A Kernel to Exploit Informative Missingness in Multivariate Time Series from EHRs

A large fraction of the electronic health records (EHRs) consists of clinical measurements collected over time, such as lab tests and vital signs, which provide important information about a patient's health status. These sequences of clinical measurements are naturally represented as time series, characterized by multiple variables and large amounts of missing data, which complicate the analysis. In this work, we propose a novel kernel which is capable of exploiting both the information from the observed values as well the information hidden in the missing patterns in multivariate time series (MTS) originating e.g. from EHRs. The kernel, called TCK$_{IM}$, is designed using an ensemble learning strategy in which the base models are novel mixed mode Bayesian mixture models which can effectively exploit informative missingness without having to resort to imputation methods. Moreover, the ensemble approach ensures robustness to hyperparameters and therefore TCK$_{IM}$ is particularly well suited if there is a lack of labels - a known challenge in medical applications. Experiments on three real-world clinical datasets demonstrate the effectiveness of the proposed kernel.Comment: 2020 International Workshop on Health Intelligence, AAAI-20. arXiv admin note: text overlap with arXiv:1907.0525

Chemotherapy effectiveness in trial-underrepresented groups with early breast cancer:A retrospective cohort study

BACKGROUND: Adjuvant chemotherapy in early stage breast cancer has been shown to reduce mortality in a large meta-analysis of over 100 randomised trials. However, these trials largely excluded patients aged 70 years and over or with higher levels of comorbidity. There is therefore uncertainty about whether the effectiveness of adjuvant chemotherapy generalises to these groups, hindering patient and clinician decision-making. This study utilises administrative healthcare data-real world data (RWD)-and econometric methods for causal analysis to estimate treatment effectiveness in these trial-underrepresented groups. METHODS AND FINDINGS: Women with early breast cancer aged 70 years and over and those under 70 years with a high level of comorbidity were identified and their records extracted from Scottish Cancer Registry (2001-2015) data linked to other routine health records. A high level of comorbidity was defined as scoring 1 or more on the Charlson comorbidity index, being in the top decile of inpatient stays, and/or having 5 or more visits to specific outpatient clinics, all within the 5 years preceding breast cancer diagnosis. Propensity score matching (PSM) and instrumental variable (IV) analysis, previously identified as feasible and valid in this setting, were used in conjunction with Cox regression to estimate hazard ratios for death from breast cancer and death from all causes. The analysis adjusts for age, clinical prognostic factors, and socioeconomic deprivation; the IV method may also adjust for unmeasured confounding factors. Cohorts of 9,653 and 7,965 were identified for women aged 70 years and over and those with high comorbidity, respectively. In the ≥70/high comorbidity cohorts, median follow-up was 5.17/6.53 years and there were 1,935/740 deaths from breast cancer. For women aged 70 years and over, the PSM-estimated HR was 0.73 (95% CI 0.64-0.95), while for women with high comorbidity it was 0.67 (95% CI 0.51-0.86). This translates to a mean predicted benefit in terms of overall survival at 10 years of approximately3% (percentage points) and 4%, respectively. A limitation of this analysis is that use of observational data means uncertainty remains both from sampling uncertainty and from potential bias from residual confounding. CONCLUSIONS: The results of this study, as RWD, should be interpreted with caution and in the context of existing and emerging randomised data. The relative effectiveness of adjuvant chemotherapy in reducing mortality in patients with early stage breast cancer appears to be generalisable to the selected trial-underrepresented groups.</p

The emerging landscape of health research based on biobanks linked to electronic health records: Existing resources, statistical challenges, and potential opportunities

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/1/sim8445_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154448/2/sim8445.pd

Track D Social Science, Human Rights and Political Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138414/1/jia218442.pd

Host Defenses in Experimental Scrub Typhus: Role of Spleen and Peritoneal Exudate Lymphocytes in Cellular Immunity

Lymphocytes obtained from spleens or peritoneal exudates of immune donor mice were evaluated for their ability to passively confer protection on recipients subsequently challenged with virulent scrub typhus rickettsiae. Peritoneal exudate lymphocytes (PELs) injected intraperitoneally were able to transfer complete protection against rickettsial challenge by 5 days after immunization, whereas splenic lymphocytes (SpL's) required 15 days to exhibit similar resistance. When immune lymphocytes were transferred intravenously, cells from both anatomical compartments required 15 days after immunization before they were able to completely protect recipients. PELs maintained this protective capacity for 2 weeks, but the passive immunity induced by intravenously transferred SpL's rapidly diminished to insignificant levels. It was particularly interesting that the protective effect of SpL's could be dramatically reduced by the concomitant presence of a mineral oil-induced peritoneal exudate. Almost total abrogation of resistance was observed when SpL's obtained from exudate-bearing mice were transferred intravenously. The protective capacity of both PELs and SpL's was resistant to 1,200 rads of gamma radiation at 7 to 10 days after immunization, but resistance was transient and by 3 weeks was undetectable. It was not possible to determine from this study whether the transferred lymphocytes were proximate mediators of protection in scrub typhus infection of mice or whether they served to recruit the host's own defenses, or both. However, it was possible to conclude that PEL's and SpLs exhibited functional heterogeneity and that PELs were more efficient mediators of protection.</jats:p