The effect of a decision aid on informed decision-making in the era of non-invasive prenatal testing : A randomised controlled trial

Early in pregnancy women and their partners face the complex decision on whether or not to participate in prenatal testing for fetal chromosomal abnormalities. Several studies show that the majority of pregnant women currently do not make informed decisions regarding prenatal testing. As the range of prenatal tests is expanding due to the development of new techniques such as non-invasive prenatal testing (NIPT), autonomous reproductive decision-making is increasingly challenging. In this study, a randomised controlled trial was conducted to evaluate the effect of a web-based multimedia decision aid on decision-making regarding prenatal testing. The decision aid provided both written and audiovisual information on prenatal tests currently available, that is, prenatal screening by first-trimester combined testing, NIPT and invasive diagnostic testing through chorionic villus sampling or amniocentesis. Furthermore, it contained values clarification exercises encouraging pregnant women to reflect on the potential harms and benefits of having prenatal tests performed. The use of the decision aid improved informed decision-making regarding prenatal testing. Of pregnant women allocated to the intervention group (n=130) 82.3% made an informed choice compared with 66.4% of women in the control group (n=131), P=0.004. As the vast majority of pregnant women made decisions consistent with their attitudes towards having prenatal testing performed, this improvement in informed decision-making could be attributed mainly to an increase in decision-relevant knowledge. This study shows that the implementation of a web-based multimedia decision aid directly facilitates the ultimate goal of prenatal testing for fetal chromosomal abnormalities, which is enabling informed autonomous reproductive choice

Identification of Functional HLA-A*01 :01-Restricted EBV-LMP2-Specific T-cell Receptors

BACKGROUND: Adoptive transfer of genetically engineered T cells expressing antigen-specific T-cell receptors (TCRs), is an appealing therapeutic approach for Epstein-Barr virus (EBV)-associated malignancies of latency type II/III that express EBV-antigens (LMP1/2). Patients who are HLA-A*01:01pos could benefit from such products, since no T cells recognizing any EBV-derived peptide in this common HLA allele have been found thus far. METHODS: HLA-A*01:01-restricted EBV-(LMP2)-specific T-cells were isolated using peptide-MHC-tetramers. Functionality was assessed by production of IFNγ and cytotoxicity when stimulated with EBV-LMP2-expressing cell-lines. Functionality of primary T cells transduced with HLA-A*01:01-restricted EBV-LMP2-specific TCRs was optimized by knocking out the endogenous TCR of primary T cells (ΔTCR) using CRISPR-Cas9 technology. RESULTS: EBV-LMP2-specific T cells were successfully isolated and their TCRs were characterized. TCR gene-transfer in primary T cells resulted in specific peptide-MHC-tetramer binding and reactivity against EBV-LMP2-expressing cell-lines. The mean-fluorescence intensity of peptide-MHC-tetramer binding was increased 1.5-2 fold when the endogenous TCR of CD8pos T cells was knocked out. CD8pos/ΔTCR T cells modified to express EBV-LMP2-specific TCRs showed IFNγ secretion and cytotoxicity towards EBV-LMP2-expressing malignant cell-lines. DISCUSSION: We isolated the first functional HLA-A*01:01-restricted EBV-LMP2-specific T-cell populations and TCRs, which can potentially be used in future TCR gene-therapy to treat EBV-associated latency type II/III malignancies

Dapagliflozin for prednisone-induced hyperglycemia in acute exacerbation of chronic obstructive pulmonary disease

This study aimed to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in subjects with prednisone-induced hyperglycemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicenter double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared to placebo. Glycemic control and incidence of hypoglycemia were measured through a blinded subcutaneous continuous glucose measurement device. Subjects in the dapagliflozin group, spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and this was 53.6 ± 23.4% in the placebo group (p = 0.96). Mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (p = 0.66). One patient using dapagliflozin and 2 patients using placebo experienced a symptomatic hypoglycemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycemia compared to placebo. Dapagliflozin did not result in better glycemic control compared to placebo in patients with prednisone-induced hyperglycemia during AECOP

The Power of Flash Mob Research Conducting a Nationwide Observational Clinical Study on Capillary Refill Time in a Single Day

BACKGROUND: Capillary refill time (CRT) is a clinical test used to evaluate the circulatory status of patients; various methods are available to assess CRT. Conventional clinical research often demands large numbers of patients, making it costly, labor-intensive, and time-consuming. We studied the interobserver agreement on CRT in a nationwide study by using a novel method of research called flash mob research (FMR). METHODS: Physicians in the Netherlands were recruited by using word-of-mouth referrals, conventional media, and social media to participate in a nationwide, single-day, "nineto-five," multicenter, cross-sectional, observational study to evaluate CRT. Patients aged >= 18 years presenting to the ED or who were hospitalized were eligible for inclusion. CRT was measured independently (by two investigators) at the patient's sternum and distal phalanx after application of pressure for 5 s (5s) and 15 s (15s). RESULTS: On October 29, 2014, a total of 458 investigators in 38 Dutch hospitals enrolled 1,734 patients. The mean CRT measured at the distal phalanx were 2.3 s (5s, SD1.1) and 2.4 s (15s, SD1.3). The mean CRT measured at the sternum was 2.6 s (5s, SD1.1) and 2.7 s (15s, SD1.1). Interobserver agreement was higher for the distal phalanx (k value, 0.40) than for the sternum (k value, 0.30). CONCLUSIONS: Interobserver agreement on CRT is, at best, moderate. CRT measured at the distal phalanx yielded higher interobserver agreement compared with sternal CRT measurements. FMR proved a valuable instrument to investigate a relatively simple clinical question in an inexpensive, quick, and reliable manner