Attendance in a national screening program for diabetic retinopathy: a population-based study of 205,970 patients.

AIMS: A nationwide diabetic retinopathy (DR) screening program has been established in Denmark since 2013. We aimed to perform an evaluation of adherence to DR screenings and to examine whether non-adherence was correlated to DR progression. METHODS: The population consisted of a register-based cohort, who participated in the screening program from 2013 to 2018. We analyzed age, gender, marital status, DR level (International Clinical DR severity scale, none, mild-, moderate-, severe non-proliferative DR (NPDR) and proliferative DR (PDR)), comorbidities and socioeconomic factors. The attendance pattern of patients was grouped as either timely (no delays > 33%), delayed (delays > 33%) or one-time attendance (unexplained). RESULTS: We included 205,970 patients with 591,136 screenings. Rates of timely, delayed and one-time attendance were 53.0%, 35.5% and 11.5%, respectively. DR level at baseline was associated with delays (mild-, moderate-, severe NPDR and PDR) and one-time attendance (moderate-, severe NPDR and PDR) with relative risk ratios (RRR) of 1.68, 2.27, 3.14, 2.44 and 1.18, 2.07, 1.26, respectively (P < 0.05). Delays at previous screenings were associated with progression to severe NPDR or PDR (hazard ratio (HR) 2.27, 6.25 and 12.84 for 1, 2 and 3+ delays, respectively). Any given delay doubled the risk of progression (HR 2.28). CONCLUSIONS: In a national cohort of 205,970 patients, almost half of the patients attended DR screening later than scheduled or dropped out after first screening episode. This was, in particular, true for patients with any levels of DR at baseline. DR progression in patients with delayed attendance, increased with the number of missed appointments.

Accuracy and sensitivity of three-dimensional echocardiography to detect changes in right ventricular volumes: comparison study with cardiac magnetic resonance.

We aimed to investigate the ability of three-dimensional transthoracic echocardiography (3DE) to detect changes in RV volumes compared to cardiac magnetic resonance (CMR). Eighty-five subjects including 45 with no known cardiac disease and 40 patients with a variety of cardiac diseases were included. Two- and three-dimensional echocardiography as well as CMR of the RV was performed before and after infusion of on average two litres of saline. Examinations were analysed with estimation of RV dimensions, volumes and ejection fraction (RVEF). Intra- and inter-examiner variability was evaluated in 25 patients randomly selected from the cohort. Three-dimensional echocardiography underestimated volumes and RVEF compared to CMR with mean differences and 95% limits of agreement of 110.3 ± 59 mL for RV end-diastolic volume (RVEDV), 43.3 ± 32 mL for RV end-systolic volume (RVESV) and 3.5 ± 10.7% for RVEF. CMR was more reproducible than 3DE, with intra-observer coefficient of variation (CV) of 4% vs. 14.2% for RVEDV, 9.7% vs. 16.7% for RVESV and 6.3% vs. 8.6% for RVEF. The RVEDV, RVESV and RV stroke volume (RVSV) by CMR significantly increased after saline infusion by 15.3 ± 16.2 mL, 3.5 ± 14.2 mL and 11.8 ± 12.6 mL, respectively, as well as RVEF by 1.5 ± 4.6% (p < 0.05). However, 3DE was not able to detect any of these changes in RV volumes (p ≥ 0.05). Compared to CMR imaging of the RV, three-dimensional echocardiography appears unable and unreliable in detecting RV volume changes of less than 15%, highlighting the need for cautious utility of 3DE in these circumstances.

Helicopter vs. ground transportation of patients bound for primary percutaneous coronary intervention.

BACKGROUND: Implementation of the first Danish helicopter emergency medical service (HEMS) was associated with reduced time from first medical contact to treatment at a specialized centre for patients with suspected ST elevation myocardial infarction (STEMI). We aimed to investigate effects of HEMS on mortality and labour market affiliation in patients admitted for primary percutaneous coronary intervention (PCI). METHODS: In this prospective observational study, we included patients with suspected STEMI within the region covered by the HEMS from January 1, 2010, to April 30, 2013, transported by either HEMS or ground emergency medical services (GEMS) to the regional PCI centre. The primary outcome was 30-day mortality. RESULTS: Among the 384 HEMS and 1220 GEMS patients, time from diagnostic ECG to PCI centre arrival was lower with HEMS (median 71 min vs. 78 min with GEMS; P = 0.004). Thirty-day mortality was 5.0% and 6.2%, respectively (adjusted OR = 0.82, 95% CI 0.44-1.51, P = 0.52. Involuntary early retirement rates were 0.62 (HEMS) and 0.94 (GEMS) per 100 PYR (adjusted IRR = 0.68, 0.15-3.23, P = 0.63). The proportion of patients on social transfer payments longer than half of the follow-up time was 22.1% (HEMS) vs. 21.2% (adjusted OR = 1.10, 0.64-1.90, P = 0.73). CONCLUSION: In an observational study of patients with suspected STEMI in eastern Denmark, no significant beneficial effect of helicopter transport could be detected on mortality, premature labour market exit or work ability. Only a study with random allocation to one system vs. another, along with a large sample size, will allow determination of superiority of helicopter transport.

Real-Time Elucidation of Catalytic Pathways in CO Hydrogenation on Ru.

The direct elucidation of the reaction pathways in heterogeneous catalysis has been challenging due to the short-lived nature of reaction intermediates. Here, we directly measured on ultrafast time scales the initial hydrogenation steps of adsorbed CO on a Ru catalyst surface, which is known as the bottleneck reaction in syngas and CO2 reforming processes. We initiated the hydrogenation of CO with an ultrafast laser temperature jump and probed transient changes in the electronic structure using real-time X-ray spectroscopy. In combination with theoretical simulations, we verified the formation of CHO during CO hydrogenation.

Red blood cell storage duration and long-term mortality in patients undergoing cardiac intervention: a Danish register study.

OBJECTIVES: To study the effect of red blood cell (RBC) storage duration on long-term mortality in patients undergoing cardiac intervention. BACKGROUND: RBCs undergo numerous structural and functional changes during storage. Observational studies have assessed the association between RBC storage duration and patient outcomes with conflicting results. METHODS: Between January 2006 and December 2014, 82 408 patients underwent coronary angiography. Of these, 1856 patients received one to four RBC units within 30 days after this procedure. Patients were allocated according to length of RBC storage duration: short-term (≤11 days), intermediate (IM)-term (12-23 days) and long-term (≥24 days). The study endpoints were 30-day and long-term all-cause mortality. RESULTS: A total of 4168 RBC units were given to 1856 patients. The mean RBC storage duration was 8.5 ± 2.1, 17.7 ± 3.4 and 29.9 ± 3.4 days in the short-term, IM-term and long-term storage groups, respectively. There was no difference in baseline characteristics between the groups. The long-term storage group received significantly more units (2.4 ± 1.0 units) as compared to the short-term (2.0 ± 1.0 units; P < 0.001) and IM-term storage group (2.2 ± 1.0 units; P < 0.01). In the survival analysis, there was no significant difference in all-cause mortality between the groups (log-rank: 0.509 for 30-days mortality; 0.493 for 5-year mortality). Additional stratified analysis demonstrated no association between RBC storage duration and long-term mortality. CONCLUSION: This study did not find an association between RBC storage duration and 30-days or long-term mortality in patients undergoing cardiac intervention.

Low Barrier Carbon Induced CO Dissociation on Stepped Cu.

Using x-ray photoelectron spectroscopy we observe the breaking of the strong interatomic bond in molecular CO at low temperature on a stepped Cu surface. Since the electronic structure of Cu does not allow for the splitting of CO at such low temperatures it suggests that there may be a less obvious pathway for the process. Through x-ray photoelectron spectroscopy we can clearly identify products associated with the dissociation of CO and the subsequent formation of stable graphitic carbon on the surface. However, the dissociation of CO can be inhibited when the stepped Cu surface is kept clean from surface carbon. These observations imply that the reaction is driven by the presence of small amounts of weakly bound carbon at the surface. Density-functional theory calculations confirm that carbon atoms on a stepped Cu surface indeed are the preferred adsorption sites for CO, which increases the stabilization of CO on the surface and weakens the C-O bond. This results in the breaking of the C-O bond at the step edge via the Boudouard reaction (2CO(ads)→C(ads)+CO(2)) with a barrier of 0.71 eV.

Strong Influence of Coadsorbate Interaction on CO Desorption Dynamics on Ru(0001) Probed by Ultrafast X-Ray Spectroscopy and Ab Initio Simulations.

We show that coadsorbed oxygen atoms have a dramatic influence on the CO desorption dynamics from Ru(0001). In contrast to the precursor-mediated desorption mechanism on Ru(0001), the presence of surface oxygen modifies the electronic structure of Ru atoms such that CO desorption occurs predominantly via the direct pathway. This phenomenon is directly observed in an ultrafast pump-probe experiment using a soft x-ray free-electron laser to monitor the dynamic evolution of the valence electronic structure of the surface species. This is supported with the potential of mean force along the CO desorption path obtained from density-functional theory calculations. Charge density distribution and frozen-orbital analysis suggest that the oxygen-induced reduction of the Pauli repulsion, and consequent increase of the dative interaction between the CO 5σ and the charged Ru atom, is the electronic origin of the distinct desorption dynamics. Ab initio molecular dynamics simulations of CO desorption from Ru(0001) and oxygen-coadsorbed Ru(0001) provide further insights into the surface bond-breaking process.

Surface chemistry. Probing the transition state region in catalytic CO oxidation on Ru.

Femtosecond x-ray laser pulses are used to probe the carbon monoxide (CO) oxidation reaction on ruthenium (Ru) initiated by an optical laser pulse. On a time scale of a few hundred femtoseconds, the optical laser pulse excites motions of CO and oxygen (O) on the surface, allowing the reactants to collide, and, with a transient close to a picosecond (ps), new electronic states appear in the O K-edge x-ray absorption spectrum. Density functional theory calculations indicate that these result from changes in the adsorption site and bond formation between CO and O with a distribution of OC-O bond lengths close to the transition state (TS). After 1 ps, 10% of the CO populate the TS region, which is consistent with predictions based on a quantum oscillator model.

Prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction and non-significant coronary artery disease.

BACKGROUND AND PURPOSE: We aimed to study the prevalence of acute cardiac disorders in patients with suspected ST-segment elevation myocardial infarction (STEMI) and non-significant coronary artery disease (CAD). METHODS: From January to October 2012 we consecutively included patients admitted with suspected STEMI and non-significant CAD (coronary artery stenosis diameter <50%). Patients were diagnosed with acute cardiac disorder in the presence of elevated cardiac biomarkers (troponin T >50ng/l or creatine kinase MB >4µg/l) or dynamic ECG changes (ST-segment changes or T-wave inversion). RESULTS: Of the 871 patients admitted with suspected STEMI, 11% (n=95) had non-significant CAD. Of these, 67% (n=64) had elevated cardiac biomarkers or dynamic ECG changes and were accordingly diagnosed with acute cardiac disorders. In the remaining 33% (n=31) of patients, cardiac biomarkers were normal and ECG changes remained stationary. CONCLUSIONS: Acute cardiac disorders were diagnosed in two thirds of patients with suspected STEMI and non-significant CAD.

Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures.

The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 µm for surfaces with small pillar sizes of 1 and 2 µm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 µm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine.

Current status of the Scandiatransplant acceptable mismatch program.

This article describes the Scandiatransplant Acceptable Mismatch Program (STAMP), which was set into action in 2009. The aim of STAMP is to define human leukocyte antigens (HLA) toward which the potential kidney recipient has not developed antibodies, as "acceptable mismatches" in the Scandiatransplant database. In many cases this may improve the probability for a highly immunized recipient to receive a suitable kidney graft from a deceased donor. Using data extracted from the Scandiatransplant database on the outcomes of the program after the first 3 years, 31/115 recipients included in the program have undergone transplantation. From 2008 to 2011 the mean waiting time for highly immunized patients has decreased from 42 to 37 months. Continuous evaluation and follow-up of the program is essential to improve the procedures and outcomes. Calculation of transplantability based on a given set of acceptable mismatches was added to the program in 2011, based on the historical deceased donor pool providing the possibility of a specific patient to receive a kidney through STAMP. It is still a challenge for the tissue typing laboratories to determine which detected HLA antibodies are clinical relevant. We concluded that STAMP has had the intended effects, however adjustments and improvements is an ongoing process. As an improvment of the program HLA-C was added to the STAMP search algorithm in September 2012.

Screening performance for trisomy 21 comparing first trimester combined screening and a first trimester contingent screening protocol including ductus venosus and tricuspid flow.

OBJECTIVE: To compare the standard first trimester combined risk assessment for trisomy 21 with a contingent screening protocol including tricuspid flow and ductus venosus flow. MATERIAL AND METHOD: Women with singleton pregnancies and a first trimester combined risk assessment>1:1000 were included. They all had additional assessment of the ductus venosus and the tricuspid flow. We compared screening performance in two screening strategies: (a) First trimester combined screening strategy based on the individual risk results from the routine screening test and (b) Contingent screening strategy based on a combination of the routine test results and additional ultrasound markers. RESULTS: We included 917 women in the study, 894 in the euploid group and 23 in the trisomy 21 group. Using a contingent screening strategy resulted in a significant decrease in screen positive rate from 48.3% to 17.7% (p<0.001) in the studied population. There was no statistical difference in detection rate between the two screening strategies. CONCLUSION: There is increasing evidence in favour of using additional ultrasound markers as part of contingent screening protocols in the first trimester. We do suggest performing further studies in routine clinical settings to provide validation of the available risk algorithms.

Long-term outcome in patients with juvenile dermatomyositis: a cross-sectional follow-up study.

OBJECTIVE: To evaluate a group of 53 patients with juvenile dermatomyositis (JDM), on average 13.9 years after disease onset, in order to describe the long-term disease outcome and to identify disease-related parameters associated with poor disease outcome. METHODS: Baseline information at disease onset was obtained from medical records. Disease status at follow-up was evaluated by physical examination. The Myositis Damage Index (MDI) and the Myositis Disease Damage by Visual Analogue Scale (MYODAM-VAS) were used to describe disease damage. RESULTS: Disease damage was seen in 60.4% of patients. The most common damage was cutaneous scarring (39.6%) and muscle dysfunction (34%). Calcinosis was found in 20%, lipodystrophy in 13%, and severe damage affecting more than two organ systems in 24.5% of patients. A disease duration > 4 years increased the risk of damage based on: MDI score [adjusted odds ratio (AOR) 8.3, 95% confidence interval (CI) 1.7-41.7], MYODAM-VAS score (AOR 26.2, 95% CI 3.1-223.7), and number of affected organs (AOR 16.3, 95% CI 1.1-232.4). Disease onset age ≥ 7.4 years increased the risk of more than two affected organs (AOR 15.8, 95% CI 1.9-129.4). Disease duration ≥ 4 years increased the risk of calcinosis (OR 4.8, 95% CI 1.1-20.9) and continuous muscle dysfunction (OR 4.2, 95% CI 1.1-17.3). CONCLUSION: In a long-term follow-up study, 60% of JDM patients had disease damage at a mean of 14 years after disease onset. Longer disease duration was the most important predictor of damage, calcinosis, and impaired muscle function, and higher age at disease onset predicted more organs involved at follow-up.

Universal transition state scaling relations for (de)hydrogenation over transition metals.

We analyse the transition state energies for 249 hydrogenation/dehydrogenation reactions of atoms and simple molecules over close-packed and stepped surfaces and nanoparticles of transition metals using Density Functional Theory. Linear energy scaling relations are observed for the transition state structures leading to transition state scaling relations for all the investigated reactions. With a suitable choice of reference systems the transition state scaling relations form a universality class that can be approximated with one single linear relation describing the entire range of reactions over all types of surfaces and nanoclusters.

On the behavior of Brønsted-Evans-Polanyi relations for transition metal oxides.

Versatile Brønsted-Evans-Polanyi (BEP) relations are found from density functional theory for a wide range of transition metal oxides including rutiles and perovskites. For oxides, the relation depends on the type of oxide, the active site, and the dissociating molecule. The slope of the BEP relation is strongly coupled to the adsorbate geometry in the transition state. If it is final state-like the dissociative chemisorption energy can be considered as a descriptor for the dissociation. If it is initial state-like, on the other hand, the dissociative chemisorption energy is not suitable as descriptor for the dissociation. Dissociation of molecules with strong intramolecular bonds belong to the former and molecules with weak intramolecular bonds to the latter group. We show, for the prototype system La-perovskites, that there is a "cyclic" behavior in the transition state characteristics upon change of the active transition metal of the oxide.

Spatial and temporal changes in the morphology of preosteoblastic cells seeded on microstructured tantalum surfaces.

It has been widely reported that surface morphology on the micrometer scale affects cell function as well as cell shape. In this study, we have systematically compared the influence of 13 topographically micropatterned tantalum surfaces on the temporal development of morphology, including spreading, and length of preosteoblastic cells (MC3T3-E1). Cells were examined after 0.5, 1, 4, and 24 h on different Ta microstructures with vertical dimensions (heights) of 0.25 and 1.6 mum. Cell morphologies depended upon the underlying surface topography, and the length and spreading of cells varied as a function of time with regard to the two-dimensional pattern and vertical dimension of the structure. Microstructures of parallel grooves/ridges caused elongated cell growth after 1 and 4 h in comparison to a flat, nonstructured, reference surface. For microstructures consisting of pillars, cell spreading was found to depend on the distance between the pillars with one specific pillar structure exhibiting a decreased spreading combined with a radical change in morphology of the cells. Interestingly, this morphology on the particular pillar structure was associated with a markedly different distribution of the actin cytoskeleton. Our results provide a basis for further work toward topographical guiding of cell function.

Using scaling relations to understand trends in the catalytic activity of transition metals.

A method is developed to estimate the potential energy diagram for a full catalytic reaction for a range of late transition metals on the basis of a calculation (or an experimental determination) for a single metal. The method, which employs scaling relations between adsorption energies, is illustrated by calculating the potential energy diagram for the methanation reaction and ammonia synthesis for 11 different metals on the basis of results calculated for Ru. It is also shown that considering the free energy diagram for the reactions, under typical industrial conditions, provides additional insight into reactivity trends.

Scaling properties of adsorption energies for hydrogen-containing molecules on transition-metal surfaces.

Density functional theory calculations are presented for CHx, x=0,1,2,3, NHx, x=0,1,2, OHx, x=0,1, and SHx, x=0,1 adsorption on a range of close-packed and stepped transition-metal surfaces. We find that the adsorption energy of any of the molecules considered scales approximately with the adsorption energy of the central, C, N, O, or S atom, the scaling constant depending only on x. A model is proposed to understand this behavior. The scaling model is developed into a general framework for estimating the reaction energies for hydrogenation and dehydrogenation reactions.