Effect of Trans-Nasal Evaporative Intra-arrest Cooling on Functional Neurologic Outcome in Out-of-Hospital Cardiac Arrest : The PRINCESS Randomized Clinical Trial

© 2019 American Medical Association. All rights reserved.Importance: Therapeutic hypothermia may increase survival with good neurologic outcome after cardiac arrest. Trans-nasal evaporative cooling is a method used to induce cooling, primarily of the brain, during cardiopulmonary resuscitation (ie, intra-arrest). Objective: To determine whether prehospital trans-nasal evaporative intra-arrest cooling improves survival with good neurologic outcome compared with cooling initiated after hospital arrival. Design, Setting, and Participants: The PRINCESS trial was an investigator-initiated, randomized, clinical, international multicenter study with blinded assessment of the outcome, performed by emergency medical services in 7 European countries from July 2010 to January 2018, with final follow-up on April 29, 2018. In total, 677 patients with bystander-witnessed out-of-hospital cardiac arrest were enrolled. Interventions: Patients were randomly assigned to receive trans-nasal evaporative intra-arrest cooling (n = 343) or standard care (n = 334). Patients admitted to the hospital in both groups received systemic therapeutic hypothermia at 32°C to 34°C for 24 hours. Main Outcomes and Measures: The primary outcome was survival with good neurologic outcome, defined as Cerebral Performance Category (CPC) 1-2, at 90 days. Secondary outcomes were survival at 90 days and time to reach core body temperature less than 34°C. Results: Among the 677 randomized patients (median age, 65 years; 172 [25%] women), 671 completed the trial. Median time to core temperature less than 34°C was 105 minutes in the intervention group vs 182 minutes in the control group (P < .001). The number of patients with CPC 1-2 at 90 days was 56 of 337 (16.6%) in the intervention cooling group vs 45 of 334 (13.5%) in the control group (difference, 3.1% [95% CI, -2.3% to 8.5%]; relative risk [RR], 1.23 [95% CI, 0.86-1.72]; P = .25). In the intervention group, 60 of 337 patients (17.8%) were alive at 90 days vs 52 of 334 (15.6%) in the control group (difference, 2.2% [95% CI, -3.4% to 7.9%]; RR, 1.14 [95% CI, 0.81-1.57]; P = .44). Minor nosebleed was the most common device-related adverse event, reported in 45 of 337 patients (13%) in the intervention group. The adverse event rate within 7 days was similar between groups. Conclusions and Relevance: Among patients with out-of-hospital cardiac arrest, trans-nasal evaporative intra-arrest cooling compared with usual care did not result in a statistically significant improvement in survival with good neurologic outcome at 90 days. Trial Registration: ClinicalTrials.gov Identifier: NCT01400373.Peer reviewedFinal Accepted Versio

Diffuse reflection of a Bose-Einstein condensate from a rough evanescent wave mirror

We present experimental results showing the diffuse reflection of a Bose-Einstein condensate from a rough mirror, consisting of a dielectric substrate supporting a blue-detuned evanescent wave. The scattering is anisotropic, more pronounced in the direction of the surface propagation of the evanescent wave. These results agree very well with theoretical predictions.Comment: submitted to J Phys B, 10 pages, 6 figure

Development of an action programme tackling obesity-related behaviours in adolescents:a participatory system dynamics approach

System dynamics approaches are increasingly addressing the complexity of public health problems such as childhood overweight and obesity. These approaches often use system mapping methods, such as the construction of causal loop diagrams, to gain an understanding of the system of interest. However, there is limited practical guidance on how such a system understanding can inform the development of an action programme that can facilitate systems changes. The Lifestyle Innovations Based on Youth Knowledge and Experience (LIKE) programme combines system dynamics and participatory action research to improve obesity-related behaviours, including diet, physical activity, sleep and sedentary behaviour, in 10–14-year-old adolescents in Amsterdam, the Netherlands. This paper illustrates how we used a previously obtained understanding of the system of obesity-related behaviours in adolescents to develop an action programme to facilitate systems changes. A team of evaluation researchers guided interdisciplinary action-groups throughout the process of identifying mechanisms, applying the Intervention Level Framework to identify leverage points and arriving at action ideas with aligning theories of change. The LIKE action programme consisted of 8 mechanisms, 9 leverage points and 14 action ideas which targeted the system’s structure and function within multiple subsystems. This illustrates the feasibility of developing actions targeting higher system levels within the confines of a research project timeframe when sufficient and dedicated effort in this process is invested. Furthermore, the system dynamics action programme presented in this study contributes towards the development and implementation of public health programmes that aim to facilitate systems changes in practice.</p

Development of an action programme tackling obesity-related behaviours in adolescents:a participatory system dynamics approach

System dynamics approaches are increasingly addressing the complexity of public health problems such as childhood overweight and obesity. These approaches often use system mapping methods, such as the construction of causal loop diagrams, to gain an understanding of the system of interest. However, there is limited practical guidance on how such a system understanding can inform the development of an action programme that can facilitate systems changes. The Lifestyle Innovations Based on Youth Knowledge and Experience (LIKE) programme combines system dynamics and participatory action research to improve obesity-related behaviours, including diet, physical activity, sleep and sedentary behaviour, in 10–14-year-old adolescents in Amsterdam, the Netherlands. This paper illustrates how we used a previously obtained understanding of the system of obesity-related behaviours in adolescents to develop an action programme to facilitate systems changes. A team of evaluation researchers guided interdisciplinary action-groups throughout the process of identifying mechanisms, applying the Intervention Level Framework to identify leverage points and arriving at action ideas with aligning theories of change. The LIKE action programme consisted of 8 mechanisms, 9 leverage points and 14 action ideas which targeted the system’s structure and function within multiple subsystems. This illustrates the feasibility of developing actions targeting higher system levels within the confines of a research project timeframe when sufficient and dedicated effort in this process is invested. Furthermore, the system dynamics action programme presented in this study contributes towards the development and implementation of public health programmes that aim to facilitate systems changes in practice.</p

A simple approach for detecting HLA-A02 alleles in archival formalin-fixed paraffin-embedded tissue samples and an application example for studying cancer immunoediting

The HLA system represents a central component of the antigen presentation machinery. As every patient possesses a defined set of HLA molecules, only certain antigens can be presented on the cell surface. Thus, studying HLA type-dependent antigen presentation can improve the understanding of variation in susceptibility to various diseases, including infectious diseases and cancer. In archival formalin-fixed paraffin-embedded (FFPE) tissue, the HLA type is difficult to analyze because of fragmentation of DNA, hindering the application of commonly used assays that rely on long DNA stretches. Addressing these difficulties, we present a refined approach for characterizing presence or absence of HLA-A*02, the most common HLA-A allele in the Caucasian population, in archival samples. We validated our genotyping strategy in a cohort of 90 samples with HLA status obtained by an NGS-based method. 90% (n = 81) of the samples could be analyzed with the approach. For all of them, the presence or absence of HLA-A*02 alleles was correctly determined with the method, demonstrating 100% sensitivity and specificity (95% CI: 91.40%-100% and 91.19%-100%). Furthermore, we provide an example of application in an independent cohort of 73 FFPE microsatellite-unstable (MSI) colorectal cancer samples. As MSI cancer cells encompass a high number of mutations in coding microsatellites, leading to the generation of highly immunogenic frameshift peptide antigens, they are ideally suited for studying relations between the mutational landscape of tumor cells and interindividual differences in the immune system, including the HLA genotype. Overall, our method can help to promote studying HLA type-dependency during the pathogenesis of a wide range of diseases, making archival and historic tissue samples accessible for identifying HLA-A*02 alleles.Peer reviewe

Detection, Treatment, and Survival of Pancreatic Cancer Recurrence in the Netherlands A Nationwide Analysis

OBJECTIVE: To evaluate whether detection of recurrent pancreatic ductal adenocarcinoma (PDAC) in an early, asymptomatic stage increases the number of patients receiving additional treatment, subsequently improving survival. SUMMARY OF BACKGROUND DATA: International guidelines disagree on the value of standardized postoperative surveillance for early detection and treatment of PDAC recurrence. METHODS: A nationwide, observational cohort study was performed including all patients who underwent PDAC resection (2014-2016). Prospective baseline and perioperative data were retrieved from the Dutch Pancreatic Cancer Audit. Data on follow-up, treatment, and survival were collected retrospectively. Overall survival (OS) was evaluated using multivariable Cox regression analysis, before and after propensity-score matching, stratified for patients with symptomatic and asymptomatic recurrence. RESULTS: Eight hundred thirty-six patients with a median follow-up of 37 months (interquartile range 30-48) were analyzed. Of those, 670 patients (80%) developed PDAC recurrence after a median follow-up of 10 months (interquartile range 5-17). Additional treatment was performed in 159/511 patients (31%) with symptomatic recurrence versus 77/159 (48%) asymptomatic patients (P < 0.001). After propensity-score matching on lymph node ratio, adjuvant therapy, disease-free survival, and recurrence site, additional treatment was independently associated with improved OS for both symptomatic patients [hazard ratio 0.53 (95% confidence interval 0.42-0.67); P < 0.001] and asymptomatic patients [hazard ratio 0.45 (95% confidence interval 0.29-0.70); P < 0.001]. CONCLUSIONS: Additional treatment of PDAC recurrence was independently associated with improved OS, with asymptomatic patients having a higher probability to receive recurrence treatment. Therefore, standardized postoperative surveillance aiming to detect PDAC recurrence before the onset of symptoms has the potential to improve survival. This provides a rationale for prospective studies on standardized surveillance after PDAC resection

Mental health screening: Severity and cut-off point sensitivity of the Athlete Psychological Strain Questionnaire in male and female elite athletes

Objectives: To examine the sensitivity/specificity of the Athlete Psychological Strain Questionnaire (APSQ) in both male and female elite athletes, and also assess internal consistency and convergent/divergent validity, and determine discriminative validity relative to current injury status. Methods: Data were provided by 1093 elite athletes (males n=1007; females n=84). Scale validity and reliability values were benchmarked against validated measures of general psychological distress and well-being. ROC curve analysis determined a range of optimal severity cut-points. Results: Bias-corrected area under curve (AUC) values supported three APSQ cut-points for moderate (AUC=0.901), high (AUC=0.944) and very high (AUC=0.951) categories. APSQ total score Cronbach coefficients exceeded those observed for the Kessler 10 (K-10). Gender ×injury status interactions were observed for the APSQ total score and K-10, whereby injured female athletes reported higher scores relative to males and non-injured female counterparts. Conclusion: By providing a range of cut-off scores identifying those scoring in the marginal and elevated ranges, the APSQ may better facilitate earlier identification for male and female elite athletes vulnerable to mental health symptoms and developing syndromes. Use of the APSQ may support sports medicine practitioners and allied health professionals to detect early mental ill health manifestations and facilitate timely management and ideally, remediation of symptoms

Preoperative predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma

BACKGROUND: This study aimed to identify predictors for early and very early disease recurrence in patients undergoing resection of pancreatic ductal adenocarcinoma (PDAC) resection with and without neoadjuvant therapy. METHODS: Included were patients who underwent PDAC resection (2014-2016). Multivariable multinomial regression was performed to identify preoperative predictors for manifestation of recurrence within 3, 6 and 12 months after PDAC resection. RESULTS: 836 patients with a median follow-up of 37 (interquartile range [IQR] 30-48) months and overall survival of 18 (IQR 10-32) months were analyzed. 670 patients (80%) developed recurrence: 82 patients (10%) <3 months, 96 patients (11%) within 3-6 months and 226 patients (27%) within 6-12 months. LogCA 19-9 (OR 1.25 [95% CI 1.10-1.41]; P < 0.001) and neoadjuvant treatment (OR 0.09 [95% CI 0.01-0.68]; P = 0.02) were associated with recurrence <3 months. LogCA 19-9 (OR 1.23 [95% CI 1.10-1.38]; P < 0.001) and 0-90° venous involvement on CT imaging (OR 2.93 [95% CI 1.60-5.37]; P < 0.001) were associated with recurrence within 3-6 months. A Charlson Age Comorbidity Index ≥4 (OR 1.53 [95% CI 1.09-2.16]; P = 0.02) and logCA 19-9 (OR 1.24 [95% CI 1.14-1.35]; P < 0.001) were related to recurrence within 6-12 months. CONCLUSION: This study demonstrates preoperative predictors that are associated with the manifestation of early and very early recurrence after PDAC resection. Knowledge of these predictors can be used to guide individualized surveillance and treatment strategies