Social and Medical Determinants of Diabetes: A Time-Constrained Multiple Mediator Analysis.

Background A number of studies have shown an association between social determinants of health and the emergence of obesity and diabetes, but whether the relationship is causal is not clear. Objective To test whether social, environmental, and medical determinants directly or indirectly affect population-level diabetes prevalence after controlling for mediator-mediator interactions. Methods Data were obtained from the CDC and supplemented with nine other data sources for 3,109 US counties. The dependent variable was the prevalence of diabetes in 2017. Independent variables were a given county's 30 social, environmental, and medical characteristics in 2015 and 2016. A network multiple mediation analysis was conducted. First, we used Least Absolute Shrinkage and Selection Operator (LASSO) regression to relate the 2017 diabetes rate in each county to 30 predictors measured in 2016, identifying statistically significant and robust predictors as the mediators within the network model and as direct determinants of 2017 diabetes. Second, each of the direct causes of diabetes was taken as a new response variable and LASSO-regressed on the same 30 independent variables measured in 2015, identifying the indirect (mediated) causes of diabetes. Subsequently, these direct and indirect predictors were used to construct a network model. The completed network was then employed to estimate the direct and mediated impact of variables on diabetes. Results For 2017 diabetes rates, 63% of the variation was explained by five variables measured in 2016: the percentage of residents who were (1) obese, (2) African American, (3) physically inactive, (4) in poor health condition, and (5) had a history of diabetes. These five direct predictors, measured in 2016, mediated the effect of indirect variables measured in 2015, including the percentage of residents who were (1) Hispanic, (2) physically distressed, (3) smokers, (4) living with children in poverty, (5) experiencing limited access to healthy foods, and (6) had low income. Conclusion All of the direct predictors of diabetes prevalence, except the percentage of residents who were African American, were medical conditions potentially influenced by lifestyles. Counties characterized by higher levels of obesity, inactivity, and poor health conditions exhibited increased diabetes rates in the following year. The impact of social determinants of illness, such as low income, children in poverty, and limited access to healthy foods, had an indirect effect on the health of residents and, consequently, increased the prevalence of diabetes.

Guidelines for Triage of COVID-19 Patients Presenting With Multisystemic Symptoms.

BACKGROUND AND OBJECTIVES: This article describes how multisystemic symptoms, both respiratory and nonrespiratory, can be used to differentiate coronavirus disease-2019 (COVID-19) from other diseases at the point of patient triage in the community. The article also shows how combinations of symptoms could be used to predict the probability of a patient having COVID-19. METHODS: We first used a scoping literature review to identify symptoms of COVID-19 reported during the first year of the global pandemic. We then surveyed individuals with reported symptoms and recent reverse transcription polymerase chain reaction (RT-PCR) test results to assess the accuracy of diagnosing COVID-19 from reported symptoms. The scoping literature review, which included 81 scientific articles published by February 2021, identified 7 respiratory, 9 neurological, 4 gastrointestinal, 4 inflammatory, and 5 general symptoms associated with COVID-19 diagnosis. The likelihood ratio associated with each symptom was estimated from sensitivity and specificity of symptoms reported in the literature. A total of 483 individuals were then surveyed to validate the accuracy of predicting COVID-19 diagnosis based on patient symptoms using the likelihood ratios calculated from the literature review. Survey results were weighted to reflect age, gender, and race of the US population. The accuracy of predicting COVID-19 diagnosis from patient-reported symptoms was assessed using area under the receiver operating curve (AROC). RESULTS: In the community, cough, sore throat, runny nose, dyspnea, and hypoxia, by themselves, were not good predictors of COVID-19 diagnosis. A combination of cough and fever was also a poor predictor of COVID-19 diagnosis (AROC = 0.56). The accuracy of diagnosing COVID-19 based on symptoms was highest when individuals presented with symptoms from different body systems (AROC of 0.74-0.81); the lowest accuracy was when individuals presented with only respiratory symptoms (AROC = 0.48). CONCLUSIONS: There are no simple rules that clinicians can use to diagnose COVID-19 in the community when diagnostic tests are unavailable or untimely. However, triage of patients to appropriate care and treatment can be improved by reviewing the combinations of certain types of symptoms across body systems.

Combined Symptom Screening and At-Home Tests for COVID-19.

BACKGROUND AND OBJECTIVE: At-home rapid antigen tests provide a convenient and expedited resource to learn about severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection status. However, low sensitivity of at-home antigen tests presents a challenge. This study examines the accuracy of at-home tests, when combined with computer-facilitated symptom screening. METHODS: The study used primary data sources with data collected during 2 phases at different periods (phase 1 and phase 2): one during the period in which the alpha variant of SARS-CoV-2 was predominant in the United States and another during the surge of the delta variant. Four hundred sixty-one study participants were included in the analyses from phase 1 and 374 subjects from phase 2. Phase 1 data were used to develop a computerized symptom screening tool, using ordinary logistic regression with interaction terms, which predicted coronavirus disease-2019 (COVID-19) reverse transcription polymerase chain reaction (RT-PCR) test results. Phase 2 data were used to validate the accuracy of predicting COVID-19 diagnosis with (1) computerized symptom screening; (2) at-home rapid antigen testing; (3) the combination of both screening methods; and (4) the combination of symptom screening and vaccination status. The McFadden pseudo-R2 was used as a measure of percentage of variation in RT-PCR test results explained by the various screening methods. RESULTS: The McFadden pseudo-R2 for the first at-home test, the second at-home test, and computerized symptom screening was 0.274, 0.140, and 0.158, respectively. Scores between 0.2 and 0.4 indicated moderate levels of accuracy. The first at-home test had low sensitivity (0.587) and high specificity (0.989). Adding a second at-home test did not improve the sensitivity of the first test. Computerized symptom screening improved the accuracy of the first at-home test (added 0.131 points to sensitivity and 6.9% to pseudo-R2 of the first at-home test). Computerized symptom screening and vaccination status was the most accurate method to screen patients for COVID-19 or an active infection with SARS-CoV-2 in the community (pseudo-R2 = 0.476). CONCLUSION: Computerized symptom screening could either improve, or in some situations, replace at-home antigen tests for those individuals experiencing COVID-19 symptoms.

Order of Occurrence of COVID-19 Symptoms.

BACKGROUND AND OBJECTIVES: COVID-19 symptoms change after onset-some show early, others later. This article examines whether the order of occurrence of symptoms can improve diagnosis of COVID-19 before test results are available. METHODS: In total, 483 individuals who completed a COVID-19 test were recruited through Listservs. Participants then completed an online survey regarding their symptoms and test results. The order of symptoms was set according to (a) whether the participant had a "history of the symptom" due to a prior condition; and (b) whether the symptom "occurred first," or prior to, other symptoms of COVID-19. Two LASSO (Least Absolute Shrinkage and Selection Operator) regression models were developed. The first model, referred to as "time-invariant," used demographics and symptoms but not the order of symptom occurrence. The second model, referred to as "time-sensitive," used the same data set but included the order of symptom occurrence. RESULTS: The average cross-validated area under the receiver operating characteristic (AROC) curve for the time-invariant model was 0.784. The time-sensitive model had an AROC curve of 0.799. The difference between the 2 accuracy levels was statistically significant (α < .05). CONCLUSION: The order of symptom occurrence made a statistically significant, but small, improvement in the accuracy of the diagnosis of COVID-19.

Testing the Acceptability and Usability of an AI-Enabled COVID-19 Diagnostic Tool Among Diverse Adult Populations in the United States.

BACKGROUND AND OBJECTIVES: Although at-home coronavirus disease-2019 (COVID-19) testing offers several benefits in a relatively cost-effective and less risky manner, evidence suggests that at-home COVID-19 test kits have a high rate of false negatives. One way to improve the accuracy and acceptance of COVID-19 screening is to combine existing at-home physical test kits with an easily accessible, electronic, self-diagnostic tool. The objective of the current study was to test the acceptability and usability of an artificial intelligence (AI)-enabled COVID-19 testing tool that combines a web-based symptom diagnostic screening survey and a physical at-home test kit to test differences across adults from varying races, ages, genders, educational, and income levels in the United States. METHODS: A total of 822 people from Richmond, Virginia, were included in the study. Data were collected from employees and patients of Virginia Commonwealth University Health Center as well as the surrounding community in June through October 2021. Data were weighted to reflect the demographic distribution of patients in United States. Descriptive statistics and repeated independent t tests were run to evaluate the differences in the acceptability and usability of an AI-enabled COVID-19 testing tool. RESULTS: Across all participants, there was a reasonable degree of acceptability and usability of the AI-enabled COVID-19 testing tool that included a physical test kit and symptom screening website. The AI-enabled COVID-19 testing tool demonstrated overall good acceptability and usability across race, age, gender, and educational background. Notably, participants preferred both components of the AI-enabled COVID-19 testing tool to the in-clinic testing. CONCLUSION: Overall, these findings suggest that our AI-enabled COVID-19 testing approach has great potential to improve the quality of remote COVID testing at low cost and high accessibility for diverse demographic populations in the United States.

The Role of Symptom Clusters in Triage of COVID-19 Patients.

BACKGROUND AND OBJECTIVE: COVID-19 manifests with a broad range of symptoms. This study investigates whether clusters of respiratory, gastrointestinal, or neurological symptoms can be used to diagnose COVID-19. METHODS: We surveyed symptoms of 483 subjects who had completed COVID-19 laboratory tests in the last 30 days. The survey collected data on demographic characteristics, self-reported symptoms for different types of infections within 14 days of onset of illness, and self-reported COVID-19 test results. Robust LASSO regression was used to create 3 nested models. In all 3 models, the response variable was the COVID-19 test result. In the first model, referred to as the "main effect model," the independent variables were demographic characteristics, history of chronic symptoms, and current symptoms. The second model, referred to as the "hierarchical clustering model," added clusters of variables to the list of independent variables. These clusters were established through hierarchical clustering. The third model, referred to as the "interaction-terms model," also added clusters of variables to the list of independent variables; this time clusters were established through pairwise and triple-way interaction terms. Models were constructed on a randomly selected 80% of the data and accuracy was cross-validated on the remaining 20% of the data. The process was bootstrapped 30 times. Accuracy of the 3 models was measured using the average of the cross-validated area under the receiver operating characteristic curves (AUROCs). RESULTS: In 30 bootstrap samples, the main effect model had an AUROC of 0.78. The hierarchical clustering model had an AUROC of 0.80. The interaction-terms model had an AUROC of 0.81. Both the hierarchical cluster model and the interaction model were significantly different from the main effect model (α = .04). Patients with different races/ethnicities, genders, and ages presented with different symptom clusters. CONCLUSIONS: Using clusters of symptoms, it is possible to more accurately diagnose COVID-19 among symptomatic patients.

Modeling the Probability of COVID-19 Based on Symptom Screening and Prevalence of Influenza and Influenza-Like Illnesses.

BACKGROUND: The importance of various patient-reported signs and symptoms to the diagnosis of coronavirus disease 2019 (COVID-19) changes during, and outside, of the flu season. None of the current published studies, which focus on diagnosis of COVID-19, have taken this seasonality into account. OBJECTIVE: To develop predictive algorithm, which estimates the probability of having COVID-19 based on symptoms, and which incorporates the seasonality and prevalence of influenza and influenza-like illness data. METHODS: Differential diagnosis of COVID-19 and influenza relies on demographic characteristics (age, race, and gender), and respiratory (eg, fever, cough, and runny nose), gastrointestinal (eg, diarrhea, nausea, and loss of appetite), and neurological (eg, anosmia and headache) signs and symptoms. The analysis was based on the symptoms reported by COVID-19 patients, 774 patients in China and 273 patients in the United States. The analysis also included 2885 influenza and 884 influenza-like illnesses in US patients. Accuracy of the predictions was calculated using the average area under the receiver operating characteristic (AROC) curves. RESULTS: The likelihood ratio for symptoms, such as cough, depended on the flu season-sometimes indicating COVID-19 and other times indicating the reverse. In 30-fold cross-validated data, the symptoms accurately predicted COVID-19 (AROC of 0.79), showing that symptoms can be used to screen patients in the community and prior to testing. CONCLUSION: Community-based health care providers should follow different signs and symptoms for diagnosing COVID-19 during, and outside of, influenza season.

Differential diagnosis of COVID-19 and influenza.

This study uses two existing data sources to examine how patients' symptoms can be used to differentiate COVID-19 from other respiratory diseases. One dataset consisted of 839,288 laboratory-confirmed, symptomatic, COVID-19 positive cases reported to the Centers for Disease Control and Prevention (CDC) from March 1, 2019, to September 30, 2020. The second dataset provided the controls and included 1,814 laboratory-confirmed influenza positive, symptomatic cases, and 812 cases with symptomatic influenza-like-illnesses. The controls were reported to the Influenza Research Database of the National Institute of Allergy and Infectious Diseases (NIAID) between January 1, 2000, and December 30, 2018. Data were analyzed using case-control study design. The comparisons were done using 45 scenarios, with each scenario making different assumptions regarding prevalence of COVID-19 (2%, 4%, and 6%), influenza (0.01%, 3%, 6%, 9%, 12%) and influenza-like-illnesses (1%, 3.5% and 7%). For each scenario, a logistic regression model was used to predict COVID-19 from 2 demographic variables (age, gender) and 10 symptoms (cough, fever, chills, diarrhea, nausea and vomiting, shortness of breath, runny nose, sore throat, myalgia, and headache). The 5-fold cross-validated Area under the Receiver Operating Curves (AROC) was used to report the accuracy of these regression models. The value of various symptoms in differentiating COVID-19 from influenza depended on a variety of factors, including (1) prevalence of pathogens that cause COVID-19, influenza, and influenza-like-illness; (2) age of the patient, and (3) presence of other symptoms. The model that relied on 5-way combination of symptoms and demographic variables, age and gender, had a cross-validated AROC of 90%, suggesting that it could accurately differentiate influenza from COVID-19. This model, however, is too complex to be used in clinical practice without relying on computer-based decision aid. Study results encourage development of web-based, stand-alone, artificial Intelligence model that can interview patients and help clinicians make quarantine and triage decisions.

Using observed sequence to orient causal networks.

In learning causal networks, typically cross-sectional data are used and the sequence among the network nodes is learned through conditional independence. Sequence is inherently a longitudinal concept. We propose to learn sequence of events in longitudinal data and use it to orient arc directions in a network learned from cross-sectional data. The network is learned from cross-sectional data using various established algorithms, with one modification. Arc directions that do not agree with the longitudinal sequence were prohibited. We established longitudinal sequence through two methods: Probabilistic Contrast, and Goodman and Kruskal error reduction methods. In simulated data, the error reduction method was used to learn the sequence in the data. The procedure reduced the number of arc direction errors and larger improvements were observed with increasing number of events in the network. In real data, different algorithms were used to learn the network from cross-sectional data, while prohibiting arc directions not supported by longitudinal information. The agreement among learned networks increased significantly. It is possible to combine sequence information learned from longitudinal data with algorithms organized for learning network models from cross-sectional data. Such models may have additional causal interpretation as they more explicitly take into account observed sequence of events.

A psychological approach to learning causal networks.

We examine the role of a common cognitive heuristic in unsupervised learning of Bayesian probability networks from data. Human beings perceive a larger association between causal than diagnostic relationships. This psychological principal can be used to orient the arcs within Bayesian networks by prohibiting the direction that is less predictive. The heuristic increased predictive accuracy by an average of 0.51 % percent, a small amount. It also increased total agreement between different network learning algorithms (Max Spanning Tree, Taboo, EQ, SopLeq, and Taboo Order) by 25 %. Prior to use of the heuristic, the multiple raters Kappa between the algorithms was 0.60 (95 % confidence interval, CI, from 0.53 to 0.67) indicating moderate agreement among the networks learned through different algorithms. After the use of the heuristic, the multiple raters Kappa was 0.85 (95 % CI from 0.78 to 0.92). There was a statistically significant increase in agreement between the five algorithms (alpha < 0.05). These data suggest that the heuristic increased agreement between networks learned through use of different algorithms, without loss of predictive accuracy. Additional research is needed to see if findings persist in other data sets and to explain why a heuristic used by humans could improve construct validity of mathematical algorithms.

Genetic markers anticipate response to citalopram in a majority of patients.

OBJECTIVE: Scientists have concluded that genetic profiles cannot predict a large percentage of variation in response to citalopram, a common antidepressant. Using the same data, we examined if a different conclusion can be arrived at when the results are personalized to fit specific patients. METHODS: We used data available through the Sequenced Treatment Alternatives to Relieve Depression database. We created three boosted Classification and Regression Trees to identify 16 subgroups of patients, among whom anticipation of positive or negative response to citalopram was significantly different from 0.5 (P≤0.1). RESULTS: In a 10-fold cross-validation, this ensemble of trees made no predictions in 33% of cases. In the remaining 67% of cases, it accurately classified response to citalopram in 78% of cases. CONCLUSION: For the majority of the patients, genetic markers can be used to guide selection of citalopram. The rules identified in this study can help personalize prescription of antidepressants.

Probabilistic master lists: integration of patient records from different databases when unique patient identifier is missing.

We show how Bayesian probability models can be used to integrate two databases, one of which does not have a key for uniquely identifying clients (e.g., social security number or medical record number). The analyst selects a set of imperfect identifiers (last visit diagnosis, first name, etc.). The algorithm assesses the likelihood ratio associated with the identifier from the database of known cases. It estimates the probability that two records belong to the same client from the likelihood ratios. As it proceeds in examining various identifiers, it accounts for inter-dependencies among them by allowing overlapping and redundant identifiers to be used. We test that the procedure is effective by examining data from the Medical Expenditure Panel Survey (MEPS) Population Characteristics data set, a publicly available data set. We randomly selected 1,000 cases for training data set--these constituted the known cases. The algorithm was used to identify if 100 cases not in the training data set would be misclassified in terms of being a case in the training set or a new case. With 12 fields as identifiers, all 100 cases were correctly classified as new cases. We also selected 100 known cases from the training set and asked the algorithm to classify these cases. Again, all 100 cases were correctly classified. Less accurate results were obtained when the training data set was too small (e.g., less than 100 records) or the number of fields used as identifiers was too small (e.g., less than seven fields). In a test of performance of the algorithm, when the ratio of testing to training data set exceeds 4 to 1, the accuracy of the algorithm exceeded 90% of cases. As the ratio increases, the accuracy of algorithm improves further. These data suggest the accuracy of our automated and mathematical procedure to merge data from two different data sets without the presence of a unique identifier. The algorithm uses imperfect and overlapping clues to re-identify cases from information not typically considered to be a patient identifier.

Costs and benefits of combining probation and substance abuse treatment.

AIMS OF THE STUDY: We compared seamless combination of probation and treatment (where the probation officer is co-located with treatment provider or is actively engaged in treatment) to traditional probation where treatment is left to the client's choice. METHODS: Clients were randomly assigned to either seamless or traditional probation. We used a decision analytic approach which had two advantages: First it separated estimation of probability of adverse events (e.g. hospitalization) from the daily cost of the adverse event, thereby allowing use of estimates of daily costs available within the literature. Second, the reliance on daily probability of various adverse events also had the benefit of reflecting both length of the event and its intermittent re-occurrence. Subjects were 272 clients on probation in Northern Virginia and Maryland in the United States. Clients were randomly assigned to seamless and traditional probation and were followed for an average of 2.75 years (arrest information was only available for 1 year); 77% of clients participated in the follow-up interviews. At baseline, there was no statistically significant difference among the clients. RESULTS: During the follow-up period, clients in the seamless probation had less recidivism but the cost savings from this component (dollar 2.31 per client per follow-up day) was not sufficient to overcome increased costs due to mental hospitalization of seamless clients (dollar 13.50 per client per follow-up day), cost of delivery of seamless probation (dollar 2.58 per client per follow-up day), more frequent use of jail/prison for clients in the seamless group (dollar 2.08 per client per follow-up day) and additional treatment costs (dollar 1.24 per client per follow-up day). The expected cost of seamless probation and its consequences was dollar 38.84 per follow-up day. The expected cost of traditional probation and its consequences was dollar 21.60 per follow-up day. Seamless probation was dollar 6,293 more expensive than traditional probation per client per year. DISCUSSION: Sensitivity analysis suggested that the analysis was not sensitive to small change in any single cost or probability estimate. Sensitivity analysis suggested that increased supervision intensity and use of sanctions had contributed to lower cost-effectiveness. IMPLICATIONS: One possible way of improving seamless probation is to improve the intensity of the substance abuse treatment while reducing the intensity of supervision to its traditional levels. This analysis was limited to 2.75 years follow-up period and does not address cost savings that might occur after this period.