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Abstract Context Endoscopic ultrasound-guided radiofrequency ablation (EUS-RFA) is rapidly emerging as feasible therapy for patients with pancreatic neuroendocrine tumors (pNETs) in selected cases, as a result of its favorable safety profile. Objective To assess the feasibility, safety, and efficacy of EUS-RFA in a cohort of patients with functional and nonfunctional pNETs (NF-pNETs). Design Data on pNET patients treated with EUS-RFA between March 2017 and October 2018 at two tertiary centers was retrospectively analyzed. Results The cohort included 18 adults (eight women, 10 men), aged 60.4 ± 14.4 years (mean ± SD), seven insulinoma patients, and 11 patients with NF-pNETs. Twenty-seven lesions with a mean diameter of 14.3 ± 7.3 mm (range 4.5 to 30) were treated. Technical success defined as typical postablative changes on a surveillance imaging was achieved in 26 out of 27 lesions. Clinical response with normalization of glucose levels was observed in all (seven of seven) insulinoma cases within 24 hours of treatment. Overall, there were no major complications 48 hours postprocedure. No clinically significant recurrences were observed during mean follow-up of 8.7 ± 4.6 months (range 2 to 21 months). Conclusions EUS-guided RFA of pNETs is a minimally invasive, safe, and technically feasible procedure for selected patients. The initial experience with endoscopic ultrasound-guided radiofrequency ablation for functional and nonfunctional pancreatic neuroendocrine tumors was found to be a safe and feasible therapeutic modality in a selected cohort of patients with small tumors.

Objective. The purpose of the study was to compare suicidal ideation among medical and pharmacy students and characterize related symptoms. Methods. The authors conducted a cross-sectional, retrospective study to compare suicidal ideation among medical and pharmacy students at a single public university during 2009 to 2020. Respondents’ voluntary and anonymous responses to the Interactive Screening Program (ISP) Stress and Depression Questionnaire are reported. Results. The authors analyzed responses from 619 medical and 214 pharmacy students collected over 11 academic years. There was no significant difference between medical and pharmacy students who endorsed suicidal ideation (13.5% vs 17.3%, respectively). The Patient Health Questionnaire-9 (PHQ-9) scores were significantly different between medical and pharmacy students, with more pharmacy students reporting moderate to severe depression (24.3% for medical vs 35.1% for pharmacy). Compared to medical students, more pharmacy students also endorsed anhedonia, a reduced capacity for pleasure (13.4% vs 24.3%, respectively), sleep problems (29.6% vs 42.6%, respectively), and fatigue (46% vs 64.4%, respectively). Pharmacy students also reported more intense affective states such as “feeling your life is too stressful” and “feeling intensely anxious or having anxiety attacks.” Relationships and physical/mental health/substance abuse were common themes that emerged from the qualitative data. Conclusion. While there was no significant difference in suicidal ideation between pharmacy and medical students, the prevalence is alarming compared to the general population. More pharmacy students endorsed symptoms of depression and intense affective states that could impair functioning. Future studies may focus on mitigation strategies for suicidal ideation among health professions students.

Objective. The purpose of the study was to compare suicidal ideation among medical and pharmacy students and characterize related symptoms. Methods. The authors conducted a cross-sectional, retrospective study to compare suicidal ideation among medical and pharmacy students at a single public university during 2009 to 2020. Respondents' voluntary and anonymous responses to the Interactive Screening Program (ISP) Stress and Depression Questionnaire are reported. Results. The authors analyzed responses from 619 medical and 214 pharmacy students collected over 11 academic years. There was no significant difference between medical and pharmacy students who endorsed suicidal ideation (13.5% vs 17.3%, respectively). The Patient Health Questionnaire-9 (PHQ-9) scores were significantly different between medical and pharmacy students, with more pharmacy students reporting moderate to severe depression (24.3% for medical vs 35.1% for pharmacy). Compared to medical students, more pharmacy students also endorsed anhedonia, a reduced capacity for pleasure (13.4% vs 24.3%, respectively), sleep problems (29.6% vs 42.6%, respectively), and fatigue (46% vs 64.4%, respectively). Pharmacy students also reported more intense affective states such as \"feeling your life is too stressful\" and \"feeling intensely anxious or having anxiety attacks.\" Relationships and physical/mental health/substance abuse were common themes that emerged from the qualitative data. Conclusion. While there was no significant difference in suicidal ideation between pharmacy and medical students, the prevalence is alarming compared to the general population. More pharmacy students endorsed symptoms of depression and intense affective states that could impair functioning. Future studies may focus on mitigation strategies for suicidal ideation among health professions students. Keywords: suicidal ideation, pharmacy, medical, students, depression

Major depressive disorder (MDD) contributes to suicide risk. Treating MDD effectively is considered a key suicide prevention intervention. Yet many patients with MDD do not respond to their initial medication and require a 'next-step'. The relationship between next-step treatments and suicidal thoughts and behaviors is uncharted. The VA Augmentation and Switching Treatments for Depression trial randomized 1522 participants to one of three next-step treatments: Switching to Bupropion, combining with Bupropion, and augmenting with Aripiprazole. In this secondary analysis, features associated with lifetime suicidal ideation (SI) and attempts (SA) at baseline and current SI during treatment were explored. Compared to those with SI only, those with lifetime SI + SA were more likely to be female, divorced, or separated, unemployed; and to have experienced more childhood adversity. They had a more severe depressive episode and were more likely to respond to 'next-step' treatment. The prevalence of SI decreased from 46.5% (694/1492) at baseline to 21.1% (315/1492) at end-of-treatment. SI during treatment was associated with baseline SI; low positive mental health, more anxiety, greater severity and longer duration of current MDD episode; being male and White; and treatment with S-BUP or C-BUP as compared to A-ARI. SI declines for most patients during next-step medication treatments. But about 1 in 5 experienced emergent or worsening SI during treatment, so vigilance for suicide risk through the entire 12-week acute treatment period is necessary. Treatment selection may affect the risk of SI.

PurposeThe decreased life expectancy of MEN-1 patients is mainly related to pancreatic neuroendocrine tumors (pNETs). At best, limited data is available on the natural history of MEN-1-associated pNETs, as these tumors are rare and have a wide range of biologic behavior. Our study aims to explore the clinical course of patients with MEN-1-associated pNETs and the long-term outcomes.MethodsThis longitudinal study was conducted on the MEN-1 cohort treated at our referral center over a 22-year period (1996–2018). Relevant clinical data were retrospectively analysed.ResultsAmong the 33 MEN-1 patients included in our study, pNETs were identified in 21 subjects with a penetrance of 48% by the age of 50. Non-functioning and functioning pNETs were diagnosed in sixteen (76%) and five (24%) patients, respectively. Two-thirds of the patients had multifocal tumors. The median number of pancreatic macroscopic lesions per individual was 4.0 ± 3.9 (range 1–8) with a mean size of 1.3 ± 2.1 cm (range 0.5–10). The metastatic rate according to the dominant pNET lesion reached 100%, 62% and 6% for tumors sized > 4 cm, 2.1–4 cm, and 1–2 cm, respectively. Over the study period, one or more therapeutic interventions for pNETs were required in 20 out of the 21 patients. pNET-related metastatic complication was the main cause of death within this MEN-1 cohort. The overall survival rate for the pNETs patients was 86% during a mean follow-up period of 8.0 ± 4.6 years.ConclusionsIn our MEN-1 cohort, non-functioning pNETs were the most frequent type of pancreaticoduodenal tumor, and the tumor size correlated with the risks of metastasis and death. Increased awareness, early diagnosis, and a multidisciplinary approach may improve the associated morbidity and mortality in these patients.

Background In this secondary analysis of the VA Augmentation and Switching Treatments for Improving Depression Outcomes (VAST‐D) study we used antidepressant response trajectories to assess the association of treatment and multiple clinical/demographic factors with the probability of response. Methods Using data from VAST‐D, a multi‐site, randomized, single‐blind trial with parallel‐assignment to one of three treatment interventions in 1522 Veterans whose major depressive disorder was unresponsive to at least one antidepressant trial, we evaluated response patterns using group‐based trajectory modeling (GBTM). A weighted multinomial logistic regression analysis with backward elimination and additional exploratory analyses were performed to evaluate the association of multiple clinical/demographic factors with the probability of inclusion into specific trajectories. Additional exploratory analyses were used to identify factors associated with trajectory group membership that could have been missed in the primary analysis. Results GBTM showed the best fit for depression symptom change was comprised of six trajectories, with some trajectories demonstrating minimal improvement and others showing a high probability of remission. High baseline depression and anxiety severity scores decreased, and early improvement increased, the likelihood of inclusion into the most responsive trajectory in both the GBTM and exploratory analyses. Conclusion While multiple factors influence responsiveness, the probability of inclusion into a specific depression symptom trajectory is most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement. Highlights In a large study of U.S. Veterans with moderate to severe depression group‐based trajectory modeling demonstrated six response trajectories as the best fit for depression symptom change over time. A weighted multinomial logistic regression analysis with backward elimination identified multiple factors influencing antidepressant responsiveness, but response trajectories are most strongly influenced by three factors: baseline depression, baseline anxiety, and the presence of early improvement.

Objective Being a healthcare professional can be a uniquely rewarding calling. However, the demands of training and practice can lead to chronic distress and serious psychological, interpersonal, and personal health burdens. Although higher burnout, depression, and suicide rates have been reported in healthcare professionals, only a minority receive treatment. Concerns regarding confidentiality, stigma, potential career implications, and cost and time constraints are cited as key barriers. Web-based and mobile applications have been shown to mitigate stress, burnout, depression, and suicidal ideation among several populations and may circumvent these barriers. Here, we reviewed published data on such resources and selected a small sample that readily can be used by healthcare providers. Methods We searched PubMed for articles evaluating stress, burnout, depression, and suicide prevention or intervention for healthcare students or providers and identified five categories of programs with significant effectiveness: Cognitive Behavioral Therapy (online), meditation, mindfulness, breathing, and relaxation techniques. Using these categories, we searched for Web-based (through Google and beacon.anu.edu.au —a wellness resource website) and mobile applications (Apple and mobile. va.gov/appstore ) for stress, burnout, depression, and suicide prevention and identified 36 resources to further evaluate based on relevance, applicability to healthcare providers (confidentiality, convenience, and cost), and the strength of findings supporting their effectiveness. Results We selected seven resources under five general categories designed to foster wellness and reduce burnout, depression, and suicide risk among healthcare workers: breathing (Breath2Relax), meditation (Headspace, guided meditation audios), Web-based Cognitive Behavioral Therapy (MoodGYM, Stress Gym), and suicide prevention apps (Stay Alive, Virtual Hope Box). Conclusions This list serves as a starting point to enhance coping with stressors as a healthcare student or professional in order to help mitigate burnout, depression, and suicidality. The next steps include adapting digital health strategies to specifically fit the needs of healthcare providers, with the ultimate goal of facilitating in-person care when warranted.

This analysis of the VAST-D data aimed to explore the utility of using early improvement at 1, 2, 4, and 6 weeks of antidepressant medication treatment (i.e., a drop from baseline depression severity as measured by the QIDS-C) to predict remission, response, or greater than minimal improvement by week 12. Objective:In this secondary analysis of data from the Veterans Affairs Augmentation and Switching Treatments for Improving Depression Outcomes (VAST-D) study, the authors sought to determine the effectiveness of early improvement (or lack thereof) for predicting remission from depression with antidepressant therapy.Methods:This study used data from the VAST-D study, a multisite, randomized, single-blind trial with parallel assignment to one of three medication interventions for 1,522 veterans whose major depressive disorder was unresponsive to at least one course of antidepressant treatment meeting minimal standards for dosage and duration. The authors calculated the positive predictive value (PPV) and negative predictive value (NPV) of early improvement on remission, response, or greater than minimal improvement from depression for various degrees of improvement (10%–50%) on the Quick Inventory of Depressive Symptomatology–Clinician Rated (QIDS-C) at 1, 2, 4, and 6 weeks.Results:The end of week 2 of treatment was identified as the best time to evaluate early improvement. The presence of a ≥20% drop from the baseline QIDS-C score by the end of week 2 resulted in a PPV for remission of 38% and an NPV of 93% by week 12. Extending the observational window to week 6 minimally improved NPV (97%). This association did not differ across treatment groups.Conclusions:A lack of early improvement at the end of week 2 of antidepressant therapy can be used to inform clinical decisions on the likelihood of nonremission of depression during the subsequent 10 weeks, even when dosage optimization is incomplete.

The Major Histocompatibility Complex (MHC) is a large chromosomal region of immune system genes that function in self/non-self recognition. Research shows that MHC is detectable by smell, and that humans and nonhumans may prefer mates that are MHC-dissimilar to themselves. One explanation of this effect is that the output of MHC dissortative mating, MHC heterozygosity in offspring, provides a fitness advantage via increased pathogen resistance. Researchers have also suggested that the preference for dissimilarity at the MHC genes may be a proximate mechanism of incest aversion, but to date there has been no research on scent-mediated MHC mate preferences among human relatives. Further, it is unclear if MHC-dependent mate preferences in humans are self-referent or family-referent. In addition, while there is evidence of human olfactory kin recognition, there are presently no published studies that implicate MHC as the mediator of this phenomenon. For the present study, I used the t-shirt study method to investigate MHC-dependent mate preferences in humans, as well as MHC-dependent olfactory kin recognition. The participants in this study were college-aged students and their opposite-sex siblings, recruited at the University of New Mexico and the University of Hawaii. All participants slept in a previously unworn t-shirt for two nights without introducing confounding odors to the shirts. Each participant smelled all the shirts, including their siblings, and rated them on several traits, including sex appeal. All participants also provided saliva samples, which were genotyped for MHC at three loci: HLA-A, HLA-B, and HLA-DRβ. In statistical analyses, the MHC similarity between shirt-smellers and shirt-wearers was used to predict scent ratings of the t-shirts' sexiness and familial resemblance. Participants' own MHC and their siblings' MHC were compared as predictors of the outcome variables to determine the referent used in determining MHC-dependent mate preferences and MHC-dependent kin recognition. This study provides evidence that MHC-dependent dissortative mate preferences are self-referent, while MHC-mediated kin recognition may be family referent. The implications of these findings on the evolution of MHC-dependent mate preferences and inbreeding avoidance are discussed.

Suicide bereavement is common, can be life-altering, and has both societal and intergenerational implications and effects. Despite the fact that every bereaved person’s grief is unique, grieving the loss of a loved one to suicide adds layers of complexity to what can be an already profoundly painful experience. Suicide bereavement often is characterized by prominent symptoms of overwhelming guilt, confusion, shame, rejection, and anger. The experience of suicide bereavement is also often steeped in the context of stigma. Many aspects of suicide bereavement add to its complexity and set it apart from bereavement in general. This chapter will focus on these factors, delineating the unique context, qualitative features, sequelae, and treatment considerations for suicide bereavement.