Workplace bullying and risk of suicide and suicide attempts: A register-based prospective cohort study of 98 330 participants in Denmark

ObjectivesThe aim of this study was to analyze whether individuals reporting exposure to workplace bullying had a higher risk of suicidal behavior, including both suicide attempt and death by suicide, than those not reporting such exposure.MethodsUsing a prospective cohort study design, we linked data from nine Danish questionnaire-based surveys (2004–2014) to national registers up to 31 December 2016. Exposure to workplace bullying was measured by a single item. Suicide attempts were identified in hospital registers and death by suicide in the Cause of Death Register. Among participants with no previous suicide attempts, we estimated hazard ratios (HR) and 95% confidence intervals (CI), adjusting for sex, age, marital status, socioeconomic status, and history of psychiatric morbidity.ResultsThe sample consisted of 98 330 participants (713 798 person-years), 63.6% were women, and the mean age was 44.5 years. Of these participants, 10 259 (10.4%) reported workplace bullying. During a mean follow-up of 7.3 years, we observed 184 cases of suicidal behavior, including 145 suicide attempts, 35 deaths by suicide and 4 cases that died by suicide after surviving a suicide attempt. The fully-adjusted HR for the association between workplace bullying and suicidal behavior was 1.65 (95% CI 1.06–2.58). The HR for suicide attempts and death by suicide were 1.65 (1.09–2.50) and 2.08 (0.82–5.27), respectively. Analyses stratified by sex showed a statistically significant association between workplace bullying and suicidal behavior among men but not women.ConclusionsThe results suggest that exposure to workplace bullying is associated with an elevated risk of suicidal behavior among men.     

Low radiation dose ECG-gated chest CT angiography on a 256-slice multidetector CT scanner

Computed tomography angiography (CTA) of the thorax other than cardiac CTA, is utilized for a multitude of conditions and ranges in application from a diagnostic test, to presurgical planning and postsurgical follow-up. Helical CTA without electrocardiogram (ECG) gating has been routinely utilized for the evaluation of thoracic vasculature. However, its applicability can be limited in the evaluation of the thoracic aorta and pulmonary vasculature because of the artifacts resulting from cardiac motion. Traditional retrospective ECG-gated helical scans address this issue but at the price of a high radiation dose to the patient. In this paper we review CTA dose reduction strategies for non-coronary indications, examine field of view requirements, and discuss breath hold challenges for ECG-gated acquisitions. In addition, we present clinical examples performed using low-dose prospective gating technique for evaluation of the aorta acquired on a 256-slice multidetector computed tomography system.     

Occurrence of apoptosis, secondary necrosis, and cytolysis in eosinophilic nasal polyps

The paradigm states that inflammatory cells disappear from airway tissues through apoptosis and phagocytosis. However, cells may also be cleared through primary cytolysis, necrosis secondary to apoptosis, or transepithelial migration. This study examines the occurrence of apoptosis, secondary necrosis, and cytolysis of eosinophils in human nasal polyps in vivo and blood eosinophils in vitro. Eosinophils abounded in subepithelium and in paracellular epithelial pathways. Macrophages commonly occurred but without engulfed eosinophils. Scattered cells, including epithelial cells, were stained by antibody to the caspase cleavage product of poly(ADP-ribose) polymerase. Few cells were apoptotic (stained by terminal deoxy RNase nick end labeling). Of more than 3,000 examined tissue eosinophils, 110 were caspase cleavage positive, but only one was apoptotic. Transmission electron microscopy analysis of more than 500 eosinophils revealed viable and cytolytic eosinophils but not apoptosis, secondary necrosis, or engulfment of eosinophils. Plasma cells but neither epithelial cells nor eosinophils exhibited apoptotic ultrastructural morphology. Eosinophils in vitro exhibited different stages of apoptosis, ending with secondary necrosis distinct from in vivo eosinophil cytolysis. Our results show that the clearance of eosinophils from nasal polyps largely occurs through nonapoptosis pathways, including cytolysis and paraepithelial migration, and they challenge the belief that apoptosis is important for clearance of eosinophils from respiratory tissues.     

The changing face of Crohn’s disease: a population-based study of the natural history of Crohn’s disease in Örebro,Sweden 1963–2005

Objective: Changes in medical therapy and surgery might have influenced the natural history of Crohn’s disease (CD). Our aim was to explore the short-term outcome of CD and to specifically assess trends in disease phenotype, medications and surgery in the first five years from diagnosis. Material and methods: A population-based cohort comprising 472 CD patients diagnosed within the primary catchment area of Örebro University Hospital 1963–2005 were identified retrospectively and described. Data on medication, surgery, progression in disease location and behavior, were extracted from the medical records. Patients were divided into three cohorts based on year of diagnosis. Results: The proportion of patients with complicated disease behavior five years after diagnosis decreased from 54.4% (95%CI, 43.9–65.6) to 33.3% (27.4–40.0) in patients diagnosed 1963–1975 and 1991–2005, respectively (p?=?0.002), whereas the proportion of patients progressing to complicated disease behavior was stable among those with non-stricturing, non-penetrating disease at diagnosis (p?=?0.435). The proportion of patients undergoing surgery decreased from 65.8% (55.4–76.0) to 34.6% (28.6–41.5) in patients diagnosed 1963–1975 and 1991–2005, respectively (p?p?=?0.001). Conclusions: We observed a striking decrease in complicated disease behavior and surgery five years after CD diagnosis, the latter largely due to a decrease in early surgery. Our findings suggest that the introduction of new treatments alone does not explain the reduction in surgery rates, the increasing proportion of patients with inflammatory disease at diagnosis also play an important role.     

Hope and Disappointment: Covalent Inhibitors to Overcome Drug Resistance in Non-Small Cell Lung Cancer

In the last five years, the detailedunderstanding of how to overcomeT790M drug resistance in non-small cell lung cancer (NSCLC) has culminatedin the development of a third-generation of covalent EGFR inhibitorswith excellent clinical outcomes. However, the emergence of a newlydiscovered acquired drug resistance challenges the concept of smallmolecule targeted cancer therapy in NSCLC.     

Design and Rationale of the RE‐DUAL PCI Trial: A Prospective,Randomized, Phase 3b Study Comparing the Safety and Efficacy of Dual Antithrombotic Therapy With Dabigatran Etexilate Versus Warfarin Triple Therapy in Patients With Nonvalvular Atrial Fibrillation Who Have Undergone Percutaneous Coronary Intervention With Stenting

Antithrombotic management of patients with atrial fibrillation (AF) undergoing coronary stenting is complicated by the need for anticoagulant therapy for stroke prevention and dual antiplatelet therapy for prevention of stent thrombosis and coronary events. Triple antithrombotic therapy, typically comprising warfarin, aspirin, and clopidogrel, is associated with a high risk of bleeding. A modest‐sized trial of oral anticoagulation with warfarin and clopidogrel without aspirin showed improvements in both bleeding and thrombotic events compared with triple therapy, but large trials are lacking. The RE‐DUAL PCI trial (NCT 02164864) is a phase 3b, a strategy of prospective, randomized, open‐label, blinded‐endpoint trial. The main objective is to evaluate dual antithrombotic therapy with dabigatran etexilate (110 or 150 mg twice daily) and a P2Y12 inhibitor (either clopidogrel or ticagrelor) compared with triple antithrombotic therapy with warfarin, a P2Y12 inhibitor (either clopidogrel or ticagrelor, and low‐dose aspirin (for 1 or 3 months, depending on stent type) in nonvalvular AF patients who have undergone percutaneous coronary intervention with stenting. The primary endpoint is time to first International Society of Thrombosis and Hemostasis major bleeding event or clinically relevant nonmajor bleeding event. Secondary endpoints are the composite of all cause death or thrombotic events (myocardial infarction, or stroke/systemic embolism) and unplanned revascularization; death or thrombotic events; individual outcome events; death, myocardial infarction, or stroke; and unplanned revascularization. A hierarchical procedure for multiple testing will be used. The plan is to randomize ～ 2500 patients at approximately 550 centers worldwide to try to identify new treatment strategies for this patient population.