A prospective study comparing the predictions of doctors versus models for treatment outcome of lung cancer patients: A step toward individualized care and shared decision making

Background

Decision Support Systems, based on statistical prediction models, have the potential to change the way medicine is being practiced, but their application is currently hampered by the astonishing lack of impact studies. Showing the theoretical benefit of using these models could stimulate conductance of such studies. In addition, it would pave the way for developing more advanced models, based on genomics, proteomics and imaging information, to further improve the performance of the models.

Purpose

In this prospective single-center study, previously developed and validated statistical models were used to predict the two-year survival (2yrS), dyspnea (DPN), and dysphagia (DPH) outcomes for lung cancer patients treated with chemo radiation. These predictions were compared to probabilities provided by doctors and guideline-based recommendations currently used. We hypothesized that model predictions would significantly outperform predictions from doctors.

Materials and methods

Experienced radiation oncologists (ROs) predicted all outcomes at two timepoints: (1) after the first consultation of the patient, and (2) after the radiation treatment plan was made. Differences in the performances of doctors and models were assessed using Area Under the Curve (AUC) analysis.

Results

A total number of 155 patients were included. At timepoint #1 the differences in AUCs between the ROs and the models were 0.15, 0.17, and 0.20 (for 2yrS, DPN, and DPH, respectively), with p-values of 0.02, 0.07, and 0.03. Comparable differences at timepoint #2 were not statistically significant due to the limited number of patients. Comparison to guideline-based recommendations also favored the models.

Conclusion

The models substantially outperformed ROs’ predictions and guideline-based recommendations currently used in clinical practice. Identification of risk groups on the basis of the models facilitates individualized treatment, and should be further investigated in clinical impact studies.     

Influence of Factors in the Photopolymerization Process on Dental Composites Microhardness

The aim of the present paper is to investigate the influence of factors in photopolymerization process that govern microhardness of three types of dental composites—universal (UC), bulk-fill (BC), and flowable (FC). Cylindrical specimens with different thicknesses are made and light cured. The significance of light intensity, irradiation time, and layer thickness on Vickers microhardness is evaluated by experimental design, analysis of variance, and regression analysis. It is found that the main factor influencing the microhardness on the top surface of the three composites is light intensity. The second factor is layer thickness for the UC and FC, while for BC, it is curing time. The third factor is curing time for the first two composites and layer thickness for bulk-fill. The significance of factors’ influence on the microhardness of the bottom surface is the same for the UC and FC, but different for BC. The main factor for the first two composites is layer thickness, followed by curing time and light intensity. For bulk-fill, curing time is main factor, light intensity is second, and layer thickness is last. Different significance of factors influencing the microhardness on top and bottom surfaces of investigated composites is revealed for the first time in the present study.     

Production of justicidin B, a cytotoxic arylnaphthalene lignan from genetically transformed root cultures of Linum leonii

Callus and hairy root cultures of Linum leonii were established. The genetic transformation in hairy roots was proven by PCR analysis, which showed integration of rol A and rol C genes into the plant genome. Calli and hairy roots accumulate the arylnaphthalene lignan justicidin B as a major constituent. Hairy roots produce 5-fold higher yields of justicidin B (10.8 mg g(-1) DW) compared to calli. Justicidin B shows strong cytotoxicity on the chronic myeloid leukemia LAMA-8 and K-562 cell lines and on the chronic lymphoid leukemia SKW-3 cell line with IC(50) values of 1.11, 6.08, and 1.62 microM, respectively. Apoptotic properties of justicidin B are reported for the first time.     

Base-promoted direct amidation of esters: beyond the current scope and practical applications

The base-promoted direct amidation of unactivated esters is among the most useful reactions for amide bond formation in contemporary organic chemistry. The intensive research in this area has led to the development of a number of new methods to achive this transformation. However, to date, the existing literature is more methodological and in many instances lacks practical directions. Therefore, the full potential of this transformation is yet to be revealed by broadening the substrate scope. In a search for new practical applications of the amidation reaction, herein we present a comprehensive study of a number of base-promoted direct amidations that encompass a wide range of amines and esters. Furthermore, we applied our findings in the synthesis of phosphoramidates and several industrially relevant products.

A new method for direct amidation of unactivated esters with unprecedented substrate scope is developed.     

γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

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Globin Chain Electrophoresis: a New Approach to the Determination of the Gγ/Aγ Ratio in Fetal Haemoglobin and to Studies of Globin Synthesis

Separation of globin chains by electrophoresis provides a simple and rapid method for the determination of the G gamma/A gamma ratio in human fetal haemoglobin, and of biosynthetic rates of the globin chains. Whole haemolysates were analysed by electrophoresis on polyacrylamide gels in urea, acetic acid and Triton X-100. Electrophoresis of haemolysates from newborn infants led to four bands: A gamma, G gamma, beta and alpha. The identity of these bands was indicated by examination of haemoglobins of known globin chain composition. In 15 samples, the % G gamma was similar by Triton gels and by amino acid analysis of the gamma CB-3 peptide. Some mutant globin chains were also separable with the electrophoretic technique. Triton gel electrophoresis provides rapid analysis of very small amounts of haemoglobin, and permits examination of globin chain composition as well as globin synthetic ratios.     

Coronary surgery in dialysis-dependent patients with end stage renal failure

The number of patients with dialysis-dependent end stage renal failure (ESRF) and coronary heart disease (CAD) has increased in recent years. Coronary artery bypass grafting (CABG) has become the standard treatment for CAD in this patient group, but is still considered as a risk procedure due to increased mortality and morbidity. In a retrospective study we analyzed our clinical results of isolated CABG in 40 dialysis-dependent patients with ESRF (5 female and 35 male, mean age 65+/-8.4 years) and the use of extracorporeal circulation. The perioperative control group comprised 51 patients (10 female and 41 male, mean age 67+/-7.3 years) with normal renal function and isolated CABG. Demographic and preoperative data were comparable in both groups. Hospital mortality was 2.5% in patients with ESRF and 0% in patients with normal renal function. Morbidity was comparable in both groups. The mean number of grafts was 3.1+/-0.9 in the dialysis group and 2.9+/-0.8 in the control group. In the follow-up of the dialysis group (34+/-23 months) 8 patients died. CABG in patients with dialysis-dependent ESRF can be performed with good clinical results and morbidity comparable to patients with normal renal function.     

Influenza surveillance on ‘foie gras’ duck farms in Bulgaria, 2008–2012

Objectives

Ducks can shed and spread influenza A viruses (IAVs) while showing no disease signs. Our objective was to clarify the role of ‘foie gras’ ducks in the circulation of IAVs in Bulgaria.

Methods

Monthly avian influenza surveillance was conducted on 63 ‘foie gras’ duck farms, 52 of which were surveyed throughout the study between November 2008 and April 2012. Virologic and serologic samples were collected and tested. During this time, wild bird samples were collected at major wild bird‐resting areas near the Black Sea coast and Danube River.

Results

The study showed high isolation frequency of low‐pathogenicity avian influenza viruses. In the raising population (<75 days old), subtypes H3, H4, and H6 were detected monthly and H5 LPAIV, sporadically. Different subtypes (H1, H10, H11) were isolated from the fattening premises (75‐ to 100‐day‐old ducks), suggesting different routes of introduction. Only 6 of the 52 farms that were surveyed both virologically and serologically were influenza‐free throughout the study, possibly due to higher biosecurity measures implemented. No evidence of direct transmission of IAV from wild birds was found. Wild bird surveillance showed low isolation frequency of IAV. IAV prevalence of 0·55% for migratory ducks and 0·53% for migratory geese was estimated in November–December 2011 and January–February 2012, respectively, at two ornithologically important locations near the Black Sea coast.

Conclusions

The ‘foie gras’ duck farms in Bulgaria are an optimal niche where Eurasian‐like IAVs are maintained and reassorted unapparent to farmers and veterinarians.