Acquired Brain Injury Among Adolescents and Young Adults: A Nationwide Study of Labor Market Attachment.

Purpose Young patients represent a particularly vulnerable group regarding vocational prognosis after an acquired brain injury (ABI). We aimed to investigate how sequelae and rehabilitation needs are associated with vocational prognosis up to 3 years after an ABI in 15-30-year-old patients. Methods An incidence cohort of 285 patients with ABI completed a questionnaire on sequelae and rehabilitation interventions and needs 3 months after the index hospital contact. They were followed-up for up to 3 years with respect to the primary outcome "stable return to education/work (sRTW)", which was defined using a national register of public transfer payments. Data were analyzed using cumulative incidence curves and cause-specific hazard ratios. Results Young individuals reported a high frequency of mainly pain-related (52%) and cognitive sequelae (46%) at 3 months. Motor problems were less frequent (18%), but negatively associated with sRTW within 3 years (adjusted HR 0.57, 95% CI 0.39-0.84). Rehabilitation interventions were received by 28% while 21% reported unmet rehabilitation needs, and both factors were negatively associated with sRTW (adjusted HR 0.66, 95% CI 0.48-0.91 and adjusted HR 0.72, 95% CI 0.51-1.01). Conclusions Young patients frequently experienced sequelae and rehabilitation needs 3 months post ABI, which was negatively associated with long-term labor market attachment. The low rate of sRTW among patients with sequelae and unmet rehabilitation needs indicates an untapped potential for ameliorated vocational and rehabilitating initiatives targeted at young patients.

Cognitive impairments among patients in a long-COVID clinic: Prevalence, pattern and relation to illness severity, work function and quality of life.

BACKGROUND: A considerable proportion of people experience lingering symptoms after Coronavirus Disease 2019 (COVID-19). The aim of this study was to investigate the frequency, pattern and functional implications of cognitive impairments in patients at a long-COVID clinic who were referred after hospitalisation with COVID-19 or by their general practitioner. METHODS: Patients underwent cognitive screening and completed questionnaires regarding subjective cognition, work function and quality of life. Patients' cognitive performance was compared with that of 150 age-, sex-, and education-matched healthy controls (HC) and with their individually expected performance calculated based on their age, sex and education. RESULTS: In total, 194 patients were assessed, on average 7 months (standard deviation: 4) after acute COVID-19.44-53 % of the patients displayed clinically relevant cognitive impairments compared to HC and to their expected performance, respectively. Moderate to large impairments were seen in global cognition and in working memory and executive function, while mild to moderate impairments occurred in verbal fluency, verbal learning and memory. Hospitalised (n = 91) and non-hospitalised (n = 103) patients showed similar degree of cognitive impairments in analyses adjusted for age and time since illness. Patients in the cognitively impaired group were older, more often hospitalised, had a higher BMI and more frequent asthma, and were more often female. More objective cognitive impairment was associated with more subjective cognitive difficulties, poorer work function and lower quality of life. LIMITATIONS: The study was cross-sectional, which precludes causality inferences. CONCLUSIONS: These findings underscore the need to assess and treat cognitive impairments in patients at long-COVID clinics.

Vocational/educational prognosis in adolescents and young adults with acquired brain injury: a nationwide cohort study.

OBJECTIVE: To determine prognostic factors for work ability and employment/educational status among young patients referred to outpatient neurorehabilitation clinics after an acquired brain injury. METHODS: A nationwide cohort study of 471 15-30-year-old patients who attended an interdisciplinary clinical assessment and provided questionnaire data at baseline and after one year. The outcomes were the Work Ability Score (WAS, 0-10 (best)) and employment/educational status after one year. Prognostic performance was analyzed using univariable regression and multivariable Ridge regression in a five-fold cross-validated procedure. RESULTS: Preinjury, 86% of the patients were employed, while the percentage had decreased to 55% at baseline and 52% at follow-up. The model, which included clinical measures of function, showed moderate prognostic performance with respect to WAS (R2=0.29) and employment/educational status (area under the curve (AUC)=0.77). Glasgow Outcome Scale Extended (R2=0.15, AUC=0.68) and the cognitive subscale of the Functional Independence Measure (R2=0.09, AUC=0.64), along with fatigue measured with the Multidimensional Fatigue Inventory (R2=0.15, AUC=0.60) were the single predictors with the highest predictive performance. CONCLUSION: Despite generally high scores in motor and cognitive tests, only about half of the patients were employed at baseline and this proportion remained stable. Global disability, cognitive sequelae and fatigue had the highest prognostic performance.

Trajectory of cognitive impairments over 1 year after COVID-19 hospitalisation: Pattern, severity, and functional implications.

The ongoing Coronavirus Disease (COVID-19) pandemic has so far affected more than 500 million people. Lingering fatigue and cognitive difficulties are key concerns because they impede productivity and quality of life. However, the prevalence and duration of neurocognitive sequelae and association with functional outcomes after COVID-19 are unclear. This longitudinal study explored the frequency, severity and pattern of cognitive impairment and functional implications 1 year after hospitalisation with COVID-19 and its trajectory from 3 months after hospitalisation. Patients who had been hospitalised with COVID-19 from our previously published 3-months study at the Copenhagen University Hospital were re-invited for a 1-year follow-up assessment of cognitive function, functioning and depression symptoms. Twenty-five of the 29 previously assessed patients (86%) were re-assessed after 1 year (11±2 months). Clinically significant cognitive impairments were identified in 48-56 % of patients depending on the cut-off, with verbal learning and executive function being most severely affected. This was comparable to the frequency of impairments observed after 3 months. Objectively measured cognitive impairments scaled with subjective cognitive difficulties, reduced work capacity and poorer quality of life. Further, cognitive impairments after 3 months were associated with the severity of subsequent depressive symptoms after 1 year. In conclusion, the stable cognitive impairments in approximately half of patients hospitalized with COVID-19 and negative implications for work functioning, quality of life and mood symptoms underline the importance of screening for and addressing cognitive sequelae after severe COVID-19.

Testosterone, signal coloration, and signal color perception in male zebra finch contests.

Many animals use assessment signals to resolve contests over limited resources while minimizing the costs of those contests. The carotenoid-based orange to red bills of male zebra finches (Taeniopygia guttata) are thought to function as assessment signals in male-male contests, but behavioral analyses relating contest behaviors and outcomes to bill coloration have yielded mixed results. We examined the relationship between bill color and contests while incorporating measurements of color perception and testosterone (T) production, for an integrative view of aggressive signal behavior, production, and perception. We assayed the T production capabilities of 12 males in response to a gonadotropin-releasing hormone (GnRH) challenge. We then quantified the initiation, escalation, and outcome of over 400 contests in the group, and measured bill color using calibrated photography. Finally, because signal perception can influence signal function, we tested how males perceive variation in bill coloration, asking if males exhibit categorical perception of bill color, as has been shown recently in female zebra finches. The data suggest that males with greater T production capabilities than their rivals were more likely to initiate contests against those rivals, while males with redder bills than their rivals were more likely to win contests. Males exhibited categorical color perception, but individual variation in the effect of categorical perception on color discrimination abilities did not predict any aspects of contest behavior or outcomes. Our results are consistent with the hypotheses that T plays a role in zebra finch contests and that bill coloration functions as an aggressive signal. We suggest future approaches, based on animal contest theory, for how links among signals, perception, and assessment can be tested.

Predictors of disability in adolescents and young adults with acquired brain injury after the acute phase.

AIM: To develop and validate a prediction model for disability among young patients with acquired brain injury (ABI) after the acute phase. METHODS: Within a nationwide cohort of 446 15-30-year-old ABI-patients, we predicted disability in terms of Glasgow Outcome Scale - Extended (GOS-E) <7 12 months after baseline assessment in outpatient neurorehabilitation clinics. We studied 22 potential predictors covering demographic and medical factors, clinical tests, and self-reported fatigue and alcohol/drug consumption. The model was developed using multivariable logistic regression analysis and validated by 5-fold cross-validation and geographical validation. The model's performance was assessed by receiver operating characteristic curves and calibration plots. RESULTS: Baseline assessment took place a median of 12 months post-ABI. Low GOS-E (range 1-8 (best)) and Functional Independence Measure (range 18-126 (best)) along with high mental fatigue (range 4-20 (worst)) predicted disability. The model showed high validity and performance with an area under the curve of 0.82 (95% confidence interval (CI) 0.77, 0.87) in the cross-validation and 0.81 (95% CI 0.73, 0.88) in the geographical validation. CONCLUSION: We developed and validated a parsimonious model which effectively predicted disability. The model may be useful to guide decision-making in outpatient neurorehabilitation clinics treating young patients with ABI.

Cognitive impairments four months after COVID-19 hospital discharge: Pattern, severity and association with illness variables.

The ongoing Coronavirus Disease 2019 (COVID-19) pandemic has affected more than 100 million people and clinics are being established for diagnosing and treating lingering symptoms, so called long-COVID. A key concern are neurological and long-term cognitive complications. At the same time, the prevalence and nature of the cognitive sequalae of COVID-19 are unclear. The present study aimed to investigate the frequency, pattern and severity of cognitive impairments 3-4 months after COVID-19 hospital discharge, their relation to subjective cognitive complaints, quality of life and illness variables. We recruited patients at their follow-up visit at the respiratory outpatient clinic, Copenhagen University Hospital, Bispebjerg, approximately four months after hospitalisation with COVID-19. Patients underwent pulmonary, functional and cognitive assessments. Twenty-nine patients were included. The percentage of patients with clinically significant cognitive impairment ranged from 59% to 65% depending on the applied cut-off for clinical relevance of cognitive impairment, with verbal learning and executive functions being most affected. Objective cognitive impairment scaled with subjective cognitive complaints, lower work function and poorer quality of life. Cognitive impairments were associated with d-dimer levels during acute illness and residual pulmonary dysfunction. In conclusion, these findings provide new evidence for frequent cognitive sequelae of COVID-19 and indicate an association with the severity of the lung affection and potentially restricted cerebral oxygen delivery. Further, the associations with quality of life and functioning call for systematic cognitive screening of patients after recovery from severe COVID-19 illness and implementation of targeted treatments for patients with persistent cognitive impairments.

Specialized Outpatient Clinic vs Stroke Unit for TIA and Minor Stroke: A Cohort Study.

Objective: To evaluate the effects of an outpatient clinic set-up for minor stroke/TIA using subsequent admission of patients at 'high risk' of re-stroke.Methods: A cohort study of all patients with suspected minor stroke/TIA seen in an outpatient clinic at Aarhus University Hospital, Denmark, between September 2013 and August 2014. Stroke patients were compared to historic (same hospital) and contemporary (another comparable hospital) matched, hospitalized controls on the non-prioritized outcomes: Length-of-stay, re-admissions, care quality (10 process-performance measures) and mortality. TIA patients were compared to contemporary matched, hospitalized controls.Following complete diagnostic work-up, patients with stroke/TIA were classified into 'low'/high risk' of re-stroke ≤7 days. RESULTS: We analyzed 1,076 consecutive patients of whom 253 (23.5%) were subsequently admitted to the stroke ward. Stroke/TIA was diagnosed in 215/171 patients, respectively. Fifty-six percent (121/215) of the stroke patients were subsequently admitted to the stroke ward. Comparison with the historic stroke cohort (n=191) showed a shorter acute hospital stay for the strokes (median 1 vs 3 days); adjusted length-of-stay ratio 0.49 (95% CI 0.33-0.71). Furthermore, 30-day readmission rate was 3.2% vs 11.6%; adjusted hazard ratio 0.23 (0.09-0.59); and care quality was higher with a risk ratio of 1.30 (1.15-1.47). The comparison of stroke and TIAs to contemporary controls showed similar results. Only one patient in the 'low risk' category and not admitted experienced stroke within 7 days (0.6%). CONCLUSIONS: An outpatient clinic set-up for patients with minor stroke/TIA yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that a neurovascular specialist driven outpatient clinic for minor stroke/TIA patients with the ability of subsequent admission is safe and yields shorter acute hospital stay, lower re-admissions rates, and better quality than hospitalization in stroke units.

Managing COVID-19 within and across health systems: why we need performance intelligence to coordinate a global response.

BACKGROUND: The COVID-19 pandemic is a complex global public health crisis presenting clinical, organisational and system-wide challenges. Different research perspectives on health are needed in order to manage and monitor this crisis. Performance intelligence is an approach that emphasises the need for different research perspectives in supporting health systems' decision-makers to determine policies based on well-informed choices. In this paper, we present the viewpoint of the Innovative Training Network for Healthcare Performance Intelligence Professionals (HealthPros) on how performance intelligence can be used during and after the COVID-19 pandemic. DISCUSSION: A lack of standardised information, paired with limited discussion and alignment between countries contribute to uncertainty in decision-making in all countries. Consequently, a plethora of different non-data-driven and uncoordinated approaches to address the outbreak are noted worldwide. Comparative health system research is needed to help countries shape their response models in social care, public health, primary care, hospital care and long-term care through the different phases of the pandemic. There is a need in each phase to compare context-specific bundles of measures where the impact on health outcomes can be modelled using targeted data and advanced statistical methods. Performance intelligence can be pursued to compare data, construct indicators and identify optimal strategies. Embracing a system perspective will allow countries to take coordinated strategic decisions while mitigating the risk of system collapse.A framework for the development and implementation of performance intelligence has been outlined by the HealthPros Network and is of pertinence. Health systems need better and more timely data to govern through a pandemic-induced transition period where tensions between care needs, demand and capacity are exceptionally high worldwide. Health systems are challenged to ensure essential levels of healthcare towards all patients, including those who need routine assistance. CONCLUSION: Performance intelligence plays an essential role as part of a broader public health strategy in guiding the decisions of health system actors on the implementation of contextualised measures to tackle COVID-19 or any future epidemic as well as their effect on the health system at large. This should be based on commonly agreed-upon standardised data and fit-for-purpose indicators, making optimal use of existing health information infrastructures. The HealthPros Network can make a meaningful contribution.

Segmentation, retardation and mass approximation of birefringent particles on a standard light microscope.

This study presents a simple technique for the approximation of retardation, thickness and mass of birefringent particles with a retardation from 8 to 231 nm retardation. Tuning of the imaging system (standard light microscope equipped with a left and a right circular polarizer) to match grey values of polymer retarder films of known retardation with rendered grey values allows for a robust calibration and accurate approximation of retardation. In addition, a technique for accurate particle segmentation using a Canny-Deriche algorithm was used to minimize the bias on mass estimated from different thresholding techniques. The technique was tested using microscopic calcitic plates called coccoliths produced by the marine algal group coccolithophores, and the results compare well with published coccolith mass estimates obtained from volumetric analysis. LAY DESCRIPTION: Material with certain optical properties display interference colours when observed in a light microscope under circular polarized light. This study presents a simple technique for measuring the thickness and retardation of small particles within the 8 to 231 nm retardation range based on the grey values of their interference colours. Retardation is a measure of the distance between waves of two mutually perpendicular polarized light waves after passing through material. The technique involves the tuning of a standard light microscope system equipped with a left and a right circular polarizer and a digital camera to match grey values of polymer retarder films with a known retardation with grey values of a digitially rendered Michel-Lévy chart. A technique for accurate isolation of particles from the image background using a Canny-Deriche algorithm is also described, which avoids possible biased results from thresholding. The techniques were tested using microscopic calcitic plates called coccoliths produced by the marine algal group coccolithophores, and the results compare well with published estimates obtained from volumetric analysis.

A changing landscape: Temporal trends in incidence and characteristics of patients hospitalized with venous thromboembolism 2006-2015.

BACKGROUND: Venous thromboembolism (VTE) has major clinical and public health impact. However, only sparse data on calendar time trends in incidence from unselected populations reflecting current clinical practice are available. OBJECTIVES: To examine temporal trends in the incidence and characteristics of patients hospitalized with first-time VTE in Denmark between 2006 and 2015. PATIENTS/METHODS: Using nationwide health care registries, we calculated yearly hospitalization rates for first-time VTE from 2006 to 2015. The rates were standardized to the age and sex distribution in 2006. Based on the hospitalization and prescription history of each patient, we assessed the risk profile and evaluated changes over time. RESULTS: We identified 67,426 patients with a first-time VTE hospitalization. The age- and sex-standardized incidence rate increased from 12.6 (95% CI: 12.3-12.9) per 10,000 person years at risk in 2006 to 15.1 (95% CI: 14.7-15.4) in 2015, corresponding to an increase of 19.8%. The increase was due to a 73.9% increase in the standardized incidence rate of pulmonary embolism (PE), whereas no increase was observed for deep vein thrombosis. The risk profile changed with an increasing proportion of elderly patients and patients with comorbidity (proportion of patients with a Charlson's Comorbidity Index score of ≥1). CONCLUSIONS: The hospitalization rate of first-time VTE, and particularly PE, has increased substantially within the last decade in Denmark. In addition, the risk profile of the VTE population has changed with more elderly and more patients with comorbidity being diagnosed. Further efforts are warranted to explore the changes in VTE epidemiology and the clinical implications.

Acute endovascular reperfusion treatment in patients with ischaemic stroke and large-vessel occlusion (Denmark 2011-2017).

BACKGROUND AND PURPOSE: Acute endovascular reperfusion treatment (aERT) of stroke patients with large-vessel occlusions is efficacious and safe according to several clinical trials. Data on outcome and safety of aERT in daily clinical routine are warranted and, in this study, we present national data from Denmark during 2011-2017. METHODS: National data for Denmark from 2011 to 2017 on all aERT procedures in patients with acute ischaemic stroke and computed tomography angiography/magnetic resonance angiography-verified large-vessel occlusion were derived from the Danish Stroke Registry, a national clinical quality registry to which reporting is mandatory for all hospitals treating stroke patients. Outcome (modified Rankin Scale score) after 3 months, including time of death, was assessed prospectively based on clinical examination or the Danish Civil Registration System. RESULTS: During the 7 years of observation, a total of 1720 patients were treated with aERT. The annual number of procedures increased from 128 in 2011 to 409 in 2017. The median age was 70 years, 58% were males and median National Institutes of Health Stroke Scale score at baseline was 16. Median time from symptom onset to groin puncture was 238 min with a decreasing trend during the years. Successful recanalization was reported in 1306 (76%) patients. At 3-month follow-up, an modified Rankin Scale score of 0-2 was reported in 46% of patients, whereas 14% of patients had died. CONCLUSION: Routine data on aERT in acute ischaemic stroke in Denmark from 2011 to 2017 suggest that the procedure is safe and efficacious.

Preoperative antithrombotic therapy and risk of blood transfusion and mortality following hip fracture surgery: a Danish nationwide cohort study.

Hip fracture surgery is associated with high risk of bleeding and mortality. The patients often have cardiovascular comorbidity, which requires antithrombotic treatment. This study found that preoperative use of oral anticoagulants was not associated with transfusion or mortality following hip fracture surgery, whereas increased risk may exist for antiplatelet drugs. INTRODUCTION: Hip fracture surgery is associated with high bleeding risk and mortality; however, data on operative outcomes of hip fracture patients admitted while on antithrombotic therapy is sparse. We examined if preoperative antithrombotic treatment was associated with increased use of blood transfusion and 30-day mortality following hip fracture surgery. METHODS: Using data from the Danish Multidisciplinary Hip Fracture Registry, we identified 74,791 hip fracture surgery patients aged ≥ 65 years during 2005-2016. Exposure was treatment with non-vitamin K antagonist oral anticoagulant (NOAC), vitamin K antagonists (VKA), or antiplatelet drugs at admission for hip fracture. Outcome was blood transfusion within 7 days postsurgery and death within 30 days. RESULTS: A 45.3% of patients received blood transfusion and 10.6% died. Current NOAC use was associated with slightly increased risk of transfusion (adjusted relative risk (aRR) 1.07, 95% confidence interval (CI) 1.01-1.14), but similar mortality risk (adjusted hazard ratio (aHR) 0.88, 95% CI 0.75-1.03) compared with non-users. The pattern remained when restricting to patients with short surgical delay (< 24 h). VKA users did not have increased risk of transfusion or mortality. The risks of transfusion (aRR 1.15 95% CI 1.12-1.18) and 30-day mortality (aHR 1.18 95% CI 1.14-1.23) were increased among antiplatelet users compared with non-users. CONCLUSIONS: In an observational setting, neither preoperative NOAC nor VKA treatments were associated with increased risk of 30-day postoperative mortality among hip fracture patients. NOAC was associated with slightly increased risk of transfusion. Preoperative use of antiplatelet drugs was associated with increased risk of transfusion and mortality.

The influence of blood pressure management on neurological outcome in endovascular therapy for acute ischaemic stroke.

BACKGROUND: Observational studies have suggested that low blood pressure and blood pressure variability may partially explain adverse neurological outcome after endovascular therapy with general anaesthesia (GA) for acute ischaemic stroke. The aim of this study was to further examine whether blood pressure related parameters during endovascular therapy are associated with neurological outcome. METHODS: The GOLIATH trial randomised 128 patients to either GA or conscious sedation for endovascular therapy in acute ischaemic stroke. The primary outcome was 90 day modified Rankin Score. The haemodynamic protocol aimed at keeping the systolic blood pressure >140 mm Hg and mean blood pressure >70 mm Hg during the procedure. Blood pressure related parameters of interest included 20% reduction in mean blood pressure; mean blood pressure <70 mm Hg, <80 mm Hg, and <90 mm Hg, respectively; time with systolic blood pressure <140 mm Hg; procedural minimum and maximum mean and systolic blood pressure; mean blood pressure at the time of groin puncture; postreperfusion mean blood pressure; blood pressure variability; and use of vasopressors. Sensitivity analyses were performed in the subgroup of reperfused patients. RESULTS: Procedural average mean and systolic blood pressures were higher in the conscious sedation group (P<0.001). The number of patients with mean blood pressure <70-90 mm Hg and systolic blood pressure <140 mm Hg, blood pressure variability, and use of vasopressors were all higher in the GA group (P<0.001). There was no statistically significant association between any of the examined blood pressure related parameters and the modified Rankin Score in the overall patient population, and in the subgroup of patients with full reperfusion. CONCLUSION: We found no statistically significant association between blood pressure related parameters during endovascular therapy and neurological outcome. CLINICAL TRIAL REGISTRATION: NCT 02317237.

Prescription and predictors of post-stroke antidepressant treatment: A population-based study.

OBJECTIVES: Post-stroke depression and pathological crying are common and potentially serious complications after stroke and should be diagnosed and treated accordingly. Diagnosis and treatment probably rely on clinical experience and may pose certain challenges. We aimed to examine prescription and predictors of antidepressant treatment after ischemic stroke in a clinical setting. MATERIALS AND METHODS: In this registry-based follow-up study, consecutive ischemic stroke patients were identified from the Danish Stroke Registry, holding information on antidepressant treatment during admission in Aarhus County from 2003 to 2010. Information on prescription after discharge was obtained from the Danish Prescription Database. Treatment initiation was analyzed using the cumulative incidence method including death as a competing risk. Multiple logistic regression was used to identify potential predictors of treatment. RESULTS: Among 5070 consecutive first-ever ischemic stroke patients without prior antidepressant treatment, the cumulative incidence of antidepressant treatment and prescription over 6 months was 35.2% (95% CI: 33.8-36.6). Overall 16.5% (95% CI: 15.5-17.6) started treatment within 14 days corresponding to 48.1% (95% CI: 45.8-50.5) of all treated patients, and the most widely prescribed group of antidepressants was selective serotonin reuptake inhibitors (86%). Increasing stroke severity was associated with higher odds of initiating treatment. CONCLUSION: Antidepressant treatment in this real-life clinical setting was common and initiated early, in almost half the treated patients within 14 days. Our results suggest that special focus should be given to the severe strokes as they may have a greater risk of requiring treatment.

Accurate representation of interference colours (Michel-Lévy chart): from rendering to image colour correction.

Here a work flow towards an accurate representation of interference colours (Michel-Lévy chart) digitally captured on a polarised light microscope using dry and oil immersion objectives is presented. The work flow includes accurate rendering of interference colours considering the colour temperature of the light source of the microscope and chromatic adaptation to white points of RGB colour spaces as well as the colour correction of the camera using readily available colour targets. The quality of different colour correction profiles was tested independently on an IT8.7/1 target. The best performing profile was using the XYZ cLUT algorithm and it revealed a ΔE00 of 1.9 (6.4 no profile) at 5× and 1.1 (8.4 no profile) at 100× magnification, respectively. The overall performance of the workflow was tested by comparing rendered interference colours with colour-corrected images of a quartz wedge captured over a retardation range from 80-2500 nm at 5× magnification. Uncorrected images of the quartz wedge in sRGB colour space revealed a mean ΔE00 of 12.3, which could be reduced to a mean of 4.9 by applying a camera correction profile based on an IT8.7/1 target and the Matrix only algorithm (ΔE00 < 1.0 signifies colour differences imperceptible by the human eye). ΔE00 varied significantly over the retardation range of 80-2500 nm of the quartz wedge, but the reasons for this variation is not well understood and the quality of colour correction might be further improved in future by using custom made colour targets specifically designed for the analysis of high-order interference colours.

Fibroblast drug scavenging increases intratumoural gemcitabine accumulation in murine pancreas cancer.

OBJECTIVE: Desmoplasia and hypovascularity are thought to impede drug delivery in pancreatic ductal adenocarcinoma (PDAC). However, stromal depletion approaches have failed to show clinical responses in patients. Here, we aimed to revisit the role of the tumour microenvironment as a physical barrier for gemcitabine delivery. DESIGN: Gemcitabine metabolites were analysed in LSL-KrasG12D/+ ; LSL-Trp53R172H/+ ; Pdx-1-Cre (KPC) murine tumours and matched liver metastases, primary tumour cell lines, cancer-associated fibroblasts (CAFs) and pancreatic stellate cells (PSCs) by liquid chromatography-mass spectrometry/mass spectrometry. Functional and preclinical experiments, as well as expression analysis of stromal markers and gemcitabine metabolism pathways were performed in murine and human specimen to investigate the preclinical implications and the mechanism of gemcitabine accumulation. RESULTS: Gemcitabine accumulation was significantly enhanced in fibroblast-rich tumours compared with liver metastases and normal liver. In vitro, significantly increased concentrations of activated 2',2'-difluorodeoxycytidine-5'-triphosphate (dFdCTP) and greatly reduced amounts of the inactive gemcitabine metabolite 2',2'-difluorodeoxyuridine were detected in PSCs and CAFs. Mechanistically, key metabolic enzymes involved in gemcitabine inactivation such as hydrolytic cytosolic 5'-nucleotidases (Nt5c1A, Nt5c3) were expressed at low levels in CAFs in vitro and in vivo, and recombinant expression of Nt5c1A resulted in decreased intracellular dFdCTP concentrations in vitro. Moreover, gemcitabine treatment in KPC mice reduced the number of liver metastases by >50%. CONCLUSIONS: Our findings suggest that fibroblast drug scavenging may contribute to the clinical failure of gemcitabine in desmoplastic PDAC. Metabolic targeting of CAFs may thus be a promising strategy to enhance the antiproliferative effects of gemcitabine.

Return to work predictors after traumatic brain injury in a welfare state.

OBJECTIVE: To identify predictors of return to work (RTW) and stable labour market attachment (LMA) after severe traumatic brain injury (TBI) in Denmark. MATERIALS & METHODS: Patients aged 18-64 years, admitted to highly specialized neurorehabilitation after severe TBI 2004-2012 were included and followed up for ≤6 years. Weekly LMA data were retrieved from a national register of public assistance benefits. Weeks without or with supplemental public assistance benefits were defined as LMA weeks. Time of RTW was defined as first week with LMA. Stable LMA was defined as weeks with LMA ≥75% first year after RTW. Multivariable regressions were used to identify predictors of RTW and stable LMA among preinjury characteristics, injury severity, functional ability and rehabilitation trajectories. RESULTS: For the analyses of RTW and stable LMA, 651 and 336 patients were included, respectively. RTW was significantly associated with age (adjusted subhazard ratio 0.98, 95% CI 0.97-0.99), education (1.83, 95% CI 1.16-2.89), supplemental benefits (3.97, 95% CI 2.04-7.71), no benefits (4.86, 95% CI 2.90-8.17), length of stay in acute care (0.77, 95% CI 0.60-0.99) and time period of injury (1.56, 95% CI 1.15-2.10). The only significant predictor of stable LMA was age (adjusted odds ratio 0.97, 95% CI 0.95-0.99). CONCLUSION: RTW after severe TBI was associated with several socio-economic factors, whereas maintaining LMA depended on age only. We suggest that RTW rates could be improved by extensive rehabilitation targeting people that are older and low-educated, as these were less likely to RTW.

Repeated measurements of carotid atherosclerosis and future risk of venous thromboembolism: the Tromsø Study.

Essentials The relationship between atherosclerosis and venous thromboembolism (VTE) is controversial. In total, 10 426 participants recruited from the general population were included. Carotid intima media thickness and total plaque area was not associated with VTE. There was no association between plaque initiation or plaque progression and subsequent VTE. SUMMARY: Background Whether a relationship between atherosclerosis and subsequent venous thromboembolism (VTE) exists is controversial. Objective To investigate the association between carotid atherosclerosis and VTE by using repeated measurements of intima media thickness (IMT) and total plaque area (TPA) in participants recruited from the general population. Methods Participants were recruited from the fourth (1994-1995), fifth (2001-2002) and sixth (2007-2008) surveys of the Tromsø Study. In total, 10 426 participants attended, for whom measurements of carotid IMT and TPA and potential confounders were updated at each available survey. Time-varying Cox regression models were used to calculate hazard ratios (HRs) of VTE across various levels of IMT and TPA adjusted for age, sex, and body mass index. Results There were 368 incident VTE events during a median follow-up of 10.8 years. Participants with increasing IMT were, on average, older and had a less favorable cardiovascular risk profile. There was no association between tertiles of increasing TPA and the risk of VTE in the time-varying model, and increasing IMT was not associated with an increased risk of VTE (HR 0.96, 95% confidence interval [CI] 0.86-1.07). Neither plaque formation nor plaque progression was associated with the risk of VTE (respectively: HR 1.00, 95% CI 0.98-1.02; and HR 0.96, 95% CI 0.84-1.11). Conclusion Carotid IMT and TPA were not associated with an increased risk of VTE in time-varying analyses. Furthermore, there was no association between plaque initiation or plaque progression and subsequent VTE.

Mid-childhood outcomes after pre-viable preterm premature rupture of membranes.

OBJECTIVES: Investigate cardiorespiratory outcomes in children surviving previable preterm premature rupture of membranes (PV-PPROM) before 22 weeks' gestational age (GA) with minimum 2 weeks latency. STUDY DESIGN: Single institution, follow-up of retrospectively identified children who were born after PV-PPROM during 2000-2004, and individually matched preterm-born controls. RESULTS: Eleven PV-PPROM and matched control children were included at mean age of 10.5 and 10.7 years. Rupture of membranes occurred at mean GA 182 and 276 weeks and birth at 283 and 286 weeks, respectively. Compared to controls, the PV-PPROM group had significantly poorer lung function, findings on echocardiography indicating mild pulmonary hypertension, and lower peak oxygen consumption. Chart reviews suggested more motor difficulties and a tendency towards more problems with learning and attention. CONCLUSION: The findings highlight a preterm-born sub-group in need of targeted long-term monitoring and possibly interventions regarding future cardiorespiratory and neurodevelopmental function.