Admission levels of serum biomarkers have additive and cumulative prognostic value in traumatic brain injury.

Elevated levels of CNS-derived serum proteins are associated with poor outcome in traumatic brain injury (TBI), but the value of adding acute serum biomarker levels to common clinical outcome predictors lacks evaluation. We analyzed admission serum samples for Total-Tau (T-Tau), Neurofilament light chain (Nfl), Glial fibrillary acidic protein (GFAP), and Ubiquitin C-terminal hydrolase L1 (UCHL1) in a cohort of 396 trauma patients including 240 patients with TBI. We assessed the independent association of biomarkers with 1-year mortality and 6-12 months Glasgow Outcome Scale Extended (GOSE) score, as well as the additive and cumulative value of biomarkers on Glasgow Coma Scale (GCS) and Marshall Score for outcome prediction. Nfl and T-Tau levels were independently associated with outcome (OR: Nfl = 1.65, p = 0.01; T-Tau = 1.99, p < 0.01). Nfl or T-Tau improved outcome prediction by GCS (Wald Chi, Nfl = 6.8-8.8, p < 0.01; T-Tau 7.2-11.3, p < 0.01) and the Marshall score (Wald Chi, Nfl = 16.2-17.5, p < 0.01; T-Tau 8.7-12.4, p < 0.01). Adding T-Tau atop Nfl further improved outcome prediction in majority of tested models (Wald Chi range 3.8-9.4, p ≤ 0.05). Our data suggest that acute levels of serum biomarkers are independently associated with outcome after TBI and add outcome predictive value to commonly used clinical scores.

Longitudinal Change in Serum Neurofilament Light Chain in Type 2 Diabetes and Early Diabetic Polyneuropathy: ADDITION-Denmark.

OBJECTIVE: To investigate the longitudinal development of neurofilament light chain (NfL) levels in type 2 diabetes with and without diabetic polyneuropathy (+/-DPN) and to explore the predictive potential of NfL as a biomarker for DPN. RESEARCH DESIGN AND METHODS: We performed retrospective longitudinal case-control analysis of data from 178 participants of the Anglo-Danish-Dutch Study of Intensive Treatment in People with Screen-Detected Diabetes in Primary Care-Denmark (ADDITION-Denmark) cohort of people with screen-detected type 2 diabetes. Biobank samples acquired at the ADDITION-Denmark 5- and 10-year follow-ups were analyzed for serum NfL (s-NfL) using single-molecule array, and the results were compared with established reference material to obtain NfL z-scores. DPN was diagnosed according to Toronto criteria for confirmed DPN at the 10-year follow-up. RESULTS: s-NfL increased over time in +DPN (N = 39) and -DPN participants (N = 139) at levels above normal age-induced s-NfL increase. Longitudinal s-NfL change was greater in +DPN than in -DPN participants (17.4% [95% CI 4.3; 32.2] or 0.31 SD [95% CI 0.03; 0.60] higher s-NfL or NfL z-score increase in +DPN compared with -DPN). s-NfL at the 5-year follow-up was positively associated with nerve conduction studies at the 10-year follow-up (P = 0.02 to <0.001), but not with DPN risk. Areas under the curve (AUCs) for s-NfL were not inferior to AUCs for the Michigan Neuropathy Screening Instrument questionnaire score or vibration detection thresholds. Higher yearly s-NfL increase was associated with higher DPN risk (odds ratio 1.36 [95% CI 1.08; 1.71] per 1 ng/L/year). CONCLUSIONS: Our findings suggest that preceding s-NfL trajectories differ slightly between those with and without DPN and imply a possible biomarker value of s-NfL trajectories in DPN.

Health-related quality of life, needs, and concerns among cancer survivors referred to rehabilitation in primary healthcare setting.

BACKGROUND AND PURPOSE: There is a growing need for rehabilitation services beyond hospitals. This study aims to describe challenges faced by cancer survivors (CSs) referred for rehabilitation in primary healthcare, employing standardized scales measuring health-related quality of life (HRQOL) and open-ended questions. Furthermore, the study explores the applicability of patient-reported outcomes (PROs) in comprehensively understanding challenges encountered by CSs. MATERIAL AND METHODS: This cross-sectional study involves CSs referred for cancer rehabilitation in a primary healthcare setting, including those participating in PROs as a part of routine practice. HRQOL was assessed using the Functional Assessment of Cancer Therapy-General (FACT-G). The International Classification of Functioning, Disability and Health (ICF) framed the analysis of responses to open-ended questions 'what concerns you the most?' and 'what matters to you?'  Results: FACT-G showed the lowest scores for functional well-being (14.4) and emotional well-being (16.6), with higher scores for physical well-being (18.9) and social/family well-being (21.1). Responses to open-ended questions unveiled worries about everyday life and how cancer will impact family well-being presently and in the future. Furthermore, CSs reported a need to maintain normality and proactively address the challenges posed by the disease. INTERPRETATION: CSs referred for rehabilitation in primary healthcare experience comprehensive challenges necessitating a holistic rehabilitation approach. This includes interventions supporting CSs in dealing with uncertainty, regaining a sense of control, and addressing family well-being concerns. When using PROs for need assessment, the combination of validated HRQOL scales and open-ended questions is crucial for an in-depth understanding of CSs' challenges.

Serum glial fibrillary acidic protein and neurofilament light chain in treatment-naïve patients with unipolar depression.

BACKGROUND: Unipolar depression has been associated with increased levels of glial dysfunction and neurodegeneration biomarkers, such as Glial Fibrillary Acidic Protein (GFAP) and Neurofilament light chain (NfL). However, previous studies were conducted on patients taking psychotropic medication and did not monitor longitudinal associations between disease status and GFAP/NfL. METHODS: Treatment-naïve patients with unipolar depression (n = 110) and healthy controls (n = 33) were included. GFAP/NfL serum levels were analyzed by Single Molecule Array at baseline and 3-month follow-up. The primary endpoint was GFAP/NfL levels in patients with depression compared with healthy controls. The secondary endpoint was the associations between GFAP/NfL with depression severity and cognitive function. RESULTS: The patients' mean HAM-D17 score was 18.9 (SD 3.9) at baseline and improved by 7.9 (SD 6.8) points during follow-up. GFAP/NfL was quantified in all individuals. At baseline, the adjusted GFAP levels were -16.8 % (95 % CI: -28.8 to -1.9, p = 0.03) lower among patients with depression compared to healthy controls, while NfL levels were comparable between the groups (p = 0.57). In patients with depression, mean NfL levels increased from baseline to follow-up (0.68 pg/ml, p = 0.03), while GFAP levels were unchanged (p = 0.24). We did not find consistent associations between NfL/GFAP with depression scores or cognitive function. CONCLUSION: This largest study of serum NfL/GFAP levels in patients with depression did not support previous findings of elevated GFAP/NfL in patients with depression or positive associations with depression severity. Although limited by a small control group, our study may support the presence of glial dysfunction but not damage to neurons in depression.

Navigating (un)certainty in 'downhill' trajectories: An ethnographic study about rehabilitees' and professionals' experiences of goal-setting in Parkinson's disease rehabilitation.

OBJECTIVE: To explore rehabilitees' and professionals' experiences of goal-setting in a context of (un)certainty with a progressive neurodegenerative disease and how they navigate this (un)certainty in Parkinson's disease rehabilitation. DESIGN: A long-term multi-sited ethnographic fieldwork (2019-2020) following 20 rehabilitees and their goals over time and settings. Observation at 30 goal-setting meetings. PARTICIPANTS: Rehabilitees and professionals in Danish Parkinson's disease rehabilitation. Two randomly chosen groups of rehabilitees attending a Parkinson's disease course at a rehabilitation centre participated. METHODS: Semi-structured interviews and participant observation. RESULTS: Living with Parkinson's disease holds a certainty that the condition will progress yet an uncertainty regarding the pace and severity, as indicated by the notion (un)certainty. The (un)certainty challenges goal-setting. Reflecting on goal-setting, rehabilitees brought forth existential, economical, and societal considerations. Some expressed an ambivalent view, questioning the value of goal-setting with a progressive condition, yet finding own rehabilitation goals relevant. Others expressed a pragmatic view, attuning goals to fit the situation. Professionals found that the visible and invisible symptoms and the uncertain pace of Parkinson's made goal-setting challenging. They had to strike a balance between mentioning symptoms to come, yet not rendering the future too bleak. CONCLUSIONS: Rehabilitees and professionals found that setting goals in a condition that progresses is no easy task. They made use of strategies such as observation, repetition, future-proofing strategies, and attuning goals to navigate the (un)certainty. In goal-setting, to maintain functioning with progressive Parkinson's disease was a viable goal. Participants found they just do the best they can to navigate (un)certainty.

Age-dependent thrombin generation predicts 30-day mortality and symptomatic thromboembolism after multiple trauma.

Trauma-induced coagulopathy (TIC) is a risk factor for death and is associated with deviations in thrombin generation. TIC prevalence and thrombin levels increase with age. We assayed in vivo and ex vivo thrombin generation in injured patients (n = 418) to specifically investigate how age impacts thrombin generation in trauma and to address the prognostic ability of thrombin generation. Biomarkers of thrombin generation were elevated in young (< 40 years) and older (≥ 40 years) trauma patients. In vivo thrombin generation was associated with Injury Severity Score (ISS) and this association was stronger in young than older patients. In vivo thrombin generation decreased faster after trauma in the young than the older patients. Across age groups, in vivo thrombin generation separated patients dying/surviving within 30 days at a level comparable to the ISS score (AUC 0.80 vs. 0.82, p > 0.76). In vivo and ex vivo thrombin generation also predicted development of thromboembolic events within the first 30 days after the trauma (AUC 0.70-0.84). In conclusion, younger trauma patients mount a stronger and more dynamic in vivo thrombin response than older patients. Across age groups, in vivo thrombin generation has a strong ability to predict death and/or thromboembolic events 30 days after injury.

Dysphagia and QoL 3 Years After Treatment of Oropharyngeal Cancer With TORS or Radiotherapy.

OBJECTIVE(S): To investigate dysphagia and quality of life (QoL) outcomes 3 years after treatment of oropharyngeal cancer with either primary trans oral robotic surgery (TORS) or radiotherapy (RT). METHODS: A prospective cohort study conducted at the Copenhagen University Hospital. Endpoints were objective swallowing function, examined using fiberoptic endoscopic evaluation of swallowing (FEES) and video fluoroscopy (VF). QoL was assessed with the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core (EORTC QLQ-C30), Head & Neck Module (EORTC QLQ-HN35), and MD Anderson Dysphagia Inventory (MDADI). A comparison was made between 1-, and 3-year results. RESULTS: Forty-four patients were included prior to treatment, 31 treated with TORS and 13 with RT. One-year results for this cohort have previously been published (https://doi.org/10.1080/00016489.2020.1836395). Significant improvement on FEES in retention at the piriform sinus was noted in both groups. Patients treated with TORS had improved safety scores as well as dynamic imaging grade of swallowing toxicity (DIGEST) and efficiency scores, whereas patients treated with RT only had improvements in the latter two. Improvement in QoL scores was only noted for patients treated with TORS in composite MDADI scores. CONCLUSION: We found significant improvements in objective swallowing function from one to 3 years after treatment, particularly in patients treated with TORS. However, these improvements were not reflected as clinically meaningful improvements in QoL. LEVEL OF EVIDENCE: 3, cohort follow-up study Laryngoscope, 133:1893-1898, 2023.

Serum neurofilament light chain - A potential biomarker for polyneuropathy in type 2 diabetes?

AIMS: To investigate the relationship between neurofilament light chain (NfL) and the presence and severity of diabetic polyneuropathy (DPN). METHODS: We performed cross-sectional analysis of data from 178 participants of the ADDITION-Denmark cohort of people with screen-detected type 2 diabetes and 32 healthy controls. Biobank serum samples were analyzed for NfL using single-molecule array. DPN was defined by Toronto criteria for confirmed DPN. Original and axonal nerve conduction study (NCS) sum z-scores were used as indicators of the severity of DPN and peripheral nerve damage. RESULTS: 39 (21.9%) participants had DPN. Serum NfL (s-NfL) was significantly higher in participants with DPN (18.8 ng/L [IQR 14.4; 27.9]) than in participants without DPN (15.4 ng/L [IQR 11.7; 20.1]). There were no unadjusted s-NfL differences between controls (17.6 ng/L [IQR 12.7; 19.8]) and participants with or without DPN. Higher original and axonal NCS sum z-scores were associated with 10% higher s-NfL (10.2 and 12.1% [95% CI's 4.0; 16.8 and 6.6; 17.9] per 1 SD). The AUC of s-NfL for DPN was 0.63 (95% CI 0.52; 0.73). CONCLUSIONS: S-NfL is unlikely to be a reliable biomarker for the presence of DPN. S-NfL is however associated tothe severity of the nerve damage underlying DPN.

Reduced platelet function in preterm neonates compared with term neonates.

Background: A reduced platelet function might contribute to the longer bleeding time seen in preterm neonates. However, the previously used platelet function testing in neonates is limited due to methodological limitations, mainly caused by difficulties in obtaining adequate blood volume. Therefore, the platelet function in preterm neonates is sparsely investigated. The aim of this study was to compare platelet function in preterm neonates at birth and at expected term age with platelet function in term neonates at birth. Methods: We included 43 preterm neonates born at gestational age (GA) 28 + 0 to 34 + 0 and 21 term neonates born at GA 38 + 0 to 41 + 0. Within the first 24 hours of life, 1-1.5 mL peripheral blood was obtained and for preterm neonates, resampling was performed at expected term age (GA 38 + 0 to 41 + 0). Platelet function testing included impedance aggregometry and platelet activation measured by flow cytometry. In addition, platelet count was determined. Results: Platelet count and platelet activation were reduced in preterm neonates compared with term neonates at birth, but we found no difference in impedance aggregometry at birth. At expected term age, platelet count and aggregation exceeded term levels, but platelet activation remained impaired in the preterm. Conclusion: Preterm neonatal function is decreased at birth and does not seem to reach term levels during the first 4 to 13 weeks of life.

Serum glial fibrillary acidic protein (GFAP) predicts outcome after intracerebral and subarachnoid hemorrhage.

BACKGROUND AND PURPOSE: Intracerebral and subarachnoid hemorrhage are critical conditions with a high mortality, and the outcome for the individual patient is notoriously difficult to predict. Biomarkers that reflect disease severity and predict outcome are therefore warranted. METHODS: Blood samples from 40 patients with intracerebral, 46 patients with subarachnoid hemorrhage, and 70 healthy individuals were collected. Levels of glial fibrillary acidic protein (GFAP) and neuroglobin were measured by ultra-sensitive single molecule array and enzyme-linked immunosorbent assay, respectively. Clinical information including mortality and functional outcome was recorded. RESULTS: Blood levels of GFAP and neuroglobin in intracerebral and subarachnoid hemorrhage patients were significantly elevated when compared to healthy individuals (all p < 0.0001). GFAP levels were significantly higher in patients dying or with poor functional outcome than in healthy individuals (all p ≤ 0.01). GFAP levels separated survivors from non-survivors with an area under receiver operating characteristics (AUROC) = 0.78 (confidence interval (CI) 0.59-0.98) for intracerebral hemorrhage and 0.82 (CI 0.69-0.94) for subarachnoid hemorrhage patients. The Akaike and Bayesian information criteria (AIC/BIC) for mortality/poor outcome prediction improved when combining GFAP levels with hematoma volume (p = 0.04/p < 0.01), National Institutes of Health Stroke Scale (NIHSS) (p = 0.09/p < 0.01), Hunt-Hess (p < 0.05/p = 0.21), or Fischer score (p < 0.05/p = 0.02). CONCLUSIONS: Elevated GFAP levels at admission to hospital predicted mortality and poor outcome in our cohort of intracerebral and subarachnoid hemorrhage patients. Neuroglobin levels did not provide additional information. Combining GFAP measurements with clinical disease severity scores increased outcome prediction precision. This may suggest that GFAP measurement could improve prognostication in patients with intracerebral or subarachnoid hemorrhage. REGISTRATION: This sub-trial was not registered.

A bioinformatic pipeline for simulating viral integration data.

Viral integration is a complex biological process, and it is useful to have a reference integration dataset with known properties to compare experimental data against, or for comparing with the results from computational tools that detect integration. To generate these data, we developed a pipeline for simulating integrations of a viral or vector genome into a host genome. Our method reproduces more complex characteristics of vector and viral integration, including integration of sub-genomic fragments, structural variation of the integrated genomes, and deletions from the host genome at the integration site. Our method [1] takes the form of a snakemake [2] pipeline, consisting of a Python [3] script using the Biopython [4] module that simulates integrations of a viral reference into a host reference. This produces a reference containing integrations, from which sequencing reads are simulated using ART [5]. The IDs of the reads crossing integration junctions are then annotated using another python script to produce the final output, consisting of the simulated reads and a table of the locations of those integrations and the reads crossing each integration junction. To illustrate our method, we provide simulated reads, integration locations, as well as the code required to simulate integrations using any virus and host reference. This simulation method was used to investigate the performance of viral integration tools in our research [6].

Two-Year Follow-Up on Return to Work in a Randomised Controlled Trial Comparing Brief and Multidisciplinary Intervention in Employees on Sick Leave Due to Low Back Pain.

PURPOSE: To study return to work (RTW) at 2-year follow-up in a randomised controlled trial comparing brief intervention (BI) and multidisciplinary intervention (MDI) in employees on sick leave due to low back pain (LBP) stratified for job relations. METHODS: In total 476 employees on sick leave for 4-12 weeks due to LBP were divided into strata with weak or strong job relations, based on perceived risk of losing job and influence on job planning. In each stratum participants were allocated to BI or MDI. All participants received BI, i.e. a clinical examination by a rheumatologist and physiotherapist. In addition, MDI involved a case manager who made a rehabilitation plan in collaboration with the participant. The primary outcome was time to RTW. Secondary outcomes were median weeks in different employment status and selfreported pain, disability and psychological health. Sustained RTW was estimated by work status the last 4 weeks before the 2-year date. RESULTS: Participants with strong job relations who received BI had a higher RTW rate (hazard ratio = 0.74 (95% CI 0.57; 0.96)) and spent more weeks working than participants who received MDI. In the stratum of weak job relations, no difference was seen regarding RTW and weeks working. For health-related outcomes and sustained RTW no significant results were found in neither stratum. CONCLUSIONS: Employees with strong job relations achieved higher RTW rates when receiving BI compared to MDI, while no difference was found between intervention groups for employees with weak job relations. TRIAL REGISTRATION: Current Controlled Trials ISRCTN14136384. Registered 4 August.

Labor Market Attachment 2 Years After Colorectal Cancer Surgery: A Population-based Study.

Objectives: To investigate the association between clinical/sociodemographic factors and labor market attachment, and to estimate employment probability 2 years after colorectal cancer (CRC) surgery. Background: A rising prevalence of younger CRC survivors commands a stronger focus on labor market attachment. The association between clinical factors like type of surgery and CRC survivors' labor market attachment remains poorly investigated. Methods: National registries provided information on employment status and clinical/sociodemographic variables for all 20- to 60-year-old CRC patients without previous cancer diagnosed in Denmark from 2001 to 2014, undergoing surgery and being attached to the labor market. Associations between clinical/sociodemographic factors and labor market attachment were investigated in multiple logistic regression analyses. Results: A total of 5755 CRC patients were included. Two years after surgery, 59.7% were working. Factors significantly associated with a higher probability of working were being in the 46 to 50 years age group, male gender, higher educational level, no comorbidity, working at the time of diagnosis, lower Union for International Cancer Control stage, and undergoing surgery in the most recent of four time-periods. Two years after undergoing surgery, the probability of working was significantly higher for left-sided than for right-sided colon resections, higher for low anterior resection (LAR)/high tumor than for LAR/low tumor, and higher for abdominoperineal resection than for Hartmann's procedure. Of the 4798 (86.8%) patients alive 2 years after surgery, 68.8% were working, 7.8% had retired, whereas 23.4% were on temporary benefits, sick leave, or disability pension. Conclusions: Clinical/sociodemographic factors were associated with the probability of working 2 years after surgery. This knowledge can be used to inform patients and target interventions towards patients with low post-CRC probability of working.

Isling: A Tool for Detecting Integration of Wild-Type Viruses and Clinical Vectors.

Detecting viral and vector integration events is a key step when investigating interactions between viral and host genomes. This is relevant in several fields, including virology, cancer research and gene therapy. For example, investigating integrations of wild-type viruses such as human papillomavirus and hepatitis B virus has proven to be crucial for understanding the role of these integrations in cancer. Furthermore, identifying the extent of vector integration is vital for determining the potential for genotoxicity in gene therapies. To address these questions, we developed isling, the first tool specifically designed for identifying viral integrations in both wild-type and vector from next-generation sequencing data. Isling addresses complexities in integration behaviour including integration of fragmented genomes and integration junctions with ambiguous locations in a host or vector genome, and can also flag possible vector recombinations. We show that isling is up to 1.6-fold faster and up to 170% more accurate than other viral integration tools, and performs well on both simulated and real datasets. Isling is therefore an efficient and application-agnostic tool that will enable a broad range of investigations into viral and vector integration. These include comparisons between integrations of wild-type viruses and gene therapy vectors, as well as assessing the genotoxicity of vectors and understanding the role of viruses in cancer.

Soluble PD-1 (sPD-1) is expressed in human macrophages.

The PD-1/PD-L1 axis plays a crucial role in regulating the anti-tumour immune response. A soluble PD-1 protein (sPD-1) has previously been observed, which could block the binding of PD-L1 to PD-1. Tumour associated macrophages are abundant in tumours, and evidence suggest they express PD-1. However, whether they also express sPD-1 remains unclear. The objective of this study was to investigate expression of sPD-1 in two in vitro models of human macrophages: THP-1 cells and monocyte-derived macrophages (MDM). Cells were polarised with either LPS + IFN-γ or IL-4 + IL-13 or left unpolarised. PD-1 and sPD-1 mRNAs were measured using droplet digital PCR, sPD-1 protein by electrochemiluminescence immunoassay and PD-1 by flow cytometry. sPD-1 mRNA was induced in both THP-1 cells and MDM after polarisation with LPS + IFN-γ, while IL-4 + IL-13 induced sPD-1 mRNA in MDM only. sPD-1 protein was measurable in culture supernatants. These findings show that macrophages can be induced to express sPD-1.

'Work is a motivator in life' Strategies in managing work participation among highly educated employees with depression.

BACKGROUND: Work participation among employees with depression is hampered due to cognitive impairments. Although studies show higher levels of work disability among people with a lower education, highly educated employees may encounter specific challenges in fulfilling their work role due to the cognitive impairments of depression, as they often perform cognitively demanding jobs. There is little knowledge about their challenges and opportunities with regard to work participation. OBJECTIVE: To investigate how highly educated employees with depression manage work participation by focusing on their views on opportunities and challenges in fulfilling their work role. METHODS: Eight individual interviews with highly educated employees with depression were conducted. Transcripts were analysed using qualitative content analysis. RESULTS: The analysis revealed four categories: struggling with acknowledging depression and disclosure; fear of being stigmatised at work; work is a motivator in life; and striving to fulfil the work role at the expense of private life activities. CONCLUSIONS: Highly educated employees with depression need guidance regarding the disclosure of information about health issues and work ability. To successfully manage their work role, they need a clear plan with outlined tasks, demands and goals. Healthcare professionals and workplaces should support them in setting limits with regard to work tasks and working hours.

Needs for occupational assistance among young adults with ADHD to deal with executive impairments and promote occupational participation - a qualitative study.

PURPOSE: To examine perceived aspects of importance among young adults with ADHD to participate and engage in occupational activities, and to explain how support from occupational specialists can assist them to deal with executive impairments. MATERIALS AND METHODS: Individual interviews with eight young adults with attention-deficit/hyperactivity disorder. The interview guide was based on assumptions derived from the literature regarding executive functioning and issues related to participation in occupational activities, alongside the needs for social support. Interview transcripts were analysed using qualitative content analysis. RESULTS: Four categories emerged from the analysed interviews: (1) Being involved in an occupational environment fulfils a need for social contact, (2) Occupational activities must be clear and within interest (3) Self-confidence and daily routines are prerequisites for occupational participation (4) Having a lifeline providing continuous support is important. CONCLUSIONS: Routines, interest and structure in everyday life are important to engage in occupational activities. There is a need for continuous support from a trusted person to establish and maintain healthy daily routines. Occupational specialists can be a vital resource, as they possess specific knowledge on the possibilities for occupation, and additionally, they can fulfil the young adults' needs for continuous support. There is a need for studies questioning how some young adults with ADHD fulfil their work role despite executive impairments. Focusing on executive functioning can be a valuable supplement to the focus on specific diagnoses in research and practice.

Urine soluble CD163 (sCD163) as biomarker in glomerulonephritis: stability, reference interval and diagnostic performance.

OBJECTIVES: Soluble (s) CD163 is a well-established macrophage biomarker, and recent data suggests urine sCD163 to reflect disease activity in crescentic glomerulonephritis (GN). Other types of GN may also be associated with glomerular inflammation but the potential usefulness of urine sCD163 as a general biomarker of GN remains unaddressed. METHODS: An in-house sCD163 enzyme-linked immunosorbent assay (ELISA) was validated for urinary use and compared to a frequently used commercial ELISA. The pre-analytical stability of urine sCD163 was assessed and a reference interval was established according to the CLSI guidelines using specimens from 253 healthy individuals. Urine samples from 64 patients with different types of renal disorders were also analysed. RESULTS: Urine sCD163 was highly stable during storage. An upper reference limit of 5.1 µg/L (1.9 µg/mmol, normalised to creatinine) was established using the in-house ELISA. Urine sCD163 was generally increased in GN patients (3.9 µg/mmol, p<0.0001, AUROC=0.97) and decreased upon treatment, but did not perform better than urine albumin (AUROC=1.00). Patients with proliferative GN had higher urine sCD163/albumin (p=0.0001) ratio. The commercial assay had a higher detection limit, and patient levels were 4-6 times lower than in the in-house assay. CONCLUSIONS: Urine sCD163 is a stable biomarker that can be measured with acceptable accuracy using our in-house ELISA. Its pre-analytical characteristics makes it a reliable biomarker and our findings point towards the use of urine sCD163 as a biomarker of specific subtypes of GN.

Associations between work environment, health status and sick leave among pregnant employees.

Aims: To study the associations between and timing of psychosocial and physical work factors and health status on sick leave among Danish pregnant employees. Methods: A total of 910 pregnant women completed a questionnaire in gestational weeks 12 (baseline) and 27 (follow-up). Information about psychosocial and physical work factors and health status was obtained at baseline. Associations with sick leave ⩾14 days were estimated using logistic regression. Further, the impact of timing and duration of exposure on sick leave were examined. Results: A total of 133 women (14.6%) reported ⩾14 days of sick leave at follow-up (27 weeks of gestation). Work-related risk factors for sick leave were high work pace, low influence, low recognition, low job satisfaction, conflict in work-family balance, standing/walking, heavy lifting, and shift work/night shift. Health-related risk factors were burnout, stress, possibility of depression, low work ability, previous sick leave, and poor self-rated health. Being exposed to work-related risk factors during the first 27 weeks of pregnancy or at follow-up increased the risk of sick leave compared with those not exposed at any time or only exposed at baseline. Poor health status increased the risk if women were exposed in the first 27 weeks of pregnancy; however, high possibility of depression was also a risk factor when experienced in early pregnancy. Conclusions: Psychosocial and physical work-related risk factors and poor health status were associated with more sick leave in pregnant employees. Early adjustment of work-related risk factors at the workplace is needed to reduce sick leave.

Navigating a Middle Ground - Exploring Health Professionals' Experiences and Perceptions of Providing Rehabilitation in Outdoor Community Settings.

Contemporary practice has started to rethink use of outdoor and community environments for advancing comprehensive rehabilitation outcomes. The aim is to examine health professionals' experiences and perceptions of providing rehabilitation in outdoor community settings. The purpose is to use these experiences to generate practice-based knowledge in using the outdoors as a means to guide community-based rehabilitation. The Interpretive Description methodology was accompanied by social practice theory. Fieldwork was conducted utilizing participant observation, photovoice, and focus-group interviews. Included were 27 health professionals. The analysis revealed how "naturalistic learning opportunities" offered health professionals strategies to empower activity and participation levels and yet invoked "rehabilitation setting tensions." A continuum was engaged in the theme "navigating a middle ground," representing an integrated environment approach; rehabilitation in conventional indoor and outdoor community settings. Development of a sustainable concept for outdoor community-based rehabilitation involves strengthening health professionals' competencies and skills for providing outdoor and community work.