Health-Related Quality of Life in KEYNOTE-010: a Phase II/III Study of Pembrolizumab Versus Docetaxel in Patients With Previously Treated Advanced,Programmed Death Ligand 1–Expressing NSCLC

Introduction

In the phase II/III KEYNOTE-010 study (ClinicalTrials.gov, NCT01905657), pembrolizumab significantly prolonged overall survival over docetaxel in patients with previously treated, programmed death ligand 1–expressing (tumor proportion score ≥ 1%), advanced NSCLC. Health-related quality of life (HRQoL) results are reported here.

Adolescents'' opinions about genetic risk information, prenatal diagnosis, and pregnancy termination

Advances in genetics create increasing possibilities of diagnosing and preventing genetic disease. In most countries, the community is poorly informed about the role of genetic factors in human disease and about genetic testing and its social, emotional, and ethical implications. School education about genetics may improve this situation. Students are, of course, the adults of the future and the potential users of the new genetic tests. To gain further insight into the perception of genetic risk of adolescents and their perception of the new genetic techniques and as a starting point for setting up an adequate information campaign in Flanders, we assessed the opinions and beliefs of students with regard to health, genetic diseases, genetic risk, and genetic testing.

A standardised interview and questionnaire were administered within the scope of the two yearly medical check up of 166 fifth grade students. They were randomly selected from the group of all fifth grade high school students in seven different schools.

This paper focuses on the attitudes of adolescents towards obtaining genetic information, towards prenatal diagnosis and pregnancy termination. Adolescents in Flanders are interested in being informed about genetic risks and genetic diseases and in making use of prenatal diagnosis because they want to make informed reproductive decisions in the future and to be emotionally prepared for the birth of an affected child. They adopt a critical attitude towards pregnancy termination. The association between these attitudes and several relevant factors was investigated. This showed significant correlations between some attitudes and general health related prevention, perceived burden of genetic diseases, the importance of the value “own health”, the perceived role of society, and the regularity of religious practice. Some points for special attention were formulated with regard to information campaigns for adolescents.

     

Fluconazole and amphotericin B antifungal susceptibility testing by National Committee for Clinical Laboratory Standards broth macrodilution method compared with E-test and semiautomated broth microdilution test.

A comparative study of fluconazole and amphotericin B susceptibility testing was performed with 68 clinical Candida species isolates and three test methods. The methods used were an agar diffusion method (E-test) and two broth dilution methods, the National Committee for Clinical Laboratory Standards (NCCLS) reference broth macrodilution method and an in-house-prepared semiautomated broth microdilution method based on the Bioscreen turbidometer. In the microdilution method, growth of the yeasts was measured continuously by the automatic turbidometer (Bioscreen), which permitted precise and objective determination of endpoints. MIC endpoints were read after 24 h for the microdilution method and the E-test. Amphotericin B susceptibility testing with the NCCLS method and the E-test yielded comparable results in 89% of the tests, meaning that the endpoints obtained were identical or differed by no more than 2 twofold dilutions. The NCCLS and broth microdilution tests scored 97% comparable results, and the E-test and the broth microdilution test yielded 90% comparable results. Fluconazole susceptibility testing produced 96% comparable results with the NCCLS test and the E-test, 100% comparable results with the NCCLS and the microdilution methods, and 98.5% comparable results with the microdilution method and the E-test. We conclude that the E-test and the Bioscreen microdilution method are valuable alternatives to the NCCLS reference method for routine susceptibility testing of Candida species with fluconazole and amphotericin B.     

A pulmonary infection caused by Coprinus cinereus (Hormographiella aspergillata) diagnosed after a neutropenic episode.

In a patient treated for a non-Hodgkin's lymphoma, a lung abscess caused by Hormographiella aspergillata (stat. anamorph. Coprinus cinereus) was diagnosed using an ultrasound-guided puncture of the lesion. The patient appeared to respond to amphotericin B, but at the same time was also recovering from her neutropenic episode. The extent to which each of these two factors explains the complete resolution of the infection is unclear. Expert classical morphological examination and molecular typing methods were needed to identify this filamentous basidiomycetous fungus.     

Using Metamodeling to Identify the Optimal Strategy for Colorectal Cancer Screening

ObjectivesMetamodeling can address computational challenges within decision-analytic modeling studies evaluating many strategies. This article illustrates the value of metamodeling for evaluating colorectal cancer screening strategies while accounting for colonoscopy capacity constraints.MethodsIn a traditional approach, the best screening strategy was identified from a limited subset of strategies evaluated with the validated Adenoma and Serrated pathway to Colorectal CAncer model. In a metamodeling approach, metamodels were fitted to this limited subset to evaluate all potentially plausible strategies and determine the best overall screening strategy. Approaches were compared based on the best screening strategy in life-years gained compared with no screening. Metamodel runtime and accuracy was assessed.ResultsThe metamodeling approach evaluated >40 000 strategies in <1 minute with high accuracy after 1 adaptive sampling step (mean absolute error: 0.0002 life-years) using 300 samples in total (generation time: 8 days). Findings indicated that health outcomes could be improved without requiring additional colonoscopy capacity. Obtaining similar insights using the traditional approach could require at least 1000 samples (generation time: 28 days). Suggested benefits from screening at ages <40 years require adequate validation of the underlying Adenoma and Serrated pathway to Colorectal CAncer model before making policy recommendations.ConclusionsMetamodeling allows rapid assessment of a vast set of strategies, which may lead to identification of more favorable strategies compared to a traditional approach. Nevertheless, metamodel validation and identifying extrapolation beyond the support of the original decision-analytic model are critical to the interpretation of results. The screening strategies identified with metamodeling support ongoing discussions on decreasing the starting age of colorectal cancer screening.     

Cell salvage in burn excisional surgery

BackgroundHemostasis during burn surgery is difficult to achieve, and high blood loss commonly occurs. Bleeding control measures are limited, and many patients require allogeneic blood transfusions. Cell salvage is a well-known method used to reduce transfusions. However, its evidence in burns is limited. Therefore, this study aimed to examine the feasibility of cell salvage during burn surgery.Study design and methodsA prospective, observational study was conducted with 16 patients (20 measurements) scheduled for major burn surgery. Blood was recovered by washing saturated gauze pads with heparinized saline, which was then processed using the Cell Saver. Erythrocyte concentrate quality was analyzed by measuring hemoglobin, hematocrit, potassium, and free hemoglobin concentration. Microbial contamination was assessed based on cultures at every step of the process. Differences in blood samples were tested using the Student’s t-test.ResultsThe red blood cell mass recovered was 29 ± 11% of the mass lost. Patients’ preoperative hemoglobin and hematocrit levels were 10.5 ± 1.8 g/dL and 0.33 ± 0.05 L/L, respectively. The erythrocyte concentrate showed hemoglobin and hematocrit levels of 13.2 ± 3.9 g/dL and 0.40 ± 0.11 L/L thus showing a concentration effect. The potassium level was lower in the erythrocyte concentrate (2.5 ± 1.5 vs. 4.1 ± 0.4 mmol/L, p < 0.05). The free hemoglobin level was low (0.16 ± 0.21 μmol/L). All cultures of the erythrocyte concentrate showed bacterial growth compared to 21% of wound cultures.ConclusionRecovering erythrocytes during burn excisional surgery using cell salvage is possible. Despite strict sterile handling, erythrocyte concentrates of all patients showed bacterial contamination. The consequence of this contamination remains unclear and should be investigated in future studies.     

A decision tree for the treatment of caries in posterior teeth

Because of a better understanding of the caries process, a decrease in the prevalence of caries, and the rapid development of dental materials, a renewed approach to the treatment of dental caries in the posterior region is possible. A decision tree for the treatment of caries in posterior teeth, taking into account some of the most recent tooth substance-saving treatment options, is presented. These possibilities gradually evolve from nondestructive to conventional cavity preparations. In addition, the "preventive Class II restoration" is introduced. The application of this conservative attitude toward invasive techniques offers great advantages for both the patient and the dentist. Unfortunately, this approach is time-consuming. Long-term clinical evaluation of the application of the proposed decision tree on a wide scale is needed to confirm its potential benefits or to modify and improve treatment options.     

Sister-to-sister oocyte donation: couples’ experiences with regard to genetic ties

Objective: This study aimed to gain an in-depth understanding of the experiences of genetic ties in intrafamily oocyte donation families. Background: Previous research has shown that most mothers have a good and stable relationship with their donor. Little is known about the meaning of the difference in genetic ties for parents who conceived through sister-to-sister oocyte donation. Methods: An Interpretative Phenomenological Analysis was performed and focused on both individual experiences and couple experiences with regard to genetic ties. Ten participants were recruited via an infertility clinic and took part in semistructured couple interviews. Results: Our analysis revealed that the donation was seen as a way to equal genetic parenthood. Participants struggled with this prevailing ideal of genetic parenthood and questioned the legitimacy of their motherhood. Several dynamics were identified when couples tried to deal with the imbalance in genetic ties: they acknowledged each other, convinced one another, or pushed away the difference in genetic ties. Couples also managed the presence of a genetic tie with the donor by negotiating the closeness in their family relationships. Conclusion: The lack of a full genetic tie remained a meaningful absence for some mothers and the way couples dealt with this varied. We plead that the option of post-donation care should be offered to support couples with the complexities they try to deal with.