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Borderline Personality Disorder (BPD) is characterized by rapidly shifting emotional, interpersonal, and behavioral symptoms, often co-morbid with mood and anxiety disorders. Females are more likely to be diagnosed with BPD than males and exhibit greater functional impairment. Hormonal fluctuations may influence the manifestation of BPD symptoms. Here, we investigated the influence of ovulation-suppressing contraceptives on behavioral and functional difficulties in BPD. The sample included 348 females ages 18-50 undergoing residential treatment for psychiatric disorders, with 131 having a BPD diagnosis. Patients were categorized by their contraceptive method: Ovulation-suppressing contraceptives (N = 145) and naturally cycling (N = 203). Interaction models tested the impact of ovulation-suppressing contraceptives on the relationship between BPD diagnosis and behavioral and functional difficulties at admission and discharge, assessed by the four Behavior and Symptom Identification Scale (BASIS-32) domains: difficulties in relationships, daily living, depression/anxiety, and impulsivity. Females with a BPD diagnosis were more likely to use ovulation-suppressing contraceptives compared to those without BPD (p = 0.04). However, ovulation-suppressing contraceptive use was not associated with behavioral and functional difficulties at admission, discharge, or over time. Ovulation-suppressing contraceptives moderated the association between BPD diagnosis and difficulties in relationships (p = 0.004), difficulties in daily living (p = 0.01), and depression/anxiety symptoms (p = 0.004). Specifically, patients with BPD experienced more behavioral and functional difficulties only if naturally cycling, whereas patients without BPD showed higher symptom severity only if using ovulation-suppressing contraceptives. Our findings suggest that the impact of ovulation-suppressing contraceptives on behavioral and functional difficulties varies depending on BPD diagnosis and underscores the need for further clinical studies.

Post-traumatic stress disorder (PTSD) genetics are characterized by lower discoverability than most other psychiatric disorders. The contribution to biological understanding from previous genetic studies has thus been limited. We performed a multi-ancestry meta-analysis of genome-wide association studies across 1,222,882 individuals of European ancestry (137,136 cases) and 58,051 admixed individuals with African and Native American ancestry (13,624 cases). We identified 95 genome-wide significant loci (80 new). Convergent multi-omic approaches identified 43 potential causal genes, broadly classified as neurotransmitter and ion channel synaptic modulators (for example, GRIA1, GRM8and CACNA1E), developmental, axon guidance and transcription factors (for example, FOXP2, EFNA5and DCC), synaptic structure and function genes (for example, PCLO, NCAM1and PDE4B) and endocrine or immune regulators (for example, ESR1, TRAF3and TANK). Additional top genes influence stress, immune, fear and threat-related processes, previously hypothesized to underlie PTSD neurobiology. These findings strengthen our understanding of neurobiological systems relevant to PTSD pathophysiology, while also opening new areas for investigation.

ObjectivesThis study aims to determine (1) which providers in US healthcare systems order lead tests, why and at what frequency and (2) whether current patient population lead levels are predictive of clinical outcomes.MethodsRetrospective medical record study of all blood lead tests in the Medical University of South Carolina healthcare system 2012–2016 and consequent evidence of central nervous system (CNS)-related disease across a potential 10-year window (2012–2022).ResultsAcross 4 years, 9726 lead tests resulted for 7181 patients (49.0% female; 0–94 years), representing 0.2% of the hospital population. Most tests were for young (76.6%≤age 3) and non-Hispanic black (47.2%) and Hispanic (26.7%) patients. A wide variety of providers ordered tests; however, most were ordered by paediatrics, psychiatry, internal medicine and neurology. Lead levels ranged from ≤2.0 µg/dL (80.8%) to ≥10 µg/dL (0.8%; max 36 µg/dL). 201 children (3.1%) had initial lead levels over the reference value for case management at the time (5.0 µg/dL). Many high level children did not receive follow-up testing in the system (36.3%) and those that did often failed to see levels fall below 5.0 µg/dL (80.1%). Non-Hispanic black and Hispanic patients were more likely to see lead levels stay high or go up over time. Over follow-up, children with high lead levels were more likely to receive new attention-deficit/hyperactivity disorder and conduct disorder diagnoses and new psychiatric medications. No significant associations were found between lead test results and new CNS diagnoses or medications among adults.ConclusionsHospital lead testing covers a small portion of patients but includes a wide range of ages, presentations and provider specialities. Lack of lead decline among many paediatric patients suggests there is room to improve provider guidance around when to test and follow-up.

Posttraumatic stress disorder (PTSD) is a heritable (h2= 24–71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P= 6.3 × 10−8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P= 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q< 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.

Paruresis, considered a category of social phobia, is the fear of being unable to initiate or sustain urination in the presence of others or in situations where others may become [...]

Although aspects of brain morphology have been associated with chronic posttraumatic stress disorder (PTSD), limited work has investigated multimodal patterns in brain morphology that are linked to acute posttraumatic stress severity. In the present study, we utilized multimodal magnetic resonance imaging to investigate if structural covariance networks (SCNs) assessed acutely following trauma were linked to acute posttraumatic stress severity.

Injury mechanism and post-injury mental health trajectories are known to differ in relation to race and ethnicity. This study found that Black and White patients served by a Level I trauma center had comparable levels of enrollment and engagement in mental health services.

Female individuals are more likely to be diagnosed with PTSD following trauma exposure than males, potentially due, in part, to underlying neurobiological factors. Several brain regions underlying fear learning and expression have previously been associated with PTSD, with the hippocampus, amygdala, dorsal anterior cingulate cortex (dACC), and rostral ACC (rACC) showing altered volume and function in those with PTSD. However, few studies have examined how sex impacts the predictive value of subcortical volumes and cortical thickness in longitudinal PTSD studies. As part of an emergency department study completed at the Grady Trauma Project in Atlanta, GA, N= 93 (40 Female) participants were enrolled within 24 h following a traumatic event. Multi-echo T1-weighted MRI images were collected one-month post-trauma exposure. Bilateral amygdala and hippocampal volumes and rACC and dACC cortical thickness were segmented. To assess the longitudinal course of PTSD, the PTSD Symptom Scale (PSS) was collected 6 months post-trauma. We investigated whether regional volume/thickness interacted with sex to predict later PTSD symptom severity, controlling for PSS score at time of scan, age, race, and trauma type, as well as intracranial volume (ICV) for subcortical volumes. There was a significant interaction between sex and rACC for 6-month PSS, such that right rACC thickness was positively correlated with 6-month PSS scores in females, but not in males. In examining PTSD symptom subtypes and depression symptoms, greater rACC thickness in females predicted greater avoidance symptoms, while smaller rACC thickness in males predicted greater depression symptoms. Amygdala and hippocampus volume and dACC thickness showed no main effect or interaction with sex. The current findings provide evidence for sex-based differences in how brain volume predicts future PTSD severity and symptoms and supports the rACC as being a vital region regarding PTSD. Gender differences should be assessed in future longitudinal PTSD MRI studies for more accurate identification of future PTSD risk following trauma.

* Following 12 weeks of open-label antidepressant pharmacotherapy, non-remitting chronically depressed patients were randomized to a second 12 weeks that compared: 1) continued pharmacotherapy and augmentation with cognitive behavioral analysis system of psychotherapy (CBASP); 2) continued pharmacotherapy and augmentation with brief supportive psychotherapy (BSP); and 3) continued pharmacotherapy (MEDS) alone. * At the end of randomized treatment, 37.5% of patients experienced remission or partial response, but outcomes did not differ among CBASP, BSP, or MEDS., A large-scale prospective study of chronically depressed patients found that among those who did not remit after 12 weeks of open-label, algorithm-guided pharmacotherapy, 37.5% later remitted after 12 additional weeks [...]

[ILLUSTRATION OMITTED] It all started with just a couple of shelves of vodka. Then like something out of the musical Little Shop of Horrors the vodka selection in retail shops [...]

This article describes the rationale and the specific methods for an open label pilot trial of 100 mg MDMA in combination with massed exposure therapy for PTSD, a treatment which involves daily exposure therapy sessions for two weeks which has found to be effective. We review the need for novel PTSD treatments and the existing research on MDMA-assisted therapy, and then describe the rationale for this novel treatment approach, including combining MDMA with a gold standard treatment, translational support for this treatment, strong dissemination potential, and strengths of providing massed exposure treatment. The specific methods of the open label pilot study are presented, followed by conclusions and future directions for this research. This study will enroll at least 15 adults with PTSD over the next 2 years in order to identify feasibility and lead to a manual describing how to combine MDMA with exposure therapy, tested in a randomized, placebo-controlled trial, with significant promise for dissemination and improving our ability to treat PTSD.

Fear extinction is a reduction in conditioned fear following repeated exposure to the feared cue in the absence of any aversive event. Extinguished fear often reappears after extinction through spontaneous recovery. Animal studies suggest that spontaneous recovery can be abolished if extinction occurs within minutes of acquisition. However, a limited number of human extinction studies have shown that short interval extinction does not prevent the return of fear. For this reason, we performed an in-depth parametric analysis of human fear extinction using fear-potentiated startle. Using separate single-cue and differential conditioning paradigms, participants were fear conditioned and then underwent extinction either 10 min (Immediate) or 72 hr (Delayed) later. Testing for spontaneous recovery occurred 96 hr after acquisition. In the single cue paradigm, the Immediate and Delayed groups exhibited differences in context, but not fear, conditioning. With differential conditioning, there were no differences in context conditioning and the Immediate group displayed less spontaneous recovery. Thus, the results remain inconclusive regarding spontaneous recovery and the timing of extinction and are discussed in terms of performing translational studies of fear in humans. Keywords: fear conditioning, fear extinction in humans, spontaneous recovery, startle

Posttraumatic stress disorder (PTSD) is a debilitating syndrome with substantial morbidity and mortality that occurs in the aftermath of trauma. Symptoms of major depressive disorder (MDD) are also a frequent consequence of trauma exposure. Identifying novel risk markers in the immediate aftermath of trauma is a critical step for the identification of novel biological targets to understand mechanisms of pathophysiology and prevention, as well as the determination of patients most at risk who may benefit from immediate intervention. Our study utilizes a novel approach to computationally integrate blood-based transcriptomics, genomics, and interactomics to understand the development of risk vs. resilience in the months following trauma exposure. In a two-site longitudinal, observational prospective study, we assessed over 10,000 individuals and enrolled >700 subjects in the immediate aftermath of trauma (average 5.3 h post-trauma (range 0.5–12 h)) in the Grady Memorial Hospital (Atlanta) and Jackson Memorial Hospital (Miami) emergency departments. RNA expression data and 6-month follow-up data were available for 366 individuals, while genotype, transcriptome, and phenotype data were available for 297 patients. To maximize our power and understanding of genes and pathways that predict risk vs. resilience, we utilized a set-cover approach to capture fluctuations of gene expression of PTSD or depression-converting patients and non-converting trauma-exposed controls to find representative sets of disease-relevant dysregulated genes. We annotated such genes with their corresponding expression quantitative trait loci and applied a variant of a current flow algorithm to identify genes that potentially were causal for the observed dysregulation of disease genes involved in the development of depression and PTSD symptoms after trauma exposure. We obtained a final list of 11 driver causal genes related to MDD symptoms, 13 genes for PTSD symptoms, and 22 genes in PTSD and/or MDD. We observed that these individual or combined disorders shared ESR1, RUNX1, PPARA, and WWOX as driver causal genes, while other genes appeared to be causal driver in the PTSD only or MDD only cases. A number of these identified causal pathways have been previously implicated in the biology or genetics of PTSD and MDD, as well as in preclinical models of amygdala function and fear regulation. Our work provides a promising set of initial pathways that may underlie causal mechanisms in the development of PTSD or MDD in the aftermath of trauma.

Exposure therapy is a well-established treatment for Posttraumatic Stress Disorder (PTSD) that requires the patient to focus on and describe the details of a traumatic experience. Exposure methods include confrontation with frightening, yet realistically safe, stimuli that continues until anxiety is reduced. A review of the literature on exposure therapy indicates strong support from well-controlled studies applied across trauma populations. However, there are many misconceptions about exposure therapy that may interfere with its widespread use. These myths and clinical guidelines are addressed. It is concluded that exposure therapy is a safe and effective treatment for PTSD when applied as directed by experienced therapists.

Objective: The study examined the efficacy of sertraline, compared with placebo, in sustaining improvement and preventing relapse over 28 weeks in patients with posttraumatic stress disorder (PTSD) who had completed a 12-week double-blind, placebo-controlled acute treatment study and a subsequent 24-week open-label study of continuation treatment with sertraline. Method: Ninety-six patients were randomly assigned, in a double-blind design, to 28 weeks of maintenance treatment with sertraline (50-200 mg, N=46; 78% were women) or placebo (N=50; 62% were women). Measures used in biweekly assessments included the Clinician-Administered PTSD Scale, the Impact of Event Scale, and the Clinical Global Impression severity and improvement ratings. Kaplan-Meier analyses were used to estimate time to discontinuation from the study due to relapse, relapse or study discontinuation due to clinical deterioration, and acute exacerbation. Results: Continued treatment with sertraline yielded lower PTSD relapse rates than placebo (5% versus 26%). Patients who received placebo were 6.4 times as likely to experience relapse as were patients who received sertraline. Kaplan-Meier analyses confirmed the protective effect of sertraline in significantly extending time in remission. The ability of sertraline to sustain improvement was comparable across the three core PTSD symptom clusters (reexperiencing/intrusion, avoidance/numbing, and hyperarousal). A regression analysis found early response during acute treatment to be associated with a more than 16-fold reduced risk of relapse after placebo substitution. Sertraline, at a mean endpoint dose of 137 mg, was well tolerated, with no sertraline-related adverse events observed at a rate of 10% or higher. Conclusions: The results provide evidence for the ability of sertraline both to sustain improvement in PTSD symptoms and to provide prophylactic protection against relapse. (Am J Psychiatry 2001; 158: 1974-1981)

We test an improved imputation technique, sequential regression multivariate imputation (SRMI), for the Current Population Survey Annual Social and Economic Supplement to address match bias. Furthermore, we augment the model with administrative tax data to test for nonignorable nonresponse. Using data from 2009, 2011, and 2013, we find that the current hot deck imputation used by the Census Bureau produces different distribution statistics, downward for poverty and inequality and upward for median income, relative to the SRMI model-based estimates. Our results suggest that these differences are a result of match bias, not nonignorable nonresponse. Nearly all poverty, median income, and inequality estimates are not significantly different when comparing imputation models with and without administrative data. However, there are clear efficiency gains from using administrative data.

? Alcohol is like fat: It carries flavor. Typically, the higher the hooch's proof, the stronger the flavor. That's especially true of cask-strength whiskeys, which are not watered down at [...]

The clinical construct of “anxiety neurosis” was broad and poorly defined, so that the delineation of specific anxiety disorders in the DSM‐III was an important advance. However, anxiety and related disorders are not only frequently comorbid, but each is also quite heterogeneous; thus diagnostic manuals provide only a first step towards formulating a management plan, and the development of additional decision support tools for the treatment of anxiety conditions is needed. This paper aims to describe systematically important domains that are relevant to the personalization of management of anxiety and related disorders in adults. For each domain, we summarize the available research evidence and review the relevant assessment instruments, paying special attention to their suitability for use in routine clinical practice. We emphasize areas where the available evidence allows the clinician to personalize the management of anxiety conditions, and we point out key unmet needs. Overall, the evidence suggests that we are becoming able to move from simply recommending that anxiety and related disorders be treated with selective serotonin reuptake inhibitors, cognitive‐behavioral therapy, or their combination, to a more complex approach which emphasizes that the clinician has a broadening array of management modalities available, and that the treatment of anxiety and related disorders can already be personalized in a number of important respects.

To determine the efficacy of percutaneous excimer laser coronary angioplasty as an adjunct or alternative to conventional balloon angioplasty, 55 patients were studied in a multicenter trial. These patients underwent the procedure using a modification of conventional balloon angioplasty technique. A first-generation, 1.6-mm diameter catheter constructed of 12 individual silica fibers concentrically arranged around a guidewire lumen was used. Catheter tip energy density varied from 35 to 50 mJ/m[m.sup.2]. The mean number of pulses delivered at 20 Hz was 1,272 [+ or -] 1,345. Acute success was defined as a [is greater than or equal to]20% increase in stenotic diameter and a lumen of [is greater than or equal to]1 mm in diameter after laser treatment. Acute success was achieved in 46 of 55 (84%) patients. Adjunctive balloon angioplasty was performed on 41 patients (75%). The percent diameter stenosis as determined by quantitative angiography decreased from a baseline of 83 [+ or -] 14 to 49 [+ or -] 11% after laser treatment and to 38 [+ or -] 12% in patients undergoing adjunctive balloon angioplasty. The mean minimal stenotic diameter increased from a baseline of 0.5 [+ or -] 0.4 to 1.6 [+ or -] 0.5 mm after laser treatment and to 2.1 [+ or -] 0.5 mm after balloon angioplasty. There were no deaths and no vascular perforations. One patient (1.8%) required emergency coronary bypass surgery. These data suggest that excimer laser energy delivered percutaneously by specially constructed catheters can safely ablate atheroma and reduce coronary stenoses., Percutaneous transluminal coronary angioplasty (PTCA) is a procedure for dilating narrowed or blocked coronary arteries, the major blood vessels supplying the heart. In PTCA, a small balloon attached to a catheter is inserted into the narrowed portion of the coronary artery, and brief inflation of the balloon widens the vessel. Although PTCA is effective, it does not reduce the size of the substance blocking the artery, usually an atheroma (a mass consisting of lipids, or fats, and cell debris). Laser angioplasty is a technique in which a laser is used to remove the arterial occlusions caused by atherosclerosis. The pulsed excimer type of laser was shown to remove even calcified tissue without causing thermal (heat) injury. The effectiveness of percutaneous excimer laser coronary angioplasty was assessed in 55 patients with stenosis or narrowing of the coronary arteries. The conventional balloon angioplasty technique was modified, and detailed changes in the catheter are described. The procedure was successful in 46 of 55 patients. Forty-one patients underwent further treatment by conventional balloon angioplasty. The narrowing decreased from 83 percent of the vessel before treatment, to 49 percent after laser treatment and 38 percent after additional balloon angioplasty. The diameter of the narrowed vessel increased from 0.5 millimeters (mm) before treatment, to 1.6 mm after laser treatment and 2.1 mm after balloon angioplasty. There were no deaths or ruptures of the blood vessels. One patient required coronary bypass surgery, an operation in which a healthy blood vessel is attached to the diseased coronary artery, bypassing the area of damage, to provide an alternate route of blood flow to the heart. These findings demonstrate that percutaneous excimer laser coronary angioplasty can safely remove atheromatous occlusions and reduce narrowing of coronary arteries. (Consumer Summary produced by Reliance Medical Information, Inc.)

Virtual reality exposure therapy (VRE) for posttraumatic stress disorder (PTSD) is an innovative and increasingly popular approach to delivering trauma-focused exposure therapy to a range of populations exposed to trauma. VRE is best viewed as another medium for prolonged exposure (PE), which is the most extensively researched treatment for PTSD and is one of the universally recommended psychotherapies in clinical practice guidelines. The unique application of VRE is imaginal exposure to the trauma memory conducted with the eyes open within a VR environment to help activate and sustain the memory sufficiently. Since its proof of concept over two decades ago, the availability and acceptability of VR technologies in the context of mental health treatment has greatly increased. This article describes the theory, evidence, and procedures of VRE. Clinicians interested in VRE are encouraged to pursue appropriate training and consultation. Virtual reality exposure therapy (VRE) for posttraumatic stress disorder (PTSD) is an innovative and increasingly popular approach to delivering trauma-focused exposure therapy to a range of populations exposed to trauma. VRE is best viewed as another medium for prolonged exposure (PE), which is the most extensively researched treatment for PTSD and is one of the universally recommended psychotherapies in clinical practice guidelines. The unique application of VRE is imaginal exposure to the trauma memory conducted with the eyes open within a VR environment to help activate and sustain the memory sufficiently. Since its proof of concept over two decades ago, the availability and acceptability of VR technologies in the context of mental health treatment has greatly increased. This article describes the theory, evidence, and procedures of VRE. Clinicians interested in VRE are encouraged to pursue appropriate training and consultation. [[Psychiatr Ann.2019;49(8):343–347.]

Shelter in place orders in the coronavirus disease 2019 (COVID-19) pandemic necessitate changes in how medical care is delivered. We describe our method for team telemedicine visits for California Children's Services, a state insurance for children requiring multidisciplinary care, to demonstrate how such visits can be efficiently conducted. Although the physical distance provides some obstacles, telemedicine visits can also improve some elements of the team visit.

Biomarkers that predict symptom trajectories after trauma can facilitate early detection or intervention for posttraumatic stress disorder (PTSD) and may also advance our understanding of its biology. Here, we aimed to identify trajectory-based biomarkers using blood transcriptomes collected in the immediate aftermath of trauma exposure. Participants were recruited from an Emergency Department in the immediate aftermath of trauma exposure and assessed for PTSD symptoms at baseline, 1, 3, 6, and 12 months. Three empirical symptom trajectories (chronic-PTSD, remitting, and resilient) were identified in 377 individuals based on longitudinal symptoms across four data points (1, 3, 6, and 12 months), using latent growth mixture modeling. Blood transcriptomes were examined for association with longitudinal symptom trajectories, followed by expression quantitative trait locus analysis. GRIN3Band AMOTL1blood mRNA levels were associated with chronic vs. resilient post-trauma symptom trajectories at a transcriptome-wide significant level (N= 153, FDR-corrected pvalue = 0.0063 and 0.0253, respectively). We identified four genetic variants that regulate mRNA blood expression levels of GRIN3B. Among these, GRIN3Brs10401454 was associated with PTSD in an independent dataset (N= 3521, p= 0.04). Examination of the BrainCloud and GTEx databases revealed that rs10401454 was associated with brain mRNA expression levels of GRIN3B. While further replication and validation studies are needed, our data suggest that GRIN3B, a glutamate ionotropic receptor NMDA type subunit-3B, may be involved in the manifestation of PTSD. In addition, the blood mRNA level of GRIN3Bmay be a promising early biomarker for the PTSD manifestation and development.

•What are the best approaches to enhance engagement and improve outcomes in evidence-based psychotherapies for post-traumatic stress disorder (PTSD) in older adults, particularly for low or nonresponders?•This paper reviews the current state of the research on augmentations to first-line treatments for PTSD, including medications, neuromodulation, and changes to the structure of treatment. A case illustration of an older adult with PTSD who received prolonged exposure with multiple augmentations is reviewed.•Older adults with PTSD may benefit from augmentations to evidence-based psychotherapy to enhance response.

Annually, approximately 30 million patients are discharged from the emergency department (ED) after a traumatic event1. These patients are at substantial psychiatric risk, with approximately 10–20% developing one or more disorders, including anxiety, depression or post-traumatic stress disorder (PTSD)2–4. At present, no accurate method exists to predict the development of PTSD symptoms upon ED admission after trauma5. Accurate risk identification at the point of treatment by ED services is necessary to inform the targeted deployment of existing treatment6–9to mitigate subsequent psychopathology in high-risk populations10,11. This work reports the development and validation of an algorithm for prediction of post-traumatic stress course over 12 months using two independently collected prospective cohorts of trauma survivors from two level 1 emergency trauma centers, which uses routinely collectible data from electronic medical records, along with brief clinical assessments of the patient’s immediate stress reaction. Results demonstrate externally validated accuracy to discriminate PTSD risk with high precision. While the predictive algorithm yields useful reproducible results on two independent prospective cohorts of ED patients, future research should extend the generalizability to the broad, clinically heterogeneous ED population under conditions of routine medical care.

Therapeutic targeting of Bruton tyrosine kinase (BTK) has dramatically improved survival outcomes for patients with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Acalabrutinib is an oral, highly selective BTK inhibitor that allows for twice-daily dosing due to its selectivity. In this phase 1b/2 study, 134 patients with relapsed/refractory CLL or SLL (median age, 66 years [range, 42-85 years]; median prior therapies, 2 [range, 1-13]) received acalabrutinib 100 mg twice daily for a median of 41 months (range, 0.2-58 months). Median trough BTK occupancy at steady state was 97%. Most adverse events (AEs) were mild or moderate, and were most commonly diarrhea (52%) and headache (51%). Grade =3 AEs (occurring in =5% of patients) were neutropenia (14%), pneumonia (11%), hypertension (7%), anemia (7%), and diarrhea (5%). Atrial fibrillation and major bleeding AEs (all grades) occurred in 7% and 5% of patients, respectively. Most patients (56%) remain on treatment; the primary reasons for discontinuation were progressive disease (21%) and AEs (11%). The overall response rate, including partial response with lymphocytosis, with acalabrutinib was 94%; responses were similar regardless of genomic features (presence of del(11)(q22.3), del(17)(p13.1), complex karyotype, or immunoglobulin variable region heavy chain mutation status). Median duration of response and progression-free survival (PFS) have not been reached; the estimated 45-month PFS was 62% (95% confidence interval, 51% to 71%). BTK mutation was detected in 6 of 9 patients (67%) at relapse. This updated and expanded study confirms the efficacy, durability of response, and long-term safety of acalabrutinib, justifying its further investigation in previously untreated and treated patients with CLL/SLL. This trial was registered at www.clinicaltrials.gov as #NCT02029443.

Byline: Rothbaum, Noah Jon Cryer Actor, Two and a Half Men 44, Los Angeles Interview by Noah Rothbaum I grew up as a sedentary kid who never did athletic things. [...]

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First there was one for pillows, then another for pools. Now meet the grocery concierge, who will not only shop for you but also unpack the bags and arrange your [...]

Byline: Rothbaum, Noah Ed Hochuli NFL Referee 57, Phoenix Interview by Noah Rothbaum A football game is like fartleks; you'll sprint over here, then stop. You'll jog over here, then [...]

When Encantado, the newest luxury resort from Auberge Resorts (aubergeresorts.com), opens in Santa Fe this month, guests will find all the comforts now expected of a sybaritic escape: a full-service [...]

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•The assessment of PTSD is hindered by the absence of an objective biological measure.•Psychophysiological measures can provide objective assessment of PTSD symptoms.•HPA axis dysfunction in PTSD may predate trauma or biomarkers of disease process.•Virtual humans assess behavioral markers that may go unnoticed by a human assessor.•The future includes early identification of risk for and prevention of PTSD.

Byline: Rothbaum, Noah Principal Cellist, New York Philharmonic, 50, New York City I was definitely a nerd in high school. Most of the popular kids played sports like football. But [...]

Posttraumatic stress disorder (PTSD) is often difficult to treat, and many patients do not achieve full remission. Complementary and integrative health approaches, such as mindfulness meditation, are intended to be integrated with evidence‐based treatment. This study examined the efficacy of mindfulness‐based stress reduction (MBSR) in the treatment of PTSD in U.S. military veterans. Veterans with a diagnosis of PTSD (N=214) were randomly assigned to either 90‐minute group MBSR or present‐centered group therapy (PCGT) for eight weeks. Follow‐up assessments were obtained at baseline and weeks 3, 6, 9 (primary endpoint), and 16. Both the MBSR and PCGT groups achieved significant improvement in PTSD as measured by the Clinician‐Administered PTSD Scale for DSM‐IV (CAPS‐IV), with no statistically significant differences between groups. However, compared with PCGT, the MBSR group showed a statistically significant improvement in PTSD on the self‐reported PTSD Checklist for DSM‐IV over the nine weeks. This difference was not maintained posttreatment, at week 16. Strengths of the study include its large sample size, multisite design, active control group, single‐blind outcome ratings, fidelity monitoring, large minority representation, and randomized approach. The study was limited by its high attrition rate and low representation of women. Both MBSR and PCGT appear to have beneficial effects in treating PTSD in veterans, with greater improvement observed in self‐reported PTSD symptoms in the MBSR group. No differences between groups were observed on the CAPS‐IV scale.

While nausea often develops following exposure to trauma, little is known regarding the relationship between peri-traumatic nausea and prospective risk for developing posttraumatic stress disorder (PTSD). We examined the association between peri-traumatic nausea and PTSD symptom development in three independent cohorts. Participants were recruited from (1) the Emergency Departments (ED) at Grady Memorial Hospital (GMH) in Atlanta, GA, (2) from multiple other ED sites in the TRYUMPH Research Network, and (3) from the ED during evaluation for suspected acute coronary syndrome in the REACH cohort. Administration of IV ondansetron, the most predominant antiemetic used at GMH, was used as a surrogate marker for nausea in the initial GMH cohort; nausea was then directly assessed in the internal validation at GMH, and within the replication TRYUMPH Research Network and REACH cohorts. In the GMH cohort (N= 363), ondansetron administration was associated with increased 1- and 3-month posttrauma PTSD symptoms in adjusted models (all p’s < 0.05). In the GMH internal validation, nausea significantly predicted 1 month (p= 0.009; n= 68) and 3 month (p= 0.029; n= 54) PTSD symptoms. In the TRYUMPH cohort (N= 1846), patient reported nausea in the ED was significantly associated with increased PTSD symptoms (p= 0.009) in adjusted models. In the REACH cohort (N= 758), peri-traumatic nausea was associated with PTSD symptom severity at the 1-month follow-up in adjusted models (p’s ≤ 0.008). The current prospective data from three independent cohorts suggest that peri-traumatic nausea is a prospective predictor of PTSD symptom development. Further studies are needed to determine the mechanistic role of nausea as an intermediate phenotype of PTSD risk.

Introduction:The tumor suppressor p53 ( TP53) maintains genomic integrity, and nearly 50% of cancers are characterized by a loss or mutation in the TP53gene. Murine double minute 2 (MDM2) negatively regulates p53 expression and promotes oncogenesis in TP53wild-type ( TP53WT) tumors. Navtemadlin (nvtm) is a potent, selective, orally available MDM2 inhibitor that overcomes MDM2 dysregulation by restoring p53 activity and inducing apoptosis in TP53WTtumors.

Background: