Mapping of critical events in disease progression through binary classification: Application to amyotrophic lateral sclerosis.

BACKGROUND: The progression of many degenerative diseases is tracked periodically using scales evaluating functionality in daily activities. Although estimating the timing of critical events (i.e., disease tollgates) during degenerative disease progression is desirable, the necessary data may not be readily available in scale records. Further, analysis of disease progression poses data challenges, such as censoring and misclassification errors, which need to be addressed to provide meaningful research findings and inform patients. METHODS: We developed a novel binary classification approach to map scale scores into disease tollgates to describe disease progression leveraging standard/modified Kaplan-Meier analyses. The approach is demonstrated by estimating progression pathways in amyotrophic lateral sclerosis (ALS). Tollgate-based ALS Staging System (TASS) specifies the critical events (i.e., tollgates) in ALS progression. We first developed a binary classification predicting whether each TASS tollgate was passed given the itemized ALSFRS-R scores using 514 ALS patients' data from Mayo Clinic-Rochester. Then, we utilized the binary classification to translate/map the ALSFRS-R data of 3,264 patients from the PRO-ACT database into TASS. We derived the time trajectories of ALS progression through tollgates from the augmented PRO-ACT data using Kaplan-Meier analyses. The effects of misclassification errors, condition-dependent dropouts, and censored data in trajectory estimations were evaluated with Interval Censored Kaplan Meier Analysis and Multistate Model for Panel Data. RESULTS: The approach using Mayo Clinic data accurately estimated tollgate-passed states of patients given their itemized ALSFRS-R scores (AUCs > 0.90). The tollgate time trajectories derived from the augmented PRO-ACT dataset provide valuable insights; we predicted that the majority of the ALS patients would have modified arm function (67%) and require assistive devices for walking (53%) by the second year after ALS onset. By the third year, most (74%) ALS patients would occasionally use a wheelchair, while 48% of the ALS patients would be wheelchair-dependent by the fourth year. Assistive speech devices and feeding tubes were needed in 49% and 30% of the patients by the third year after ALS onset, respectively. The onset body region alters some tollgate passage time estimations by 1-2 years. CONCLUSIONS: The estimated tollgate-based time trajectories inform patients and clinicians about prospective assistive device needs and life changes. More research is needed to personalize these estimations according to prognostic factors. Further, the approach can be leveraged in the progression of other diseases.

The value of missing information in severity of illness score development.

OBJECTIVE: We aim to investigate the hypothesis that using information about which variables are missing along with appropriate imputation improves the performance of severity of illness scoring systems used to predict critical patient outcomes. STUDY DESIGN AND SETTING: We quantify the impact of missing and imputed variables on the performance of prediction models used in the development of a sepsis-related severity of illness scoring system. Electronic health records (EHR) data were compiled from Christiana Care Health System (CCHS) on 119,968 adult patients hospitalized between July 2013 and December 2015. Two outcomes of interest were considered for prediction: (1) first transfer to intensive care unit (ICU) and (2) in-hospital mortality. Five different prediction models were employed. Indicators were utilized in these prediction models to identify when variables were missing and imputed. RESULTS: We observed statistically significant gains in prediction performance when moving from models that did not indicate missing information to those that did. Moreover, this increase was higher in models that use summary variables as predictors compared to those that use all variables. CONCLUSION: When developing prediction models using longitudinal EHR data, researchers should explore the incorporation of indicators for missing variables along with appropriate imputation.

Quantifying association and disparities between diabetes complications and COVID-19 outcomes: A retrospective study using electronic health records.

BACKGROUND: Despite established relationships between diabetic status and an increased risk for COVID-19 severe outcomes, there is a limited number of studies examining the relationships between diabetes complications and COVID-19-related risks. We use the Adapted Diabetes Complications Severity Index to define seven diabetes complications. We aim to understand the risk for COVID-19 infection, hospitalization, mortality, and longer length of stay of diabetes patients with complications. METHODS: We perform a retrospective case-control study using Electronic Health Records (EHRs) to measure differences in the risks for COVID-19 severe outcomes amongst those with diabetes complications. Using multiple logistic regression, we calculate adjusted odds ratios (OR) for COVID-19 infection, hospitalization, and in-hospital mortality of the case group (patients with diabetes complications) compared to a control group (patients without diabetes). We also calculate adjusted mean difference in length of stay between the case and control groups using multiple linear regression. RESULTS: Adjusting demographics and comorbidities, diabetes patients with renal complications have the highest odds for COVID-19 infection (OR = 1.85, 95% CI = [1.71, 1.99]) while those with metabolic complications have the highest odds for COVID-19 hospitalization (OR = 5.58, 95% CI = [3.54, 8.77]) and in-hospital mortality (OR = 2.41, 95% CI = [1.35, 4.31]). The adjusted mean difference (MD) of hospital length-of-stay for diabetes patients, especially those with cardiovascular (MD = 0.94, 95% CI = [0.17, 1.71]) or peripheral vascular (MD = 1.72, 95% CI = [0.84, 2.60]) complications, is significantly higher than non-diabetes patients. African American patients have higher odds for COVID-19 infection (OR = 1.79, 95% CI = [1.66, 1.92]) and hospitalization (OR = 1.62, 95% CI = [1.39, 1.90]) than White patients in the general diabetes population. However, White diabetes patients have higher odds for COVID-19 in-hospital mortality. Hispanic patients have higher odds for COVID-19 infection (OR = 2.86, 95% CI = [2.42, 3.38]) and shorter mean length of hospital stay than non-Hispanic patients in the general diabetes population. Although there is no significant difference in the odds for COVID-19 hospitalization and in-hospital mortality between Hispanic and non-Hispanic patients in the general diabetes population, Hispanic patients have higher odds for COVID-19 hospitalization (OR = 1.83, 95% CI = [1.16, 2.89]) and in-hospital mortality (OR = 3.69, 95% CI = [1.18, 11.50]) in the diabetes population with no complications. CONCLUSIONS: The presence of diabetes complications increases the risks of COVID-19 infection, hospitalization, and worse health outcomes with respect to in-hospital mortality and longer hospital length of stay. We show the presence of health disparities in COVID-19 outcomes across demographic groups in our diabetes population. One such disparity is that African American and Hispanic diabetes patients have higher odds of COVID-19 infection than White and Non-Hispanic diabetes patients, respectively. Furthermore, Hispanic patients might have less access to the hospital care compared to non-Hispanic patients when longer hospitalizations are needed due to their diabetes complications. Finally, diabetes complications, which are generally associated with worse COVID-19 outcomes, might be predominantly determining the COVID-19 severity in those infected patients resulting in less demographic differences in COVID-19 hospitalization and in-hospital mortality.

Septic shock prediction and knowledge discovery through temporal pattern mining.

Sepsis is the body's adverse response to infection which can lead to septic shock and eventually death if not treated in a timely manner. Analyzing patterns in sepsis patients' health status over time can help predict septic shock before its onset allowing healthcare providers to be more proactive. Temporal pattern mining methods can be used to identify trends in a patient's health status over time. If these methods return too many patterns, however, this can hinder knowledge discovery and practical implementation at the bedside in acute care settings. We propose a framework to find a small number of relevant temporal patterns in electronic health records for the early prediction of septic shock. Our framework consists of a temporal pattern mining method and three pattern selection techniques based on non-contrasted group support (PST1), contrasted group support (PST2), and model predictive power (PST3, PST4). We find that model-based feature selection approaches PST3 and PST4 yield the best prediction performance among these techniques. However, PST2 identifies more multi-state patterns with abnormal health states, which can give healthcare providers indicators of patient deterioration towards septic shock. Hence, from a knowledge discovery perspective, it may be worthwhile to sacrifice a small amount of prediction power for actionable patient health information through the implementation of PST2.

Tollgate-based progression pathways of ALS patients.

OBJECTIVE: To capture ALS progression in arm, leg, speech, swallowing, and breathing segments using a disease-specific staging system, namely tollgate-based ALS staging system (TASS), where tollgates refer to a set of critical clinical events including having slight weakness in arms, needing a wheelchair, needing a feeding tube, etc. METHODS: We compiled a longitudinal dataset from medical records including free-text clinical notes of 514 ALS patients from Mayo Clinic, Rochester-MN. We derived tollgate-based progression pathways of patients up to a 1-year period starting from the first clinic visit. We conducted Kaplan-Meier analyses to estimate the probability of passing each tollgate over time for each functional segment. RESULTS: At their first clinic visit, 93%, 77%, and 60% of patients displayed some level of limb, bulbar, and breathing weakness, respectively. The proportion of patients at milder tollgate levels (tollgate level < 2) was smaller for arm and leg segments (38% and 46%, respectively) compared to others (> 65%). Patients showed non-uniform TASS pathways, i.e., the likelihood of passing a tollgate differed based on the affected segments at the initial visit. For instance, stratified by impaired segments at the initial visit, patients with limb and breathing impairment were more likely (62%) to use bi-level positive airway pressure device in a year compared to those with bulbar and breathing impairment (26%). CONCLUSION: Using TASS, clinicians can inform ALS patients about their individualized likelihood of having critical disabilities and assistive-device needs (e.g., being dependent on wheelchair/ventilation, needing walker/wheelchair or communication devices), and help them better prepare for future.

Models for predicting the evolution of influenza to inform vaccine strain selection.

Influenza vaccine composition is reviewed before every flu season because influenza viruses constantly evolve through antigenic changes. To inform vaccine updates, laboratories that contribute to the World Health Organization Global Influenza Surveillance and Response System monitor the antigenic phenotypes of circulating viruses all year round. Vaccine strains are selected in anticipation of the upcoming influenza season to allow adequate time for production. A mismatch between vaccine strains and predominant strains in the flu season can significantly reduce vaccine effectiveness. Models for predicting the evolution of influenza based on the relationship of genetic mutations and antigenic characteristics of circulating viruses may inform vaccine strain selection decisions. We review the literature on state-of-the-art tools and prediction methodologies utilized in modeling the evolution of influenza to inform vaccine strain selection. We then discuss areas that are open for improvement and need further research.

Deriving effective vaccine allocation strategies for pandemic influenza: Comparison of an agent-based simulation and a compartmental model.

Individuals are prioritized based on their risk profiles when allocating limited vaccine stocks during an influenza pandemic. Computationally expensive but realistic agent-based simulations and fast but stylized compartmental models are typically used to derive effective vaccine allocation strategies. A detailed comparison of these two approaches, however, is often omitted. We derive age-specific vaccine allocation strategies to mitigate a pandemic influenza outbreak in Seattle by applying derivative-free optimization to an agent-based simulation and also to a compartmental model. We compare the strategies derived by these two approaches under various infection aggressiveness and vaccine coverage scenarios. We observe that both approaches primarily vaccinate school children, however they may allocate the remaining vaccines in different ways. The vaccine allocation strategies derived by using the agent-based simulation are associated with up to 70% decrease in total cost and 34% reduction in the number of infections compared to the strategies derived by using the compartmental model. Nevertheless, the latter approach may still be competitive for very low and/or very high infection aggressiveness. Our results provide insights about potential differences between the vaccine allocation strategies derived by using agent-based simulations and those derived by using compartmental models.