Effectiveness of Antidepressants in Combination with Psychotherapy.

BACKGROUND: Consensus-guidelines for prescribing antidepressants recommend that clinicians should be vigilant to match antidepressants to patient's medical history but provide no specific advice on which antidepressant is best for a given medical history. AIMS OF THE STUDY: For patients with major depression who are in psychotherapy, this study provides an empirically derived guideline for prescribing antidepressant medications that fit patients' medical history. METHODS: This retrospective, observational, cohort study analyzed a large insurance database of 3,678,082 patients. Data was obtained from healthcare providers in the U.S. between January 1, 2001, and December 31, 2018. These patients had 10,221,145 episodes of antidepressant treatments. This study reports the remission rates for the 14 most commonly prescribed single antidepressants (amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, sertraline, trazodone, and venlafaxine) and a category named "Other" (other antidepressants/combination of antidepressants). The study used robust LASSO regressions to identify factors that affected remission rate and clinicians' selection of antidepressants. The selection bias in observational data was removed through stratification. We organized the data into 16,770 subgroups, of at least 100 cases, using the combination of the largest factors that affected remission and selection bias. This paper reports on 2,467 subgroups of patients who had received psychotherapy. RESULTS: We found large, and statistically significant, differences in remission rates within subgroups of patients. Remission rates for sertraline ranged from 4.5% to 77.86%, for fluoxetine from 2.86% to 77.78%, for venlafaxine from 5.07% to 76.44%, for bupropion from 0.5% to 64.63%, for desvenlafaxine from 1.59% to 75%, for duloxetine from 3.77% to 75%, for paroxetine from 6.48% to 68.79%, for escitalopram from 1.85% to 65%, and for citalopram from 4.67% to 76.23%. Clearly these medications are ideal for patients in some subgroups but not others. If patients are matched to the subgroups, clinicians can prescribe the medication that works best in the subgroup. Some medications (amitriptyline, doxepin, nortriptyline, and trazodone) always had remission rates below 11% and therefore were not suitable as single antidepressant therapy for any of the subgroups. DISCUSSIONS: This study provides an opportunity for clinicians to identify an optimal antidepressant for their patients, before they engage in repeated trials of antidepressants. IMPLICATIONS FOR HEALTH CARE PROVISION AND USE: To facilitate the matching of patients to the most effective antidepressants, this study provides access to a free, non-commercial, decision aid at http://MeAgainMeds.com. IMPLICATIONS FOR HEALTH POLICIES:  Policymakers should evaluate how study findings can be made available through fragmented electronic health records at point-of-care. Alternatively, policymakers can put in place an AI system that recommends antidepressants to patients online, at home, and encourages them to bring the recommendation to their clinicians at their next visit. IMPLICATIONS FOR FURTHER RESEARCH:  Future research could investigate (i) the effectiveness of our recommendations in changing clinical practice, (ii) increasing remission of depression symptoms, and (iii) reducing cost of care. These studies need to be prospective but pragmatic. It is unlikely random clinical trials can address the large number of factors that affect remission.

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.

Impact of Political Leaning on COVID-19 Vaccine Hesitancy: A Network-Based Multiple Mediation Analysis.

Prior studies have shown that political affiliation affected COVID-19 vaccine hesitancy. This study re-examined the data to see if these findings hold after controlling for alternative explanations. The dependent variable in the study was COVID-19 vaccination rates in 3,109 counties in the United States as of April 2022. The study examined 36 possible alternative explanations for vaccine hesitancy, including demographic, social, economic, environmental, and medical variables known to affect vaccine hesitancy. County-level political affiliation was measured as a percent of voters in the county who were affiliated with Democratic or Republican political parties. Data were analyzed using a temporally constrained multiple mediation network, which allowed for the identification of both direct and indirect predictors of vaccination rates. Despite controlling for alternative explanations of hesitancy, there was a statistically significant relationship between the percentage of Republican supporters and rates of vaccine hesitancy. The higher the Republican affiliation, the lower the vaccination rates. It is possible that the Republican Party has played an organizing role in encouraging vaccine hesitancy and patient harm.

Selecting Antidepressants Based on Medical History and Stress Mechanism.

Purpose At present, clinicians typically prescribe antidepressants based on the widely accepted "serotonin hypothesis." This study explores an alternative mechanism, the stress mechanism, for selecting antidepressants based on patients' medical history. Methods This study investigated clinicians' prescribing patterns for the 15 most common antidepressants, including amitriptyline, bupropion, citalopram, desvenlafaxine, doxepin, duloxetine, escitalopram, fluoxetine, mirtazapine, nortriptyline, paroxetine, ropinirole, sertraline, trazodone, and Venlafaxine. The least absolute shrinkage and selection operator (LASSO) logistic regression was used to identify factors that affect the remission of depression symptoms after receiving an antidepressant. Results The study found that a wide range of factors influenced the propensity of clinicians to prescribe antidepressants, with the number of predictors ranging from 51 to 206 variables. The prevalence of prescribing an antidepressant ranged from 0.5% for doxepin to 24% for the combination of more than one antidepressant. The area under the receiver operating curves (AROC) ranged from 77.2% for venlafaxine to 90.5% for ropinirole, with an average AROC of 82% for predicting the propensity of medications. A variety of diagnoses and prior medications affected remission, in agreement that the central mechanism for the impact of medications on the brain is through stress reduction. For example, psychotherapy, whether done individually or in a group, whether done for a short or long time, and whether done with evaluation/assessment or not, had an impact on remission. Specifically, teenagers and octogenarians were less likely to benefit from bupropion, citalopram, escitalopram, fluoxetine, and sertraline compared to patients between 40 and 65 years old. The findings of this study suggest that considering a patient's medical history and individual characteristics is crucial for selecting the most effective antidepressant treatment. Conclusions Many studies have raised doubt about the serotonin hypothesis as the central mechanism for depression treatment. The identification of a wide range of predictors for prescribing antidepressants highlights the complexity of depression treatment and the need for individualized approaches that consider patients' comorbidities and previous treatments. The significant impact of comorbidities on the response to treatment makes it improbable that the mechanism of action of antidepressants is solely based on the serotonin hypothesis. It is hard to explain how comorbidities lead to the depletion of serotonin. These findings open up a variety of courses of action for the clinical treatment of depression, each addressing a different source of chronic stress in the brain. Overall, this study contributes to a better understanding of depression treatment and provides valuable insights for clinicians in selecting antidepressants based on patients' medical history.

Social Determinants of COVID-19 Vaccination Rates: A Time-Constrained Multiple Mediation Analysis.

Objective To estimate the multiple direct/indirect effects of social, environmental, and economic factors on COVID-19 vaccination rates (series complete) in the 3109 continental counties in the United States (U.S.). Study design  The dependent variable was the COVID-19 vaccination rates in the U.S. (April 15, 2022). Independent variables were collected from reliable secondary data sources, including the Census and CDC. Independent variables measured at two different time frames were utilized to predict vaccination rates. The number of vaccination sites in a given county was calculated using the geographic information system (GIS) packages as of April 9, 2022. The Internet Archive (Way Back Machine) was used to look up data for historical dates. Methods  A chain of temporally-constrained least absolute shrinkage and selection operator (LASSO) regressions was used to identify direct and indirect effects on vaccination rates. The first regression identified direct predictors of vaccination rates. Next, the direct predictors were set as response variables in subsequent regressions and regressed on variables that occurred before them. These regressions identified additional indirect predictors of vaccination. Finally, both direct and indirect variables were included in a network model. Results  Fifteen variables directly predicted vaccination rates and explained 43% of the variation in vaccination rates in April 2022. In addition, 11 variables indirectly affected vaccination rates, and their influence on vaccination was mediated by direct factors. For example, children in poverty rate mediated the effect of (a) median household income, (b) children in single-parent homes, and (c) income inequality. For another example, median household income mediated the effect of (a) the percentage of residents under the age of 18, (b) the percentage of residents who are Asian, (c) home ownership, and (d) traffic volume in the prior year. Our findings describe not only the direct but also the indirect effect of variables. Conclusions  A diverse set of demographics, social determinants, public health status, and provider characteristics predicted vaccination rates. Vaccination rates change systematically and are affected by the demographic composition and social determinants of illness within the county. One of the merits of our study is that it shows how the direct predictors of vaccination rates could be mediators of the effects of other variables.

Predicting 6-month mortality of patients from their medical history: Comparison of multimorbidity index to Deyo-Charlson index.

While every disease could affect a patient's prognosis, published studies continue to use indices that include a selective list of diseases to predict prognosis, which may limit its accuracy. This paper compares 6-month mortality predicted by a multimorbidity index (MMI) that relies on all diagnoses to the Deyo version of the Charlson index (DCI), a popular index that utilizes a selective set of diagnoses. In this retrospective cohort study, we used data from the Veterans Administration Diabetes Risk national cohort that included 6,082,018 diabetes-free veterans receiving primary care from January 1, 2008 to December 31, 2016. For the MMI, 7805 diagnoses were assigned into 19 body systems, using the likelihood that the disease will increase risk of mortality. The DCI used 17 categories of diseases, classified by clinicians as severe diseases. In predicting 6-month mortality, the cross-validated area under the receiver operating curve for the MMI was 0.828 (95% confidence interval of 0.826-0.829) and for the DCI was 0.749 (95% confidence interval of 0.748-0.750). Using all available diagnoses (MMI) led to a large improvement in accuracy of predicting prognosis of patients than using a selected list of diagnosis (DCI).

The Gender Self-Report: A multidimensional gender characterization tool for gender-diverse and cisgender youth and adults.

Gender identity is a core component of human experience, critical to account for in broad health, development, psychosocial research, and clinical practice. Yet, the psychometric characterization of gender has been impeded due to challenges in modeling the myriad gender self-descriptors, statistical power limitations related to multigroup analyses, and equity-related concerns regarding the accessibility of complex gender terminology. Therefore, this initiative employed an iterative multi-community-driven process to develop the Gender Self-Report (GSR), a multidimensional gender characterization tool, accessible to youth and adults, nonautistic and autistic people, and gender-diverse and cisgender individuals. In Study 1, the GSR was administered to 1,654 individuals, sampled through seven diversified recruitments to be representative across age (10-77 years), gender and sexuality diversity (∼33% each gender diverse, cisgender sexual minority, cisgender heterosexual), and autism status (> 33% autistic). A random half-split subsample was subjected to exploratory factor analytics, followed by confirmatory analytics in the full sample. Two stable factors emerged: Nonbinary Gender Diversity and Female-Male Continuum (FMC). FMC was transformed to Binary Gender Diversity based on designated sex at birth to reduce collinearity with designated sex at birth. Differential item functioning by age and autism status was employed to reduce item-response bias. Factors were internally reliable. Study 2 demonstrated the construct, convergent, and ecological validity of GSR factors. Of the 30 hypothesized validation comparisons, 26 were confirmed. The GSR provides a community-developed gender advocacy tool with 30 self-report items that avoid complex gender-related "insider" language and characterize diverse populations across continuous multidimensional binary and nonbinary gender traits. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

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.

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.

Procedure for Organizing a Post-FDA-approval Evaluation of Antidepressants.

PURPOSE: The study reports the construction of a cohort used to study the effectiveness of antidepressants. METHODS: The cohort includes experiences of 3,678,082 patients with depression in the United States on antidepressants between January 1, 2001, and December 31, 2018. A total of 10,221,145 antidepressant treatment episodes were analyzed. Patients who had no utilization of health services for at least two years, or who had died, were excluded from the analysis. Follow-up was passive, automatic, and collated from fragmented clinical services of diverse providers. RESULTS: The average follow-up was 2.93 years, resulting in 15,096,055 person-years of data. The mean age of the cohort was 46.54 years (standard deviation of 17.48) at first prescription of antidepressant, which was also the enrollment event (16.92% were over 65 years), and most were female (69.36%). In 10,221,145 episodes, within the first 100 days of start of the episode, 4,729,372 (46.3%) continued their treatment, 1,306,338 (12.8%) switched to another medication, 3,586,156 (35.1%) discontinued their medication, and 599,279 (5.9%) augmented their treatment. CONCLUSIONS: We present a procedure for constructing a cohort using claims data. A surrogate measure for self-reported symptom remission based on the patterns of use of antidepressants has been proposed to address the absence of outcomes in claims. Future studies can use the procedures described here to organize studies of the comparative effectiveness of antidepressants.

Emerging approaches to multiple chronic condition assessment.

Older adults experience a higher prevalence of multiple chronic conditions (MCCs). Establishing the presence and pattern of MCCs in individuals or populations is important for healthcare delivery, research, and policy. This report describes four emerging approaches and discusses their potential applications for enhancing assessment, treatment, and policy for the aging population. The National Institutes of Health convened a 2-day panel workshop of experts in 2018. Four emerging models were identified by the panel, including classification and regression tree (CART), qualifying comorbidity sets (QCS), the multimorbidity index (MMI), and the application of omics to network medicine. Future research into models of multiple chronic condition assessment may improve understanding of the epidemiology, diagnosis, and treatment of older persons.

Neighborhood Socioeconomic Environment and Risk of Type 2 Diabetes: Associations and Mediation Through Food Environment Pathways in Three Independent Study Samples.

OBJECTIVE: We examined whether relative availability of fast-food restaurants and supermarkets mediates the association between worse neighborhood socioeconomic conditions and risk of developing type 2 diabetes (T2D). RESEARCH DESIGN AND METHODS: As part of the Diabetes Location, Environmental Attributes, and Disparities Network, three academic institutions used harmonized environmental data sources and analytic methods in three distinct study samples: 1) the Veterans Administration Diabetes Risk (VADR) cohort, a national administrative cohort of 4.1 million diabetes-free veterans developed using electronic health records (EHRs); 2) Reasons for Geographic and Racial Differences in Stroke (REGARDS), a longitudinal, epidemiologic cohort with Stroke Belt region oversampling (N = 11,208); and 3) Geisinger/Johns Hopkins University (G/JHU), an EHR-based, nested case-control study of 15,888 patients with new-onset T2D and of matched control participants in Pennsylvania. A census tract-level measure of neighborhood socioeconomic environment (NSEE) was developed as a community type-specific z-score sum. Baseline food-environment mediators included percentages of 1) fast-food restaurants and 2) food retail establishments that are supermarkets. Natural direct and indirect mediating effects were modeled; results were stratified across four community types: higher-density urban, lower-density urban, suburban/small town, and rural. RESULTS: Across studies, worse NSEE was associated with higher T2D risk. In VADR, relative availability of fast-food restaurants and supermarkets was positively and negatively associated with T2D, respectively, whereas associations in REGARDS and G/JHU geographies were mixed. Mediation results suggested that little to none of the NSEE-diabetes associations were mediated through food-environment pathways. CONCLUSIONS: Worse neighborhood socioeconomic conditions were associated with higher T2D risk, yet associations are likely not mediated through food-environment pathways.

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.

Multi-omic molecular profiling guide's efficacious treatment selection in refractory metastatic breast cancer: a prospective phase II clinical trial.

This prospective phase II clinical trial (Side Out 2) explored the clinical benefits of treatment selection informed by multi-omic molecular profiling (MoMP) in refractory metastatic breast cancers (MBCs). Core needle biopsies were collected from 32 patients with MBC at trial enrollment. Patients had received an average of 3.94 previous lines of treatment in the metastatic setting before enrollment in this study. Samples underwent MoMP, including exome sequencing, RNA sequencing (RNA-Seq), immunohistochemistry, and quantitative protein pathway activation mapping by Reverse Phase Protein Microarray (RPPA). Clinical benefit was assessed using the previously published growth modulation index (GMI) under the hypothesis that MoMP-selected therapy would warrant further investigation for GMI ≥ 1.3 in ≥ 35% of the patients. Of the 32 patients enrolled, 29 received treatment based on their MoMP and 25 met the follow-up criteria established by the trial protocol. Molecular information was delivered to the tumor board in a median time frame of 14 days (11-22 days), and targetable alterations for commercially available agents were found in 23/25 patients (92%). Of the 25 patients, 14 (56%) reached GMI ≥ 1.3. A high level of DNA topoisomerase I (TOPO1) led to the selection of irinotecan-based treatments in 48% (12/25) of the patients. A pooled analysis suggested clinical benefit in patients with high TOPO1 expression receiving irinotecan-based regimens (GMI ≥ 1.3 in 66.7% of cases). These results confirmed previous observations that MoMP increases the frequency of identifiable actionable alterations (92% of patients). The MoMP proposed allows the identification of biomarkers that are frequently expressed in MBCs and the evaluation of their role as predictors of response to commercially available agents. Lastly, this study confirmed the role of MoMP for informing treatment selection in refractory MBC patients: more than half of the enrolled patients reached a GMI ≥ 1.3 even after multiple lines of previous therapies for metastatic disease.

Effectiveness of common antidepressants: a post market release study.

BACKGROUND: This study summarizes the experiences of patients, who have multiple comorbidities, with 15 mono-treated antidepressants. METHODS: This is a retrospective, observational, matched case control study. The cohort was organized using claims data available through OptumLabs for depressed patients treated with antidepressants between January 1, 2001 and December 31, 2018. The cohort included patients from all states within United States of America. The analysis focused on 3,678,082 patients with major depression who had 10,221,145 antidepressant treatments. Using the robust, and large predictors of remission, and propensity to prescribe an antidepressant, the study created 16,770 subgroups of patients. The study reports the remission rate for the antidepressants within the subgroups. The overall impact of antidepressant on remission was calculated as the common odds ratio across the strata. FINDINGS: The study accurately modelled clinicians' prescription patterns (cross-validated Area under the Receiver Operating Curve, AROC, of 82.0%, varied from 77% to 90%) and patients' remission (cross-validated AROC of 72.0%, varied from 69.5% to 78%). In different strata, contrary to published randomized studies, remission rates differed significantly and antidepressants were not equally effective. For example, in age and gender subgroups, the best antidepressant had an average remission rate of 50.78%, 1.5 times higher than the average antidepressant (30.30% remission rate) and 20 times higher than the worst antidepressant. The Breslow-Day chi-square test for homogeneity showed that across strata a homogenous common odds-ratio did not exist (alpha<0.0001). Therefore, the choice of the optimal antidepressant depended on the strata defined by the patient's medical history. INTERPRETATION: Study findings may not be appropriate for specific patients. To help clinicians assess the transferability of study findings to specific patient, the web site http://hi.gmu.edu/ad assesses the patient's medical history, finds similar cases in our data, and recommends an antidepressant based on the experience of remission in our data. Patients can share this site's recommendations with their clinicians, who can then assess the appropriateness of the recommendations. FUNDING: This project was funded by the Robert Wood Johnson foundation grant #76786. The development of related web site was supported by grant 247-02-20 from Virginia's Commonwealth Health Research Board.