Integrating monitor alarms with laboratory test results to enhance patient deterioration prediction

AbstractPatient monitors in modern hospitals have become ubiquitous but they generate an excessive number of false alarms causing alarm fatigue. Our previous work showed that combinations of frequently co-occurring monitor alarms, called SuperAlarm patterns, were capable of predicting in-hospital code blue events at a lower alarm frequency. In the present study, we extend the conceptual domain of a SuperAlarm to incorporate laboratory test results along with monitor alarms so as to build an integrated data set to mine SuperAlarm patterns. We propose two approaches to integrate monitor alarms with laboratory test results and use a maximal frequent itemsets mining algorithm to find SuperAlarm patterns. Under an acceptable false positive rate FPRmax, optimal parameters including the minimum support threshold and the length of time window for the algorithm to find the combinations of monitor alarms and laboratory test results are determined based on a 10-fold cross-validation set. SuperAlarm candidates are generated under these optimal parameters. The final SuperAlarm patterns are obtained by further removing the candidates with false positive rate>FPRmax. The performance of SuperAlarm patterns are assessed using an independent test data set. First, we calculate the sensitivity with respect to prediction window and the sensitivity with respect to lead time. Second, we calculate the false SuperAlarm ratio (ratio of the hourly number of SuperAlarm triggers for control patients to that of the monitor alarms, or that of regular monitor alarms plus laboratory test results if the SuperAlarm patterns contain laboratory test results) and the work-up to detection ratio, WDR (ratio of the number of patients triggering any SuperAlarm patterns to that of code blue patients triggering any SuperAlarm patterns). The experiment results demonstrate that when varying FPRmax between 0.02 and 0.15, the SuperAlarm patterns composed of monitor alarms along with the last two laboratory test results are triggered at least once for [56.7–93.3%] of code blue patients within an 1-h prediction window before code blue events and for [43.3–90.0%] of code blue patients at least 1-h ahead of code blue events. However, the hourly number of these SuperAlarm patterns occurring in control patients is only [2.0–14.8%] of that of regular monitor alarms with WDR varying between 2.1 and 6.5 in a 12-h window. For a given FPRmax threshold, the SuperAlarm set generated from the integrated data set has higher sensitivity and lower WDR than the SuperAlarm set generated from the regular monitor alarm data set. In addition, the McNemar’s test also shows that the performance of the SuperAlarm set from the integrated data set is significantly different from that of the SuperAlarm set from the regular monitor alarm data set. We therefore conclude that the SuperAlarm patterns generated from the integrated data set are better at predicting code blue events

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least $4m$. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the $6.5m$ James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 years, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit.Comment: Accepted by PASP for the special issue on The James Webb Space Telescope Overview, 29 pages, 4 figure

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Electrocardiographic Autonomic Nervous System Predictors of Outcomes in Acute Coronary Syndrome Patients

Autonomic nervous system (ANS) dysfunction has been associated with cardiac arrhythmias and death. The aim of this research was to determine whether electrocardiographic (ECG) measures of ANS function, heart rate variability (HRV) and heart rate turbulence (HRT), have prognostic value in patients with acute coronary syndrome (ACS). A secondary analysis was performed using 24-hour ECG recordings from patients enrolled in the IMMEDIATE AIM Trial, a prospective NIH-funded study conducted from 2002 - 2005. The ECG recordings were begun within minutes (median, 45 minutes) from patients' presentation to the UCSF Emergency Department with ACS symptoms. HRV and HRT were computed using research software (HRV Laboratory, St. Louis, MO). A total of 193 patients had recordings with sufficient data for analysis. Multivariate analyses demonstrated that 5 HRV measurements were significantly associated with all-cause 1-year rehospitalization (p-values&lt;.05). HRT was associated with cardiac-related 30-day and 1-year ED readmission and/or death. Patients with disrupted HRT markers had greater risk of adverse 30-day outcomes compared to patients with healthy markers (hazard ratio=3.6, p=.01), and greater risk of adverse 1-year outcomes (hazard ratio=3.2, p&lt;.001). Comparison of HRT and routinely-measured TIMI risk scores showed similar sensitivity and specificity for 30-day (areas under the curve: HRT=0.647; TIMI=0.687) and 1-year outcomes (HRT=0.657; TIMI=0.605). In conclusion, HRT provides a viable alternative to TIMI scores for risk assessment in patients with ACS. With appropriate software, HRT and HRV could be obtained from the ECG monitoring nurses routinely perform. Future studies are needed to determine whether ANS ECG markers identify patients who warrant closer follow-up

The James Webb Space Telescope Mission

Twenty-six years ago a small committee report, building on earlier studies, expounded a compelling and poetic vision for the future of astronomy, calling for an infrared-optimized space telescope with an aperture of at least 4 m. With the support of their governments in the US, Europe, and Canada, 20,000 people realized that vision as the 6.5 m James Webb Space Telescope. A generation of astronomers will celebrate their accomplishments for the life of the mission, potentially as long as 20 yr, and beyond. This report and the scientific discoveries that follow are extended thank-you notes to the 20,000 team members. The telescope is working perfectly, with much better image quality than expected. In this and accompanying papers, we give a brief history, describe the observatory, outline its objectives and current observing program, and discuss the inventions and people who made it possible. We cite detailed reports on the design and the measured performance on orbit