Reaching Ambulatory Older Adults with Educational Tools: Comparative Efficacy and Cost of Varied Outreach Modalities in Primary Care.

BACKGROUND: Providing patients with access to health information that can be obtained outside of an office visit is an important part of education, yet little is known about the effectiveness of outreach modalities to connect older adults to online educational tools. The objective was to identify the effectiveness and cost of outreach modalities providing online information about advance care planning (ACP) for older adults. METHODS: Six different outreach modalities were utilized to connect patients to online educational tools (ACP video decision aids). Participants were 13,582 patients aged 65 and older of 185 primary care providers with appointments over a 30-month period within a large health system in the greater New York City area. Main outcome measures were number of online video views and costs per outreach for each modality. KEY RESULTS: There were 1150 video views for 21,407 remote outreach events. Text messages, sent to the largest volume of patients (8869), had the highest outcome rate (9.6%) and were the most economical ($0.09). Characterization of phone calls demonstrated 21.7% engagement in the topic of ACP but resulted in minimal video views (<1%) and incurred the highest cost per outreach ($2.88). In-office handouts had negligible results (<1%). CONCLUSIONS: Text was the most cost-effective modality to connect older adults to an online educational tool in this pragmatic trial, though overall efficacy of all modalities was low.

The effect of scoliosis support orthosis bracing on adult spinal deformity patients: evaluation of gait and dynamic balance.

Non-operative treatment is regarded as the first-line therapy for patients with adult spinal deformity (ASD) without neurologic deficits or significant impairment. While there is high-level evidence supporting the use of rigid bracing in adolescent idiopathic scoliosis, there is a paucity of literature pertaining to the use of scoliosis support orthosis (SSO) in ASD patients. To investigate the impact of an SSO on pain, gait parameters, and functional balance measures in symptomatic ASD patients. Thirty ASD patients (26 Females, Age: 72.7, Cobb Angle: 47.1°) were evaluated on 3 different occasions: first day of bracing: baseline (Pre), and 45-min post fitting (Post45m), and after 8-weeks of bracing for 4 hours a day (Post8w). Each patient performed a 6-minute walk (over-ground gait), a dynamic balance test, and completed VAS, ODI, and SRS22r. Significant short- and long-term improvements using SSO were found in the 6-minute walk (Pre: 278.6; Post45m: 322.2; Post8w: 338.8 m, p<0.001), walking speed (Pre: 0.88; Post45m: 0.97; Post8w: 0.97 m/s, p<0.001), head total sway distance during the balance test (Pre: 81.33; Post45m: 68.63; Post8w: 60.72 cm, p=0.048), low-back pain (VAS: Pre: 5.5; Post45m: 3.5; Post8w: 3.3, p<0.001), and for the ODI (Pre: 41.9; Post45m: 32.9; Post8w: 30.1, p=0.005).This study demonstrated clinically significant improvements in PROMs, spatiotemporal gait measures, and functional balance measures after continuous use of a SSO. These improvements were observed immediately following brace-fitting and maintained at an 8-week follow-up. Given these results, it is reasonable to consider a SSO for conservative management of patients with mild symptoms of pain and deformity, and who have not yet progressed to meet surgical indications.

Tracking ultrafast hot-electron diffusion in space and time by ultrafast thermomodulation microscopy.

The ultrafast response of metals to light is governed by intriguing nonequilibrium dynamics involving the interplay of excited electrons and phonons. The coupling between them leads to nonlinear diffusion behavior on ultrashort time scales. Here, we use scanning ultrafast thermomodulation microscopy to image the spatiotemporal hot-electron diffusion in thin gold films. By tracking local transient reflectivity with 20-nm spatial precision and 0.25-ps temporal resolution, we reveal two distinct diffusion regimes: an initial rapid diffusion during the first few picoseconds, followed by about 100-fold slower diffusion at longer times. We find a slower initial diffusion than previously predicted for purely electronic diffusion. We develop a comprehensive three-dimensional model based on a two-temperature model and evaluation of the thermo-optical response, taking into account the delaying effect of electron-phonon coupling. Our simulations describe well the observed diffusion dynamics and let us identify the two diffusion regimes as hot-electron and phonon-limited thermal diffusion, respectively.

The GABAAα5-selective Modulator, RO4938581, Rescues Protein Anomalies in the Ts65Dn Mouse Model of Down Syndrome.

Down syndrome (DS), trisomy of human chromosome 21 (Hsa21), is the most common genetic cause of intellectual disability (ID). There are no treatments for the cognitive deficits. The Ts65Dn is a partial trisomy mouse model of DS that shows learning and memory (LM) impairments and other abnormalities relevant to those seen in DS. Many drugs and small molecules have been shown to rescue the LM deficits, but little is known about the associated molecular responses. Here, patterns of protein expression are described in hippocampus of Ts65Dn and euploid littermate controls exposed to a battery of LM and behavior tests with and without chronic treatment with the GABAA receptor α5 subunit-selective negative allosteric modulator, RO4938581, that rescued LM deficits. Levels of 91 proteins/protein modifications, selected for relevance to LM and synaptic plasticity, were measured: 44 of 52 abnormalities present in vehicle-treated Ts65Dn were corrected by RO4938581. Superimposing protein data onto the molecular pathway defining long-term potentiation (LTP) shows that profiles are consistent with both abnormal LTP in vehicle-treated Ts65Dn and its observed rescue by RO4938581. Lastly, comparing these results with those from Ts65Dn treated, using a different protocol, with the NMDA receptor antagonist, memantine, that also rescues LM impairments, identifies common and divergent responses to the two drugs. Expansion of this approach to include additional drugs and DS models would aid in determining critical protein abnormalities and in identifying cocktails of drugs and/or new drug targets that would be effective in clinical trials for ID in DS.

Subcortical brain structure and suicidal behaviour in major depressive disorder: a meta-analysis from the ENIGMA-MDD working group.

The aetiology of suicidal behaviour is complex, and knowledge about its neurobiological mechanisms is limited. Neuroimaging methods provide a noninvasive approach to explore the neural correlates of suicide vulnerability in vivo. The ENIGMA-MDD Working Group is an international collaboration evaluating neuroimaging and clinical data from thousands of individuals collected by research groups from around the world. Here we present analyses in a subset sample (n=3097) for whom suicidality data were available. Prevalence of suicidal symptoms among major depressive disorder (MDD) cases ranged between 29 and 69% across cohorts. We compared mean subcortical grey matter volumes, lateral ventricle volumes and total intracranial volume (ICV) in MDD patients with suicidal symptoms (N=451) vs healthy controls (N=1996) or MDD patients with no suicidal symptoms (N=650). MDD patients reporting suicidal plans or attempts showed a smaller ICV (P=4.12 × 10-3) or a 2.87% smaller volume compared with controls (Cohen's d=-0.284). In addition, we observed a nonsignificant trend in which MDD cases with suicidal symptoms had smaller subcortical volumes and larger ventricular volumes compared with controls. Finally, no significant differences (P=0.28-0.97) were found between MDD patients with and those without suicidal symptoms for any of the brain volume measures. This is by far the largest neuroimaging meta-analysis of suicidal behaviour in MDD to date. Our results did not replicate previous reports of association between subcortical brain structure and suicidality and highlight the need for collecting better-powered imaging samples and using improved suicidality assessment instruments.

Subcortical brain alterations in major depressive disorder: findings from the ENIGMA Major Depressive Disorder working group.

The pattern of structural brain alterations associated with major depressive disorder (MDD) remains unresolved. This is in part due to small sample sizes of neuroimaging studies resulting in limited statistical power, disease heterogeneity and the complex interactions between clinical characteristics and brain morphology. To address this, we meta-analyzed three-dimensional brain magnetic resonance imaging data from 1728 MDD patients and 7199 controls from 15 research samples worldwide, to identify subcortical brain volumes that robustly discriminate MDD patients from healthy controls. Relative to controls, patients had significantly lower hippocampal volumes (Cohen's d=-0.14, % difference=-1.24). This effect was driven by patients with recurrent MDD (Cohen's d=-0.17, % difference=-1.44), and we detected no differences between first episode patients and controls. Age of onset ⩽21 was associated with a smaller hippocampus (Cohen's d=-0.20, % difference=-1.85) and a trend toward smaller amygdala (Cohen's d=-0.11, % difference=-1.23) and larger lateral ventricles (Cohen's d=0.12, % difference=5.11). Symptom severity at study inclusion was not associated with any regional brain volumes. Sample characteristics such as mean age, proportion of antidepressant users and proportion of remitted patients, and methodological characteristics did not significantly moderate alterations in brain volumes in MDD. Samples with a higher proportion of antipsychotic medication users showed larger caudate volumes in MDD patients compared with controls. This currently largest worldwide effort to identify subcortical brain alterations showed robust smaller hippocampal volumes in MDD patients, moderated by age of onset and first episode versus recurrent episode status.

A spectrum project: preterm birth and small-for-gestational age among infants with birth defects.

OBJECTIVE: The aim of this study is to investigate the association between birth defects (BDs), prematurity and small-for-gestational age (SGA) in a population-based sample. STUDY DESIGN: Participants were singleton live births enrolled in the National Birth Defects Prevention Study, including 18 737 case infants with one or more BD and 7999 controls. Logistic regression models to evaluate associations between BDs, prematurity and fetal growth were computed while adjusting for covariates. RESULT: Cases were significantly more likely to be born prematurely than controls, particularly at 24 to 28 weeks of gestation. The highest odds ratios for preterm birth were found for intestinal atresia, anencephaly, gastroschisis and esophageal atresia. Infants with BDs were also significantly more likely to be SGA than controls (17.2 and 7.8%). CONCLUSION: Infants with BDs are more likely than controls to be born prematurely and SGA. Findings from this study present additional evidence demonstrating a complex interaction between the development of BDs, prematurity and intrauterine growth.

Bloch oscillations in plasmonic waveguide arrays.

The combination of modern nanofabrication techniques and advanced computational tools has opened unprecedented opportunities to mold the flow of light. In particular, discrete photonic structures can be designed such that the resulting light dynamics mimics quantum mechanical condensed matter phenomena. By mapping the time-dependent probability distribution of an electronic wave packet to the spatial light intensity distribution in the corresponding photonic structure, the quantum mechanical evolution can be visualized directly in a coherent, yet classical wave environment. On the basis of this approach, several groups have recently observed discrete diffraction, Bloch oscillations and Zener tunnelling in different dielectric structures. Here we report the experimental observation of discrete diffraction and Bloch oscillations of surface plasmon polaritons in evanescently coupled plasmonic waveguide arrays. The effective external potential is tailored by introducing an appropriate transverse index gradient during nanofabrication of the arrays. Our experimental results are in excellent agreement with numerical calculations.

Dual energy imaging using a clinical on-board imaging system.

Dual energy (DE) imaging consists of obtaining kilovoltage (kV) x-ray images at two different diagnostic energies and performing a weighted subtraction of these images. A third image is then produced that highlights soft tissue. DE imaging has been used by radiologists to aid in the detection of lung malignancies. However, it has not been used clinically in radiotherapy. The goal of this study is to assess the feasibility of performing DE imaging using a commercial on-board imaging system. Both a simple and an anthropomorphic phantom were constructed for this analysis. Planar kV images of the phantoms were obtained using varied imaging energies and mAs. Software was written to perform DE subtraction using empirically determined weighting factors. Tumor detectability was assessed quantitatively using the signal-difference-to-noise ratio (SDNR). Overall DE subtraction suppressed high density objects in both phantoms. The optimal imaging technique, providing the largest SDNR with a dose less than our reference technique was 140 kVp, 1.0 mAs and 60 kVp, 3.2 mAs. Based on this analysis, DE subtraction imaging is feasible using a commercial on-board imaging system and may improve the visualization of tumors in lung cancer patients undergoing image-guided radiotherapy.

[A 44-year-old woman with hereditary nonpolyposis colon carcinoma: screening examinations for non-colonic tumors]. / 44-jährige Patientin mit hereditärem nichtpolypösem Kolonkarzinom: Vorsorgeuntersuchungen nichtkolonischer Tumoren.

A 44-year-old woman presented in March 2010 for surveillance esophagogastroduodenoscopy (EGD). In October 2004, rectal cancer had been diagnosed and treated by resection of the rectum with adjuvant chemotherapy. A diagnosis of hereditary nonpolyposis colon carcinoma (HNPCC) was established on the basis of the Amsterdam II criteria. Due to a lack of clear guidelines we decided to perform annual systematic surveillance examinations of the stomach and the most frequent tumor manifestations. Until 2009, extracolonic tumors were not observed in the patient. In March 2010, EGD showed a discrete erosive lesion in the gastric antrum, which was biopsied. Most notably, the histopathological examination revealed a poorly differentiated mucinous adenocarcinoma. Due to the poor differentiation, we decided against technically possible, endoscopic resection. The patient underwent subtotal gastrectomy and is still doing fine 28 months after surgery. This case prompted us to evaluate our surveillance approach in HNPCC patients and to review the literature.

Development of the mandibular, hyoid arch and gill arch skeleton in the Chinese barb Puntius semifasciolatus: comparisons of ossification sequences among Cypriniformes.

The morphogenesis and sequence of ossification and chondrification of skeletal elements of the jaws, and hyoid arch and gill arches of Puntius semifasciolatus are described. These data provide a baseline for further studies and enable comparisons with other described cypriniforms. Some general patterns of ossification in the hyoid arch and branchial arches in cypriniforms were notable. First, the overall development is from anterior to posterior, with the exception of the fifth ceratobranchial bone, which ossifies first. Second, where ossification of iterated elements is sequential, it tends to proceed from posterior to anterior, even when more posterior chondrifications are the smallest in the series. Ossification of the ceratobranchial, epibranchial and pharyngobranchial bones tends to proceed from ventral to dorsal. The comparisons revealed small sets of skeletal elements whose ossification sequence appears to be relatively conserved across cyprinid cypriniforms. Several potentially key timing changes in the ossification sequence of the jaws, hyoid arch and gill arches were identified, such as the accelerated timing of ossification of the fifth ceratobranchial bone, which may be unique to cypriniforms.

[Is there a role for risk-scoring methods in ruptured abdominal aortic aneurysm (rAAA)?]. / Was leisten Risiko-Scores beim rupturierten abdominellen Aortenaneurysma (rAAA)?

BACKGROUND: Rupture of an abdominal aortic aneurysm (rAAA) is associated with a high mortality both before and after admission to hospital. In spite of the use of expensive intensive medical therapeutic interventions 30 - 50 % of the operated patients still die. The ASA score is one of the most used scores world-wide. Use of the Glasgow aneurysm score (GAS) and the Hardman index (HI) is frequently reported in the literature to predict survival after surgical management of rAAA. With regard to the comorbidity factor severity score (CSS) no evaluated data on the mortality in cases of rAAA are available. On the basis of our own patient collective we intended to assess to what extent the risk score could give an answer to the question of therapeutic options. METHODS: In a retrospective study (7/1998 - 8/2007), 94 patients (m : f = 78 : 16) were assessed after operative management of rAAA. The validity of preoperative risk assessments on the basis of the ASA score, the CSS, the GAS and the HI with regard to intra- or postoperative death in the initial hospitalisation period was examined. Sensitivity and specificity of the score systems were determined by receiver operating characteristics (ROC) analyses. RESULTS: The age of the patients was 72.3 ±â€†9.5 years (mean ±â€†SD). Thirty-five (37.2 %) patients died in the immediate postoperative period. The areas under the receiver operating characteristics curves for ASA, GAS, HI and CSS were 0.598, 0.787, 0.742 and 0.614, respectively. CONCLUSIONS: This study revealed clear differences in the prognostic predictions of the various scores. In accord with the literature, no score gave a 100 % positive result with regard to mortality. Thus, an individual decision or, respectively, a therapeutic option cannot be reached with the help of the investigated scores. Further parameters need to be evaluated in order to make decisions about postoperative therapy.

Three-year outcomes from BENEFIT-EXT: a phase III study of belatacept versus cyclosporine in recipients of extended criteria donor kidneys.

Recipients of extended-criteria donor (ECD) kidneys have poorer long-term outcomes compared to standard-criteria donor kidney recipients. We report 3-year outcomes from a randomized, phase III study in recipients of de novo ECD kidneys (n = 543) assigned (1:1:1) to either a more intensive (MI) or less intensive (LI) belatacept regimen, or cyclosporine. Three hundred twenty-three patients completed treatment by year 3. Patient survival with a functioning graft was comparable between groups (80% in MI, 82% in LI, 80% in cyclosporine). Mean calculated GFR (cGFR) was 11 mL/min higher in belatacept-treated versus cyclosporine-treated patients (42.7 in MI, 42.2 in LI, 31.5 mL/min in cyclosporine). More cyclosporine-treated patients (44%) progressed to GFR <30 mL/min (chronic kidney disease [CKD] stage 4/5) than belatacept-treated patients (27-30%). Acute rejection rates were similar between groups. Posttransplant lymphoproliferative disorder (PTLD) occurrence was higher in belatacept-treated patients (two in MI, three in LI), most of which occurred during the first 18 months; four additional cases (3 in LI, 1 in cyclosporine) occurred after 3 years. Tuberculosis was reported in two MI, four LI and no cyclosporine patients. In conclusion, at 3 years after transplantation, immunosuppression with belatacept resulted in similar patient survival, graft survival and acute rejection, with better renal function compared with cyclosporine. As previously reported, PTLD and tuberculosis were the principal safety findings associated with belatacept in this study population.

SU-E-J-91: FFT Based Medical Image Registration Using a Graphics Processing Unit (GPU).

PURPOSE: To evaluate the efficiency gains obtained from using a Graphics Processing Unit (GPU) to perform a Fourier Transform (FT) based image registration. METHODS: Fourier-based image registration involves obtaining the FT of the component images, and analyzing them in Fourier space to determine the translations and rotations of one image set relative to another. An important property of FT registration is that by enlarging the images (adding additional pixels), one can obtain translations and rotations with sub-pixel resolution. The expense, however, is an increased computational time. GPUs may decrease the computational time associated with FT image registration by taking advantage of their parallel architecture to perform matrix computations much more efficiently than a Central Processor Unit (CPU). In order to evaluate the computational gains produced by a GPU, images with known translational shifts were utilized. A program was written in the Interactive Data Language (IDL; Exelis, Boulder, CO) to performCPU-based calculations. Subsequently, the program was modified using GPU bindings (Tech-X, Boulder, CO) to perform GPU-based computation on the same system. Multiple image sizes were used, ranging from 256×256 to 2304×2304. The time required to complete the full algorithm by the CPU and GPU were benchmarked and the speed increase was defined as the ratio of the CPU-to-GPU computational time. RESULTS: The ratio of the CPU-to- GPU time was greater than 1.0 for all images, which indicates the GPU is performing the algorithm faster than the CPU. The smallest improvement, a 1.21 ratio, was found with the smallest image size of 256×256, and the largest speedup, a 4.25 ratio, was observed with the largest image size of 2304×2304. CONCLUSIONS: GPU programming resulted in a significant decrease in computational time associated with a FT image registration algorithm. The inclusion of the GPU may provide near real-time, sub-pixel registration capability.

SU-E-J-93: Fourier Transform-Based Medical Image Registration.

PURPOSE: To evaluate the use of a Fast Fourier Transform (FFT) based pattern-matching algorithm for two-dimensional translational and rotational medical image registration. METHODS: The FFT pattern matching algorithm is based on the Fourier shift theorem. Briefly, image registration is accomplished by obtaining the Fourier Transform (FT) of two images, taking the normalized cross-correlation of the two FT, and performing an inverse FT on this correlation matrix. This results in a Dirchlet delta function that has a maximum value at a location corresponding to the translational shift between the two images. Rotational registration can also be achieved by performing this algorithm on the polar transformation of the FT images. The FT registration method was evaluated through the use of clinical images with induced translational and rotational shifts. RESULTS: Over a range of induced shifts of +/-10 mm in both the x and y directions, and induced rotations of +/-10 degrees, all recovered rotations were within 0.1 degree of the induced rotation, and all recovered translations were within 0.5 mm of the induced translation. The computational time of the FT registration on a 1024×1024 image was approximately 2.23 sec. CONCLUSIONS: An FFT based image registration algorithm is computationally efficient and provides a high degree of accuracy for two dimensional image registrations. The FFT registration approach provides a distinct analytical solution and does not rely on iterative methods to converge on a solution. In addition, the discrete nature of the FFT means that the accuracy of the solution is directly related to the size of the pixels in the images. The equivalent of sub-pixel registration can be achieved by simply resizing the image to a larger matrix (i.e. 512×512 to 1024×1024).

SU-E-J-44: Dual Energy Subtraction Imaging to Improve Tumor Visibility at Oblique Angles.

PURPOSE: To characterize the contrast improvement of simulated tumors in an anthropomorphic phantom using Dual Energy (DE) subtraction with a clinical on-board imager (OBI) at oblique angles. METHODS: An Alderson lung/chest anthropomorphic phantom with simulated tumors in the thoracic cavity was imaged using a sequential DE imaging methodology. High (120kVp) and low (60kVp) planar images were obtained in pairs every 100 in a full (3600) rotation using the OBI (Varian Medical Systems, Palo Alto, CA). Optimal mAs settings for DE component images were determined byvarying the x-ray exposure time, while maintaining a constant tube current. DE images were created to best suppress the bone overlaying the simulated tumors. Tumor visibility in DE images was quantified using the Contrast-to-Noise Ratio (CNR). The ratio of the CNR from the DE image relative to a single image (standard protocol) was evaluated as a function of gantry angle. RESULTS: CNR was improved with DE imaging by an average ratio of 1.66 over all gantry angles. The greatest improvement occurred at gantry angles where the tumor was obstructed by the ribs alone. More modest improvements were observed where the tumor overlapped other soft tissue structures (such as the heart) or the dense spine, on a given projection. CONCLUSIONS: This study illustrates the feasibility of performing DE imaging at oblique gantry angles using a clinical on-board imaging system. Incorporating DE imaging into clinical practice may allow for verification of tumor position at oblique gantry angles, and may facilitate the development of markerless motion tracking techniques. Supported by a grant from Varian Medical Systems.

Dose-volume factors to select patient-specific image-guidance action thresholds in prostate cancer.

For radiation delivery tracking systems that monitor intrafraction prostate motion, generalized departmental threshold protocols may be used. The purpose of this study is to determine whether predefined action thresholds can be generally applied or if patient-specific action thresholds may be required. Software algorithms were developed in the MatLab (The Mathworks Inc., Natick, MA) software environment to simulate shifts of the patient structure set consisting of prostate, bladder, and rectum. These structures were shifted by 1/2 10 mm in each direction in 1 mm increments to simulate displacements during treatment, without taking into consideration organ deformity. Dose-volume data at each shift were plotted and analyzed. A linear relationship was observed between planning dose-volume parameters and shifted dose-volume parameters. For a 5 mm anterior shift, it was observed that individual rectal V70 values increased by absolute magnitudes of 6-15%, dependent on the planning rectal V70 of each patient. Likewise, for a 5 mm inferior shift, individual bladder V70 values increased by 1-14%, dependent on planning bladder V70. This linear relationship was observed for all levels of shifts up to 10 mm. Since rectum and bladder dose-volume changes due to patient shifts are dependent on dose-volume parameters, this study suggests that patient-specific action thresholds may be necessary.

Primary cytomegalovirus ileitis complicated by massive gastrointestinal haemorrhage in a patient with steroid refractory Crohn's disease.

A young man with known steroid refractory terminal ileal Crohn's disease developed torrential gastrointestinal bleeding necessitating an emergency ileal resection. Serology was indicative of primary cytomegalovirus (CMV) infection and this was confirmed with histopathology of the resected ileum. We highlight the difficulty in clinical practice of distinguishing between CMV infection and CMV disease as well as the different investigations available to aid in the diagnosis of pathogenic CMV disease.