopressin and methylprednisolone when administered during in-hospital cardiac arrest improves outcomes.

Ingestion of foreign bodies is most common in small children and older children with developmental disabilities and is not always clinically obvious. We report a case of a 4 years and 8 months old boy with infantile autism and mental retardation who underwent a magnetic resonance imaging (MRI) scan of the brain with unrecognized 15 pieces of magnetic toys located in the abdomen. The MRI revealed severe artefacts and the presence of the magnets was confirmed by an abdominal plain X-ray. At operation there were no abdominal lesions that could be ascribed to the MRI. A total of 15 magnetic toys were removed. A screening of foreign bodies with a plain X-ray of the abdomen and chest may be advised in disabled children with a history of recent abdominal pain prior to MRI.

There are multiple reasons for not participating in colorectal cancer screening, but the role of health literacy in screening uptake is not well understood.The aims of this study were to determine the association between health literacy and colorectal cancer screening uptake and to explore whether socioeconomic and -demographic characteristics and worry and attitude variables modify this association.In a cross-sectional study, 10,030 53–74-year-old randomly selected citizens resident in Central Denmark Region received a questionnaire assessing health literacy using the European Health Literacy Survey Short Scale 16-item. Data on colorectal cancer screening uptake were obtained from the Danish Colorectal Cancer Screening database, and socioeconomic and -demographic data were linked from Statistics Denmark.The response rate was 71% (n = 7142). Odds ratio (OR) for uptake was 1.06 (95% confidence interval (CI): 0.96, 1.19) for problematic health literacy and 1.00 (95% CI: 0.87, 1.16) for inadequate health literacy, when using adequate health literacy as the reference value. The association was not modified by socioeconomic or -demographic characteristics, worry or attitude.No association was found between health literacy and colorectal cancer screening uptake. Future research needs to clarify which dimensions of health literacy may predict screening uptake and how it is best measured.

Background: Gaucher Disease is caused by mutations of the GBA gene which encodes the lysosomal enzyme acid beta-glucosidase (GCase). GBA mutations commonly affect GCase function by perturbing its protein homeostasis rather than its catalytic activity. Heat shock proteins are well known cytoprotective molecules with functions in protein homeostasis and lysosomal function and their manipulation has been suggested as a potential therapeutic strategy for GD. The investigational drug arimoclomol, which is in phase II/III clinical trials, is a well-characterized HSP amplifier and has been extensively clinically tested. Importantly, arimoclomol efficiently crosses the blood-brain-barrier presenting an opportunity to target the neurological manifestations of GD, which remains without a disease-modifying therapy. Methods: We used a range of biological and biochemical in vitro assays to assess the effect of arimoclomol on GCase activity in ex vivo systems of primary fibroblasts and neuronal-like cells from GD patients. Findings: We found that arimoclomol induced relevant HSPs such as ER-resident HSP70 (BiP) and enhanced the folding, maturation, activity, and correct cellular localization of mutated GCase across several genotypes including the common L444P and N370S mutations in primary cells from GD patients. These effects where recapitulated in a human neuronal model of GD obtained by differentiation of multipotent adult stem cells. Interpretation: These data demonstrate the potential of HSP-targeting therapies in GCase-deficiencies and strongly support the clinical development of arimoclomol as a potential therapeutic option for the neuronopathic forms of GD. Funding: The research was funded by Orphazyme A/S, Copenhagen, Denmark. Keywords: Gaucher disease, GBA, Heat shock response, Arimoclomol, Heat shock proteins, HSP, HSP70, Proteostasis, GCase, Lysosomes, Lysosomal storage diseases, Sphingolipidoses

Background: Colorectal cancer screening uptake is associated with knowledge, attitudes and worries about screening. People with higher levels of health literacy usually have higher screening-related knowledge, but its association with attitudes and worries is sparsely described.The aim of this study was to describe knowledge, attitudes, and worries about colorectal cancer screening among unscreened citizens, and to estimate the association between these and health literacy. Methods: In a cross-sectional study 10,030 53–74 year-old Central Denmark Region citizens received a questionnaire assessing knowledge, attitudes, worry and health literacy. Socioeconomic and –demographic data were linked from Statistics Denmark after data collection. Results: In total, 7142 (71.2%) questionnaires were completed. A good general level of knowledge was observed (4.91 and 5.13 out of 7 for men and women, respectively). Citizens tended to be positive towards screening (21.4 and 21.3 on a 4–28 range scale for men and women respectively), and showed low levels of worries (8.8 and 9.09 on a 3–15 range scale for men and women respectively). Knowledge decreased and worries increased with lower levels of health literacy. Further, attitudes tended to be more positive with higher levels of health literacy. Conclusions: In general, citizens tend to have good knowledge, positive attitudes and few worries about colorectal cancer screening. People with lower health literacy could benefit from targeted interventions that address knowledge and worries about screening to support informed decision making. Keywords: Colorectal neoplasms, Mass screening, Health literacy, Educational status, Health knowledge, attitudes, practice, Patient participation, Socioeconomic factors, Cross-sectional studies

Background: VIBATIV is a once-daily, injectable lipoglycopeptide antibiotic approved in the U.S. for the treatment of hospital-acquired and ventilator-associated bacterial pneumonia (HABP/VABP) caused by susceptible isolates of Staphylococcus aureus when alternative treatments are not suitable. In addition, VIBATIV is approved in the U.S. for the treatment of adult patients with complicated skin & skin structure infections (cSSSI) caused by susceptible isolates of Gram-positive bacteria, including Staphylococcus aureus, both methicillin-susceptible (MSSA) and methicillin-resistant (MRSA) strains. Objective: To evaluate the chemical stability of telavancin (Vibativ; Theravance Biopharma US, Inc, Northbrook, Illinois), a lipoglycopeptide antibiotic with activity against methicillin-resistant Staphylococcus aureus, in 2 types of elastomeric pumps, the Intermate Infusion System (Baxter International Inc) and the Homepump Eclipse (I-Flow Corporation). Methods: Different sizes of the Baxter (Ontario, Canada) (105 mL and 275 mL) and I-Flow (Stoughton, Massachusetts) (100 mL and 250 mL) pumps were compared with glass controls. The telavancin drug product was reconstituted and diluted to concentrations of 0.6 mg/mL and 8.0 mg/mL using either 0.9% saline, 5% dextrose in water, or sterilized water for injection (0.6 mg/mL telavancin) or saline (8.0 mg/mL telavancin) followed by Ringer’s Lactate solution. Pumps were filled and stored at 2°C to 8°C, protected from light. Aliquots from both pump types and for all telavancin reconstitution/dilution schemes and concentrations were taken over a period of 8 days and analyzed for appearance, pH, telavancin concentration and purity, and degradation products. Results: The pH of all pump solutions remained consistent throughout the 8-day analysis period, within a range of 4.6 to 5.7 for the 0.6 mg/mL and 4.4 to 4.9 for the 8.0 mg/mL telavancin solutions. There was no significant change in the chromatographic purity for any of the pump solutions examined. All decreases in telavancin concentration were ≤2.7%. Comparison of each test sample solution to the corresponding glass control indicated no loss of active drug due to absorption by the elastomeric material of the pumps. The greatest increase in the amount of total degradants observed over the 8-day period was ~0.7 w/w%. Conclusions: The results of this study indicate that telavancin remains chemically stable when diluted in the Intermate Infusion System and the Homepump Eclipse elastomeric pumps and stored at 2°C to 8°C for up to 8 days protected from light at the concentration range and dilution schemes evaluated.

Lysosomes play a vital role in the maintenance of cellular homeostasis through the recycling of cell constituents, a key metabolic function which is highly dependent on the correct function of the lysosomal hydrolases and membrane proteins, as well as correct membrane lipid stoichiometry and composition. The critical role of lysosomal functionality is evident from the severity of the diseases in which the primary lesion is a genetically defined loss-of-function of lysosomal hydrolases or membrane proteins. This group of diseases, known as lysosomal storage diseases (LSDs), number more than 50 and are associated with severe neurodegeneration, systemic disease, and early death, with only a handful of the diseases having a therapeutic option. Another key homeostatic system is the metabolic stress response or heat shock response (HSR), which is induced in response to a number of physiological and pathological stresses, such as protein misfolding and aggregation, endoplasmic reticulum stress, oxidative stress, nutrient deprivation, elevated temperature, viral infections, and various acute traumas. Importantly, the HSR and its cardinal members of the heat shock protein 70 family has been shown to protect against a number of degenerative diseases, including severe diseases of the nervous system. The cytoprotective actions of the HSR also include processes involving the lysosomal system, such as cell death, autophagy, and protection against lysosomal membrane permeabilization, and have shown promise in a number of LSDs. This review seeks to describe the emerging understanding of the interplay between these two essential metabolic systems, the lysosomes and the HSR, with a particular focus on their potential as a therapeutic target for LSDs.

Objectives: This study aimed to investigate the perspectives of international experts and Danish citizens on relevant knowledge about population-based breast, colorectal and cervical cancer screening., Methods: This was a qualitative interview study with focus group interviews with experts and Danish citizens eligible for breast, colorectal and/or cervical cancer screening. Data were collected using semi-structured interview guides, audio-recorded and transcribed verbatim. A thematic analysis was conducted., Results: Participants were nine international experts from Germany, Canada, the USA, Sweden, the Netherlands and Australia, and 54 citizens from Denmark. Most citizens had 'adequate' or 'problematic' levels of health literacy. Themes that experts and citizens agreed on were: knowledge about the disease and symptoms, practical information about screening, benefits of screening, the option of non-participation and the importance of having numeric information of possible screening outcomes. Experts agreed on the importance of knowledge about the harms of screening, but only a minority of citizens considered this important., Conclusions: The experts and citizens disagreed on the relevance of knowledge about harms of screening and agreed on other relevant knowledge., Practice Implications: What experts and citizens find important may not align when making informed decisions. Therefore, experts and citizens needs to be involved when developing questionnaires., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Objective: To provide a systematic review of self-administered decision aids (DAs) for citizens invited to participate in colorectal cancer screening synthesizing the effectiveness of self-administered DAs on informed choice or the components hereof; knowledge, attitudes, and participation., Methods: The literature search was undertaken in PubMed, CINAHL, PsycINFO, Embase and Scopus and last updated 19 March 2021. Results were presented by narrative synthesis, meta-analyses and vote counting based on direction of effect., Results: Fourteen studies of fair methodological quality were included. One study reported on informed choice and 13 studies reported on the components. Self-administered DAs increased participation and knowledge whereas it was inconclusive with regard to attitudes towards screening. The studies were very heterogeneous with different comparators, outcomes and means of measurement., Conclusion: This systematic review showed a potential for self-administered DAs to support informed choice in colorectal cancer screening, especially by increasing knowledge., Practice Implications: It seems reasonable to consider informed choice to be one of the main outcomes of self-administered DAs. Yet there is a need for consensus on how to measure informed choice in cancer screening, especially a validated measurement of knowledge defining what constitutes 'adequate knowledge'., (Copyright © 2021. Published by Elsevier B.V.)

Objectives: This trial tested the effectiveness of a self-administered web-based decision aid, targeted at citizens with lower educational attainment, on informed choice about colorectal cancer screening participation as assessed by group levels of knowledge, attitudes and uptake., Methods: The randomised controlled trial was conducted among 2702 screening-naïve Danish citizens, 53-74 years old, with lower educational attainment. Baseline questionnaire respondents (62%) were allocated to intervention and control groups. Intervention group citizens received the decision aid. Outcomes were informed choice, worries and decisional conflict., Results: Analyses were conducted among 339 eligible citizens. The mean difference in knowledge score change between intervention and control group was 0.00 (95% confidence interval (CI): -0.38;0.38). Trends towards more positive screening attitudes (mean difference in score change: 0.72, 95% CI: -0.38;1.81) and higher screening uptake (7.6%, 95% CI:-2.2;17.4%) were observed. Worries (-0.33, 95% CI: -0.97;0.32) and decisional conflict (mean difference: -3.5, 95%CI: -7.0;-0.1) were slightly reduced., Conclusions: The decision aid did not affect informed choice or knowledge. However, there were trends towards increased screening uptake and more positive screening attitudes., Practice Implications: Being a simple intervention and easily administered, the decision aid could represent a cost-effective way of enhancing screening uptake, and some elements of informed decision-making., Competing Interests: Declaration of Competing Interest None., (Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.)

Objectives: To explore perceptions of colorectal cancer (CRC) screening among participants who have experienced a 'false alarm' for CRC, and to explore perceptions about the relevance of screening for themselves or others., Methods: Semi-structured interviews with screening participants who had participated in the Danish CRC screening program and experienced a 'false alarm' for colorectal cancer. A thematic analysis was performed, based on an interpretive tradition of ethnography., Results: Perceptions about CRC screening after a non-cancer colonoscopy result were characterized by trust in the colonoscopy result showing no CRC, and satisfaction with the screening offer despite the risk for 'false alarm'. The patient-involving behavior of the healthcare professionals during the examination was for most participants a cornerstone for trusting the validity of the colonoscopy result showing no CRC. Strong notions about perceived obligation to participate in screening were common., Conclusions: Prominent themes were trust in the result, satisfaction with the procedure, and moral obligations to participate both for themselves and for others., Practice Implications: Information to future invitees after a 'false alarm' experience could build on peoples' trust in the validity of a previous non-cancer result and should underscore the importance of subsequent screening even after a 'false alarm' for cancer., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Unanticipated difficult intubation remains a challenge in anaesthesia. The Simplified Airway Risk Index (SARI) is a multivariable risk model consisting of seven independent risk factors for difficult intubation. Our aim was to compare preoperative airway assessment based on the SARI with usual airway assessment., Methods: From 01.10.2012 to 31.12.2013, 28 departments were cluster-randomized to apply the SARI model or usual airway assessment. The SARI group implemented the SARI model. The Non-SARI group continued usual airway assessment, thus reflecting a group of anaesthetists' heterogeneous individual airway assessments. Preoperative prediction of difficult intubation and actual intubation difficulties were registered in the Danish Anaesthesia Database for both groups. Patients who were preoperatively scheduled for intubation by advanced techniques (e.g. video laryngoscopy; flexible optic scope) were excluded from the primary analysis. Primary outcomes were the proportions of unanticipated difficult and unanticipated easy intubation., Results: A total of 26 departments (15 SARI and 11 Non-SARI) and 64 273 participants were included. In the primary analyses 29 209 SARI and 30 305 Non-SARI participants were included.In SARI departments 2.4% (696) of the participants had an unanticipated difficult intubation vs 2.4% (723) in Non-SARI departments. Odds ratio (OR) adjusted for design variables was 1.03 (95% CI: 0.77-1.38). The proportion of unanticipated easy intubation was 1.42% (415) in SARI departments vs 1.00% (302) in Non-SARI departments. Adjusted OR was 1.26 (0.68-2.34)., Conclusions: Using the SARI compared with usual airway assessment we detected no statistical significant changes in unanticipated difficult- or easy intubations., Clinical Trial Registration: NCT01718561., (© The Author 2016. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Background/aims: The results of liver transplantation for Budd-Chiari syndrome (BCS) are poorly known and the role and timing of the procedure are still controversial. The aim of this study was to investigate the results of transplantation for BCS, focusing on overall outcome, on prognostic factors and on the impact of the underlying disease., Methods: An enquiry on 248 patients representing 84% of the patients transplanted for BCS in the European Liver Transplantation Registry between 1988 and 1999., Results: Of the 248 patients, 70.4% were female and 29.6% male. The mean age was 35.7 years. The overall actuarial survival was 76% at 1 year, 71% at 5 years and 68% at 10 years. 77% of deaths occurred in the first 3 months: 47% were due to infection and multiple organ failure, and 18% to graft failure or hepatic artery thrombosis. Late mortality (>1 year) occurred in nine patients, due to BCS recurrence in four of them. The only pre-transplant predictors of mortality on multivariate analysis (Cox) were impaired renal function and a history of a shunt., Conclusions: Liver transplantation for BCS is an effective treatment, irrespective of the underlying cause, and should be considered before renal failure occurs.

Background/aims: Hepatobiliary malignancies are frequently seen in primary sclerosing cholangitis (PSC) and they complicate the evaluation of patients and timing of liver transplantation., Methods: Data from all Nordic PSC patients listed for liver transplantation during 1990-2001 were recorded prospectively. Predictors of hepatobiliary malignancy and patient survival rates have been analysed., Results: Hepatobiliary malignancy was found in 52/255 (20%) patients accepted to the waiting list. Recent diagnosis of PSC, no ursodeoxycholic acid (UDCA) treatment, clinical suspicion and previous colorectal-cancer were predictors of malignancy. Among 89 patients with a strong suspicion of malignancy prior to acceptance, 35 (39%) had confirmed malignancy. A clinical suspicion had been raised in 35/52 (67%) patients with malignancy. Malignancy was found in 31/223 patients who received a liver allograft. The 1-, 3- and 5-year patient survival rates following transplantation for patients with PSC and cholangiocarcinoma were 65, 35 and 35%, respectively., Conclusions: Hepatobiliary malignancy is suspected in 1/3 of the PSC patients and found in 1/5. Although cholangiocarcinoma is regarded as a contraindication to liver transplantation (LTX), PSC patients with cholangiocarcinoma had a 35% 5-year survival following transplantation.

In Denmark, a new survey of indoor radon-222 has been carried out, 1-year alpha track measurements (CR-39) have been made in 3019 single-family houses. There are from 3 to 23 house measurements in each of the 275 municipalities. Within each municipality, houses have been selected randomly. One important outcome of the survey is the prediction of the fraction of houses in each municipality with an annual average radon concentration above 200 Bq m(-3). To obtain the most accurate estimate and to assess the associated uncertainties, a statistical model has been developed. The purpose of this paper is to describe the design of this model, and to report results of model tests. The model is based on a transformation of the data to normality and on analytical (conditionally) unbiased estimators of the quantities of interest. Bayesian statistics are used to minimize the effect of small sample size. In each municipality, the correction is dependent on the fraction of area where sand and gravel is a dominating surface geology. The uncertainty analysis is done with a Monte-Carlo technique. It is demonstrated that the weighted sum of all municipality model estimates of fractions above 200 Bq m(-3) (3.9% with 95%-confidence interval = [3.4,4.5]) is consistent with the weighted sum of the observations for Denmark taken as a whole (4.6% with 95%-confidence interval = [3.8,5.6]). The total number of single-family houses within each municipality is used as weight. Model estimates are also found to be consistent with observations at the level of individual counties. These typically include a few hundred house measurements. These tests indicate that the model is well suited for its purpose.

Transplantation of the liver results in surgical denervation of the organ. However, it is not known whether and to what extent sympathetic reinnervation occurs postoperatively in the transplanted human liver. Thirty-two liver biopsies (right lobe) were obtained from 13 liver-transplanted patients 1, 3, 6, 12 or 30 months after transplantation and 11 biopsies were obtained from 11 non-transplanted subjects with normal liver tests. The concentrations of the sympathetic neurotransmitter norepinephrine and of epinephrine were determined in liver tissue homogenates. The concentration of norepinephrine was 0.019 +/- 0.05 nmol. g wet liver tissue-1 (mean and SE, n = 32) in the transplanted patients, which was only 1% of the concentration in biopsies from control subjects (2.180 +/- 0.420 nmol.g wet liver tissue-1). The hepatic norepinephrine concentration did not increase significantly over time in liver-transplanted patients during the observation period (0.015 +/- 0.008 nmol.g wet wt-1 (1 month post) (n = 8) vs. 0.024 +/- 0.018 nmol.g wet wt-1 (12 months post) (n = 6) and 0.012 +/- 0.006 nmol.g wet wt-1 (30 months post) (n = 5)) (p < 0.05). The liver tissue concentration of epinephrine was markedly lower in liver-transplanted subjects (0.01 +/- 0.003 nmol.g wet tissue-1) than in control subjects (0.04 +/- 0.007 nmol.g-1) (p < 0.01). This study indicates that within the first years after transplantation, there is no evidence of sympathetic liver nerve reinnervation in liver-transplanted patients.

The aminoterminal propeptide of type III collagen was monitored in serum during liver transplantation in nine pigs. The aim was to investigate whether removal of the liver causes any changes in the serum concentration of the propeptide. Another connective tissue component, hyaluronan, a glycosaminoglycan known to be degraded in the liver endothelial cells, was also measured. Removal of the liver caused a significant increase in the concentration of the intact propeptide as well as of hyaluronan. Gel filtration confirmed the increase in the amount of intact propeptide. However, another large propeptide-related antigen, eluted near the void volume, appeared in the antigen profile during the anhepatic phase. This peak probably represents the propeptide still attached to the collagen molecule (pN collagen). The findings indicate that the liver is involved in the degradation of the propeptide and of larger propeptide-holding proteins.