Does adding risk-trends to survival models improve in-hospital mortality predictions? A cohort study

<p>Abstract</p> <p>Background</p> <p>Clinicians informally assess changes in patients' status over time to prognosticate their outcomes. The incorporation of trends in patient status into regression models could improve their ability to predict outcomes. In this study, we used a unique approach to measure trends in patient hospital death risk and determined whether the incorporation of these trend measures into a survival model improved the accuracy of its risk predictions.</p> <p>Methods</p> <p>We included all adult inpatient hospitalizations between 1 April 2004 and 31 March 2009 at our institution. We used the daily mortality risk scores from an existing time-dependent survival model to create five trend indicators: absolute and relative percent change in the risk score from the previous day; absolute and relative percent change in the risk score from the start of the trend; and number of days with a trend in the risk score. In the derivation set, we determined which trend indicators were associated with time to death in hospital, independent of the existing covariates. In the validation set, we compared the predictive performance of the existing model with and without the trend indicators.</p> <p>Results</p> <p>Three trend indicators were independently associated with time to hospital mortality: the absolute change in the risk score from the previous day; the absolute change in the risk score from the start of the trend; and the number of consecutive days with a trend in the risk score. However, adding these trend indicators to the existing model resulted in only small improvements in model discrimination and calibration.</p> <p>Conclusions</p> <p>We produced several indicators of trend in patient risk that were significantly associated with time to hospital death independent of the model used to create them. In other survival models, our approach of incorporating risk trends could be explored to improve their performance without the collection of additional data.</p

Small global-mean cooling due to volcanic radiative forcing

In both the observational record and atmosphere-ocean general circulation model (AOGCM) simulations of the last ∼∼ 150 years, short-lived negative radiative forcing due to volcanic aerosol, following explosive eruptions, causes sudden global-mean cooling of up to ∼∼ 0.3 K. This is about five times smaller than expected from the transient climate response parameter (TCRP, K of global-mean surface air temperature change per W m−2 of radiative forcing increase) evaluated under atmospheric CO2 concentration increasing at 1 % yr−1. Using the step model (Good et al. in Geophys Res Lett 38:L01703, 2011. doi:10.​1029/​2010GL045208), we confirm the previous finding (Held et al. in J Clim 23:2418–2427, 2010. doi:10.​1175/​2009JCLI3466.​1) that the main reason for the discrepancy is the damping of the response to short-lived forcing by the thermal inertia of the upper ocean. Although the step model includes this effect, it still overestimates the volcanic cooling simulated by AOGCMs by about 60 %. We show that this remaining discrepancy can be explained by the magnitude of the volcanic forcing, which may be smaller in AOGCMs (by 30 % for the HadCM3 AOGCM) than in off-line calculations that do not account for rapid cloud adjustment, and the climate sensitivity parameter, which may be smaller than for increasing CO2 (40 % smaller than for 4 × CO2 in HadCM3)

External fixation compared to intramedullary nailing of tibial fractures in the rat

Background and purpose It is not known whether there is a difference in bone healing after external fixation and after intramedullary nailing. We therefore compared fracture healing in rats after these two procedures

The Procedural Index for Mortality Risk (PIMR): an index calculated using administrative data to quantify the independent influence of procedures on risk of hospital death

<p>Abstract</p> <p>Background</p> <p>Surgeries and other procedures can influence the risk of death in hospital. All published scales that predict post-operative death risk require clinical data and cannot be measured using administrative data alone. This study derived and internally validated an index that can be calculated using administrative data to quantify the independent risk of hospital death after a procedure.</p> <p>Methods</p> <p>For all patients admitted to a single academic centre between 2004 and 2009, we estimated the risk of all-cause death using the Kaiser Permanente Inpatient Risk Adjustment Methodology (KP-IRAM). We determined whether each patient underwent one of 503 commonly performed therapeutic procedures using Canadian Classification of Interventions codes and whether each procedure was emergent or elective. Multivariate logistic regression modeling was used to measure the association of each procedure-urgency combination with death in hospital independent of the KP-IRAM risk of death. The final model was modified into a scoring system to quantify the independent influence each procedure had on the risk of death in hospital.</p> <p>Results</p> <p>275 460 hospitalizations were included (137,730 derivation, 137,730 validation). In the derivation group, the median expected risk of death was 0.1% (IQR 0.01%-1.4%) with 4013 (2.9%) dying during the hospitalization. 56 distinct procedure-urgency combinations entered our final model resulting in a Procedural Index for Mortality Rating (PIMR) score values ranging from -7 to +11. In the validation group, the PIMR score significantly predicted the risk of death by itself (c-statistic 67.3%, 95% CI 66.6-68.0%) and when added to the KP-IRAM model (c-index improved significantly from 0.929 to 0.938).</p> <p>Conclusions</p> <p>We derived and internally validated an index that uses administrative data to quantify the independent association of a broad range of therapeutic procedures with risk of death in hospital. This scale will improve risk adjustment when administrative data are used for analyses.</p

Overlay of conventional angiographic and en-face OCT images enhances their interpretation

BACKGROUND: Combining characteristic morphological and functional information in one image increases pathophysiologic understanding as well as diagnostic accuracy in most clinical settings. En-face optical coherence tomography (OCT) provides a high resolution, transversal OCT image of the macular area combined with a confocal image of the same area (OCT C-scans). Creating an overlay image of a conventional angiographic image onto an OCT image, using the confocal part to facilitate transformation, combines structural and functional information of the retinal area of interest. This paper describes the construction of such overlay images and their aid in improving the interpretation of OCT C-scans. METHODS: In various patients, en-face OCT C-scans (made with a prototype OCT-Ophthalmoscope (OTI, Canada) in use at the Department of Ophthalmology (Academic Medical Centre, Amsterdam, The Netherlands)) and conventional fluorescein angiography (FA) were performed. ImagePro, with a custom made plug-in, was used to make an overlay-image. The confocal part of the OCT C-scan was used to spatially transform the FA image onto the OCT C-scan, using the vascular arcades as a reference. To facilitate visualization the transformed angiographic image and the OCT C-scan were combined in an RGB image. RESULTS: The confocal part of the OCT C-scan could easily be fused with angiographic images. Overlay showed a direct correspondence between retinal thickening and FA leakage in Birdshot retinochoroiditis, localized the subretinal neovascular membrane and correlated anatomic and vascular leakage features in myopia, and showed the extent of retinal and pigment epithelial detachment in retinal angiomatous proliferation as FA leakage was subject to blocked fluorescence. The overlay mode provided additional insight not readily available in either mode alone. CONCLUSION: Combining conventional angiographic images and en-face OCT C-scans assists in the interpretation of both imaging modalities. By combining the physiopathological information in the angiograms with the structural information in the OCT scan, zones of leakage can be correlated to structural changes in the retina or pigment epithelium. This strategy could be used in the evaluation and monitoring of patients with complex central macular pathology

Potential climatic transitions with profound impact on Europe

We discuss potential transitions of six climatic subsystems with large-scale impact on Europe, sometimes denoted as tipping elements. These are the ice sheets on Greenland and West Antarctica, the Atlantic thermohaline circulation, Arctic sea ice, Alpine glaciers and northern hemisphere stratospheric ozone. Each system is represented by co-authors actively publishing in the corresponding field. For each subsystem we summarize the mechanism of a potential transition in a warmer climate along with its impact on Europe and assess the likelihood for such a transition based on published scientific literature. As a summary, the ‘tipping’ potential for each system is provided as a function of global mean temperature increase which required some subjective interpretation of scientific facts by the authors and should be considered as a snapshot of our current understanding. <br/

Interaction of Polysialic Acid with CCL21 Regulates the Migratory Capacity of Human Dendritic Cells

Dendritic cells (DCs) are the most potent antigen-presenting cells (APCs). Immature DCs (iDCs) are situated in the periphery where they capture pathogen. Subsequently, they migrate as mature DCs (mDCs) to draining lymph nodes to activate T cells. CCR7 and CCL21 contribute to the migratory capacity of the DC, but it is not completely understood what molecular requirements are involved. Here we demonstrate that monocyte-derived DCs dramatically change ST8Sia IV expression during maturation, leading to the generation of polysialic acid (polySia). PolySia expression is highly upregulated after 2 days Toll-like receptor-4 (TLR4) triggering. Surprisingly, only immunogenic and not tolerogenic mDCs upregulated polySia expression. Furthermore, we show that polySia expression on DCs is required for CCL21-directed migration, whereby polySia directly captures CCL21. Corresponding to polySia, the expression level of CCR7 is maximal two days after TLR4 triggering. In contrast, although TLR agonists other than LPS induce upregulation of CCR7, they achieve only a moderate polySia expression. In situ we could detect polySia-expressing APCs in the T cell zone of the lymph node and in the deep dermis. Together our results indicate that prolonged TLR4 engagement is required for the generation of polySia-expressing DCs that facilitate CCL21 capture and subsequent CCL21-directed migration

A randomised clinical trial on a comprehensive geriatric assessment and intensive home follow-up after hospital discharge: the Transitional Care Bridge

<p>Abstract</p> <p>Background</p> <p>Older patients are at high risk for poor outcomes after acute hospital admission. The mortality rate in these patients is approximately 20%, whereas 30% of the survivors decline in their level of activities of daily living (ADL) functioning three months after hospital discharge. Most diseases and geriatric conditions that contribute to poor outcomes could be subject to pro-active intervention; not only during hospitalization, but also after discharge. This paper presents the design of a randomised controlled clinical trial concerning the effect of a pro-active, multi-component, nurse-led transitional care program following patients for six months after hospital admission.</p> <p>Methods/Design</p> <p>Three hospitals in the Netherlands will participate in the multi-centre, double-blind, randomised clinical trial comparing a pro-active multi-component nurse-led transitional care program to usual care after discharge. All patients acutely admitted to the Department of Internal Medicine who are 65 years and older, hospitalised for at least 48 hours and are at risk for functional decline are invited to participate in the study. All patients will receive integrated geriatric care by a geriatric consultation team during hospital admission. Randomization, which will be stratified by study site and cognitive impairment, will be conducted during admission. The intervention group will receive the transitional care bridge program, consisting of a handover moment with a community care Care Nurse (CN) during hospital admission and five home visits after discharge. The control group will receive 'care as usual' after discharge. The main outcome is the level of ADL functioning six months after discharge compared to premorbid functioning measured with the Katz ADL index. Secondary outcomes include; survival, cognitive functioning, quality of life, and health care utilization, satisfaction of the patient and primary care giver with the transitional care bridge program. All outcomes will be measured at three, six and twelve months after discharge. Approximately 674 patients will be enrolled to either the intervention or control group.</p> <p>Discussion</p> <p>The study will provide new knowledge on a combined intervention of integrated care during hospital admission, a proactive handover moment before discharge and intensive home visits after discharge.</p> <p>Trial registration</p> <p><b>Trial registration number: NTR 2384</b></p

Changes in physical activity following a genetic-based internet-delivered personalized intervention: randomized controlled trial (Food4Me)

Background: There is evidence that physical activity (PA) can attenuate the influence of the fat mass- and obesity-associated (FTO) genotype on the risk to develop obesity. However, whether providing personalized information on FTO genotype leads to changes in PA is unknown. Objective: The purpose of this study was to determine if disclosing FTO risk had an impact on change in PA following a 6-month intervention. Methods: The single nucleotide polymorphism (SNP) rs9939609 in the FTO gene was genotyped in 1279 participants of the Food4Me study, a four-arm, Web-based randomized controlled trial (RCT) in 7 European countries on the effects of personalized advice on nutrition and PA. PA was measured objectively using a TracmorD accelerometer and was self-reported using the Baecke questionnaire at baseline and 6 months. Differences in baseline PA variables between risk (AA and AT genotypes) and nonrisk (TT genotype) carriers were tested using multiple linear regression. Impact of FTO risk disclosure on PA change at 6 months was assessed among participants with inadequate PA, by including an interaction term in the model: disclosure (yes/no) × FTO risk (yes/no). Results: At baseline, data on PA were available for 874 and 405 participants with the risk and nonrisk FTO genotypes, respectively. There were no significant differences in objectively measured or self-reported baseline PA between risk and nonrisk carriers. A total of 807 (72.05%) of the participants out of 1120 in the personalized groups were encouraged to increase PA at baseline. Knowledge of FTO risk had no impact on PA in either risk or nonrisk carriers after the 6-month intervention. Attrition was higher in nonrisk participants for whom genotype was disclosed (P=.01) compared with their at-risk counterparts. Conclusions: No association between baseline PA and FTO risk genotype was observed. There was no added benefit of disclosing FTO risk on changes in PA in this personalized intervention. Further RCT studies are warranted to confirm whether disclosure of nonrisk genetic test results has adverse effects on engagement in behavior change