Drug-eluting or bare-metal stents for large coronary vessel stenting? The BASKET-PROVE (PROspective Validation Examination) trial: study protocol and design

BACKGROUND: Based on a subgroup analysis of 18-month BAsel Stent Kosten Effektivitäts Trial (BASKET) outcome data, we hypothesized that very late (> 12 months) stent thrombosis occurs predominantly after drug-eluting stent implantation in large native coronary vessel stenting. METHODS: To prove or refute this hypothesis, we set up an 11-center 4-country prospective trial of 2260 consecutive patients treated with > or = 3.0-mm stents only, randomized to receive Cypher (Johnson ; Johnson, Miami Lakes, FL), Vision (Abbott Vascular, Abbott Laboratories, IL), or Xience stents (Abbott Vascular). Only patients with left main or bypass graft disease, in-stent restenosis or stent thrombosis, in need of nonheart surgery, at increased bleeding risk, without compliance/consent are excluded. All patients are treated with dual antiplatelet therapy for 12 months. The primary end point will be cardiac death/nonfatal myocardial infarction after 24 months with further follow-up up to 5 years. RESULTS: By June 12, 229 patients (10% of the planned total) were included with a baseline risk similar to that of the same subgroup of BASKET (n = 588). CONCLUSIONS: This study will answer several important questions of contemporary stent use in patients with large native vessel stenting. The 2-year death/myocardial infarction-as well as target vessel revascularization-and bleeding rates in these patients with a first- versus second-generation drug-eluting stent should demonstrate the benefit or harm of these stents compared to cobalt-chromium bare-metal stents in this relevant, low-risk group of everyday patients. In addition, a comparison with similar BASKET patients will allow to estimate the impact of 12- versus 6-month dual antiplatelet therapy on these outcomes.

Validation of novel 3-dimensional electrocardiographic mapping of atrial tachycardias by invasive mapping and ablation: a multicenter study

OBJECTIVES This study prospectively evaluated the role of a novel 3-dimensional, noninvasive, beat-by-beat mapping system, Electrocardiographic Mapping (ECM), in facilitating the diagnosis of atrial tachycardias (AT). BACKGROUND Conventional 12-lead electrocardiogram, a widely used noninvasive tool in clinical arrhythmia practice, has diagnostic limitations. METHODS Various AT (de novo and post-atrial fibrillation ablation) were mapped using ECM followed by standard-of-care electrophysiological mapping and ablation in 52 patients. The ECM consisted of recording body surface electrograms from a 252-electrode-vest placed on the torso combined with computed tomography-scan-based biatrial anatomy (CardioInsight Inc., Cleveland, Ohio). We evaluated the feasibility of this system in defining the mechanism of AT-macro-re-entrant (perimitral, cavotricuspid isthmus-dependent, and roof-dependent circuits) versus centrifugal (focal-source) activation-and the location of arrhythmia in centrifugal AT. The accuracy of the noninvasive diagnosis and detection of ablation targets was evaluated vis-à-vis subsequent invasive mapping and successful ablation. RESULTS Comparison between ECM and electrophysiological diagnosis could be accomplished in 48 patients (48 AT) but was not possible in 4 patients where the AT mechanism changed to another AT (n = 1), atrial fibrillation (n = 1), or sinus rhythm (n = 2) during the electrophysiological procedure. ECM correctly diagnosed AT mechanisms in 44 of 48 (92%) AT: macro-re-entry in 23 of 27; and focal-onset with centrifugal activation in 21 of 21. The region of interest for focal AT perfectly matched in 21 of 21 (100%) AT. The 2:1 ventricular conduction and low-amplitude P waves challenged the diagnosis of 4 of 27 macro-re-entrant (perimitral) AT that can be overcome by injecting atrioventricular node blockers and signal averaging, respectively. CONCLUSIONS This prospective multicenter series shows a high success rate of ECM in accurately diagnosing the mechanism of AT and the location of focal arrhythmia. Intraprocedural use of the system and its application to atrial fibrillation mapping is under way.

Biomechanical validation of computer assisted planning of periacetabular osteotomy: A preliminary study based on finite element analysis

Periacetabular Osteotomy (PAO) is a joint preserving surgical intervention intended to increase femoral head coverage and thereby to improve stability in young patients with hip dysplasia. Previously, we developed a CT-based, computer-assisted program for PAO diagnosis and planning, which allows for quantifying the 3D acetabular morphology with parameters such as acetabular version, inclination, lateral center edge (LCE) angle and femoral head coverage ratio (CO). In order to verify the hypothesis that our morphology-based planning strategy can improve biomechanical characteristics of dysplastic hips, we developed a 3D finite element model based on patient-specific geometry to predict cartilage contact stress change before and after morphology-based planning. Our experimental results demonstrated that the morphology-based planning strategy could reduce cartilage contact pressures and at the same time increase contact areas. In conclusion, our computer-assisted system is an efficient tool for PAO planning.

A multinational case-control study on childhood brain tumours, anthropogenic factors, birth characteristics and prenatal exposures: A validation of interview data.

Little is known about the aetiology of childhood brain tumours. We investigated anthropometric factors (birth weight, length, maternal age), birth characteristics (e.g. vacuum extraction, preterm delivery, birth order) and exposures during pregnancy (e.g. maternal: smoking, working, dietary supplement intake) in relation to risk of brain tumour diagnosis among 7-19 year olds. The multinational case-control study in Denmark, Sweden, Norway and Switzerland (CEFALO) included interviews with 352 (participation rate=83.2%) eligible cases and 646 (71.1%) population-based controls. Interview data were complemented with data from birth registries and validated by assessing agreement (Cohen's Kappa). We used conditional logistic regression models matched on age, sex and geographical region (adjusted for maternal age and parental education) to explore associations between birth factors and childhood brain tumour risk. Agreement between interview and birth registry data ranged from moderate (Kappa=0.54; worked during pregnancy) to almost perfect (Kappa=0.98; birth weight). Neither anthropogenic factors nor birth characteristics were associated with childhood brain tumour risk. Maternal vitamin intake during pregnancy was indicative of a protective effect (OR 0.75, 95%-CI: 0.56-1.01). No association was seen for maternal smoking during pregnancy or working during pregnancy. We found little evidence that the considered birth factors were related to brain tumour risk among children and adolescents.

In Vitro and In Vivo Validation of Human and Goat Chondrocyte Labeling by Green Fluorescent Protein Lentivirus Transduction

We investigated whether human articular chondrocytes can be labeled efficiently and for long-term with a green fluorescent protein (GFP) lentivirus and whether the viral transduction would influence cell proliferation and tissue-forming capacity. The method was then applied to track goat articular chondrocytes after autologous implantation in cartilage defects. Expression of GFP in transduced chondrocytes was detected cytofluorimetrically and immunohistochemically. Chondrogenic capacity of chondrocytes was assessed by Safranin-O staining, immunostaining for type II collagen, and glycosaminoglycan content. Human articular chondrocytes were efficiently transduced with GFP lentivirus (73.4 +/- 0.5% at passage 1) and maintained the expression of GFP up to 22 weeks of in vitro culture after transduction. Upon implantation in nude mice, 12 weeks after transduction, the percentage of labeled cells (73.6 +/- 3.3%) was similar to the initial one. Importantly, viral transduction of chondrocytes did not affect the cell proliferation rate, chondrogenic differentiation, or tissue-forming capacity, either in vitro or in vivo. Goat articular chondrocytes were also efficiently transduced with GFP lentivirus (78.3 +/- 3.2%) and maintained the expression of GFP in the reparative tissue after orthotopic implantation. This study demonstrates the feasibility of efficient and relatively long-term labeling of human chondrocytes for co-culture on integration studies, and indicates the potential of this stable labeling technique for tracking animal chondrocytes for in cartilage repair studies.

A new technique for simultaneous validation of two manual nonmercury auscultatory sphygmomanometers (A;D UM-101 and Accoson Greenlight 300) based on the International protocol

Auscultatory nonmercury manual devices seem good alternatives for the mercury sphygmomanometers in the clinic and for research settings, but individual internal validation of each device is time-consuming. The aim of this study was to validate a new technique capable of testing two devices simultaneously, based on the International protocol of the European Society of Hypertension.

German validation of the Conners Adult ADHD Rating Scales–self-report (CAARS-S) I: Factor structure and normative data

Attention-deficit/hyperactivity disorder (ADHD) often persists into adulthood. Instruments for diagnosing ADHD in childhood are well validated and reliable, but diagnosis of ADHD in adults remains problematic. Attempts have been made to develop criteria specific for adult ADHD, resulting in the development of self-report and observer-rated questionnaires. To date, the Conners Adult ADHD Rating Scales (CAARS) are the international standard for questionnaire assessment of ADHD. The current study evaluates a German version of the CAARS self-report (CAARS-S).

Validation of the Swiss Monte Carlo Plan for a static and dynamic 6 MV photon beam

Monte Carlo (MC) based dose calculations can compute dose distributions with an accuracy surpassing that of conventional algorithms used in radiotherapy, especially in regions of tissue inhomogeneities and surface discontinuities. The Swiss Monte Carlo Plan (SMCP) is a GUI-based framework for photon MC treatment planning (MCTP) interfaced to the Eclipse treatment planning system (TPS). As for any dose calculation algorithm, also the MCTP needs to be commissioned and validated before using the algorithm for clinical cases. Aim of this study is the investigation of a 6 MV beam for clinical situations within the framework of the SMCP. In this respect, all parts i.e. open fields and all the clinically available beam modifiers have to be configured so that the calculated dose distributions match the corresponding measurements. Dose distributions for the 6 MV beam were simulated in a water phantom using a phase space source above the beam modifiers. The VMC++ code was used for the radiation transport through the beam modifiers (jaws, wedges, block and multileaf collimator (MLC)) as well as for the calculation of the dose distributions within the phantom. The voxel size of the dose distributions was 2mm in all directions. The statistical uncertainty of the calculated dose distributions was below 0.4%. Simulated depth dose curves and dose profiles in terms of [Gy/MU] for static and dynamic fields were compared with the corresponding measurements using dose difference and γ analysis. For the dose difference criterion of ±1% of D(max) and the distance to agreement criterion of ±1 mm, the γ analysis showed an excellent agreement between measurements and simulations for all static open and MLC fields. The tuning of the density and the thickness for all hard wedges lead to an agreement with the corresponding measurements within 1% or 1mm. Similar results have been achieved for the block. For the validation of the tuned hard wedges, a very good agreement between calculated and measured dose distributions was achieved using a 1%/1mm criteria for the γ analysis. The calculated dose distributions of the enhanced dynamic wedges (10°, 15°, 20°, 25°, 30°, 45° and 60°) met the criteria of 1%/1mm when compared with the measurements for all situations considered. For the IMRT fields all compared measured dose values agreed with the calculated dose values within a 2% dose difference or within 1 mm distance. The SMCP has been successfully validated for a static and dynamic 6 MV photon beam, thus resulting in accurate dose calculations suitable for applications in clinical cases.

A virtual source model for kilo-voltage cone beam CT: source characteristics and model validation

The purpose of this investigation was to study the source characteristics of a clinical kilo-voltage cone beam CT unit and to develop and validate a virtual source model that could be used for treatment planning purposes.

Validation of a modified AVHRR aerosol optical depth retrieval algorithm over Central Europe

The Advanced Very High Resolution Radiometer (AVHRR) carried on board the National Oceanic and Atmospheric Administration (NOAA) and the Meteorological Operational Satellite (MetOp) polar orbiting satellites is the only instrument offering more than 25 years of satellite data to analyse aerosols on a daily basis. The present study assessed a modified AVHRR aerosol optical depth τa retrieval over land for Europe. The algorithm might also be applied to other parts of the world with similar surface characteristics like Europe, only the aerosol properties would have to be adapted to a new region. The initial approach used a relationship between Sun photometer measurements from the Aerosol Robotic Network (AERONET) and the satellite data to post-process the retrieved τa. Herein a quasi-stand-alone procedure, which is more suitable for the pre-AERONET era, is presented. In addition, the estimation of surface reflectance, the aerosol model, and other processing steps have been adapted. The method's cross-platform applicability was tested by validating τa from NOAA-17 and NOAA-18 AVHRR at 15 AERONET sites in Central Europe (40.5° N–50° N, 0° E–17° E) from August 2005 to December 2007. Furthermore, the accuracy of the AVHRR retrieval was related to products from two newer instruments, the Medium Resolution Imaging Spectrometer (MERIS) on board the Environmental Satellite (ENVISAT) and the Moderate Resolution Imaging Spectroradiometer (MODIS) on board Aqua/Terra. Considering the linear correlation coefficient R, the AVHRR results were similar to those of MERIS with even lower root mean square error RMSE. Not surprisingly, MODIS, with its high spectral coverage, gave the highest R and lowest RMSE. Regarding monthly averaged τa, the results were ambiguous. Focusing on small-scale structures, R was reduced for all sensors, whereas the RMSE solely for MERIS substantially increased. Regarding larger areas like Central Europe, the error statistics were similar to the individual match-ups. This was mainly explained with sampling issues. With the successful validation of AVHRR we are now able to concentrate on our large data archive dating back to 1985. This is a unique opportunity for both climate and air pollution studies over land surfaces.

Chlamydia infection, pelvic inflammatory disease, ectopic pregnancy and infertility: cross-national study

Objectives To describe, using routine data in selected countries, chlamydia control activities and rates of chlamydia infection, pelvic inflammatory disease (PID), ectopic pregnancy and infertility and to compare trends in chlamydia positivity with rates of PID and ectopic pregnancy. Methods Cross-national comparison including national data from Australia, Denmark, the Netherlands, New Zealand, Sweden and Switzerland. Routine data sources about chlamydia diagnosis and testing and International Classification of Disease-10 coded diagnoses of PID, ectopic pregnancy and infertility in women aged 15–39 years from 1999 to 2008 were described. Trends over time and relevant associations were examined using Poisson regression. Results Opportunistic chlamydia testing was recommended in all countries except Switzerland, but target groups differed. Rates of chlamydia testing were highest in New Zealand. Chlamydia positivity was similar in all countries with available data (Denmark, New Zealand and Sweden) and increased over time. Increasing chlamydia positivity rates were associated with decreasing PID rates in Denmark and Sweden and with decreasing ectopic pregnancy rates in Denmark, New Zealand and Sweden. Ectopic pregnancy rates appeared to increase over time in 15–19-year-olds in several countries. Trends in infertility diagnoses were very variable. Conclusions The intensity of recommendations about chlamydia control varied between countries but was not consistently related to levels of chlamydia diagnosis or testing. Relationships between levels of chlamydia infection and complication rates between or within countries over time were not straightforward. Development and validation of indicators of chlamydia-related morbidity that can be compared across countries and over time should be pursued.

Validation of the Asthma Predictive Index and comparison with simpler clinical prediction rules

Background The loose and stringent Asthma Predictive Indices (API), developed in Tucson, are popular rules to predict asthma in preschool children. To be clinically useful, they require validation in different settings. Objective To assess the predictive performance of the API in an independent population and compare it with simpler rules based only on preschool wheeze. Methods We studied 1954 children of the population-based Leicester Respiratory Cohort, followed up from age 1 to 10 years. The API and frequency of wheeze were assessed at age 3 years, and we determined their association with asthma at ages 7 and 10 years by using logistic regression. We computed test characteristics and measures of predictive performance to validate the API and compare it with simpler rules. Results The ability of the API to predict asthma in Leicester was comparable to Tucson: for the loose API, odds ratios for asthma at age 7 years were 5.2 in Leicester (5.5 in Tucson), and positive predictive values were 26% (26%). For the stringent API, these values were 8.2 (9.8) and 40% (48%). For the simpler rule early wheeze, corresponding values were 5.4 and 21%; for early frequent wheeze, 6.7 and 36%. The discriminative ability of all prediction rules was moderate (c statistic ≤ 0.7) and overall predictive performance low (scaled Brier score < 20%). Conclusion Predictive performance of the API in Leicester, although comparable to the original study, was modest and similar to prediction based only on preschool wheeze. This highlights the need for better prediction rules.

Development and validation of decision rules to guide frequency of monitoring CD4 cell count in HIV-1 infection before starting antiretroviral therapy

Background Although CD4 cell count monitoring is used to decide when to start antiretroviral therapy in patients with HIV-1 infection, there are no evidence-based recommendations regarding its optimal frequency. It is common practice to monitor every 3 to 6 months, often coupled with viral load monitoring. We developed rules to guide frequency of CD4 cell count monitoring in HIV infection before starting antiretroviral therapy, which we validated retrospectively in patients from the Swiss HIV Cohort Study. Methodology/Principal Findings We built up two prediction rules (“Snap-shot rule” for a single sample and “Track-shot rule” for multiple determinations) based on a systematic review of published longitudinal analyses of CD4 cell count trajectories. We applied the rules in 2608 untreated patients to classify their 18 061 CD4 counts as either justifiable or superfluous, according to their prior ≥5% or <5% chance of meeting predetermined thresholds for starting treatment. The percentage of measurements that both rules falsely deemed superfluous never exceeded 5%. Superfluous CD4 determinations represented 4%, 11%, and 39% of all actual determinations for treatment thresholds of 500, 350, and 200×106/L, respectively. The Track-shot rule was only marginally superior to the Snap-shot rule. Both rules lose usefulness for CD4 counts coming near to treatment threshold. Conclusions/Significance Frequent CD4 count monitoring of patients with CD4 counts well above the threshold for initiating therapy is unlikely to identify patients who require therapy. It appears sufficient to measure CD4 cell count 1 year after a count >650 for a threshold of 200, >900 for 350, or >1150 for 500×106/L, respectively. When CD4 counts fall below these limits, increased monitoring frequency becomes advisable. These rules offer guidance for efficient CD4 monitoring, particularly in resource-limited settings.

Measurements of Humidity in the Atmosphere and Validation Experiments MOHAVE-2009; overview of campaign operations and results

The Measurements of Humidity in the Atmosphere and Validation Experiment (MOHAVE) 2009 campaign took place on 11–27 October 2009 at the JPL Table Mountain Facility in California (TMF). The main objectives of the campaign were to (1) validate the water vapor measurements of several instruments, including, three Raman lidars, two microwave radiometers, two Fourier-Transform spectrometers, and two GPS receivers (column water), (2) cover water vapor measurements from the ground to the mesopause without gaps, and (3) study upper tropospheric humidity variability at timescales varying from a few minutes to several days. A total of 58 radiosondes and 20 Frost-Point hygrometer sondes were launched. Two types of radiosondes were used during the campaign. Non negligible differences in the readings between the two radiosonde types used (Vaisala RS92 and InterMet iMet-1) made a small, but measurable impact on the derivation of water vapor mixing ratio by the Frost-Point hygrometers. As observed in previous campaigns, the RS92 humidity measurements remained within 5% of the Frost-point in the lower and mid-troposphere, but were too dry in the upper troposphere. Over 270 h of water vapor measurements from three Raman lidars (JPL and GSFC) were compared to RS92, CFH, and NOAA-FPH. The JPL lidar profiles reached 20 km when integrated all night, and 15 km when integrated for 1 h. Excellent agreement between this lidar and the frost-point hygrometers was found throughout the measurement range, with only a 3% (0.3 ppmv) mean wet bias for the lidar in the upper troposphere and lower stratosphere (UTLS). The other two lidars provided satisfactory results in the lower and mid-troposphere (2–5% wet bias over the range 3–10 km), but suffered from contamination by fluorescence (wet bias ranging from 5 to 50% between 10 km and 15 km), preventing their use as an independent measurement in the UTLS. The comparison between all available stratospheric sounders allowed to identify only the largest biases, in particular a 10% dry bias of the Water Vapor Millimeter-wave Spectrometer compared to the Aura-Microwave Limb Sounder. No other large, or at least statistically significant, biases could be observed. Total Precipitable Water (TPW) measurements from six different co-located instruments were available. Several retrieval groups provided their own TPW retrievals, resulting in the comparison of 10 different datasets. Agreement within 7% (0.7 mm) was found between all datasets. Such good agreement illustrates the maturity of these measurements and raises confidence levels for their use as an alternate or complementary source of calibration for the Raman lidars. Tropospheric and stratospheric ozone and temperature measurements were also available during the campaign. The water vapor and ozone lidar measurements, together with the advected potential vorticity results from the high-resolution transport model MIMOSA, allowed the identification and study of a deep stratospheric intrusion over TMF. These observations demonstrated the lidar strong potential for future long-term monitoring of water vapor in the UTLS.