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Computed tomography (CT) is a commonly used imaging modality in Emergency Departments (EDs), however its use is questionable in many low yield settings. The Emergency CT Head score (ECHS) is a recently published clinical tool that assists in stratifying the need for CT brain (CTB) for patients presenting without a history of trauma. We sought to validate this tool in an Australian ED setting.We prospectively evaluated 412 patients who received CTB without a history of trauma at a large Australian ED. We assessed them for the 4 main ECHS data points: focal neurological deficit on physical examination, new acute onset headache, transient neurological deficit, and a combination of new onset seizures with an altered conscious state. We examined their association with acute and chronic CTB findings. We then applied the ECHS to our data, calculating its sensitivity and its appropriateness at this single site via the calculation of a receiver operating curve (ROC).10.2% of all CTB performed were positive for an acute or chronic abnormality. Only sex (male) and focal motor deficit were independent predictors of positive CTB at univariate analysis. The ECHS did not perform as anticipated in our population, with a ROC area under the curve of 0.498. An ECHS score of0, which has been proposed as the threshold to not require imaging, had sensitivity of only 83.3% in our population.Further research and validation is required in order to safely implement the ECHS clinical score in the Australian ED setting.

Background A large number of CT brain (CTB) scans are ordered in the ED for older patients with a confirmed or possible head strike but no ongoing symptoms of a head injury. This study aimed to evaluate the effect of the Canadian CT head rule supplemented by the original published minimum inclusion criteria to assist clinician assessment of the need for CTB following minimal trauma fall in patients presenting from residential aged care facilities to a major metropolitan emergency department (ED). Methods This study was conducted as a pre- and post-intervention retrospective audit. The intervention involved implementation of a decision support tool to help clinicians assess patients presenting to the ED following a fall. The tool integrated the Canadian CT Head Rule (CCHR) in conjunction with a simplified set of inclusion criteria to help clinicians define a minimum threshold for a “minor head injury”. Outcome data pertaining to CT brain ordering practices and results were compared over symmetrical 3-month time periods pre- and post-intervention in 2 consecutive years. Results The study included 233 patients in the pre-intervention arm and 241 in the post-intervention arm. Baseline demographics and clinical characteristics were similar in both groups. There was a 20% reduction in the total number of CTB scans ordered following tool implementation, with 134 (57.0%) scans in the pre-intervention group and 90 (37.3%) in the post-intervention group (p p = 0.52). No variation was observed in medical management between groups, and no patients in either group underwent neurosurgical intervention. Conclusions Use of the CCHR supplemented by the original published minimum inclusion criteria appeared to safely reduce the number of CTB scans performed in residential aged care facility residents presenting to an ED after a fall, with no associated adverse outcomes. A larger study across multiple centres is required to determine widespread efficacy and safety of this tool.

ObjectivesTo determine the negative predictive value (NPV) of the FebriDx point-of-care host response device in patients presenting with symptoms suggestive of COVID-19 infection in a mostly immunised Australian emergency department (ED) population during the late 2021 phase of the COVID-19 pandemic.DesignObservational diagnostic accuracy study comparing FebriDx point-of-care test to SARS-CoV-2 PCR.SettingAn ED in Melbourne, Australia, with 63 000 annual presentations in 2021.ParticipantsPatients aged 16 and over who met the Victorian Department of Health case definition for suspected COVID-19 infection PCR testing. Patients meeting any of the following criteria were excluded: 14 days prior to testing; current immunosuppressive or interferon therapy; live immunisation within the last 30 days; fever lasting>7 days; antibiotic or antiviral use in the preceding 14 days; experience of major trauma, major surgical intervention or severe burns within the last 30 days.Primary and secondary outcome measuresCOVID-19 PCR results (detected, not detected) and FebriDx results (bacterial positive, viral negative, viral positive).Results94 participants were enrolled (female: 46; male: 48), 34% of participants (tested positive for COVID-19 according to PCR results, with a background incidence among all adult ED attenders of 2.5%. The sensitivity of FebriDx for detection of COVID-19 was 56% (95% CI 40% to 100%) and specificity was 92% (95% CI 84% to 100%). For the population tested, this resulted in an NPV of 80% (95% CI 71% to 100%) and a positive predictive value of 78% (95% CI 60% to 100%).ConclusionsIn the context of a population with low COVID-19 infection rates, an evolved variant of COVID-19 and a very high community COVID-19 vaccination rate, FebriDx demonstrated reduced sensitivity and NPV relative to results from earlier international tests. These contextual factors should be considered during any attempt to generalise the current results.Trial registration numberACTRN12620001029987 (Australian Clinical Trials).

Objective The aim of the present study was to describe the characteristics and outcomes of patients presenting to Australian EDs with suspected and confirmed COVID‐19 during 2020, and to determine the predictors of in‐hospital death for SARS‐CoV‐2 positive patients. Methods This analysis from the COVED Project presents data from 12 sites across four Australian states for the period from 1 April to 30 November 2020. All adult patients who met local criteria for suspected COVID‐19 and underwent testing for SARS‐CoV‐2 in the ED were eligible for inclusion. Study outcomes were mechanical ventilation and in‐hospital mortality. Results Among 24 405 eligible ED presentations over the whole study period, 423 tested positive for SARS‐CoV‐2. During the ‘second wave’ from 1 July to 30 September 2020, 26 (6%) of 406 SARS‐CoV‐2 patients received invasive mechanical ventilation, compared to 175 (2%) of the 9024 SARS‐CoV‐2 negative patients (odds ratio [OR] 3.5; 95% confidence interval [CI] 2.3–5.2, P, The aim of COVED‐5 was to describe the characteristics and outcomes of patients presenting to Australian emergency departments (EDs) with suspected and confirmed COVID‐19 during 2020, and to determine the predictors of in‐hospital death for SARS‐CoV‐2 positive patients. ED patients who tested positive for SARS‐CoV‐2 had higher odds of mechanical ventilation and death in hospital. The strongest predictors of death were age, a higher triage category, obesity and receiving immunosuppressive treatment.

Conventional therapies for patients with T-cell prolymphocytic leukemia (T-PLL), such as cytotoxic chemotherapy and alemtuzumab, have limited efficacy and considerable toxicity. Several novel agent classes have demonstrated preclinical activity in T-PLL, including inhibitors of the JAK/STAT and T-cell receptor pathways, as well as histone deacetylase (HDAC) inhibitors. Recently, the BCL-2 inhibitor venetoclax also showed some clinical activity in T-PLL. We sought to characterize functional apoptotic dependencies in T-PLL to identify a novel combination therapy in this disease. Twenty-four samples from patients with primary T-PLL were studied by using BH3 profiling, a functional assay to assess the propensity of a cell to undergo apoptosis (priming) and the relative dependence of a cell on different antiapoptotic proteins. Primary T-PLL cells had a relatively low level of priming for apoptosis and predominantly depended on BCL-2 and MCL-1 proteins for survival. Selective pharmacologic inhibition of BCL-2 or MCL-1 induced cell death in primary T-PLL cells. Targeting the JAK/STAT pathway with the JAK1/2 inhibitor ruxolitinib or HDAC with belinostat both independently increased dependence on BCL-2 but not MCL-1, thereby sensitizing T-PLL cells to venetoclax. Based on these results, we treated 2 patients with refractory T-PLL with a combination of venetoclax and ruxolitinib. We observed a deep response in JAK3-mutated T-PLL and a stabilization of the nonmutated disease. Our functional, precision-medicine–based approach identified inhibitors of HDAC and the JAK/STAT pathway as promising combination partners for venetoclax, warranting a clinical exploration of such combinations in T-PLL.

Introduction: Despite recent advances in the therapy of diffuse large B cell lymphoma (DLBCL), many patients are still not cured, and therefore new therapeutic combinations are needed. The anti-apoptotic B cell lymphoma 2 (BCL-2) gene is commonly dysregulated in DLBCL due to various mechanisms such as chromosomal translocation t(14;18)(q32.3;q21.3), copy number alterations and gene amplifications; however, targeting BCL-2 with a selective inhibitor, venetoclax, led to response in only a minority of patients. Thus, we sought to identify a novel combination partner for venetoclax to improve response to therapy. Previously with dynamic BH3 profiling, we found that DNA hypomethylating agents (HMA) could increase BCL2 dependence in DLBCL cells. Here, we investigate the activity of the HMA decitabine with venetoclax in DLBCL. Methods: We utilized BH3 profiling, a functional assay to assess the mitochondrial priming of cells for apoptosis and the dependence of cells on various anti-apoptotic BCL-2 family proteins. Other standard techniques included Western blot, cell cycle (BrdU/7-AAD), CellTiter-Glo, and Seahorse XF cell mito stress test. The DLBCL cell lines (TMD8, HBL1, OCI-Ly3, OCI-Ly1, Karpas 422, SUDHL4, Toledo, OCI-Ly7) and double hit lymphoma (DHL) patient-derived xenograft cell lines were used to investigate the in vitro anti-cancer activity of decitabine and venetoclax. Results: Through BH3 profiling, we found heterogenous dependence of DLBCL, consistent with the variable expression of multiple anti-apoptotic proteins in DLBCL assessed by Western blot. DLBCL cells were less sensitive to single BH3 mimetic treatment (venetoclax, S63 (MCL-1i) and A133 (BCL-xLi)). Using dynamic BH3 profiling (which assesses the change in priming induced by ex vivo drug treatment), we found that decitabine primes DLBCL cells for apoptosis and increases BCL-2 dependence. Consequently, decitabine increases the sensitivity of DLBCL cells to venetoclax, as the combination of decitabine and venetoclax synergistically induces apoptosis and suppresses cell proliferation. Decitabine has previously been shown to increase TGF-β signaling in DLBCL by restoring the expression of a downstream target, SMAD1. Interestingly, we found that inhibition of TGF-β signaling only partially antagonizes the anti-cancer activity of decitabine, implicating other anti-cancer mechanisms of decitabine. Indeed, we found that decitabine also induces DNA damage and leads to cell cycle arrest in DLBCL cells. Furthermore, decitabine promotes activation of the key apoptotic effector proteins, BAK and BAX. Additionally, we found that this combination also suppresses oxidative phosphorylation, thus restricting the energy supply for DLBCL cells. Conclusions: The HMA decitabine sensitizes DLBCL cells to venetoclax in vitro through increasing apoptotic priming and BCL-2 dependence. This combination is worthy of further study in in vivo model systems. Citation Format: Matthew S. Davids, Fen Zhu, Stephen J. Chong, Jennifer Crombie, Liam Hackett, May C. Collins. Decitabine sensitizes diffuse large B cell lymphoma cells to venetoclax [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5377.

Introduction: BCL2 family protein dysfunction is an important mediator of chemoresistance in lymphoid malignancies. Venetoclax (VEN), a BH3 mimetic that selectively targets the anti-apoptotic protein BCL2, is FDA approved for treatment of chronic lymphocytic leukemia (CLL), with clinical trials underway for other lymphoid malignancies. Despite the clinical efficacy of VEN monotherapy, complete remission and progression free rates are still relatively low, thereby indicating the existence of inherent or acquired mechanisms of resistance. Preclinically, increases in anti-apoptotic BCL2 and MCL1 phosphorylation (BCL2-P/MCL1-P) and MCL1 protein level have been implicated in chemoresistance. We therefore question if phosphorylation of these proteins may drive VEN resistance and if removing this modification may re-sensitize resistant cells to VEN induced cell death. Methodology: BH3 profiling (a functional assay that assesses mitochondrial apoptotic priming and anti-apoptotic protein dependence), western blot and cell death assays were performed. Result: We report that VEN acquired resistant DLBCL cell line (OCI-Ly1R) has increased BCL2-P, MCL1-P and MCL1 protein levels as compared to sensitive parental cell line (OCI-Ly1S), while inherently resistant DHL cell line (Su-DHL4) possesses higher MCL1-P and MCL1 protein levels as compared to OCI-Ly1S. We further show that this increase in phosphorylation status contributes to the induction of VEN resistance. Using BH3 profiling, we demonstrate that anti-apoptotic protein phosphorylation-driven VEN resistance involves a change in sensitivity to pro-apoptotic proteins, with an increase in sensitivity to MCL1 inhibition and reciprocal decrease in sensitivity to BCL2 inhibition. We further show that BCL2 and MCL1 dephosphorylation by PP2A activating drugs (PADs) re-sensitizes resistant cells to VEN treatment. Mechanistically, PADs such as the fingolimod (FTY720) not only dephosphorylate BCL2-P and MCL1-P, but also dissociate BAX from BCL2 and destabilize MCL1 protein. These changes lead to the rewiring of cellular sensitivity to BCL2 inhibition, thereby re-sensitizing both VEN acquired and inherent resistant cells to VEN induced cell death. Importantly, the PP2A activating effects of FTY720 were recapitulated in primary cells from the peripheral blood of 16 CLL patients, where FTY720 treatment also reduced BCL2-P, MCL1-P and MCL1 protein levels and dissociated BAX from BCL2. This led to an increased sensitivity to BCL2 inhibition and enhanced cell death upon combined treatment with FTY720 and VEN. Conclusion: Our work defines a new targetable mechanism of VEN resistance in lymphoid malignancies due to the phosphorylation of anti-apoptotic BCL2 family proteins. PADs re-sensitize resistant malignant cells to VEN treatment via dephosphorylation of anti-apoptotic proteins, suggesting a promising combination approach to explore further. Citation Format: Stephen J. Chong, Fen Zhu, Jolin X. Lai, Liam Hackett, Mary C. Collins, Shazib Pervaiz, Jean-Philippe Coppe, Matthew S. Davids. Targeting BCL2 family protein phosphorylation in venetoclax resistant lymphoid malignancies [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3959.

Introduction: Although survival dependence on Bcl2 is a well-known aspect of the pathophysiology of chronic lymphocytic leukemia (CLL), the mechanisms of Bcl-2 dysregulation are incompletely understood. Recurrent translocations involving BCL2 and immunoglobulin genes, including t(14;18)(q32;q21) and variants such as t(2;18) or t(18;22), are classically observed in follicular lymphoma or germinal center diffuse large B-cell lymphoma (GC DLBCL), but are uncommon ( Methods: Clinically annotated primary samples from BCL2-R CLL patients identified by karyotype were obtained from the French Innovative Leukemia Organization network and Dana-Farber Cancer Institute. Primary samples from CLL without BCL2 rearrangement were used as a control (ctrl CLL). Next generation sequencing (NGS) was performed using a custom-designed panel of 29 genes, including among others: BIRC3, NOTCH1, FBXW7, MLL2, RAS pathway, SF3B1 and TP53. The mean coverage obtained was 2000X (limit of detection (LOD): 1%). Digital droplet PCR (ddPCR) was used to quantify NOTCH1 c.7544_7545delCT (LOD: 0.025%). Protein expression (Bcl2, Mcl1, Bim) was assessed by Western blot. Baseline BH3 profiling was performed as per Ryan et al., Bio Chem 2016. To mimic the lymph node microenvironment, viability assays were performed in co-culture with the stromal cell line NK.tert. Viability was assessed by AnnexinV/Hoechst staining. Ex vivo drug treatments included: BCL2i (inhibitor): venetoclax; MCL-1i: AZD5991, S63845 and BCLXLi: A133. Statistical analyses were by unpaired and paired t-test with a two-tailed nominal p ≤ 0.05 considered as significant. Results: In our cohort of 110 patients, the median age was 70 years old, and 79% were male. BCL2-R were t(14;18) in 77.2%, t(18;22) in 16.3% and t(2;18) in 6.3% of patients. The translocation involving BCL2 gene was isolated in 23.6% of cases, and was associated with trisomy 12 in 45.4% of patients. The most frequently mutated genes in this cohort were in the NOTCH pathway (NOTCH1 mutation: 43.6 %, mostly subclonal (mean of variant allelic frequency: 6.1%) and FBXW7: 4.5%)) and RAS pathway (KRAS, NRAS, BRAF: 9.1%). BCL2 mutations were observed in 22.8% of the 57 examined cases. No mutation previously described in venetoclax resistant CLL, such as F104L or G101V variant, were observed. Furthermore, MLL2 mutations were observed in 14.5% cases and were significantly associated with complex karyotype (p=0.01) and trisomy 12 (p=0.04). Others mutated genes were: BIRC3 (5.4%), TP53 (3.6%), SF3B1 (1%) and MYD88 L265P(1%). No mutations in EZH2, CREBBP or EP300 were found. In 15 CLL representative samples from each group (BCL2-R and ctrl), Bcl2 protein expression was significantly higher in BCL2-R CLL (ratio Bcl2/actin 0.94 vs 0.74, p=0.009) as was expression of the pro-apoptotic protein Bim (ratio Bim/actin: 2.059 vs 1.524, p=0.007). BH3 profiling demonstrated that BCL2-R CLL and ctrl CLL samples (n=23 in each group) had comparable overall priming (cyto-C release 66.1% vs 63.3%, ns) and Bcl-2 dependence (cyto-C release 75.4% vs 76.3%, ns). Both also had low dependence on Bcl-xL (cyto-C release 8.2% vs 8.8%, ns). In contrast, Mcl-1 dependence was found to be significantly lower in BCL2-R CLL (cyto-C release 15.6% vs 37.4%, p Conclusion: The genomic landscape of BCL2-R CLL is characterized by a high frequency of trisomy 12, subclonal NOTCH and RAS pathway mutations, as well as BCL2 and MLL2 mutations. Protein expression, BH3 profiling and viability assays data are consistent with nearly exclusive dependence on Bcl-2. Our data suggest that Bcl-2 inhibition should be favored over Mcl-1 inhibition in BCL2-R CLL. Disclosures Herbaux: Roche: Consultancy, Honoraria, Research Funding. Laribi:abbvie: Honoraria, Research Funding; amgen: Research Funding; novartis: Honoraria, Research Funding; takeda: Research Funding. Ysebaert:Roche: Consultancy; Janssen: Consultancy; AbbVie: Consultancy. Morel:Janssen: Honoraria. Guieze:abbvie: Honoraria, Other: advisory board, travel funds; janssen cilag: Honoraria, Other: advisory board, travel funds; roche: Other: travle funds; gilead: Honoraria, Other: travel funds; astrazanecka: Honoraria, Other: advisory board. Brown:Sun: Research Funding; Acerta: Consultancy; Pharmacyclics: Consultancy; Genentech: Consultancy; Morphosys: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other; Invectys: Membership on an entity's Board of Directors or advisory committees, Other: DSMC; Gilead: Consultancy, Research Funding; BeiGene: Consultancy; Catapult: Consultancy; Dynamo Therapeutics: Consultancy; Eli Lilly and Company: Consultancy; Juno/Celgene: Consultancy; Kite: Consultancy; MEI Pharma: Consultancy; Nextcea: Consultancy; Novartis: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy; Rigel Pharmaceuticals: Consultancy; Sunesis: Consultancy; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Loxo: Consultancy, Research Funding; Astra-Zeneca: Consultancy; Janssen: Honoraria; AbbVie: Consultancy.

Introduction Resistance to apoptosis is a hallmark of cancer, and modulation of BCL-2 family proteins is an important mediator of such resistance in hematologic malignancies. Despite the clinical efficacy of the BCL-2 inhibitor venetoclax (VEN), prolonged treatment may lead to resistance, such as the BCL2 G101V mutation (Blombery et al, Blood, 2020); however, over half of VEN resistant cases are not explained by known genetic mechanisms. Phosphorylation of BCL-2 at serine-70 (S70pBCL2) or of MCL-1 at threonine-163 (T163pMCL1) have been shown to increase sequestration of the pro-apoptotic protein BAX (Deng et al, JNCI, 2000) and stabilize the level of anti-apoptotic protein MCL-1 (Wang et al, Mol Cancer, 2014), respectively. We hypothesized that the increase in post-translational modifications of BCL-2 family members, in particular S70pBCL2 and T163pMCL1, are novel mechanisms of functional VEN resistance in lymphoid malignancies. We further hypothesized that the FDA-approved phosphatase activator drug FTY720 (fingolimod) would de-phosphorylate these BCL-2 family members and thereby re-sensitize malignant lymphoid cells to VEN-induced apoptosis. Methods A VEN resistant diffuse large B-cell lymphoma cell line (OCI-Ly1-R) as well as peripheral blood mononuclear cells from 12 previously untreated CLL patients co-cultured with human stromal NK-Tert cells were treated ex vivo with VEN +/- FTY720. A VEN sensitive cell line (OCI-Ly1-S) was treated with VEN +/- a phosphatase inhibitor okadaic acid (OA). Western blot was used to evaluate changes in S70pBCL2 and T163pMCL1 protein levels. BH3 profiling via flow cytometry was performed to determine the survival dependence on anti-apoptotic BCL-2 family members via cytochrome c release in response to specific BH3-only peptides and drugs such as VEN applied directly to mitochondria (Ryan et al, Biol Chem, 2016). Cell viability assays (CellTiter-Glo, Trypan Blue and Annexin/Hoechst) were employed to investigate the effects of FTY720 on OCI-Ly1-R resistance to VEN. The BCL-2-BAX interaction was investigated using co-immunoprecipitation in VEN resistant and sensitive cells following treatment with VEN +/- FTY720. T-test, ANOVA and multiple comparison with a statistical significance set at 2-tailed p ≤ 0.05 were used. Results OCI-Ly1-R cells displayed higher S70pBCL2, T163pMCL1 and MCL-1 expression compared to OCI-Ly1-S cells. Notably, the increase in S70pBCL2 was associated with reduced response of VEN-mediated BCL-2-BAX dissociation, while the increase in T163pMCL1 was accompanied by enhanced MCL-1 protein expression. Using BH3 profiling, we found that the increase in S70pBCL2, T163pMCL1 and MCL-1 expression were functionally associated with a decrease in BCL-2 survival dependence (-79.1%, 1μM VEN, P < 0.0001) and an increase in MCL-1 dependence (+52%, 10μM MS1, P < 0.0001) (Fig. A). The addition of FTY720 reversed these observations in OCI-Ly1-R cells, where we observed a decrease in S70pBCL2, T163pMCL1 and MCL-1 protein expression, BCL-2 and BAX interaction, as well as a "re-wired" functional dependence toward BCL-2 (-21.6% 10μM MS1, +27.9% 1μM VEN, P < 0.0001) (Fig. B). Importantly, pre-treatment with FTY720 re-sensitized OCI-Ly1-R cells to VEN-induced cell death (+56.1%, P = 0.0001) (Fig. C). Conversely, treatment with a phosphatase inhibitor, OA, led to an increase in S70pBCL2, T163pMCL1 and MCL-1 expression as well as reduced late death of OCI-Ly1-S cells (-60%, P = 0.0018). We validated our cell line results in primary CLL cells, and again the combination of FTY720 and VEN similarly reduced S70pBCL2, T163pMCL1 and MCL-1 expression, increased BCL-2 dependence, and enhanced VEN-induced cell death (+23.6%, P < 0.0001). Conclusion Increased S70pBCL2 and T163pMCL1 are associated with VEN resistance, in part by inhibiting VEN-induced BCL-2-BAX dissociation and switching the functional survival dependence from BCL-2 to MCL-1. FTY720 re-sensitizes VEN resistant cells by reducing S70pBCL2, T163pMCL1 and MCL-1 expression, dissociating BAX from BCL-2 and "re-wiring" the survival dependence to BCL-2. These preclinical findings support the exploration of this strategy clinically in patients with VEN resistant lymphoid malignancies. Disclosures Davids: Sunesis: Consultancy; AbbVie: Consultancy; Surface Oncology: Research Funding; Genentech: Consultancy, Research Funding; Eli Lilly: Consultancy; Celgene: Consultancy; AstraZeneca: Consultancy, Research Funding; BeiGene: Consultancy; Ascentage Pharma: Consultancy, Research Funding; Adaptive Biotechnologies: Consultancy; Pharmacyclics: Consultancy, Research Funding; TG Therapeutics: Consultancy, Research Funding; Verastem: Consultancy, Research Funding; Zentalis: Consultancy; Novartis: Consultancy, Research Funding; Gilead Sciences: Consultancy; Bristol Myers Squibb: Research Funding; Janssen: Consultancy; MEI Pharma: Consultancy, Research Funding; Syros Pharmaceuticals: Consultancy; Merck: Consultancy; Research to Practice: Honoraria.

Many anti-bullying programs now emphasize the role of bystanders - youth who witness peer victimization. Using a large sample of adolescents (aged 12-18) from the United Kingdom who completed an online survey, the present study examined the types of bystander interventions, their outcomes, and reasons for intervening and not intervening. No significant group differences by any demographic group were found in intervening or not. Results showed that those who had a negative affective reaction when they witnessed bullying were more likely to intervene. Two intervening behaviors (telling the bully to stop and telling an adult) were the strongest predictors of positive results. The most frequently selected reason for not intervening was not knowing what to do, and for intervening, having prosocial and altruistic motives was most common. These and other results are discussed for theoretical and practical implications.

Most health professionals would agree that stress is the biggest factor affecting the mortality rate in modern society. If left untreated, stress can have detrimental impacts on both physical and mental health, and can lead to conditions such as heart disease, insomnia and depression. It is no wonder that stress has reached epidemic levels when one considers the sheer volume of stimuli reaching our consciousness on a daily basis, not to mention the increasing demands on our time and volatile changes across political and economic systems.

The annual bullying survey by Ditch the Label has found that high numbers of young people are still experiencing bullying before the age of 18, and that teachers remain high on the list of people who victims turn to for help. Liam Hackett explains.