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To address the clinical heterogeneity of Major Depressive Disorder (MDD), this investigation determined whether resting state functional magnetic resonance imaging (fMRI) could be deployed to identify circuit based homogeneous subgroups, and whether subgroups identified show differential treatment outcomes.Pretreatment resting state fMRIs obtained from 278 outpatients with nonpsychotic MDD from Establishing Moderators and Biosignatures of Antidepressant Response for Clinical Care for Depression Study were used to create data-driven subgroups using CLICK clustering. These subgroups were then compared using baseline clinical data, as well as baseline-to-week 8 changes in depression severity measured using the 17-item Hamilton Rating Scale for Depression (HAMDThree subgroups were identified. Cluster-1 was characterized by overallhyperconnectivity coupled with profound hypoconnectivity between the supramarginal gyrus (executive control network; ECN) and the superior frontal cortex (dorsal attention network; DAN). Cluster-2 was characterized by overall hypoconnectivity coupled with hyperconnectivity between supramarginal gyrus (ECN) and superior frontal cortex (DAN). Cluster-3 showed hypoconnectivity, especially profound between the angular cortex (default mode network; DMN) and middle frontal cortex (ECN). While baseline clinical measures did not differentiate the three clusters, Cluster-3 had the remission rate (51.6%) compared to Cluster-1 and Cluster-2 (32.7% and 31.9%) when treated with sertraline.Due to the exploratory nature of these analyses, there were no adjustments for multiple comparisons.Baseline functional connectivity can be used to subgroup patients with MDD that differ in acute phase treatment outcomes. Measures of connectivity may address the heterogeneity of MDD.

Youth who experience bullying are at risk for psychopathology, indicating the necessity of identifying factors that may protect against the deleterious effects of being bullied. The present study expands upon prior research by examining resilience as a mediator of the effects of experiencing bullying on depression and anxiety within a sample of 2155 adolescents. Results indicated that youth who experienced bullying were more likely to have higher symptoms of depression and anxiety and lower resilience, while higher levels of resilience were associated with fewer symptoms of depression and anxiety. Resilience partially mediated the associations of experiencing bullying with depression and anxiety symptoms, suggesting that resilience may serve as a protective factor for adolescents who experience bullying. These findings have implications for programming that seeks to address bullying, peer victimization, and promotion of adolescent mental health.

Purpose This report from VitalSign6 project describes treatment selection, follow-up rates and remission outcomes by initial depression severity using the PCP-FIRST model. Methods This retrospective analysis included 32,106 patients aged ≥12 years screened with the Patient Health Questionnaire 2-item (PHQ-2) from November 2016 to July 2019 across 37 primary care clinics. PHQ-2 positive-screen patients (PHQ-2 ≥ 3) received 9-item PHQ (PHQ-9) and 7-item Generalized Anxiety Disorder scales, clinician assessments, and evaluation for pharmacotherapy management with measurement-based care (MBC). Results Of PHQ-2 screened patients, 18.7% (5994/32,106) were positive and received a PHQ-9. Of 5994 patients with PHQ-9, 2571 received a clinical diagnosis of depression of whom, 333 had none-mild depression (PHQ-9 Conclusions Despite this being a real-world, usual care sample, remission outcomes exceed real world remission rate expectations of 6% in primary care.

Background Emerging work has suggested worsening mental health in the general population during the COVID-19 pandemic, but there is minimal data on individuals with a prior history of depression. Methods Data regarding depression, anxiety and quality of life in adult participants with a history of a depressive disorder (n = 308) were collected before and during the COVID-19 pandemic. Mixed effects regression models were fit for these outcomes over the period May – August 2020, controlling for pre-pandemic depressive groups (none, mild, moderate-to-severe), demographic characteristics, and early COVID-19 related experiences (such as disruptions in routines, mental health treatment, and social supports). Results In pre-to-early pandemic comparisons, the 3 pre-pandemic depressive categories varied significantly in anxiety (Fdf=2,197 = 7.93, p < 0.0005) and psychological QOL (Fdf=2,196 = 8.57, p = 0.0003). The mildly depressed group (Fdf=1,201 = 6.01, p = 0.02) and moderate-to-severely depressed group (Fdf=1,201 = 38.51, p < 0.0001) had a significant reduction in anxiety. There were no changes among the groups in any outcome from May to August 2020. However, early impact on mental health care access and disruption in routines predicted worse outcomes during this time. Limitations Follow-up data were self-reported. Furthermore, the duration was a relatively short span into the pandemic. Conclusions Symptoms of depression, anxiety, and quality of life were generally stable from 2019 throughout August 2020 in adults with a history of depression. Disruption in mental health care access and routines in May 2020 predicted worse symptom outcomes through August 2020.

This prospectively designed, clinical quality improvement project compared pain scores and opioid consumption between ultrasound-guided, erector spinae plane blocks (ESPB) and thoracic paravertebral blocks (PVB) in patients undergoing total bilateral mastectomies without reconstruction. Twenty-five patients were included in an enhanced recovery pathway and received an ESPB on one side and a PVB on the contralateral side. Numeric rating scores at rest and with movement for each side were recorded in the recovery room at 2, 6, 12, 24, and 48 hours and on days 3 to 7. There were no significant differences in the resting or movement-evoked pain scores between sides receiving ESPB or PVB at any time point up to day 7 after surgery. Both ESPB and PVB confer equal analgesic effects in patients undergoing mastectomies. ESPB provides an alternative to PVB in reducing postoperative pain in patients undergoing mastectomy as part of an enhanced recovery pathway.

Background Adults with major depressive disorder (MDD) often experience reduced quality of life (QOL). Efficacious acute-phase treatments, including cognitive therapy (CT) or medication, decrease depressive symptoms and, to a lesser degree, increase QOL. We tested longer-term changes in QOL after response to acute-phase CT, including the potential effects of continuation treatment for depression and time-lagged relations between QOL and depressive symptoms. Methods Responders to acute-phase CT (N = 290) completed QOL and depressive symptom assessments repeatedly for 32 post-acute months. Higher-risk responders were randomized to 8 months of continuation treatment (CT, fluoxetine, or pill placebo) and then entered a 24-month follow-up. Lower-risk responders were only assessed for 32 months. Results On average, large gains in QOL made during acute-phase CT response were maintained for 32 months. Continuation CT or fluoxetine did not improve QOL relative to pill placebo. Controlling for residual depressive symptoms, higher QOL after acute-phase CT response was a protective factor against MDD relapse and recurrence. Higher QOL predicted subsequent reductions in depressive symptom severity, but depressive symptom severity did not predict subsequent changes in QOL. Limitations Generalization of results to other patient populations, treatments, and measures is uncertain. The clinical trial was not designed to test relations between QOL and depression. Replication is needed before clinical application of these results. Conclusions Gains in QOL made during response to acute-phase CT are relatively stable and may help protect against relapse/recurrence. Continuation CT or fluoxetine may not further improve QOL among acute-phase CT responders.

Regional nerve blocks are an effective method of managing acute pain associated with surgery. The relative benefit of preoperative versus postoperative peripheral nerve blocks is not entirely clear. The primary aim of this study was to determine differences in pain scores in patients undergoing preoperative block versus postoperative block versus no block. We hypothesized that patients receiving preoperative blocks would have reduced pain scores and decreased opioid use in the immediate postoperative period. We conducted a retrospective cohort analysis of 302 consecutive patients undergoing unilateral open reduction and internal fixation of ankle fracture under general anesthesia. We identified 3 groups: preoperative block, postoperative block, or no block. Data obtained from our electronic medical records included demographic information, postanesthesia care unit length of stay, pain scores obtained preoperatively, upon arrival to the postanesthesia care unit, and upon discharge from the postanesthesia care unit as well as intraoperative and postanesthesia care unit opioid utilization. Patients receiving preoperative block had significantly lower pain scores, less intraoperative or postanesthesia care unit opioid use, and shorter postanesthesia care unit dwell time compared with patients receiving postoperative block or no block. Preoperative popliteal sciatic and adductor canal blocks in patients undergoing ankle fracture surgery appears to be more effective than either postoperative block or no block.

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.

Background Multimodal perioperative analgesia including acetaminophen is recommended by current guidelines. The comparative efficacy of intravenous vs oral acetaminophen in sinus surgery is unknown. We aimed to determine whether intravenous or oral acetaminophen results in superior postoperative analgesia following sinus surgery. Methods This was a prospective randomized trial with blinded endpoint assessments conducted at a single large academic medical center. Subjects undergoing functional endoscopic sinus surgery were randomized to intravenous vs oral acetaminophen in addition to standard anesthetic and surgical care. The primary outcome was visual analogue scale pain score at 1 hour postoperatively. Results One hundred and ten adult patients were randomized; 9 were excluded from the data analysis. Fifty patients were assigned to intravenous acetaminophen and 51 to oral acetaminophen. Postoperative pain scores at 1 hour (primary endpoint) were not significantly different between the intravenous and oral acetaminophen groups. Similarly, there was no significant difference in pain scores at 24 hours postoperatively. Finally, there was no significant difference in postoperative opioid usage in the postanesthesia care unit or over the first 24 hours postoperatively. Conclusions This is the first comparative efficacy trial of oral vs intravenous acetaminophen in sinus surgery. There was no significant difference in pain scores at 1 or 24 hours postoperatively, and no difference in postoperative opioid use. Intravenous acetaminophen offers no apparent advantage over oral acetaminophen in patients undergoing sinus surgery. Level of evidence 1b.

STUDY DESIGN Retrospective review of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database years 2012-2015. OBJECTIVE Compare the 30-day readmission and postoperative major complications rates of 2-level lumbar decompression performed in the ambulatory and the inpatient settings. SUMMARY OF BACKGROUND DATA In recent years, there is an increasing trend toward ambulatory spine surgery. However, there remains a concern regarding risks of readmission and postoperative morbidity after discharge. METHODS The ACS-NSQIP database from 2012 to 2015 was queried for adult patients who underwent elective 2-level lumbar decompression (CPT code 63047 accompanied with code 63048). A cohort of ambulatory lumbar decompression cases was matched 1:1 with an inpatient cohort after controlling for patient demographics, comorbidities, and complexity of the procedure. The primary outcome was the 30-day readmission rate. Secondary outcomes included a composite of 30-day postoperative major complications and hospital length of stay for hospitalized patients. RESULTS A total of 7505 patients met our study criteria. The ambulatory 2-level lumbar decompression surgery rate increased significantly over the study period from 28% in 2012 to 49% in 2015 (P

BACKGROUND Cocaine has a short biological half-life, but inactive urine metabolites may be detectable for a week following use. It is unclear if patients who test positive for cocaine but have a normal electrocardiogram and vital signs have a greater percentage of hemodynamic events intraoperatively. METHODS A total of 328 patients with a history of cocaine use who were scheduled for elective noncardiac surgery under general anesthesia were enrolled. Patients were categorized into cocaine-positive versus cocaine-negative groups based on the results of their urine cocaine toxicology test. The primary aim of this study was to evaluate whether asymptomatic cocaine-positive patients had similar percentages of intraoperative hemodynamic events, defined as (1) a mean arterial blood pressure (MAP) of 105 mm Hg and (2) a heart rate (HR) of 100 beats per minute (bpm) compared to cocaine-negative patients. The study was powered to assess if the 2 groups had an equivalent mean percent of intraoperative hemodynamic events within specific limits using an equivalence test of means consisting of 2 one-sided tests. RESULTS The cocaine-positive group had a blood pressure (BP) that was outside the set limits 19.4% (standard deviation [SD] 17.7%) of the time versus 23.1% (SD 17.7%) in the cocaine-negative group (95% confidence interval [CI], 0.5-7.0). The cocaine-positive group had a HR outside the set limits 9.6% (SD 16.2%) of the time versus 8.2% (SD 14.9%) in the cocaine-negative group (95% CI, 4.3-1.5). Adjusted for age, sex, body mass index (BMI), smoking status, and the presence of comorbid hypertension, renal disease, and psychiatric illness, the cocaine-positive and cocaine-negative patients were similar within a 7.5% margin of equivalence for MAP data (β coefficient = 2%, P = .003, CI, 2-6) and within a 5% margin of equivalence for HR data (β coefficient = 0.2%, P < .001, CI, 4-3). CONCLUSIONS Asymptomatic cocaine-positive patients undergoing elective noncardiac surgery under general anesthesia have similar percentages of intraoperative hemodynamic events compared to cocaine-negative patients.

Characterise gut microbiota distributions of participants with co-occurring depression and anxiety, in those with only depression or with anxiety, and determine if gut bacteria differentially correlates with distinct clinical presentations.Participants (10 healthy controls [mean age: 33, 60% female] and 60 psychiatric subjects; major depressive disorder (comorbid with anxiety), n = 38 [mean age: 39.2, 82% female], anxiety only, n = 8 [mean age: 40.0, 100% female], depression only without anxiety, n = 14 [mean age: 41.9, 79% female]) were characterized by psychiatric assessments. Quantitative PCR and 16S rRNA sequencing were used to characterize the gut microbiota in stool samples.Altered microbiota correlated with pre-defined clinical presentation, with Bacteroides (p = 0.011) and the Clostridium leptum subgroup (p = 0.023) significantly different between clinical categories. Cluster analysis of the total sample using weighted UniFrac β-diversity of the gut microbiota identified two different clusters defined by differences in bacterial distribution. Cluster 2 had higher Bacteroides (p = 0.006), and much reduced presence of Clostridales (p0.001) compared to Cluster 1. Bifidobacterium (p = 0.0173) was also reduced in Cluster 2 compared to Cluster 1. When evaluated for clinical charateristics, anhedonia scores in Cluster 2 were higher than in Cluster 1.The sample is smaller and predominately female.Reduced or absent Clostridia was consistently seen in those with depression, independent of the presence of anxiety. Conversely, reduced Bacteroides may be more associated with the presence of anxiety, independent of the presence of depression. These differences suggest that gut microbiota distribution could help clarify the underlying pathology of comorbid clinical presentation.

Major depressive disorder (MDD) may be associated with accelerated brain aging (higher brain age than chronological age). This report evaluated whether brain age is a clinically useful biomarker by checking its test-retest reliability using magnetic resonance imaging (MRI) scans acquired one week apart and by evaluating the association of accelerated brain aging with symptom severity and antidepressant treatment outcomes.Brain age was estimated in participants of Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care (EMBARC) study using T1-weighted structural MRI [MDD N=290; female N=192; healthy control (HC) N=39; female N=24]. Intraclass correlation coefficient (ICC) were used for baseline-to-week-1 test-retest reliability. Association of baseline Δ brain age (brain age minus chronological age) with Hamilton Depression Rating Scale (HAMD-17) and Concise Health Risk Tracking Self-Report (CHRT-SR) domains [impulsivity, suicide propensity (measures pessimism, helplessness, perceived lack of social support, and despair), and suicidal thoughts] were assessed at baseline (linear regression) and during 8-week-long treatment with either sertraline or placebo (repeated-measures mixed models).Mean (±standard deviation) baseline chronological age, brain age, and Δ brain age were 37.1±13.3, 40.6±13.1, and 3.1±6.1 years in MDD and 37.1±14.7, 38.4±12.9, and 0.6±5.5 years in HC groups, respectively. Test-retest reliability was high (ICC=0.98-1.00). Higher baseline Δ brain age in MDD group was associated with higher baseline impulsivity and suicide propensity, and predicted smaller baseline-to-week-8 reductions in HAMD-17, impulsivity, and suicide propensity with sertraline but not with placebo.Brain age is a reliable and potentially clinically useful biomarker that can prognosticate antidepressant treatment outcomes.

This study compared the Macintosh blade direct laryngoscope, Glidescope, C-Mac d-Blade, and McGrath MAC X-blade video laryngoscopes in 2 cadaveric models with severe cervical spinal instability. We hypothesized that the Glidescope video laryngoscope would allow for intubation with the least amount of cervical spine movement. Our secondary endpoints were glottic visualization and intubation success.In total, 2 fresh cadavers underwent maximal surgical destabilization from the craniocervical junction to the cervicothoracic junction by a neurosurgical spine specialist, with subsequent neutral positioning of the heads with surgical head fixation devices. On each cadaver, 8 experienced anesthesiologists performed four intubations with the 4 laryngoscopes in random order. Lateral radiographic measurements determined vertebral displacement during intubation.Cervical spine displacements were not significantly different amongst video laryngoscopes. Cormack-Lehane Grade 1 views were achieved with all attempts with each of the 3 video laryngoscopes; intubation attempts with the Macintosh blade achieved only grade 3 or grade 4 views. Intubation was successful every time with a video laryngoscope but only during 1 of 16 intubation attempts with the Macintosh blade.In a cadaveric model with maximally destabilized cervical spines, cervical spine movement was observed during attempted laryngoscopy using each of 3 video laryngoscopes, although there was no significant difference between the laryngoscopes. Given cervical spine displacement occurred, these video laryngoscopes do not prevent cervical spine motion during laryngoscopy. However, with improved glottic visualization and intubation success, video laryngoscopes are superior to the Macintosh blade in both cervical spine safety and intubation efficacy in the model studied.

BACKGROUND: Disturbed sleep is a core symptom of major depressive disorder (MDD), with nearly 90% of those with MDD reporting disturbed sleep. However, combining insomnia and hypersomnia into a single diagnostic domain ignores distinct biological differences between those symptom presentations. To better understand depression it may be necessary to explore these symptoms independently, beginning with the more prevalent insomnia. METHOD: The present study evaluated global insomnia symptom severity in a broad sample of MDD outpatients from the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial, excluding patients who reported hypersomnia symptoms. The three insomnia-related symptoms from the 16-item Quick Inventory of Depressive Symptomatology- clinician rated (QIDS-C) were combined to create a global insomnia score to classify baseline insomnia severity. A modified depression severity score was then used to assess depression severity (mQIDS-C), excluding sleep-related items. RESULTS: A repeated measures ANCOVA revealed a significant improvement in insomnia score over the acute phase treatment (F = 33.1, d.f. = 6, 9897, p < 0.0001). Improvement in insomnia score over the acute phase treatment remained statistically significant even after controlling for change in depression severity (p = 0.0004). Participants with one point higher insomnia score at baseline were significantly less likely to remit at study exit (odds ratio = 0.88, 95% confidence interval = 0.85, 0.92, p < 0.0001) even after controlling for baseline depression severity. LIMITATIONS: Objective confirmation of sleep profiles was not available. CONCLUSION: Greater severity of insomnia reduces likelihood of MDD remission, and insomnia symptoms improved independent of depression remission.

Study objective To evaluate the intraoperative hemodynamics and medication requirements of cocaine-positive patients compared to matched cocaine-negative controls. Design Retrospective cohort study. Setting Public county hospital. Patients 821 patients undergoing general anesthesia. Measurements Incidence of hemodynamic events, defined by a mean arterial pressure of 105 mmHg or a heart rate of 100 beats per minute. Main results Cocaine-positive patients did not experience a higher incidence of hemodynamic events when compared with matched cocaine-negative patients. Cocaine-positive patients were not more likely to be administered vasopressors intraoperatively but did receive more anti-hypertensive agents. The minimum alveolar concentration of anesthetics used was similar between the two groups. Anesthesia duration, length of stay, and in-hospital mortality did not significantly differ between the two cohorts. Conclusions Cocaine-positive patients did not demonstrate more intraoperative hemodynamic events or adverse short-term outcomes as compared to matched cocaine-negative controls.

Major depressive disorder (MDD) and relationship discord between cohabiting partners frequently co-occur, with bidirectional effects established. As relationship quality influences understanding and treatment of MDD, the current analyses clarified the relations of pretreatment dyadic discord with outcomes during and at the end of acute phase cognitive therapy (CT) for adults with recurrent MDD. Married or cohabiting patients (n = 219) completed the Dyadic Adjustment Scale (DYS) before and after a 16-20 session, 12-14 week CT protocol. Lower levels of dyadic adjustment indicated higher levels of dyadic discord. Response to CT was defined as the absence of a major depressive episode and ≤ 12 on the 17-item Hamilton Rating Scale for Depression. Pretreatment dyadic discord, whether defined as a continuous or categorical variable (using DYS cutoff score of 97), was not associated with treatment completion or response but was positively associated with levels of depressive symptoms at the end of acute phase CT. Furthermore, CT was associated with declines in dyadic discord, with 23.3% of initially discordant couples moving to nondiscordant status at the end of CT. Depressive symptoms did not significantly mediate changes in dyadic discord. Finally, pre- (but not mid-) treatment dyadic discord was associated with subsequent changes in depressive symptoms, suggesting limited mediation. These findings replicate prior research indicating that individual CT is associated with reductions in depressive symptoms and dyadic discord while clarifying that lower pre-treatment dyadic discord may predict initial improvement in depressive symptoms.

Study objectiveTo create a preoperative predictive model for prolonged post-anaesthesia care unit (PACU) stay for outpatient surgery and compare with an existing (University of California-San Diego, UCSD) model.DesignRetrospective observational study.SettingPost-anaesthesia care unit. Patients: Outpatient surgical patients discharged on the same day in a large academic institution. Preoperative data were collected. The study period was three months in 2016. Measurements: Prolonged PACU stay defined as a length of stay longer than the third quartile. We utilized multivariate regression analyses and bootstrapping statistical techniques to create a predictive model for prolonged PACU stay. Main results: Four strong predictors for prolonged PACU stay: general anaesthesia, obstructive sleep apnoea, surgical specialty and scheduled case duration. Our model had an excellent discrimination performance and a good calibration.ConclusionWe developed a predictive model for prolonged PACU stay in our institution. This model is different from the UCSD model probably secondary to local and regional differences in outpatient surgery practice. Therefore, individual practice study outcomes may not apply to other practices without careful consideration of these differences.

Study objective Morbid obesity is associated with adverse airway events including desaturation during deep sedation. Prior works have suggested that proprietary high-flow nasal cannula devices generate positive pressure to all airway structures and may be superior to standard (low-flow) nasal cannula for prevention of desaturation. We hypothesized that, at a similar fraction of inspired oxygen (FiO2), use of a High-Flow Nasal Cannula (HFNC) at maximum flow rate would result in a lower incidence of intra-procedural desaturation episodes in morbidly obese patients compared to standard nasal cannula (SNC) during deep sedation with propofol. Design This is a pragmatic, prospective, randomized clinical trial at one hospital ( NCT03148262 , UTSW#112016-058). Morbidly obese patients were randomized to HFNC during propofol sedation for colonoscopy. HFNC was performed using maximum flow rates of 60 liters per minute (LPM) and FiO2 of 0.36–0.40, whereas SNC was performed at 4LPM. The primary endpoint was incidence of arterial oxygen desaturation Main results Patients were randomized to HFNC (n = 28) or SNC (n = 31). Interim analysis of the primary endpoint showed that the desaturation rates in the HFNC group (39.3%) and the SNC group (45.2%) were not significantly different (p = 0.79). The DMC halted the trial at that point due to futility. Conclusion At similar FiO2, HFNC was not significantly different from SNC for prevention of arterial oxygen desaturation in morbidly obese patients undergoing propofol sedation for colonoscopy.

Background Cardiac surgery–associated acute kidney injury (AKI) is associated with increased morbidity and mortality. We examined the utility of combining biomarkers of kidney function loss (serum cystatin C) and kidney tubular damage (urine neutrophil gelatinase-associated lipocalin [NGAL] and Kidney Injury Molecule-1 [KIM-1]) for the prediction of post–cardiac surgery AKI. Methods Single-center prospective cohort study of 106 adults undergoing coronary artery bypass grafting and/or valve surgery with cardiopulmonary bypass (CPB). Primary outcome was postoperative in-hospital AKI defined by serum creatinine (SCr)–Kidney Disease: Improving Global Outcomes criteria. Biomarkers were measured preoperatively, 6 hours after CPB and on postoperative days (PODs) 1 to 4. Results A total of 23 subjects (21.7%) developed AKI. After adjusting for preoperative left ventricular ejection fraction, body mass index >30 kg/m2, and estimated glomerular filtration rate (eGFR), Graphical abstract

The authors evaluated improvement in irritability with antidepressant treatment and its prognostic utility in treatment-seeking adult outpatients with major depressive disorder.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).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.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.

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 (

Diabetes has been linked to accelerated brain aging, i.e., neuroimaging-predicted age of brain is higher than chronological age. This report evaluated whether accelerated brain aging in diabetes is associated with higher levels of glycated hemoglobin (HbA1c) and increased mortality.Brain age in Dallas Heart Study (n = 1949) was estimated using T1-weighted magnetic resonance imaging (MRI) scans and a previously-published Gaussian Processes Regression model. Accelerated brain aging (adjusted Δ brain age) was computed as follows: (brain age adjusted for chronological age)-minus-(chronological age). Mortality data until 12/31/2016 were obtained from the National Death Index. Associations of adjusted Δ brain age with diabetes in full sample and with HbA1c in individuals with diabetes were evaluated. Proportion of association between diabetes and all-cause mortality that was accounted for by adjusted Δ brain age were evaluated with mediation analyses. Covariates included Framingham 10-year risk score, race/ethnicity, income, body mass index, and history of myocardial infarction.Diabetes was associated with] higher adjusted Δ brain age [estimate= 1.79; 95% confidence interval (CI): 0.889, 2.68]. Among those with diabetes, higher HbA1c (log-base-2-transformed) was associated with higher adjusted Δ brain age (estimate=3.88; 95% CI: 1.47, 6.30). Over a median follow-up of 97.5 months, 24/246 (9.8%) with diabetes and 63/1703 (3.7%) without diabetes died. Adjusted Δ brain age accounted for 65.3 (95% CI: 39.3, 100.0)% of the association between diabetes and all-cause mortality.Accelerated brain aging may be related to poor glycemic control in diabetes and partly account for the association between diabetes and all-cause mortality.

This report from VitalSignThis retrospective analysis included 32,106 patients aged ≥12 years screened with the Patient Health Questionnaire 2-item (PHQ-2) from November 2016 to July 2019 across 37 primary care clinics. PHQ-2 positive-screen patients (PHQ-2 ≥ 3) received 9-item PHQ (PHQ-9) and 7-item Generalized Anxiety Disorder scales, clinician assessments, and evaluation for pharmacotherapy management with measurement-based care (MBC).Of PHQ-2 screened patients, 18.7% (5994/32,106) were positive and received a PHQ-9. Of 5994 patients with PHQ-9, 2571 received a clinical diagnosis of depression of whom, 333 had none-mild depression (PHQ-9 10) and 2238 had moderate-severe depression (PHQ-9 ≥ 10). Of the 333 patients with none-mild depression and 2238 patients with moderate-severe depression, 266 and 1929 had at least 18 weeks of data available. Of these, 54.9% (146/266) with none-mild depression and 69.1% (1332/1929) with moderate-severe depression were started on pharmacotherapy. Of the 1478 patients with clinical diagnosis of depression, initiated on pharmacotherapy, 1046 returned for ≥1 follow-up and 616 returned for ≥3 follow-ups over 18 weeks. Of the 1046 patients with ≥1 follow-up visit within 18 weeks, remission rates for patients with mild depression, moderate-severe depression, and overall were 55.6% (66/99), 30% (282/941), and 32.4% (338/1040) respectively.Despite this being a real-world, usual care sample, remission outcomes exceed real world remission rate expectations of 6% in primary care.

Etomidate and ketamine are hemodynamically stable induction agents often used to sedate critically ill patients during emergency endotracheal intubation. In 2015, quality improvement data from our hospital suggested a survival benefit at Day 7 from avoidance of etomidate in critically ill patients during emergency intubation. In this clinical trial, we hypothesized that randomization to ketamine instead of etomidate would be associated with Day 7 survival after emergency endotracheal intubation.A prospective, randomized, open-label, parallel assignment, single-center clinical trial performed by an anesthesiology-based Airway Team under emergent circumstances at one high-volume medical center in the United States. 801 critically ill patients requiring emergency intubation were randomly assigned 1:1 by computer-generated, pre-randomized sealed envelopes to receive etomidate (0.2-0.3 mg/kg, n = 400) or ketamine (1-2 mg/kg, n = 401) for sedation prior to intubation. The pre-specified primary endpoint of the trial was Day 7 survival. Secondary endpoints included Day 28 survival.Of the 801 enrolled patients, 396 were analyzed in the etomidate arm, and 395 in the ketamine arm. Day 7 survival was significantly lower in the etomidate arm than in the ketamine arm (77.3% versus 85.1%, difference - 7.8, 95% confidence interval - 13, - 2.4, p = 0.005). Day 28 survival rates for the two groups were not significantly different (etomidate 64.1%, ketamine 66.8%, difference - 2.7, 95% confidence interval - 9.3, 3.9, p = 0.294).While the primary outcome of Day 7 survival was greater in patients randomized to ketamine, there was no significant difference in survival by Day 28.

Carbon isotope tracers have been used to determine relative rates of tricarboxylic acid cycle (TCA) cycle pathways since the 1950s. Steady-state experimental data are typically fit to a single mathematical model of metabolism to determine metabolic fluxes. Whether the chosen model is appropriate for the biological system has generally not been evaluated systematically. An overly-simple model omits known pathways while an overly-complex model may produce incorrect results due to overfitting. The objectives were to develop and study a method that systematically evaluates multiple TCA cycle mathematical models as part of the fitting process. The problem of choosing overly-simple or overly-complex models was approached by developing software that automatically explores all possible combinations of flux through pyruvate dehydrogenase, pyruvate kinase, pyruvate carboxylase and anaplerosis at propionyl-CoA carboxylase, and equivalent pathways, all relative to TCA cycle flux. Typical TCA cycle metabolic tracer experiments that use 13C nuclear magnetic resonance for detection and quantification of 13C-enriched glutamate products were simulated and analyzed. By evaluating the multiple model fits with both the conventional sum-of-squares residual error (SSRE) and the Akaike Information Criterion (AIC), the software helps the investigator understand the interaction between model complexity and goodness of fit. When fitting alternative models of the TCA cycle metabolism, the SSRE may identify more than one model that fits the data well. Among those models, the AIC provides guidance as to which is the simplest of the candidate models is sufficient to describe the observed data. However under some conditions, AIC used alone inappropriately discriminates against necessary metabolic complexity. In combination, the SSRE and AIC help the investigator identify the model that best describes the metabolism of a biological system.

PurposeData augmentation improves the accuracy of deep learning models when training data is scarce by synthesizing additional samples. This work addresses the lack of validated augmentation methods specific for synthesizing anatomically realistic 4D (3D+time) images for neuroimaging, such as fMRI, by proposing a new augmentation method.Materials and MethodsThe proposed method, BLENDS, generates new nonlinear warp fields by combining intersubject coregistration maps, computed using symmetric normalization, through spatial blending. These new warp fields can be applied to existing 4D fMRI to create new augmented images. BLENDS is tested on two neuroimaging problems using de-identified datasets: 1) the prediction of antidepressant response from task-based fMRI in the EMBARC dataset (n = 163), and 2) the prediction of Parkinson’s Disease symptom trajectory from baseline resting-state fMRI regional homogeneity in the PPMI dataset (n = 43).ResultsBLENDS readily generates hundreds of new fMRI from existing images, with unique anatomical variations from the source images, that significantly improve prediction performance. For antidepressant response prediction, augmenting each original image once (2x the original training data) significantly increased prediction R2 from 0.055 to 0.098 (p < 1e-6), while at 10x augmentation R2 increased to 0.103. For the prediction of Parkinson’s Disease trajectory, 10x augmentation R2 increased from 0.294 to 0.548 (p < 1e-6).ConclusionAugmentation of fMRI through nonlinear transformations with BLENDS significantly improves the performance of deep learning models on clinically relevant predictive tasks. This method will help neuroimaging researchers overcome dataset size limitations and achieve more accurate predictive models.

Objective The aim of this report was to evaluate the psychometric properties of the Pain Frequency, Intensity, and Burden Scale (P-FIBS), a brief measure of pain, as well as the association of pain with irritability and depression and how these symptoms relate to functional impairments. Methods Participants of 2 randomized controlled trials (Establishing Moderators and Biosignatures of Antidepressant Response in Clinical Care [EMBARC; n = 251 with DSM-IV diagnosis of major depressive disorder; study duration: August 2011-December 2015] and STimulant Reduction Intervention Using Dosed Exercise [STRIDE; n = 302 with DSM-IV diagnosis of stimulant abuse or dependence; study-duration: July 2010-February 2013]) and treatment-seeking patients in primary care clinics from an ongoing quality-improvement project (VitalSign6; n = 4,370; project duration: August 2014-July 2019) were included. Psychometric properties of the P-FIBS were evaluated with confirmatory factor and item response theory analyses in EMBARC and VitalSign6. The approach of Baron and Kenny was used to assess whether irritability accounted for the effect of pain on depression. Results Cronbach α (0.84-0.89) and model fits for single-factor structure of P-FIBS were acceptable. Pain was positively correlated with irritability (r = 0.22-0.29) and depression (r = 0.10-0.33). Irritability accounted for 40.7%-65.5% of the effect of pain on depression. Higher irritability and depression were associated with poorer social functioning, quality of life, and productivity in work- and non-work-related activities. Pain was associated with non-work-related activity impairments even after controlling for irritability and depression. Conclusions The P-FIBS is a brief and reliable measure of pain. Irritability is associated with pain and accounts for a large proportion of the effect of pain on depression. Symptoms of pain, irritability, and depression are associated with functional impairments. Trial registration ClinicalTrials.gov identifiers: NCT01407094 (EMBARC), NCT01141608 (STRIDE).

Background Prior work suggests some individual immunomarkers may be useful moderators of treatment response between antidepressant medications. The relative moderating effect of individual immunomarkers remains unclear. It is also unknown whether combinations of immunomarkers have a superior moderating effect compared to any individual immunomarker. Methods Baseline immunomarker levels were assayed using multiplex from a subset of participants in the CO-MED trial (n = 143). Individual and combinations of 19 immunomarkers were modeled as moderators between the three treatment arms (escitalopram monotherapy, escitalopram-bupropion and venlafaxine-mirtazapine) across a variety of depression outcomes. Results Only IL-13 demonstrated a consistent moderating effect across all depression outcome measures. High IL-13 (>20 pg/ml) was associated with higher remission rates to bupropion-escitalopram (67%) versus escitalopram (24%) whereas low IL-13 was associated higher remission rates to escitalopram (59%) versus bupropion-escitalopram (38%). A similar, but weaker moderating effect was observed with venlafaxine-mirtazapine versus escitalopram. The addition of multiple immunomarkers did not consistently improve predictive modeling. Limitations This is a secondary analysis of a single clinical trial with a relatively small sample size per treatment arm. The testing of specific individual and combinations of biomarkers was data-driven. Conclusions Among 19 immunomarkers, Il-13 was the best single moderator of treatment outcome. Combinations of immunomarkers were not meaningfully superior to Il-13.

Carbon isotope tracers have been used to determine relative rates of tricarboxylic acid cycle (TCA) cycle pathways since the 1950s. Steady-state experimental data are typically fit to a single mathematical model of metabolism to determine metabolic fluxes. Whether the chosen model is appropriate for the biological system has generally not been evaluated systematically. An overly-simple model omits known pathways while an overly-complex model may produce incorrect results due to overfitting.The objectives were to develop and study a method that systematically evaluates multiple TCA cycle mathematical models as part of the fitting process.The problem of choosing overly-simple or overly-complex models was approached by developing software that automatically explores all possible combinations of flux through pyruvate dehydrogenase, pyruvate kinase, pyruvate carboxylase and anaplerosis at propionyl-CoA carboxylase, and equivalent pathways, all relative to TCA cycle flux. Typical TCA cycle metabolic tracer experiments that useWhen fitting alternative models of the TCA cycle metabolism, the SSRE may identify more than one model that fits the data well. Among those models, the AIC provides guidance as to which is the simplest of the candidate models is sufficient to describe the observed data. However under some conditions, AIC used alone inappropriately discriminates against necessary metabolic complexity.In combination, the SSRE and AIC help the investigator identify the model that best describes the metabolism of a biological system.

BackgroundAn academic safety-net hospital leveraged the federally funded state Delivery System Reform Incentive Payment programme to implement a hospital-wide initiative to reduce healthcare-associated infections (HAIs) and improve sepsis care.MethodsThe study period was from 2013 to 2017. The setting is a 770-bed urban hospital with six intensive care units and a large emergency department. Key interventions implemented were (1) awareness campaign and clinician engagement, (2) implementation of HAI and sepsis bundles, (3) education of clinical personnel using standardised curriculum on bundles, (4) training of key managers, leaders and personnel in quality improvement methods, and (5) electronic medical record-based clinical decision support. Throughout the 5-year period, staff received frequent, clear, visible and consistent messages from leadership regarding the importance of their participation in this initiative, performing hand hygiene and preventing potential regulatory failures. Several process measures including bundle compliance, hand hygiene and culture of safety were monitored. The primary outcomes were rates of central line-associated bloodstream infection (CLABSI), catheter-associated urinary tract infection (CAUTI), surgical site infection (SSI) and sepsis mortality.ResultsFrom 2013 to 2017, the hospital-wide rates of HAI reduced: CLABSI from 1.6 to 0.8 per 1000 catheter-days (Poisson regression estimate: −0.19; 95% CI −0.29 to −0.09; p=0.0002), CAUTI from 4.7 to 1.3 per 1000 catheter-days (−0.34; −0.43 to −0.26; pConclusionA hospital-wide initiative incentivised by the Delivery System Reform Incentive Payment programme succeeded in reducing HAI and sepsis mortality over 5 years in a sustainable manner.

Deaths due to suicide are one of the leading causes of mortality among youths and young adults. Active suicidal ideation (SI) is considered one of the strongest risk factors for suicide. Here, we evaluated the neurocircuitry of SI in a sample of youths and young adults (aged 10-26 years) with current or past diagnosis of either major depression or bipolar disorder who were enrolled in Texas Resilience Against Depression Study (T-RAD), and had neuroimaging and SI (assessed with the 3-item Suicidal Thoughts factor of Concise Health Risk Tracking self-report scale) data available (n = 72, 53 females). Resting-state functional connectivity (FC) was computed amongst 121 cortical and subcortical regions of interest resulting in 7260 FC pairs. Mean (SD) age and SI levels of participants were 19.6 years (4.01) and 1.48 (2.36) respectively. In univariate analyses, 34 out of the 7260 FC pairs were correlated with SI (p .005). Stronger connectivity of default mode network (DMN) with striatum was associated with higher SI. Conversely, higher SI was associated with weaker connectivity of limbic network with hippocampus, DMN, dorsal attention network, and executive control network. In multivariate analyses, these 34 FC pairs together had an average correlation of 0.54 after five-fold cross-validation. In conclusion, SI was associated with distinct patterns of resting-state functional connectivity among youths and young adults with regions in DMN and the ventral striatum as key nodes.

Background While childhood maltreatment (CMT) is associated with higher rates of chronicity and recurrence in depression, whether CMT results in poorer outcomes with antidepressant medication remains unclear. Methods We performed secondary analyses with data from the large, representative, multisite trial Combining Medications to Enhance Depression Outcomes (CO-MED). CO-MED was a randomized, single-blinded, placebo-controlled study with 665 individuals (663 assessed for CMT) with chronic and/or recurrent Major Depressive Disorder (MDD). CMT was determined by a brief self-reported questionnaire assessing the four types of CMT defined by the Centers for Disease Control and Prevention: sexual abuse, emotional abuse, physical abuse, and neglect. Repeated measures and logistic regression analyses were used. Results Individuals with CMT did not have a differential improvement of depressive symptoms when compared to those without CMT (adjusted p=.203 for continuous analysis; adjusted p=.320 for remission rates). Neither type of antidepressant medication (adjusted p=.302) nor the age at which CMT occurred (adjusted p=.509) affected depressive symptom outcomes. There was no difference in functional improvement between individuals with and without CMT (adjusted p=.228). A history of CMT was associated with greater antidepressant side effects (p=.009). Limitations This study investigated treatment-seeking individuals with chronic and/or recurrent MDD. Intensity and duration of CMT were not assessed. Conclusion In a sample of treatment-seeking outpatients with chronic and/or recurrent MDD, a history of CMT was not associated with differential symptomatic or functional response to pharmacological treatment. However, those with CMT reported greater antidepressant side effect burden.

This report evaluated whether irritability in adults with stimulant use disorder is associated with suicidal ideation (SI) at the same visit (i.e., concurrently) and whether early changes in irritability predict subsequent levels of SI.Adults with stimulant use disorder (n=302) from nine residential addiction treatment programs were included. Participants were randomized to augmentation of usual care with dosed exercise or health education intervention. Irritability, SI, and depression were measured every week with 5-item irritability domain of Concise Associated Symptom Tracking scale, 3-item suicidal thoughts factor of Concise Health Risk Tracking scale, and 16-item Quick Inventory of Depressive Symptomatology Clinician-Rated version (excluding the suicide-related item) respectively during acute-(baseline-to-week-12) and continuation-(week-12-to-week-36) phase. Covariates included age, sex, race, ethnicity, treatment arm, type of substance(s) used, and comorbid psychiatric and medical disorders.Higher irritability was associated with higher SI concurrently both in the acute-phase: r=0.28 (p0.0001) and in the continuation-phase: r=0.33 (p0.0001). Irritability was associated with concurrent SI after controlling for depression [acute-phase: β=0.17 (p0.0001); continuation-phase: β=0.18 (p0.0001)]. Greater baseline-to-week-2 reductions in irritability predicted lower levels of SI from week-2-to-week-12 (β=-0.11, p=0.003) and from week-12-to-week-36 (β=-0.22, p0.0001) after controlling for baseline levels of depression and SI and baseline-to-week-2 changes in depression and SI.Secondary analyses, self-report measures of irritability and SI, limited generalizability.Irritability is associated with SI concurrently, and greater reductions in irritability earlier in treatment are associated with lower levels of subsequent SI. Therefore, targeting irritability may reduce suicidality in adults with stimulant use disorder.