Machine Learning Improves Prediction Over Logistic Regression on Resected Colon Cancer Patients.

INTRODUCTION: Despite advances, readmission and mortality rates for surgical patients with colon cancer remain high. Prediction models using regression techniques allows for risk stratification to aid periprocedural care. Technological advances have enabled large data to be analyzed using machine learning (ML) algorithms. A national database of colon cancer patients was selected to determine whether ML methods better predict outcomes following surgery compared to conventional methods. METHODS: Surgical colon cancer patients were identified using the 2013 National Cancer Database (NCDB). The negative outcome was defined as a composite of 30-d unplanned readmission and 30- and 90-d mortality. ML models, including Random Forest and XGBoost, were built and compared with conventional logistic regression. For the accounting of unbalanced outcomes, a synthetic minority oversampling technique (SMOTE) was implemented and applied using XGBoost. RESULTS: Analysis included 528,060 patients. The negative outcome occurred in 11.6% of patients. Model building utilized 30 variables. The primary metric for model comparison was area under the curve (AUC). In comparison to logistic regression (AUC 0.730, 95% CI: 0.725-0.735), AUC's for ML algorithms ranged between 0.748 and 0.757, with the Random Forest model (AUC 0.757, 95% CI: 0.752-0.762) outperforming XGBoost (AUC 0.756, 95% CI: 0.751-0.761) and XGBoost using SMOTE data (AUC 0.748, 95% CI: 0.743-0.753). CONCLUSIONS: We show that a large registry of surgical colon cancer patients can be utilized to build ML models to improve outcome prediction with differential discriminative ability. These results reveal the potential of these methods to enhance risk prediction, leading to improved strategies to mitigate those risks.

Clinically Significant Changes in the 17- and 6-Item Hamilton Rating Scales for Depression: A STAR*D Report.

OBJECTIVE: To develop clinically meaningful improvement thresholds in both the 17-item and the 6-item Hamilton Rating Scale for Depression (HRSD) total scores in depressed outpatients. METHODS: The post-hoc analysis included all adult outpatients with non-psychotic major depressive disorder in the STAR*D trial who entered and exited the first treatment step (up to 14 weeks of citalopram) with a complete set of study measures at baseline and exit and at least one post-baseline measure. Within-patient change and linear regression anchor-based analyses were conducted to define meaningful and substantial changes in the HRSD17 and HRSD6 using three patient-reported outcomes [Work and Social Adjustment Scale (WSAS), Quality of Life Enjoyment and Satisfaction-Short Form (Q-LES-Q-SF); Mini-Q-LES-Q] obtained at baseline and exit from the first treatment step in STAR*D. RESULTS: Linear regression analyses identified a meaningful change threshold for the HRSD17 as 3.9 [3.7-4.1] [lower, upper 95% CI] and a substantial change as 7.8 [7.4-8.3] with the WSAS. Analogous thresholds based on the Q-LES-Q-SF were 5.8 [5.5-6.1] and 11.6 [11.0-12.2], respectively, and 4.9 [4.7-5.2] and 9.9 [9.3-10.4] for the Mini-QLES-Q, respectively. For the HRSD6, linear regression analyses with the WSAS identified a meaningful change as 2.2 [2.1-2.4], while a substantial change was 4.5 [4.2-4.7]. Analogous figures based on the Q-LES-Q-SF were 3.2 [3.0-3.4] and 6.4 [6.1-6.8]. Similarly, based on the Mini-QLESQ, results were 2.8 [2.6-2.9] and 5.6 [5.3-5.9]. For both the HRSD17 and the HRSD6, within-patient analyses produced less precise estimates of the same change thresholds with substantial overlap between groups. Based on the WSAS, a clinically meaningful change in the HRSD17 total score was 9.6 (SD = 6.5), while a substantial change was 15.0 (SD = 6.7). Analogous change thresholds based on the Q-LESQ-SF were 12.9 (SD = 6.2) and 16.8 (SD = 6.4), respectively. For the Mini-Q-LES-Q, thresholds were 10.9 (SD = 6.5) and 16.1 (SD = 6.2). CONCLUSION: A 4-6 point change in the HRSD17 is clinically meaningful; a 7-12 point change is clinically substantial. For the HRSD6, analogous estimates were 2-3 and 4-7 point changes, respectively.

Pilot Studies to Evaluate Feasibility of a Physical Activity Intervention for Persons With Depression.

Exercise reduces depressive symptoms and improves physical health in persons with depression. However, the interventions implemented in research studies require significant resources, limiting adoption into clinical practice and suggesting the need for more efficient interventions. In two nonrandomized pilot studies, the authors evaluated the feasibility of a multicomponent intervention (group educational sessions, Fitbit, and access to exercise facility) in adult persons with depression and breast cancer survivors with depression. The participants in both pilot studies completed 12 weeks of group educational sessions to increase physical activity levels, were provided with self-monitoring devices, and were provided access to on-site exercise facilities. Depressive symptoms significantly decreased postintervention, and over 90% of the participants reported that they had benefited from the intervention. These results indicate that implementing a multicomponent intervention is feasible and may reduce depressive symptoms and improve other psychosocial outcomes.

Two Trajectories of Depressive Symptom Reduction Throughout Behavioral Activation Teletherapy Among Underserved, Ethnically Diverse, Primary Care Patients: A VitalSign6 Report.

While prior research has investigated trajectories of depressive symptom change throughout psychotherapy, such work has not been conducted exclusively among underserved patients receiving brief Behavioral Activation (BA) teletherapy, intervention modifications that should reduce barriers to therapy initiation and engagement. The current project used cluster analysis to determine discrete groups of symptom change among patients receiving an 8-session BA teletherapy intervention, and analyzed whether demographic and clinical characteristics were associated with group membership. Data from 105 patients referred from charity primary care clinics and receiving at least two therapy sessions were analyzed. Patients were predominantly female and Latina. The 9-item Patient Health Questionnaire (PHQ-9) was the outcome. Two categories were determined: a larger group (N = 61) demonstrating initially less severe symptoms and experiencing a gradual recovery, and a smaller group beginning with more severe symptoms, and experiencing a steeper recovery. In both groups, a majority of participants experienced at least a 5-point drop in depressive symptoms, while in the latter group, a majority of patients achieved depressive symptom remission (PHQ-9 < 5). Monolingual Spanish speakers were more likely to be in the former group, but no other demographic or clinical characteristics were associated with group membership. In both groups, a majority of the symptom reduction occurred by sessions 4-6. Therefore, two categories of depressive symptom change, slow responders and rapid responders, occur among patients receiving a brief BA teletherapy intervention. No demographic differences aside from primary language, nor any clinical characteristics, distinguish group membership, suggesting similar patterns of symptom reduction among a primarily underserved sample.

What to Expect When Switching to a Second Antidepressant Medication Following an Ineffective Initial SSRI: A Report From the Randomized Clinical STAR*D Study.

OBJECTIVE: An antidepressant medication switch often follows a failed initial trial with selective serotonin reuptake inhibitors (SSRIs). When, for whom, and how often second-step response and remission occur are unclear, as is preferred second-step trial duration. As more treatments are approved for use following 2 failed "adequate" trials, researchers and clinicians require an evidence-based definition of "adequate." METHODS: Following citalopram in the randomized Sequenced Treatment Alternatives to Relieve Depression (STAR*D) clinical trial (which ran July 2001-September 2006), participants with score ≥ 11 on the 16-item Quick Inventory of Depressive Symptomatology-Self-Rated (QIDS-SR16) were randomized to bupropion sustained release, sertraline, or venlafaxine extended release (up to 14 weeks). The QIDS-SR16 defined response, remission, and no clinically meaningful benefit based on the modified intent-to-treat sample. RESULTS: About 80% of 438 participants completed ≥ 6 weeks of treatment with the switch medication. All treatments had comparable outcomes. Overall, 21% (91/438) remitted, 9% (40/438) responded without remission, and 58% (255/438) had no meaningful benefit. Half of the responses and two-thirds of remissions occurred after 6 weeks of treatment. Overall, 33% of responses (43/131) occurred after ≥ 9 weeks of treatment. No baseline features differentiated early from later responders or remitters. No early triage point was found, but those with at least 20% reduction from baseline in QIDS-SR16 score around week 2 were 6 times more likely to respond or remit than those without this reduction. CONCLUSIONS: Following nonefficacy with an initial SSRI, only about 20% remit and more than half achieve no meaningful benefit with a second-step switch to another monoaminergic antidepressant. A 12-week trial duration seems necessary to capture as many second-step switch responders as possible. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00021528.

The Youth Aware of Mental Health Intervention: Impact on Help Seeking, Mental Health Knowledge, and Stigma in U.S. Adolescents.

PURPOSE: Suicide is a leading cause of death among U.S. youth aged 12-18 years. Youth Aware of Mental Health (YAM), a promising, universal, school-based mental health promotion/suicide primary prevention intervention for adolescents, has been evaluated in Europe but not in the U.S. The present study used an uncontrolled, pretest/post-test design to document the potential for YAM to reduce suicidal ideation, attempt, and suicide. A demonstration that help seeking behaviors, mental health literacy, and mental health stigmatizing attitudes improve after the intervention would suggest that the program is promising in the U.S., as well as in Europe, and that further investigation is merited. METHODS: YAM was delivered to 1,878 students in 11 schools as part of regular school curricula. A subset of these students (n = 436) completed surveys before and 3 months postdelivery. Surveys included five questions about help seeking behaviors, a measure of intent to seek help (General Help Seeking Questionnaire), two mental health literacy scales, and two mental illness stigma scales (Reported and Intended Behavior Scale and Personal Stigma and Social Distance Scale). Both McNemar's test and repeated measures linear models were used to determine whether the survey outcomes changed after YAM delivery. RESULTS: Among the 436 adolescents (286 and 150 in Montana and Texas, respectively), significant increases were found pre- to post-intervention in three of five help seeking behaviors, along with improved mental health literacy and decreased mental health-related stigma. Intent to seek help was unchanged. CONCLUSIONS: Several help seeking behavioral factors, mental health knowledge, and stigma improved post-YAM intervention. All three domains are likely protective against suicide. A randomized controlled trial testing the efficacy of YAM in preventing suicidal behaviors is warranted.

Feasibility and Acceptability of the Youth Aware of Mental Health (YAM) Intervention in US Adolescents.

Suicide is the second leading cause of death among US adolescents, and rates of suicide among youth have been increasing for the past decade. This study assessed the feasibility and acceptability of the universal, school-based Youth Aware of Mental Health (YAM) program, a promising mental health promotion and suicide primary prevention intervention, in US youth. Using an uncontrolled design, the feasibility and acceptability of delivering and studying YAM were assessed in Montana and Texas schools. Thirteen of 16 (81.3%) schools agreed to support YAM delivery, and five Montana and 6 Texas schools were included in analyses. Facilitators delivered YAM in 78 classes (1,878 students) as regular high school curriculum. Of the total number of students who received YAM, 519 (27.6%) provided parental consent and assent. 436 (84.0%) consented students participated in pre- and post-surveys. Students, parents, and school staff found YAM highly acceptable based on satisfaction surveys. In summary, this study found YAM feasible to implement in US schools. Results also suggest students, parents, and school staff supported school-based programs and were highly satisfied with the YAM program. A randomized controlled trial is warranted to test the efficacy of YAM in promoting mental health and preventing suicidal thoughts and behaviors in US adolescents.

Effect of Intrinsic Patterns of Functional Brain Connectivity in Moderating Antidepressant Treatment Response in Major Depression.

OBJECTIVE: Major depressive disorder is associated with aberrant resting-state functional connectivity across multiple brain networks supporting emotion processing, executive function, and reward processing. The purpose of this study was to determine whether patterns of resting-state connectivity between brain regions predict differential outcome to antidepressant medication (sertraline) compared with placebo. METHODS: Participants in the Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study underwent structural and resting-state functional MRI at baseline. Participants were then randomly assigned to receive either sertraline or placebo treatment for 8 weeks (N=279). A region of interest-based approach was utilized to compute functional connectivity between brain regions. Linear mixed-model intent-to-treat analyses were used to identify brain regions that moderated (i.e., differentially predicted) outcomes between the sertraline and placebo arms. RESULTS: Prediction of response to sertraline involved several within- and between-network connectivity patterns. In general, higher connectivity within the default mode network predicted better outcomes specifically for sertraline, as did greater between-network connectivity of the default mode and executive control networks. In contrast, both placebo and sertraline outcomes were predicted (in opposite directions) by between-network hippocampal connectivity. CONCLUSIONS: This study identified specific functional network-based moderators of treatment outcome involving brain networks known to be affected by major depression. Specifically, functional connectivity patterns of brain regions between and within networks appear to play an important role in identifying a favorable response for a drug treatment for major depressive disorder.

Prediction of Acute-Phase Treatment Outcomes by Adding a Single-Item Measure of Activity Impairment to Symptom Measurement: Development and Validation of an Interactive Calculator from the STAR*D and CO-MED Trials.

BACKGROUND: Day-to-day functioning is impaired in major depressive disorder. Yet there are no guidelines to systematically assess these functional changes. This report evaluates prognostic utility of changes in activity impairment to inform clinical decision-making at an individual level. METHODS: Mixed model analyses tested changes in activity impairment (sixth item of Work and Activity Impairment scale, rated 0-10) at mid-point (week 6) and end of step 1 (weeks 12-14) in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial (n = 2697) after controlling for depression severity [Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR)]. Interactive calculators for end of step 1 remission (QIDS-SR ≤5) and no meaningful benefit (<30% QIDS-SR reduction from baseline) were developed for participants with complete data (n = 1476) and independently replicated in the Combining Medications to Enhance Depression Outcomes trial (n = 399). RESULTS: Activity impairment improved independently with acute-phase treatment in STAR*D (F = 7.27; df = 2,2625; P < .001). Baseline to mid-point activity impairment change significantly predicted remission (P < .001, model area under the curve = 0.823) and no meaningful benefit (P < .001, area under the curve = 0.821) in the STAR*D trial. Adding activity impairment variables to depression severity measures correctly reclassified 28.4% and 15.8% remitters and nonremitters (net reclassification improvement analysis, P < .001), and 11.4% and 16.8% of those with no meaningful benefit and meaningful benefit (net reclassification improvement analysis, P < .001). The STAR*D trial model estimates accurately predicted remission (area under the curve = 0.80) and no meaningful benefit (area under the curve = 0.82) in the Combining Medications to Enhance Depression Outcomes trial and was used to develop an interactive calculator. CONCLUSION: A single-item self-report measure of activity impairment changes independently with antidepressant treatment. Baseline to week 6 changes in activity impairment and depression severity can be combined to predict acute-phase remission and no meaningful benefit at an individual level.

Irritability and Its Clinical Utility in Major Depressive Disorder: Prediction of Individual-Level Acute-Phase Outcomes Using Early Changes in Irritability and Depression Severity.

OBJECTIVE: The authors evaluated improvement in irritability with antidepressant treatment and its prognostic utility in treatment-seeking adult outpatients with major depressive disorder. METHODS: Mixed-model analyses were used to assess changes in irritability (as measured with the five-item irritability domain of the Concise Associated Symptom Tracking [CAST-IRR] scale) from baseline to week 4 after controlling for depression severity (as measured with the 16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C]) in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial (N=664). An interactive calculator for remission (QIDS-C score ≤5) and no meaningful benefit (<30% reduction in QIDS-C score from baseline) at week 8 was developed with logistic regression analyses in the CO-MED trial using participants with complete data (N=431) and independently replicated in the Suicide Assessment and Methodology Study (SAMS) (N=163). RESULTS: In the CO-MED trial, irritability was significantly reduced (effect size=1.06) from baseline to week 4, and this reduction remained significant after adjusting for QIDS-C change (adjusted effect size=0.36). A one-standard-deviation greater reduction in CAST-IRR score from baseline to week 4 predicted a 1.73 times higher likelihood of remission and a 0.72 times lower likelihood of no meaningful benefit at week 8, independent of baseline QIDS-C and CAST-IRR scores and reduction in QIDS-C score from baseline to week 4. The model estimates for remission (area under the curve [AUC]=0.79) and no meaningful benefit (AUC=0.76) in the CO-MED trial were used to predict remission (AUC=0.80) and no meaningful benefit (AUC=0.84) in SAMS and to develop an interactive calculator. CONCLUSIONS: Irritability is an important symptom domain of major depressive disorder that is not fully reflected in depressive symptom severity measures. Early reductions in irritability, when combined with changes in depressive symptom severity, provide a robust estimate of likelihood of remission or no meaningful benefit in outpatients with major depression.

Can targeted metabolomics predict depression recovery? Results from the CO-MED trial.

Metabolomics is a developing and promising tool for exploring molecular pathways underlying symptoms of depression and predicting depression recovery. The AbsoluteIDQ™ p180 kit was used to investigate whether plasma metabolites (sphingomyelins, lysophosphatidylcholines, phosphatidylcholines, and acylcarnitines) from a subset of participants in the Combining Medications to Enhance Depression Outcomes (CO-MED) trial could act as predictors or biologic correlates of depression recovery. Participants in this trial were assigned to one of three pharmacological treatment arms: escitalopram monotherapy, bupropion-escitalopram combination, or venlafaxine-mirtazapine combination. Plasma was collected at baseline in 159 participants and again 12 weeks later at study exit in 83 of these participants. Metabolite concentrations were measured and combined with clinical and sociodemographic variables using the hierarchical lasso to simultaneously model whether specific metabolites are particularly informative of depressive recovery. Increased baseline concentrations of phosphatidylcholine C38:1 showed poorer outcome based on change in the Quick Inventory of Depressive Symptoms (QIDS). In contrast, an increased ratio of hydroxylated sphingomyelins relative to non-hydroxylated sphingomyelins at baseline and a change from baseline to exit suggested a better reduction of symptoms as measured by QIDS score. All metabolite-based models performed superior to models only using clinical and sociodemographic variables, suggesting that metabolomics may be a valuable tool for predicting antidepressant outcomes.

Toward a very brief quality of life enjoyment and Satisfaction Questionnaire.

OBJECTIVE: To develop and evaluate a new brief self-report measure of satisfaction/quality of life in depressed outpatients. METHODS: Using the Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q-SF) self-report from Step-1 (n = 2181) of the STAR*D trial, items were selected based on their magnitude of change with treatment and correlation with 16-item Quick Inventory of Depressive Symptomatology Self-Report (QIDS-SR16). Psychometric analyses were conducted. Replication of scale performance was assessed with STAR*D Step-2 data (n = 250). RESULTS: The 7 items selected ("Mini-Q-LES-Q") rated satisfaction with work, household activities, social and family relations, leisure time activities, daily function and sense of well-being in the past week. This uni-dimensional scale captured 83-94% variance in Q-LES-Q-SF and had acceptable Item Response and Classical Test Theory characteristics. Baseline to exit percent changes in the Mini-Q-LES-Q and the QIDS-SR16 were significantly, modestly related (r = -0.552) (Step-1) and replicated (r = -0.562) (Step-2). The Mini-Q-LES-Q detected the expected improvement in satisfaction/quality of life in acute treatment, yet also identified residual deficits expected in many at acute-phase exit. LIMITATIONS: Population norms are yet undefined. Concurrent validity with detailed, well-validated scales that assess the seven Quality of Life domains incorporated in the Mini-Q-LES-Q remains unestablished. Sensitivity to symptom changes induced by psychotherapy or somatic therapies or sensitive to the effects of therapies aimed at enhancing quality of life enjoyment and function is unknown. CONCLUSION: The 7-item Mini-Q-LES-Q self-report measure satisfaction/quality of life has acceptable psychometric properties, reflects change with depressive symptom reduction, and detects residual deficits in this key clinical outcome.

A Novel Strategy to Identify Placebo Responders: Prediction Index of Clinical and Biological Markers in the EMBARC Trial.

BACKGROUND: One in three clinical trial patients with major depressive disorder report symptomatic improvement with placebo. Strategies to mitigate the effect of placebo responses have focused on modifying study design with variable success. Identifying and excluding or controlling for individuals with a high likelihood of responding to placebo may improve clinical trial efficiency and avoid unnecessary medication trials. METHODS: Participants included those assigned to the placebo arm (n = 141) of the Establishing Moderators and Biosignatures for Antidepressant Response in Clinical Care (EMBARC) trial. The elastic net was used to evaluate 283 baseline clinical, behavioral, imaging, and electrophysiological variables to identify the most robust yet parsimonious features that predicted depression severity at the end of the double-blind 8-week trial. Variables retained in at least 50% of the 100 imputed data sets were used in a Bayesian multiple linear regression model to simultaneously predict the probabilities of response and remission. RESULTS: Lower baseline depression severity, younger age, absence of melancholic features or history of physical abuse, less anxious arousal, less anhedonia, less neuroticism, and higher average theta current density in the rostral anterior cingulate predicted a higher likelihood of improvement with placebo. The Bayesian model predicted remission and response with an actionable degree of accuracy (both AUC > 0.73). An interactive calculator was developed predicting the likelihood of placebo response at the individual level. CONCLUSION: Easy-to-measure clinical, behavioral, and electrophysiological assessments can be used to identify placebo responders with a high degree of accuracy. Development of this calculator based on these findings can be used to identify potential placebo responders.

Worsening Anxiety, Irritability, Insomnia, or Panic Predicts Poorer Antidepressant Treatment Outcomes: Clinical Utility and Validation of the Concise Associated Symptom Tracking (CAST) Scale.

Background: We report on the psychometric properties of the 16-item Concise Associated Symptom Tracking Scale self-report scale and its clinical utility. Methods: The 5-domain (irritability, anxiety, mania, insomnia, and panic) structure of Concise Associated Symptom Tracking Scale was validated with confirmatory factor analysis in Combining Medications to Enhance Depression Outcomes trial participants at baseline (n=664). Correlations with other clinical measures were used for convergent and divergent validity. In participants with at least one postbaseline visit (n=630), worsening in each Concise Associated Symptom Tracking Scale domain was defined as ≥1.28 SD increase from baseline for each visit (weeks 1, 2, 4, and 6) only. Worsening in any domain (except mania) was defined as overall worsening. Association of domain-specific and overall worsening with remission was tested with logistic regression analyses. Results: The 5-domain structure had adequate model fit on confirmatory factor analysis (GFI=0.93, CFI=0.89, and RMSEA=0.07). Scores on anxiety, panic, insomnia, and mania significantly correlated with Hamilton Rating Scale for Depression anxiety subscale (rs=0.27), Psychiatric Diagnostic Screening Questionnaire-panic scale (rs=0.35), sum of 3 Quick Inventory of Depressive Symptomatology Self-Report insomnia items (rs=0.55), and Altman Self-Rating Mania scale (rs=0.41), respectively. From baseline to week 6, 5.2%, 7.5%, 47.6%, 15.6%, 6.2%, and 27.6% participants (n=630) experienced irritability, anxiety, mania, insomnia, panic, and overall worsening, respectively. Participants with overall worsening were less likely to remit (31.6%) than those without any worsening (43.9%; odds ratio=0.53, 95% CI=0.36, 0.78). Conclusion: The 16-item Concise Associated Symptom Tracking Scale self-report has acceptable psychometric properties. Clinically significant worsening of irritability, anxiety, insomnia, or panic with antidepressant treatment is associated with poorer outcomes.

Efficacy of a Behavioral Activation Teletherapy Intervention to Treat Depression and Anxiety in Primary Care VitalSign6 Program.

OBJECTIVE: Research analyzing behavioral activation (BA) teletherapy outcomes is limited. Among low-income real-world primary care patients receiving a brief BA teletherapy program for depression and anxiety, we analyzed descriptive statistics and changes in depression and anxiety scores throughout treatment. METHODS: One hundred thirty patients completed an intake assessment from June 2015 to August 2016; outcomes included the Patient Health Questionnaire-9 (PHQ-9) and the Generalized Anxiety Disorder-7 (GAD-7). Data from 74 low-income, primary care patients completing at least one therapy session were analyzed to characterize the demographics of therapy patients, to describe their depression and anxiety symptoms throughout treatment, and to examine whether patients who completed 4 or more sessions had statistically lower exit scores than those completing fewer than 4. RESULTS: Patients were moderately depressed (PHQ-9 score: mean = 14.46) and anxious (GAD-7 score: mean = 11.91) at intake. Patients were predominantly Latino/Latina (68.9%), Spanish-speaking (54.0%), and female (79.7%). The majority of patients who received at least one therapy session achieved and sustained depression remission. Patients who completed ≥ 4 therapy sessions demonstrated lower final session depression (PHQ-9: mean = 5.13, SD = 4.75) and anxiety (GAD-7: mean = 4.77, SD = 4.21) scores compared to those completing < 4 sessions (PHQ-9: mean = 8.04, SD = 6.20, P = .029; GAD-7: mean = 8.00, SD = 6.02, P = .011). CONCLUSIONS: Primary care patients demonstrated improvements in depressive and anxious symptoms throughout BA-based teletherapy. BA teletherapy is feasible and associated with improved outcomes as an adjunct or alternative intervention for primary care providers and in low-income, charity populations.​.

Pilot investigation into the sickness response to influenza vaccination in adults: Effect of depression and anxiety.

OBJECTIVE: To determine whether depressed or anxious patients experience greater affective change than mentally healthy individuals following influenza vaccination. METHODS: Participants (n=112) completed the Positive and Negative Affect Schedule (PANAS) before influenza vaccination and 1-2days post-vaccination (M=32.3h). Pre- and post-vaccination PANAS scores were compared using two-tailed, paired-samples t-tests. Change in positive affect between participants with depression or anxiety and those without was compared using two-way ANOVA. Follow up positive affect was further examined using multiple linear regression. RESULTS: Positive affect decreased following vaccination (M=2.18, 95% CI [1.07, 3.29], t(111)=3.89, p<0.001) for all participants and was more pronounced for those with anxiety or depression (F(1, 110)=7.51, p=0.009). Similarly, predicted follow up affect score was higher for those without a mental health conditions (ß=3.67, 95% CI [1.18, 6.16], t(103)=2.92, p=0.004). CONCLUSIONS: These data suggest that influenza vaccine has a greater effect on affect in patients with depression and anxiety than in mentally healthy individuals. This effect was focused on positive affect, suggesting that influenza vaccine induced inflammation may be best suited to examine alterations in positive affect and positive valence systems.

Prediction of treatment outcomes to exercise in patients with nonremitted major depressive disorder.

BACKGROUND: Only one-third of patients with major depressive disorder (MDD) achieve remission with initial treatment. Consequently, current clinical practice relies on a "trial-and-error" approach to identify an effective treatment for each patient. The purpose of this report was to determine whether we could identify a set of clinical and biological parameters with potential clinical utility for prescription of exercise for treatment of MDD in a secondary analysis of the Treatment with Exercise Augmentation in Depression (TREAD) trial. METHODS: Participants with nonremitted MDD were randomized to one of two exercise doses for 12 weeks. Participants were categorized as "remitters" (≤12 on the IDS-C), nonresponders (<30% drop in IDS-C), or neither. The least absolute shrinkage and selection operator (LASSO) and random forests were used to evaluate 30 variables as predictors of both remission and nonresponse. Predictors were used to model treatment outcomes using logistic regression. RESULTS: Of the 122 participants, 36 were categorized as remitters (29.5%), 56 as nonresponders (45.9%), and 30 as neither (24.6%). Predictors of remission were higher levels of brain-derived neurotrophic factor (BDNF) and IL-1B, greater depressive symptom severity, and higher postexercise positive affect. Predictors of treatment nonresponse were low cardiorespiratory fitness, lower levels of IL-6 and BDNF, and lower postexercise positive affect. Models including these predictors resulted in predictive values greater than 70% (true predicted remitters/all predicted remitters) with specificities greater than 25% (true predicted remitters/all remitters). CONCLUSIONS: Results indicate feasibility in identifying patients who will either remit or not respond to exercise as a treatment for MDD utilizing a clinical decision model that incorporates multiple patient characteristics.

Accurately identifying patients who are excellent candidates or unsuitable for a medication: a novel approach.

OBJECTIVE: The objective of the study was to determine whether a unique analytic approach - as a proof of concept - could identify individual depressed outpatients (using 30 baseline clinical and demographic variables) who are very likely (75% certain) to not benefit (NB) or to remit (R), accepting that without sufficient certainty, no prediction (NP) would be made. METHODS: Patients from the Combining Medications to Enhance Depression Outcomes trial treated with escitalopram (S-CIT) + placebo (n=212) or S-CIT + bupropion-SR (n=206) were analyzed separately to assess replicability. For each treatment, the elastic net was used to identify subsets of predictive baseline measures for R and NB, separately. Two different equations that estimate the likelihood of remission and no benefit were developed for each patient. The ratio of these two numbers characterized likely outcomes for each patient. RESULTS: The two treatment cells had comparable rates of remission (40%) and no benefit (22%). In S-CIT + bupropion-SR, 11 were predicted NB of which 82% were correct; 26 were predicted R - 85% correct (169 had NP). For S-CIT + placebo, 13 were predicted NB - 69% correct; 44 were predicted R - 75% correct (155 were NP). Overall, 94/418 (22%) patients were identified with a meaningful degree of certainty (69%-85% correct). Different variable sets with some overlap were predictive of remission and no benefit within and across treatments, despite comparable outcomes. CONCLUSION: In two separate analyses with two different treatments, this analytic approach - which is also applicable to pretreatment laboratory tests - identified a meaningful proportion (over 20%) of depressed patients for whom a treatment outcome was predicted with sufficient certainty that the clinician can elect to strongly recommend for or choose to avoid a particular treatment. Different persons seem to be remitting or not benefiting with these two different treatments.

Use of a pressure sensing sheath: comparison with standard means of blood pressure monitoring in catheterization procedures.

PURPOSE: Monitoring of blood pressure (BP) during procedures is variable, depending on multiple factors. Common methods include sphygmomanometer (BP cuff), separate radial artery catheterization, and side port monitoring of an indwelling sheath. Each means of monitoring has disadvantages, including time consumption, added risk, and signal dampening due to multiple factors. We sought an alternative approach to monitoring during procedures in the catheterization laboratory. METHODS: A new technology involving a 330 µm fiberoptic sensor embedded in the wall of a sheath structure was tested against both radial artery catheter and sphygmomanometer readings obtained simultaneous with readings recorded from the pressure sensing system (PSS). Correlations and Bland-Altman analysis were used to determine whether use of the PSS could substitute for these standard techniques. RESULTS: The results indicated highly significant correlations in systolic, diastolic, and mean arterial pressures (MAP) when compared against radial artery catheterization (p<0.0001), and MAP means differed by <4%. Bland-Altman analysis of the data suggested that the sheath measurements can replace a separate radial artery catheter. While less striking, significant correlations were seen when PSS readings were compared against BP cuff readings. CONCLUSIONS: The PSS has competitive functionality to that seen with a dedicated radial artery catheter for BP monitoring and is available immediately on sheath insertion without the added risk of radial catheterization. The sensor is structurally separated from the primary sheath lumen and readings are unaffected by device introduction through the primary lumen. Time delays and potential complications from radial artery catheterization are avoided.