The psychiatric sequelae of the COVID-19 pandemic in adolescents, adults, and health care workers.

BACKGROUND: The COVID-19 pandemic is the most serious global public health crisis since the 1918 influenza pandemic. This study is the first to assess its mental health impact across the lifespan in the United States in adolescents, adults, and health care workers. METHODS: We recruited 4909 participants through an online survey advertising on Facebook and Instagram to assess exposure to COVID-19 and psychiatric symptoms from April 27 to July 13. We also recruited through the University of Pittsburgh, University of Pittsburgh Medical Center, and other health care systems around Pittsburgh. The primary outcomes were clinically significant depression, anxiety, and posttraumatic stress disorder (PTSD) symptoms, suicidal ideation or behavior, and grief reactions since COVID-19. RESULTS: Adolescents were significantly more likely to report moderate to severe symptoms of depression (55% vs. 29%; χ2 = 122, df = 1; p < .001), anxiety (48% vs. 29%; χ2 = 73; df = 1; p < .001), PTSD (45% vs. 33%; χ2 = 12; df = 1; p < .001), suicidal ideation or behavior (38% vs. 16%; χ2 = 117; df = 1; p < .001), and sleep problems (69% vs. 57%; χ2 = 26; df = 1; p < .001) compared to adults. The rates of intense grief reactions among those who lost someone to COVID-19 was 55%. Loneliness was the most common predictor across outcomes and higher number of hours spent on social media and exposure to media about COVID-19 predicted depression symptoms and suicidal ideation or behavior in adolescents. CONCLUSIONS: The COVID-19 pandemic is associated with increased rates of clinically significant psychiatric symptoms. Loneliness could put individuals at increased risk for the onset of psychiatric disorders.

Effects of adjunctive inflammatory modulation on IL-1ß in treatment resistant bipolar depression.

BACKGROUND: Adjunctive inflammatory modulation improved remission rates in treatment-resistant bipolar depression (TRBDD), but reliable biomarkers must be established to characterize the biosignature of TRBDD and the mechanisms underlying treatment response. In this molecular profiling study, we describe TRBDD and treatment response from the standpoint of interleukin-1 Beta (IL-1ß) and KYN/TRP. METHODS: 47 TRBDD patients with moderately severe HAMD-17 scores were randomized to receive either escitalopram (ESC) (10 mg-40 mg daily dose range) + celecoxib (CBX) (200 mg twice daily), or ESC (10 mg-40 mg daily dose range) + placebo (PBO) (twice daily). Plasma cytokine levels were measured in both treatment arms at baseline and week 8, and in a healthy control (HC) group of subjects (N = 43) once. A linear mixed model (LMM) was applied to evaluate whether clinical outcome is related to CBX and changes to biomarkers throughout treatment. A binary logistic regression model was formulated from this series to predict both the primary outcome of treatment response to CBX, and the secondary outcome of diagnosis of TRBDD using age, BMI, gender, and IL-1ß at baseline. RESULTS: Patients receiving ESC + CBX had 4.278 greater odds of responding (p = 0.021) with NNT = 3, and 15.300 times more likely to remit (p < 0.001) with NNT = 2, compared with ESC + PBO patients. Patient BMI (p = 0.003), baseline IL-1ß (p = 0.004), and baseline KYN/TRP (p = 0.001) were most predictive of TRBDD diagnosis. By Week 8, responders showed a downtrend in IL-1ß compared to non-responders in the ESC + CBX treatment arm. However, there was no statistical difference in the IL-1ß or KYN/TRP change after treatment between placebo and ESC + CBX group responders/non-responders (p = 0.239, and p = 0.146, respectively). While baseline IL-1ß was elevated in TRBDD compared to HC (p < 0.001), there was no difference in IL-1ß between treatment responders at Week 8 compared to HC (p = 0.067). CONCLUSIONS: Elevated IL-1ß and low KYN/TRP at baseline are components of the TRBDD molecular signature. CBX but not baseline IL-1ß or KYN/TRP predict treatment response. Change in IL-1ß and KYN/TRP did not predict treatment response.

'Swear by Thy Gracious Self': North American Medical Oath-Taking in 2014/2015.

Over the past century, six studies - the most recent data from 2000 - and one review have comprehensively examined the content of medical oaths and oath-taking practices, all focusing on North America, providing an insight into the ethical beliefs of each era. Our study sought to establish a new point of reference. In 2014/2015, oaths from 150 of all 153 US and Canadian medical schools were collected and analyzed. All but one school administered medical oaths and most schools administered more than one. Since 2000, student-written oaths became more popular, and new themes, such as self-care and professionalism, were identified in the oaths for the first time. However, as was identified in 2000, the oaths' contents are disparate and even conflicting at times, raising questions as to whether medicine is being taught or practiced with a coherent ethical worldview.

Systemic Inflammatory Response Index (SIRI) at Baseline Predicts Clinical Response for a Subset of Treatment-Resistant Bipolar Depressed Patients.

Background: in a recent double-blind, placebo controlled RCT we demonstrated that selective inhibition of cyclo-oxygenase 2 (COX2) is an effective adjunctive strategy in treatment-resistant bipolar depression (TRBDD). To better clarify the mechanisms underlying TRBDD and treatment response, we conducted a retrospective exploratory analysis of the systemic inflammatory response index (SIRI = absolute neutrophils × absolute monocytes/absolute lymphocytes) in relation to other biomarkers and clinical outcomes after escitalopram (ESC), combined with the COX-2 inhibitor, celecoxib (CBX), versus placebo. Methods: Baseline measures of SIRI were compared between TRBDD and healthy controls (HC), and correlated with blood-based inflammatory cytokines, kynurenines, and growth factors. Post-treatment Hamilton Depression Rating Scale 17 (HAMD-17) total scores (clinical outcome) were modelled according to SIRI adjusting for demographics (including relevant interactions with SIRI), baseline depression, treatment arm, and treatment timepoint using multiple linear regression and robust linear mixed effects models. Results: Baseline SIRI did not distinguish TRBDD from HC groups. Baseline SIRI was significantly correlated with lower baseline MCP-1. The relationship between SIRI and HAMD-17 was significant at treatment week 8, in contrast to baseline. Finally, baseline SIRI predicted elevated post-treatment HAMD-17 scores, amongst patients with elevated depression scores at baseline. Significance: High pre-treatment SIRI may predict poorer depressive outcomes amongst TRBDD patients with baseline elevated depression.

Utilizing the Systemic Immune-Inflammation Index and Blood-Based Biomarkers in Association with Treatment Responsiveness amongst Patients with Treatment-Resistant Bipolar Depression.

(1) Background: Inflammation is associated with depressive illness and treatment resistance. This study assessed a novel inflammatory index, the Systemic Immune-Inflammation Index (SII), in patients diagnosed with treatment-resistant bipolar depression (TRBDD) before and after treatment with escitalopram (ESC) and celecoxib (CBX) add-on or ESC and placebo (PBO), and compared them to healthy control (HC) subjects. (2) Methods: This is a secondary biological analysis from a double-blind randomized placebo-controlled trial of CBX augmentation in TRBDD. Our subsample with available complete blood count (CBC) data included 52 TRBDD subjects, randomized into an ESC + CBX, (n = 29), an ESC + PBO arm (n = 23), and an HC group (n = 32). SII was calculated from the CBC with differential (SII = platelets x neutrophils/lymphocytes) at baseline and end of treatment (8 weeks). Blood inflammation biomarkers, growth factors, and kynurenine metabolites were determined at both timepoints. Depressive symptom severity was the primary outcome, using the HAMD-17 rating scale score to quantitate treatment response and remission rates. (3) Results: Baseline SII did not discriminate TRBDD from HC, nor was it associated with HAMD-17 score at any timepoint, although it was significantly associated with lower baseline VEGF (p = 0.011) and higher week 8 levels of IL1-ß (p = 0.03) and CRP (p = 0.048). Post-treatment HAMD-17 was not independently predicted using baseline SII unless an interaction with age was present (p = 0.003 was included), even after relevant adjustments. A similar effect was seen with baseline neutrophils. (4) Conclusions: While SII was not an independent predictor of treatment outcome, elevated baseline SII was a predictor of poor treatment response amongst older patients with TRBDD.

Opioid use as a proximal risk factor for suicidal behavior in young adults.

INTRODUCTION: There is a concomitant rise in suicide rates with the prevalence of opioids involved in overdose deaths, especially among adolescents and young adults. However, there are limited studies on whether opioid use prospectively predicts suicidal behavior in youth. METHODS: Our sample included 183 psychiatric patients (18-30 years) admitted for a suicide attempt (SA), have current suicidal ideation (SI), and psychiatric controls without ideation or attempt (PC). Suicidal behavior was assessed using the Columbia Suicide Severity Rating Scale. We also recruited a healthy control group (HC; n = 40). Patients and controls were followed over a year. ANOVA, regression, and cox regression were used. RESULTS: Suicide attempt (ß = 0.87, CI [0.1-1.6], p = 0.02) and SI [(ß = 0.75, CI [0.03-1.5], p = 0.04) were significantly more likely than HCs to have used opioids in the past year at baseline. Opioid use was associated with increased anxiety symptoms (ß = 0.75, CI [0.001-1.5], p = 0.05), PTSD symptoms (ß = 3.90, CI [1.1-6.7], p = 0.01), and aggression (ß = 0.02, CI [0.01-0.04], p = 0.02). Opioid use in the month prior to hospitalization predicted SA at 6 months (OR = 1.87, CI [1.06-3.31], p = 0.032). CONCLUSIONS: Opioid use is a proximal predictor for SA. These findings may help clinicians better identify patients at risk for suicidal behavior, allowing for more personalized treatment approaches.

Neurobiological biomarkers of response to ketamine.

As a field, psychiatry is undergoing an exciting paradigm shift toward early identification and intervention that will likely minimize both the burden associated with severe mental illnesses as well as their duration. In this context, the rapid-acting antidepressant ketamine has revolutionized our understanding of antidepressant response and greatly expanded the pharmacologic armamentarium for treatment-resistant depression. Efforts to characterize biomarkers of ketamine response support a growing emphasis on early identification, which would allow clinicians to identify biologically enriched subgroups with treatment-resistant depression who are more likely to benefit from ketamine therapy. This chapter presents a broad overview of a range of translational biomarkers, including those drawn from imaging and electrophysiological studies, sleep and circadian rhythms, and HPA axis/endocrine function as well as metabolic, immune, (epi)genetic, and neurotrophic biomarkers related to ketamine response. Ketamine's unique, rapid-acting properties may serve as a model to explore a whole new class of novel rapid-acting treatments with the potential to revolutionize drug development and discovery. However, it should be noted that although several of the biomarkers reviewed here provide promising insights into ketamine's mechanism of action, most studies have focused on acute rather than longer-term antidepressant effects and, at present, none of the biomarkers are ready for clinical use.

Is the Writing on the Wall for Current Medical Oaths? A Brief Historical Review of Oath Taking at Medical Schools.

Oaths recited in medical schools provide valuable insight into the medical profession's evolving core of ethical commitments. This study presents a brief overview of medical oaths, and how they came to attain their current prominence. The authors examine medical oaths used in twentieth-century North America (the USA and Canada) through a critical review of six studies on oath administration and content that were undertaken between 1928 and 2004. While oath-taking became almost universally prevalent in twentieth-century North American medical schools, the ethical content of oaths grew increasingly heterogeneous. The findings challenge assumptions about the content of medical oaths. They also create dynamic markers for gauging the variability in the current ethical milieus of medical education, providing a basis for evaluating future direction.

Factors associated with increased academic productivity among US academic radiation oncology faculty.

OBJECTIVES: Publication productivity metrics can help evaluate academic faculty for hiring, promotion, grants, and awards; however, limited benchmarking data exist, which makes intra- and interdepartmental comparisons difficult. Therefore, we sought to evaluate the scholarly activity of physician faculty at academic radiation oncology (RO) departments and establish factors associated with increased academic productivity. METHODS AND MATERIALS: Citation database searches were performed for all physician-faculty in US residency-affiliated academic RO departments. Demographics, National Institutes of Health (NIH) funding, and bibliometrics (number of publications, Hirsch-[h]-index, and m-index [Hirsch index divided by the number of years since first publication]) were collected and stratified by academic rank. Senior academic rank was defined as full professor, professor, and/or chair. Junior academic rank was defined as all others. Logistic regression was performed to determine the association of academic rank and other factors with h- and m-indices. RESULTS: A total of 1191 academic RO physician faculty from 75 institutions were included in the analysis. The mean (standard deviation) number of publications and h- and m-indices were 48.2 (71.2), 14.5 (15), and 0.86 (0.83), respectively. The median (interquartile range) number of publications and h- and m-indices were 20 (6-61), 9 (4-20), and 0.69 (0.38-1.10), respectively. Recursive partitioning analysis revealed a statistically significant numeric h-index threshold of 21 between junior and senior faculty (LogWorth 114; receiver operating characteristic, 0.828). Senior faculty status, receipt of NIH funding, and a larger department size were associated with increased h- and m-indices. CONCLUSIONS: Current academic RO departments have relatively high objective metrics of scholastic productivity compared with prior benchmarking analyses of RO departments and compared with published metrics from other academic medicine subspecialties. An h-index of 21 or greater was associated with senior faculty status. Additionally, receipt of NIH funding and greater departmental size were associated with a higher h-index. These data may be of interest to faculty preparing for promotion or award applications as well as institutional leadership evaluating their departments.

Predictors and Modulators of Synthetic Lethality: An Update on PARP Inhibitors and Personalized Medicine.

Poly(ADP-ribose) polymerase (PARP) inhibitors have proven to be successful agents in inducing synthetic lethality in several malignancies. Several PARP inhibitors have reached clinical trial testing for treatment in different cancers, and, recently, Olaparib (AZD2281) has gained both United States Food and Drug Administration (USFDA) and the European Commission (EC) approval for use in BRCA-mutated advanced ovarian cancer treatment. The need to identify biomarkers, their interactions in DNA damage repair pathways, and their potential utility in identifying patients who are candidates for PARP inhibitor treatment is well recognized. In this review, we detail many of the biomarkers that have been investigated for their ability to predict both PARP inhibitor sensitivity and resistance in preclinical studies as well as the results of several clinical trials that have tested the safety and efficacy of different PARP inhibitor agents in BRCA and non-BRCA-mutated cancers.