The moderation effect of secure attachment on the relationship between positive events and wellbeing

Positive events can reduce depression as well as enhance wellbeing. The role of secure attachment style in moderating the relationship between positive events and wellbeing is examined to further understand wellbeing models. Participants (n = 490) included two midlife groups and a student group from the UK. They completed the online Computerised Life Event Assessment Record (CLEAR), a measure of life events, the Vulnerable Attachment Style Questionnaire (VASQ) and the Warwick Emotional Wellbeing Scale (WEMWBS). Age was associated with higher rates of wellbeing and secure attachment style. A significant relationship was found between number of positive events and wellbeing, number of people close, and secure attachment score. Hierarchical multiple regression indicated a significant interaction between secure attachment style, number of positive life events and wellbeing. Simple slopes analysis demonstrated the association between positive life events and wellbeing was significant for secure attachment (B = 1.27, p = .003) but not insecure attachment (B = .04, n.s.). This suggests securely attached individuals are better able to take advantage of positive life events than insecurely attached individuals and experience a greater increase in wellbeing

Life events, depression and supportive relationships affect academic achievement in university students

Students often simultaneously deal with shifting support networks, stressful life changes and psychological distress which may affect academic achievement. Methods: 285 students completed the General Health Questionnaire (GHQ-12) to assess depression and the Computerized Life Events Assessment Record (CLEAR), to establish life events and supportive relationships. Module grades were used to measure academic achievement. A general linear model was used with student grade as the dependent variable and life events, depression and supportive relationships as independent variables. Confounding variables included age and sex. Results: A three-way interaction between life events, depression and lack of supportive relationships was found. It indicated the performance of depressed students depended on whether they had supportive relationships and that this interaction also depended on whether they had experienced a life event in the past year. Conclusions: Universities need to provide more support to students with life stress as they transition into university life

Measuring life events and their association with clinical disorder: a protocol for development of an online approach

Background: Severe life events are acknowledged as important aetiological factors in the development of clinical disorders, including major depression. Interview methods capable of assessing context and meaning of events have demonstrated superior validity compared to checklist questionnaire methods and arguments for interview approaches have resurfaced as choice of assessment tool has been implicated in gene-environment interactions in depression. Such approaches also have greater potential for understanding and treating clinical cases or for use in interventions. Objectives: (i) To argue that life events need sophisticated measurement not satisfactorily captured in checklist approaches. (ii) To review life events measures and key findings related to disorder, exemplifying depression. (iii) To describe an ongoing study with a new online measure, to assess its psychometric properties and the association of life events in relation to disorder and educational outcomes. Methods: The Computerised Life Events Assessment Record (CLEAR) is under development as a tool for online assessment of adult life events. Based on the Life Events and Difficulties Schedule (LEDS) interview, CLEAR seeks to assess life events to self and close others, link these to other events and difficulties and utilise calendar-based timing, to improve upon checklist approaches. The phases of the study are outlined in terms of its samples of midlife cases with depression, unaffected controls and students, testing of the psychometric properties of CLEAR, as well as proposed investigations of its association with disorder and educational outcomes. Conclusions: There is currently no sophisticated technological application of social risk factor assessment, such as life events and difficulties. CLEAR is designed to gather reliable and valid life event data whilst combatting the limitations of interviews (e.g. time consuming and costly) and life event checklists (e.g. inability to accurately measure severity and independence of life events). The advantages of using such innovative methodology for research, clinical practice and interventions are discussed

Web-based measure of life events using computerized life events and assessment record (CLEAR): preliminary cross-sectional study of reliability, validity, and association with depression

Background: Given the criticisms of life event checklists and the costs associated with interviews, life event research requires a sophisticated but easy-to-use measure for research and clinical practice. Therefore, the Computerised Life Events and Assessment Record (CLEAR), based on the Life Events and Difficulties Schedule (LEDS), was developed. Objectives: To test CLEAR’s reliability, validity, and association with depression. Methods: CLEAR, the General Health Questionnaire, and the List of Threatening Experiences Questionnaire (LTE-Q) were completed by 328 participants (126 students; 202 matched midlife sample: 127 unaffected controls, 75 recurrent depression cases). Test-retest reliability over 3-4 weeks was examined, and validity determined by comparing CLEAR with LEDS and LTE-Q. Both CLEAR and LTE-Q were examined in relation to depression. Results: CLEAR demonstrated good test-retest reliability for overall number of life events (.89) and severe life events (.60). Long-term problems showed similar findings. In terms of validity, CLEAR severe life events had moderate sensitivity (59.1%) and specificity (65.4%) when compared to LEDS. CLEAR demonstrated moderate sensitivity (43.1%) and specificity (78.6%) when compared to LTE-Q. CLEAR severe life events and long term problems were significantly associated with depression (OR = 3.50, 95% CI: 2.10-5.85, P < .001; OR = 3.38, 95% CI: 2.02-5.67, P < .001, respectively) whereas LTE-Q events were not (OR=1.06, 95% CI: .43-2.60, P =.90). Conclusions: CLEAR has acceptable reliability and validity and predicts depression. It therefore has great potential for effective use in research and clinical practice identifying stress-related factors for the onset and maintenance of depression and related disorders

Characteristics of severe life events, attachment style, and depression – Using a new online approach

Objectives Severe life events are established as provoking agents for depression in combination with vulnerability factors. Identifying features of severe events improves the prediction of disorder but are rarely utilized, mainly because life event research is increasingly dominated by self‐report checklists with no capacity for inferring such characteristics. This paper investigates the association of severe life events’ features with depression and insecure attachment styles using a new online measure of life events in a clinical and control sample. Methods A total of 202 participants (75 clinical and 127 matched control participants), taken from an earlier national Depression Case Control genetic study and followed up after 12 years, completed the Computerised Life Events Assessment Record to assess characteristics of life events, the Vulnerable Attachment Style Questionnaire to measure attachment insecurity, and the General Health Questionnaire to measure depression. Results The clinical group had higher self‐reported depression, severe life events, and insecure attachment style. They also reported more loss, danger, humiliation, and trauma severe events. Intra‐respondent analysis showed individuals experiencing these types of events were more likely to report depression. Insecure attachment style and severe life events were both significantly related to recent depression and history of depressive disorder. Anxious attachment style was significantly related to relationship events and bereavements, as well as severe loss or humiliation events, whereas avoidant style was not. Conclusions Identifying salient features of severe life events improves associations with depression and insecure attachment style. Utilizing a new online approach can aid research and clinical approaches for depression at low cost. Practitioner points Salient features of severe life events (e.g., loss, humiliation) give insight into the potential impact on attachment vulnerability and depression. Clinicians and researchers can use online methods to economically gain detailed life event information needed for clinical formulation and valid data on stressors. The self‐reported scale for recent depression is only a proxy measure of clinical disorder, but the clinical group selection is a more robust criterion for depression history

First-in-human pharmacokinetics of tamoxifen and its metabolites in the milk of a lactating mother. A case study

Background Breast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking. Methods We measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula. Results Tamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18. Conclusion This study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (&gt;7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment

The Great Debate at 'Immunotherapy Bridge', Naples, December 5, 2019

As part of the 2019 Immunotherapy Bridge congress (December 4–5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report

The Great Debate at \u27Immunotherapy Bridge\u27, Naples, December 5, 2019.

As part of the 2019 Immunotherapy Bridge congress (December 4-5, Naples, Italy), the Great Debate session featured counterpoint views from leading experts on six topical issues in immunotherapy today. These were the use of chimeric antigen receptor T cell therapy in solid tumors, whether the Immunoscore should be more widely used in clinical practice, whether antibody-dependent cellular cytotoxicity is important in the mode of action of anticytotoxic T-lymphocyte-associated protein 4 antibodies, whether the brain is immunologically unique or just another organ, the role of microbiome versus nutrition in affecting responses to immunotherapy, and whether chemotherapy is immunostimulatory or immunosuppressive. Discussion of these important topics are summarized in this report

The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of squamous cell carcinoma of the head and neck (HNSCC)

Head and neck cancers, including those of the lip and oral cavity, nasal cavity, paranasal sinuses, oropharynx, larynx and nasopharynx represent nearly 700,000 new cases and 380,000 deaths worldwide per annum, and account for over 10,000 annual deaths in the United States alone. Improvement in outcomes are needed for patients with recurrent and or metastatic squamous cell carcinoma of the head and neck (HNSCC). In 2016, the US Food and Drug Administration (FDA) granted the first immunotherapeutic approvals - the anti-PD-1 immune checkpoint inhibitors nivolumab and pembrolizumab - for the treatment of patients with recurrent squamous cell carcinoma of the head and neck (HNSCC) that is refractory to platinum-based regimens. The European Commission followed in 2017 with approval of nivolumab for treatment of the same patient population, and shortly thereafter with approval of pembrolizumab monotherapy for the treatment of recurrent or metastatic HNSCC in adults whose tumors express PD-L1 with a 65 50% tumor proportion score and have progressed on or after platinum-containing chemotherapy. Then in 2019, the FDA granted approval for PD-1 inhibition as first-line treatment for patients with metastatic or unresectable, recurrent HNSCC, approving pembrolizumab in combination with platinum and fluorouracil for all patients with HNSCC and pembrolizumab as a single agent for patients with HNSCC whose tumors express a PD-L1 combined positive score 65 1. These approvals marked the first new therapies for these patients since 2006, as well as the first immunotherapeutic approvals in this disease. In light of the introduction of these novel therapies for the treatment of patients with head and neck cancer, The Society for Immunotherapy of Cancer (SITC) formed an expert committee tasked with generating consensus recommendations for emerging immunotherapies, including appropriate patient selection, therapy sequence, response monitoring, adverse event management, and biomarker testing. These consensus guidelines serve as a foundation to assist clinicians' understanding of the role of immunotherapies in this disease setting, and to standardize utilization across the field for patient benefit. Due to country-specific variances in approvals, availability and regulations regarding the discussed agents, this panel focused solely on FDA-approved drugs for the treatment of patients in the U.S