BackgroundSepsis is one of the leading causes of mortality in hospitalized patients. Despite this fact, a reliable means of predicting sepsis onset remains elusive. Early and accurate sepsis onset predictions could allow more aggressive and targeted therapy while maintaining antimicrobial stewardship. Existing detection methods suffer from low performance and often require time-consuming laboratory test results.ObjectiveTo study and validate a sepsis prediction method, InSight, for the new Sepsis-3 definitions in retrospective data, make predictions using a minimal set of variables from within the electronic health record data, compare the performance of this approach with existing scoring systems, and investigate the effects of data sparsity on InSight performance.MethodsWe apply InSight, a machine learning classification system that uses multivariable combinations of easily obtained patient data (vitals, peripheral capillary oxygen saturation, Glasgow Coma Score, and age), to predict sepsis using the retrospective Multiparameter Intelligent Monitoring in Intensive Care (MIMIC)-III dataset, restricted to intensive care unit (ICU) patients aged 15 years or more. Following the Sepsis-3 definitions of the sepsis syndrome, we compare the classification performance of InSight versus quick sequential organ failure assessment (qSOFA), modified early warning score (MEWS), systemic inflammatory response syndrome (SIRS), simplified acute physiology score (SAPS) II, and sequential organ failure assessment (SOFA) to determine whether or not patients will become septic at a fixed period of time before onset. We also test the robustness of the InSight system to random deletion of individual input observations.ResultsIn a test dataset with 11.3% sepsis prevalence, InSight produced superior classification performance compared with the alternative scores as measured by area under the receiver operating characteristic curves (AUROC) and area under precision-recall curves (APR). In detection of sepsis onset, InSight attains AUROC = 0.880 (SD 0.006) at onset time and APR = 0.595 (SD 0.016), both of which are superior to the performance attained by SIRS (AUROC: 0.609; APR: 0.160), qSOFA (AUROC: 0.772; APR: 0.277), and MEWS (AUROC: 0.803; APR: 0.327) computed concurrently, as well as SAPS II (AUROC: 0.700; APR: 0.225) and SOFA (AUROC: 0.725; APR: 0.284) computed at admission (P<.001 for all comparisons). Similar results are observed for 1-4 hours preceding sepsis onset. In experiments where approximately 60% of input data are deleted at random, InSight attains an AUROC of 0.781 (SD 0.013) and APR of 0.401 (SD 0.015) at sepsis onset time. Even with 60% of data missing, InSight remains superior to the corresponding SIRS scores (AUROC and APR, P<.001), qSOFA scores (P=.0095; P<.001) and superior to SOFA and SAPS II computed at admission (AUROC and APR, P<.001), where all of these comparison scores (except InSight) are computed without data deletion.ConclusionsDespite using little more than vitals, InSight is an effective tool for predic...

ObjectivesWe validate a machine learning-based sepsis-prediction algorithm (InSight) for the detection and prediction of three sepsis-related gold standards, using only six vital signs. We evaluate robustness to missing data, customisation to site-specific data using transfer learning and generalisability to new settings.DesignA machine-learning algorithm with gradient tree boosting. Features for prediction were created from combinations of six vital sign measurements and their changes over time.SettingA mixed-ward retrospective dataset from the University of California, San Francisco (UCSF) Medical Center (San Francisco, California, USA) as the primary source, an intensive care unit dataset from the Beth Israel Deaconess Medical Center (Boston, Massachusetts, USA) as a transfer-learning source and four additional institutions’ datasets to evaluate generalisability.Participants684 443 total encounters, with 90 353 encounters from June 2011 to March 2016 at UCSF.InterventionsNone.Primary and secondary outcome measuresArea under the receiver operating characteristic (AUROC) curve for detection and prediction of sepsis, severe sepsis and septic shock.ResultsFor detection of sepsis and severe sepsis, InSight achieves an AUROC curve of 0.92 (95% CI 0.90 to 0.93) and 0.87 (95% CI 0.86 to 0.88), respectively. Four hours before onset, InSight predicts septic shock with an AUROC of 0.96 (95% CI 0.94 to 0.98) and severe sepsis with an AUROC of 0.85 (95% CI 0.79 to 0.91).ConclusionsInSight outperforms existing sepsis scoring systems in identifying and predicting sepsis, severe sepsis and septic shock. This is the first sepsis screening system to exceed an AUROC of 0.90 using only vital sign inputs. InSight is robust to missing data, can be customised to novel hospital data using a small fraction of site data and retains strong discrimination across all institutions.

Sepsis can be predicted at least three hours in advance of onset of the first five hour SIRS episode, using only nine commonly available vital signs, with better performance than methods in standard practice today. High-order correlations of vital sign measurements are key to this prediction, which improves the likelihood of early identification of at-risk patients.

The G-rich single stranded DNA at the 3′ end of human telomeres can self-fold into G-quaduplex (GQ). However, telomere lengthening by telomerase or the recombination-based alternative lengthening of telomere (ALT) mechanism requires protein loading on the overhang. Using single molecule fluorescence spectroscopy we discovered that lengthening the telomeric overhang also increased the rate of dynamic exchanges between structural conformations. Overhangs with five to seven TTAGGG repeats, compared to four repeats, showed much greater dynamics and accessibility to telomerase binding and activity, and loading of the ALT-associated proteins RAD51, WRN and BLM. Although the eight repeats are highly dynamic, they can fold into two GQs, which limited protein accessibility. In contrast, the telomere-specific protein, POT1 is unique in that it binds independently of repeat number. Our results suggest that the telomeric overhang length and dynamics may contribute to the regulation of telomere extension via telomerase action and the ALT mechanism.

ObjectivesUnplanned readmissions to the intensive care unit (ICU) are highly undesirable, increasing variance in care, making resource planning difficult and potentially increasing length of stay and mortality in some settings. Identifying patients who are likely to suffer unplanned ICU readmission could reduce the frequency of this adverse event.SettingA single academic, tertiary care hospital in the UK.ParticipantsA set of 3326 ICU episodes collected between October 2014 and August 2016. All records were of patients who visited an ICU at some point during their stay. We excluded patients who were ≤16 years of age; visited ICUs other than the general and neurosciences ICU; were missing crucial electronic patient record measurements; or had indeterminate ICU discharge outcomes or very early or extremely late discharge times. After exclusion, 2018 outcome-labelled episodes remained.Primary and secondary outcome measuresArea under the receiver operating characteristic curve (AUROC) for prediction of unplanned ICU readmission or in-hospital death within 48 hours of first ICU discharge.ResultsIn 10-fold cross-validation, an ensemble predictor was trained on data from both the target hospital and the Medical Information Mart for Intensive Care (MIMIC-III) database and tested on the target hospital’s data. This predictor discriminated between patients with the unplanned ICU readmission or death outcome and those without this outcome, attaining mean AUROC of 0.7095 (SE 0.0260), superior to the purpose-built Stability and Workload Index for Transfer (SWIFT) score (AUROC=0.6082, SE 0.0249; p=0.014, pairwise t-test).ConclusionsDespite the inherent difficulties, we demonstrate that a novel machine learning algorithm based on transfer learning could achieve good discrimination, over and above that of the treating clinicians or the value added by the SWIFT score. Accurate prediction of unplanned readmission could be used to target resources more efficiently.