Comparing the Effectiveness of Virtual and In-Person Delivery of Mindfulness-Based Skills Within Healthcare Curriculums.

Purpose: To promote well-being, healthcare education programs have incorporated mindfulness-based skills and principles into existing curriculums. Pandemic-related restrictions have compelled programs to deliver content virtually. Study objectives were to determine (1) whether teaching mindfulness-based skills within physician assistant (PA) programs can promote well-being and (2) whether delivery type (virtual vs. in-person) can impact the effectiveness. Methods: During this 2-year study, a brief mindfulness-based curriculum was delivered to incoming first-year students at six PA programs, while students at two programs served as controls. The curriculum was delivered in-person in year one and virtually in year two. Validated pre- and post-test survey items assessed mindfulness (decentering ability, present moment attention and awareness, and psychological flexibility) and well-being (perceived stress and life satisfaction). Results: As expected, coping abilities and well-being were adversely impacted by educational demands. The mindfulness-based curriculum intervention was effective in increasing mindfulness and life satisfaction, while decreasing perceived stress when delivered in-person. Virtual curricular delivery was effective in decreasing perceived stress but not improving life satisfaction. Over half of the participants receiving the curriculum reported positive changes on mindfulness measures with approximately 14-38% reporting a change of greater than one standard deviation. Changes on mindfulness measures explained 30-38% of the reported changes in perceived stress and 22-26% of the changes in life satisfaction. Therefore, the mindfulness curriculum demonstrated statistically significant improvements in measures of mindfulness and mitigated declines in life satisfaction and perceived stress. Conclusion: Mindfulness-based skills effectively taught in-person or virtually within PA programs successfully promote well-being.

A strategy to build and validate a prognostic biomarker model based on RT-qPCR gene expression and clinical covariates.

BACKGROUND: Construction and validation of a prognostic model for survival data in the clinical domain is still an active field of research. Nevertheless there is no consensus on how to develop routine prognostic tests based on a combination of RT-qPCR biomarkers and clinical or demographic variables. In particular, the estimation of the model performance requires to properly account for the RT-qPCR experimental design. RESULTS: We present a strategy to build, select, and validate a prognostic model for survival data based on a combination of RT-qPCR biomarkers and clinical or demographic data and we provide an illustration on a real clinical dataset. First, we compare two cross-validation schemes: a classical outcome-stratified cross-validation scheme and an alternative one that accounts for the RT-qPCR plate design, especially when samples are processed by batches. The latter is intended to limit the performance discrepancies, also called the validation surprise, between the training and the test sets. Second, strategies for model building (covariate selection, functional relationship modeling, and statistical model) as well as performance indicators estimation are presented. Since in practice several prognostic models can exhibit similar performances, complementary criteria for model selection are discussed: the stability of the selected variables, the model optimism, and the impact of the omitted variables on the model performance. CONCLUSION: On the training dataset, appropriate resampling methods are expected to prevent from any upward biases due to unaccounted technical and biological variability that may arise from the experimental and intrinsic design of the RT-qPCR assay. Moreover, the stability of the selected variables, the model optimism, and the impact of the omitted variables on the model performances are pivotal indicators to select the optimal model to be validated on the test dataset.

Prostate cancer biomarker annexin A3 detected in urines obtained following digital rectal examination presents antigenic variability.

OBJECTIVES: Annexin A3 (ANXA3) is a potential marker for prostate cancer (PCa). We aimed to develop robust immunoassays suitable for quantifying ANXA3 in urine samples obtained following digital rectal examination (DRE) in order to facilitate the diagnostic performance evaluation of this marker. DESIGN AND METHODS: Anti-ANXA3 monoclonal antibodies were generated and their epitopes mapped. Two different ANXA3 assay prototypes were established on the VIDAS® automated immunoanalyser and analytical validation was carried out using post-DRE urine samples obtained from patients with PCa (n=23) or benign prostate hyperplasia (n=31). RESULTS: The assays had the same capture antibody (TGC44) but different detection antibodies (13A12 or 5C5), recognizing novel distinct epitopes. Both had a lower limit of quantification <1ng/mL and were highly specific for ANXA3, not cross-reacting with other annexins. Interassay imprecision was ≤11% and ≤15% for 13A12 and 5C5 assays, respectively. Surprisingly, a total lack of correlation was observed between ANXA3 levels measured by these two assays in post-DRE urines, indicating detection of distinct antigenic variants. Two freeze-thaw cycles did not affect analyte stability in either assay, whereas a lack of stability of antigenic variants was observed when samples were stored at -80°C for 1month. CONCLUSIONS: Two different antigenic variants of ANXA3 are present in post-DRE urines and their clinical significance for diagnosis of prostate cancer should be further investigated. These variants are not stable over time in samples preserved at -80°C. Until this issue is resolved, ANXA3 should only be measured in freshly collected samples.

Delayed increase of S100A9 messenger RNA predicts hospital-acquired infection after septic shock.

OBJECTIVE: Septic shock remains a serious disease with high mortality and increased risk of hospital-acquired infection. The prediction of outcome is of the utmost importance for selecting patients for therapeutic strategies aiming to modify the immune response. The aim of this study was to assess the capability of S100A9 messenger RNA in whole blood from patients with septic shock to predict survival and the occurrence of hospital-acquired infection. DESIGN: Cohort study. SETTING: Two intensive care units in a university hospital. SUBJECTS: The study included patients with septic shock (n = 166) and healthy volunteers (n = 44). INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: For the patients with septic shock patients, overall mortality was 38% and the mean Simplified Acute Physiologic Scale II on shock onset was 52. Using quantitative reverse transcriptase-polymerase chain reactions, we found that median S100A9 messenger RNA was significantly lower in healthy volunteers than in patients with septic shock (p < .0001) between days 1 and 3 after onset of the septic shock and not significantly different between nonsurvivor and survivor patients (p = .1278). However, median S100A9 messenger RNA measured on days 7-10 was significantly higher in patients who were about to contract hospital-acquired infections compared with those who were not (p = .009). In the multivariate analysis, the S100A9 marker increased the probability of contracting hospital-acquired infections with an odds ratio of 1.12 per unit (p = .0054). CONCLUSIONS: S100A9 messenger RNA is increased in septic shock and its delayed overexpression is associated with the occurrence of secondary hospital-acquired infection. This biomarker may be of major interest in identifying patients with increased risk of hospital-acquired infection who could benefit from targeted therapy aimed at restoring their immune functions.

Early assessment of leukocyte alterations at diagnosis of septic shock.

A dramatic decrease in circulating lymphocyte number is regularly described after septic shock. However, it is unknown how early this alteration develops after diagnosis of shock and if it remains stable over time. Twenty-one septic shock patients with no comorbidities were included within 2 h after the beginning of vasopressive treatment. Flow cytometry phenotyping of circulating leukocyte subpopulations and quantitative real-time polymerase chain reaction of T-bet, GATA-3, FOXP3, and RORγ mRNA were performed in patients from the diagnosis of shock and every 6 h during the subsequent 48 h. From their admission in the intensive care unit, patients present with major alterations of circulating leukocyte count (leukocytosis, neutrophilia, and major lymphopenia). The numbers of every lymphocyte subpopulations (T, B, and natural killer cells) were diminished. Gene expression analysis of transcription factors specific for TH1, TH2, CD4CD25 regulatory, and TH17 lymphocytes showed a severe decrease in comparison with healthy individuals' values. These alterations remain stable during the first 48 h after inclusion in the protocol despite early and aggressive resuscitation and antibiotherapy administered in patients. At the time of diagnosis of shock and admission in the intensive care unit, septic patients already present with severe lymphopenia involving every lymphocyte subsets including CD4 T-cell subpopulations. No significant variation could be detected within the first 48 h. This should be taken into account in the forthcoming clinical trials testing immunomodulating therapies in septic shock patients.