American College of Cardiology/ European Society of Cardiology international study of angiographic data compression phase III Measurement of image quality differences at varying levels of data compression

AbstractOBJECTIVESWe sought to investigate up to which level of Joint Photographic Experts Group (JPEG) data compression the perceived image quality and the detection of diagnostic features remain equivalent to the quality and detectability found in uncompressed coronary angiograms.BACKGROUNDDigital coronary angiograms represent an enormous amount of data and therefore require costly computerized communication and archiving systems. Earlier studies on the viability of medical image compression were not fully conclusive.METHODSTwenty-one raters evaluated sets of 91 cine runs. Uncompressed and compressed versions of the images were presented side by side on one monitor, and image quality differences were assessed on a scale featuring six scores. In addition, the raters had to detect pre-defined clinical features. Compression ratios (CR) were 6:1, 10:1 and 16:1. Statistical evaluation was based on descriptive statistics and on the equivalence t-test.RESULTSAt the lowest CR (CR 6:1), there was already a small (15%) increase in assigning the aesthetic quality score indicating “quality difference is barely discernible—the images are equivalent.” At CR 10:1 and CR 16:1, close to 10% and 55%, respectively, of the compressed images were rated to be “clearly degraded, but still adequate for clinical use” or worse. Concerning diagnostic features, at CR 10:1 and CR 16:1 the error rate was 9.6% and 13.1%, respectively, compared with 9% for the baseline error rate in uncompressed images.CONCLUSIONSCompression at CR 6:1 provides equivalence with the original cine runs. If CR 16:1 were used, one would have to tolerate a significant increase in the diagnostic error rate over the baseline error rate. At CR 10:1, intermediate results were obtained

Extremely low frequency magnetic fields in residences in Germany. Distribution of measurements, comparison of two methods for assessing exposure, and predictors for the occurrence of magnetic fields above background level

We examined the results of 1,835 magnetic field measurements in German residences conducted between November 1997 and September 1999. The measurements were part of an epidemiological study on the relationship between magnetic fields and childhood leukemia. We performed a fixed-location measurement of the magnetic field at 50 Hz and 16 2/3 Hz (frequency of the German railway system) over 24 h in the child's bedroom in the residence of each study participant. In addition, we conducted a second 24 h-measurement in the living room at 50 Hz, and spot measurements while walking through all rooms of the respective dwelling. Median 50 Hz magnetic fields above 0.2 muT were found to be infrequent in Germany (only 1.4% of all residences). Fields produced by high-voltage power lines (123-420 kV) were lower than expected: the median magnetic field was above 0.2 muT in only 8 (32.0%) of 25 residences located 50 m or closer to a high-voltage power line indicating that power lines in Germany are usually run well below the maximum power load. We found that magnetic fields were correlated with the type of residence and higher magnetic fields were measured in apartment buildings. There was also some evidence for a positive correlation between magnetic fields and traffic density and an inverse association between magnetic fields and family net income. The 24 h-magnetic field measurements correlated well with the spot measurements (r>0.7). However, when dichotomized with a cut-off point of 0.2 muT, there was only a poor agreement between the two measurement methods. A loss of the strength of the association after categorization was also observed when comparing the arithmetic mean and median of the same 24 h-measurement. In summary, these analyses give a valuable overview of magnetic field distributions in German residences

Single Pill Regimen Leads to Better Adherence and Clinical Outcome in Daily Practice in Patients Suffering from Hypertension and/or Dyslipidemia: Results of a Meta-Analysis

Introduction!#!Cardiovascular diseases (CVD) represent the first cause of mortality in western countries. Hypertension and dyslipidemia are strong risk factors for CVD, and are prevalent either alone or in combination. Although effective substances for the treatment of both factors are available, there is space for optimization of treatment regimens due to poor patient's adherence to medication, which is usually a combination of several substances. Adherence decreases with the number of pills a patient needs to take. A combination of substances in one single-pill (single pill combination, SPC), might increase adherence, and lead to a better clinical outcome.!##!Aim!#!We conducted a meta-analysis to compare the effect of SPC with that of free-combination treatment (FCT) in patients with either hypertension, dyslipidemia or the combination of both diseases under conditions of daily practice.!##!Methods!#!Studies were identified by searching in PubMed from November 2014 until February 2015. Search criteria focused on trials in identical hypertension and/or dyslipidemia treatment as FCT therapy or as SPC. Adherence and persistence outcome included proportion-of-days-covered (PDC), medication possession ratio (MPR), time-to treatment gap of 30 and 60 days and no treatment gap of 30 days (y/n). Clinical outcomes were all cause hospitalisation, hypertension-related hospitalisation, all cause emergency room visits, hypertension-related emergency room visits, outpatient visits, hypertension-related outpatient visits, and number of patients reaching blood pressure goal. Randomized clinical studies were excluded because they usually do not reflect daily practice.!##!Results!#!11 out of 1.465 studies met the predefined inclusion criteria. PDC ≥ 80% showed an odds ratio (OR) of 1.78 (95% CI: 1.30-2.45; p = 0.004) after 6 months and an OR of 1.85 (95% CI: 1.71; 2.37; p < 0.001) after ≥ 12 months in favour to the SPC. MPR ≥ 80% after 12 months also was in favour to SPC (OR 2.13; 95% CI: 1.30; 3.47; p = 0.003). Persistence was positively affected by SPC after 6, 12, and 18 months. Time to treatment gap of 60 days resulted in a hazard ratio (HR) of 2.03 (95% CI: 1.77; 2.33, p < 0.001). The use of SPC was associated with a significant improvement in systolic blood pressure reduction, leading to a higher number of patients reaching individual blood pressure goals (FCT vs SPC results in OR = 0.77; 95% CI: 0.69; 0.85, p < 0.001). Outpatient visits, emergency room visits and hospitalisations, both overall and hypertension-related were reduced by SPC: all-cause hospitalisation (SPC vs FCT: 15.0% vs 18.2%, OR 0.79, 95% CI 0.67; 0.94, p = 0.009), all-cause emergency room visits (SPC vs FCT: 25.7% vs 31.4%, OR 0.75, 95% CI 0.65; 0.87, p = 0.001) and hypertension related emergency room visits (SPC vs FCT: 9.7% vs 14.1%, OR 0.65, 95% CI 0.54; 0.80, p < 0.001).!##!Conclusions!#!SPC improved medication adherence and clinical outcome parameter in patients suffering from hypertension and/or dyslipidemia and led to a better clinical outcome compared to FCT under conditions of daily practice

Phase Ib study evaluating a self-adjuvanted mRNA cancer vaccine (RNActive) combined with local radiation as consolidation and maintenance treatment for patients with stage IV non-small cell lung cancer

Background: Advanced non-small cell lung cancer (NSCLC) represents a significant unmet medical need. Despite advances with targeted therapies in a small subset of patients, fewer than 20% of patients survive for more than two years after diagnosis. Cancer vaccines are a promising therapeutic approach that offers the potential for durable responses through the engagement of the patient's own immune system. CV9202 is a self-adjuvanting mRNA vaccine that targets six antigens commonly expressed in NSCLC (NY ESO-1, MAGEC1, MAGEC2, 5 T4, survivin, and MUC1). Methods/Design: The trial will assess the safety and tolerability of CV9202 vaccination combined with local radiation designed to enhance immune responses and will include patients with stage IV NSCLC and a response or stable disease after first-line chemotherapy or therapy with an EGFR tyrosine kinase inhibitor. Three histological and molecular subtypes of NSCLC will be investigated (squamous and non-squamous cell with/without EGFR mutations). All patients will receive two initial vaccinations with CV9202 prior to local radiotherapy (5 GY per day for four successive days) followed by further vaccinations until disease progression. The primary endpoint of the study is the number of patients experiencing Grade >3 treatment-related adverse events. Pharmacodynamic analyses include the assessment of immune responses to the antigens encoded by CV9202 and others not included in the panel (antigen spreading) and standard efficacy assessments. Discussion: RNActive self-adjuvanted mRNA vaccines offer the potential for simultaneously inducing immune responses to a wide panel of antigens commonly expressed in tumors. This trial will assess the feasibility of this approach in combination with local radiotherapy in NSCLC patients

Hepatic uptake of cholecystokinin octapeptide by organic anion-transporting polypeptides OATP4 and OATP8 of rat and human liver

BACKGROUND & AIMS: Cholecystokinin (CCK) is a major gastrointestinal peptide hormone that is released postprandially from the small intestine and exerts marked effects on gallbladder and gastrointestinal motility. The smaller isoforms CCK-8 and CCK-4 are rapidly taken up into hepatocytes, metabolized, and excreted into bile. Our aim was to identify and characterize the hepatocellular CCK-8 uptake system. METHODS: CCK-8 uptake was measured in Xenopus laevis oocytes expressing the organic anion-transporting polypeptides of rat liver (Oatp1, Oatp2, Oatp3, or Oatp4) and of human liver (OATP-A, OATP-B, OATP-C, or OATP8) and in primary cultured rat hepatocytes. RESULTS: Rat Oatp4 and human OATP8 efficiently mediated CCK-8 uptake in oocytes, with Michaelis constant (Km) values of 14.9 +/- 2.9 micromol/L and 11.1 +/- 2.9 micromol/L, respectively. CCK-8 uptake by hepatocytes was also saturable, with a Km of 6.7 +/- 2.1 micromol/L. The Km value in rat hepatocytes is consistent with Oatp4-mediated transport. CONCLUSIONS: CCK-8 is selectively transported by rat Oatp4 and human OATP8, both of which are exclusively expressed at the basolateral membrane of hepatocytes. These 2 transporters are the first and probably the predominant hepatic uptake systems for CCK-8 and may be critical for the rapid clearance of this hormone from the circulation