Task-based EEG and fMRI paradigms in a multimodal clinical diagnostic framework for disorders of consciousness.

Disorders of consciousness (DoC) are generally diagnosed by clinical assessment, which is a predominantly motor-driven process and accounts for up to 40 % of non-communication being misdiagnosed as unresponsive wakefulness syndrome (UWS) (previously known as prolonged/persistent vegetative state). Given the consequences of misdiagnosis, a more reliable and objective multimodal protocol to diagnosing DoC is needed, but has not been produced due to concerns regarding their interpretation and reliability. Of the techniques commonly used to detect consciousness in DoC, task-based paradigms (active paradigms) produce the most unequivocal result when findings are positive. It is well-established that command following (CF) reliably reflects preserved consciousness. Task-based electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) can detect motor-independent CF and reveal preserved covert consciousness in up to 14 % of UWS patients. Accordingly, to improve the diagnostic accuracy of DoC, we propose a practical multimodal clinical decision framework centered on task-based EEG and fMRI, and complemented by measures like transcranial magnetic stimulation (TMS-EEG).

Antiviral and Antibacterial 3D-Printed Products Functionalised with Poly(hexamethylene biguanide).

Infection prevention and public health are a vital concern worldwide, especially during pandemics such as COVID-19 and seasonal influenza. Frequent manual disinfection and use of chemical spray coatings at public facilities are the typical measures taken to protect people from coronaviruses and other pathogens. However, limitations of human resources and coating durability, as well as the safety of disinfectants used are the major concerns in society during a pandemic. Non-leachable antimicrobial agent poly(hexamethylene biguanide) (PHMB) was mixed into photocurable liquid resins to produce novel and tailor-made covers for public facilities via digital light processing, which is a popular 3D printing technique for satisfactory printing resolution. Potent efficacies of the 3D-printed plastics were achieved in standard antibacterial assessments against S. aureus, E. coli and K. pneumoniae. A total of 99.9% of Human coronavirus 229E was killed after being in contact with the 3D-printed samples (containing the promising PHMB formulation) for two hours. In an eight-week field test in Hong Kong Wetland Park, antibacterial performances of the specially designed 3D-printed covers analysed by environmental swabbing were also found to be satisfactory. With these remarkable outcomes, antimicrobial products prepared by digital light processing 3D printing can be regarded as a reliable solution to long-term infection prevention and control.

Neuropsychiatric events associated with montelukast in patients with asthma: a systematic review.

BACKGROUND: The United States Food and Drug Administration issued a black box warning on the mental health adverse effects of montelukast in 2020. Age-related effects on the risk of developing specific neuropsychiatric events in montelukast users remain largely unknown. OBJECTIVE: To describe the risk of neuropsychiatric events associated with montelukast in adults and children with asthma. METHODS: A systematic search of all studies investigating neuropsychiatric events in montelukast users was performed in PubMed, the Cochrane Library and Embase from inception to 7 September 2022. Animal studies and conference abstracts were excluded. RESULTS: 59 studies (21 pharmacovigilance studies, four reviews from 172 randomised controlled trials, 20 observational studies, 10 case reports and four case series) evaluating neuropsychiatric events in patients with asthma on montelukast were reviewed. No significant association was shown between montelukast and suicide-related events in six of the observational studies. No association was found for depression as defined by the International Classification of Diseases 10th revision codes in three observational studies and a review of randomised clinical trials. However, findings from four studies using antidepressant prescriptions as the outcome identified significant associations. Consistent with nine pharmacovigilance studies, two large-scale observational studies revealed possible associations of montelukast with anxiety and sleeping disorders in adult patients with asthma, respectively. However, the results were not replicated in two observational studies on children. CONCLUSION: Montelukast is not associated with suicide- and depression-related events in asthma patients. Older adults may be particularly susceptible to anxiety and sleeping disorders.

Meta-analysis of CYP2C19 and CYP2D6 metabolic activity on antidepressant response from 13 clinical studies using genotype imputation.

Cytochrome P450 enzymes including CYP2C19 and CYP2D6 are important for antidepressant metabolism and polymorphisms of these genes have been determined to predict metabolite levels. Nonetheless, more evidence is needed to understand the impact of genetic variations on antidepressant response. In this study, individual clinical and genetic data from 13 studies of European and East Asian ancestry populations were collected. The antidepressant response was clinically assessed as remission and percentage improvement. Imputed genotype was used to translate genetic polymorphisms to metabolic phenotypes (poor, intermediate, normal, and rapid+ultrarapid) of CYP2C19 and CYP2D6. The association of CYP2C19 and CYP2D6 metabolic phenotypes with treatment response was examined using normal metabolizers as the reference. Among 5843 depression patients, a higher remission rate was found in CYP2C19 poor metabolizers compared to normal metabolizers at nominal significance but did not survive after multiple testing correction (OR=1.46, 95% CI [1.03, 2.06], p=0.033, heterogeneity I2=0%, subgroup difference p=0.72). No metabolic phenotype was associated with percentage improvement from baseline. After stratifying by antidepressants primarily metabolized by CYP2C19 and CYP2D6, no association was found between metabolic phenotypes and antidepressant response. Metabolic phenotypes showed differences in frequency, but not effect, between European- and East Asian-ancestry studies. In conclusion, metabolic phenotypes imputed from genetic variants using genotype were not associated with antidepressant response. CYP2C19 poor metabolizers could potentially contribute to antidepressant efficacy with more evidence needed. CYP2D6 structural variants cannot be imputed from genotype data, limiting inference of pharmacogenetic effects. Sequencing and targeted pharmacogenetic testing, alongside information on side effects, antidepressant dosage, depression measures, and diverse ancestry studies, would more fully capture the influence of metabolic phenotypes.

A novel approach in predicting virtual garment fitting sizes with psychographic characteristics and 3D body measurements using artificial neural network and visualizing fitted bodies using generative adversarial network.

Advances in technology have brought accessibility to garment product fitting procedures with a virtual fitting environment and, in due course, improved the supply chain socially, economically, and environmentally. 3D body measurements, garment sizes, and ease allowance are the necessary factors to ensure end-user satisfaction in the apparel industry. However, designers find it challenging to recognize customers' motivations and emotions towards their preferred fit and define ease allowances in the virtual environment. This study investigates the variations of ease preferences for apparel sizes with body dimensions and psychological orientations by developing a virtual garment fitting prediction model. An artificial neural network (ANN) was employed to develop the model. The ANN model was proved to be effective in predicting ease preferences from two major components. A non-linear relationship was modeled among pattern parameters, body dimensions, and psychographic characteristics. Also, to visualize the fitted bodies, a generative adversarial network (GAN) was applied to generate 3D samples with the predicted pattern parameters from the ANN model. This project promotes mass customization using psychographic orientations and provides the perfect fit to the end users. New size-fitting data is generated for improved ease preference charts, and it enhances end-user satisfaction with garment fit.

Loneliness in Breast Cancer Patients with Early Life Adversity: An Investigation of the Effects of Childhood Trauma and Self-Regulation.

Childhood trauma may be prevalent in the general population, and the psychosocial treatment of patients with cancer may require consideration of the effects of such early adversity on the healing and recovery process. In this study, we investigated the long-term effects of childhood trauma in 133 women diagnosed with breast cancer (mean age 51, SD = 9) who had experienced physical, sexual, or emotional abuse or neglect. We examined their experience of loneliness and its associations with the severity of childhood trauma, ambivalence about emotional expression, and changes in self-concept during the cancer experience. In total, 29% reported experiencing physical or sexual abuse, and 86% reported neglect or emotional abuse. In addition, 35% of the sample reported loneliness of moderately high severity. Loneliness was directly influenced by the severity of childhood trauma and was directly and indirectly influenced by discrepancies in self-concept and emotional ambivalence. In conclusion, we found that childhood trauma was common in breast cancer patients, with 42% of female patients reporting childhood trauma, and that these early experiences continued to exert negative effects on social connection during the illness trajectory. Assessment of childhood adversity may be recommended as part of routine oncology care, and trauma-informed treatment approaches may improve the healing process in patients with breast cancer and a history of childhood maltreatment.

Pathway linking Emotional Suppression to Depression and Anxiety in Cancer Patients undergoing Chemotherapy: The Mediating Role of Ego-strength.

BACKGROUND: Ego-strength refers to the individual's psychosocial capacity to self-regulate their emotions in the face of stress, developed over the course of the lifespan. Ego-strength may have an important role in understanding psychological adaptation to cancer, especially when considering the effects of emotional suppression in cancer populations. In the present study, we examined the effects of ego-strength and emotional suppression on depression and anxiety in patients coping with cancer. We also tested whether ego-strength may mediate the relationship between emotional suppression and psychological distress in cancer. METHODS: 120 cancer patients were recruited from a private hospital in Tabriz to complete baseline questionnaires. Depression, anxiety, ego-strength and emotional suppression were assessed by BDI-II, BAI, PIES and WAI respectively. Mediation models were tested using structural equation modeling, controlling for age and gender. RESULTS: Emotional suppression was positively associated with depression and anxiety, and negatively associated with ego-strength. Ego-strength was negatively associated with depression and anxiety. Ego-strength partially mediated the relationship between emotional suppression and depression, and fully mediated the relationship between emotional suppression and anxiety. CONCLUSION: Ego-strength may help prevent the onset or unfavorable course of depression and anxiety in cancer patients.

Cardiovascular Outcomes in Trials of New Antidiabetic Drug Classes.

Type 2 diabetes is among the most prevalent chronic diseases worldwide and the prevention of associated cardiovascular complications is an important treatment goal. Sodium-glucose co-transporter 2 (SGLT2) inhibitors, glucagon-like peptide 1 (GLP-1) receptor agonists and dipeptidyl peptidase-4 (DPP-4) inhibitors are second-line options after metformin, while cardiovascular outcome trials have been conducted to establish the cardiovascular safety of these antidiabetic drug classes. SGLT2 inhibitors have been shown to have the best overall mortality, renal and cardiovascular outcomes. Reduction in hospitalisation for heart failure is particularly consistent. GLP-1 receptor agonists have also showed some benefits, especially in stroke prevention. DPP-4 inhibitors showed neutral effects on cardiovascular outcomes, but may increase the incidence of heart failure. Favourable outcomes observed in trials of SGLT2 inhibitors mean that these should be the preferred second-line option. DPP-4 inhibitors are useful for patients with diabetes at low cardiovascular risk.

Blood lead level and risk of hypertension in the United States National Health and Nutrition Examination Survey 1999-2016.

Lead is a heavy metal without a biological role. High level of lead exposure is known to be associated with hypertension, but the risk at low levels of exposure is uncertain. In this study, data from US NHANES 1999-2016 were analyzed. Adults with blood lead and blood pressure measurements, or self-reported hypertension diagnosis, were included. If not already diagnosed, hypertension was defined according to the AHA/ACC 2017 hypertension guideline. Results were analyzed using R statistics version 3.5.1 with sample weight adjustment. Logistic regression was used to study the association between blood lead level and hypertension. Odds ratio (OR) and 95% confidence interval (95% CI) were estimated. Altogether, 39,477 participants were included. Every doubling in blood lead level was associated with hypertension (OR [95%CI] 1.45 [1.40-1.50]), which remained significant after adjusting for demographics. Using quartile 1 as reference, higher blood lead levels were associated with increased adjusted odds of hypertension (Quartile 4 vs. Quartile 1: 1.22 [1.09-1.36]; Quartile 3 vs. Quartile 1: 1.15 [1.04-1.28]; Quartile 2 vs. Quartile 1: 1.14 [1.05-1.25]). In conclusion, blood lead level is associated with hypertension in the general population with blood lead levels below 5 µg/dL. Our findings suggest that reducing present levels of environmental lead exposure may bring cardiovascular benefits by reducing blood pressure.

Development of a psychoeducational intervention for people affected by pancreatic cancer.

BACKGROUND: Pancreatic cancer has one of the highest mortality rates of any malignancy, placing a substantial burden on patients and families with high unmet informational and supportive care needs. Nevertheless, access to psychosocial and palliative care services for the individuals affected is limited. There is a need for standardized approaches to facilitate adjustment and to improve knowledge about the disease and its anticipated impact. In this intervention-development paper guided by implementation science principles, we report the rationale, methods, and processes employed in developing an interdisciplinary group psychoeducational intervention for people affected by pancreatic cancer. The acceptability and feasibility of implementation will be evaluated as a part of a subsequent feasibility study. METHODS: The Schofield and Chambers framework for designing sustainable self-management interventions in cancer care informed the development of the intervention content and format. The Consolidated Framework for Implementation Research served as an overarching guide of the implementation process, including the development phase and the formative evaluation plan of implementation. RESULTS: A representative team of stakeholders collaboratively developed and tailored the intervention content and format with attention to the principles of implementation science, including available resourcing. The final intervention prototype was designed as a single group-session led by an interdisciplinary clinical team with expertise in caring for patients with pancreatic cancer and their families and in addressing nutrition guidelines, disease and symptom management, communication with family and health care providers, family impact of cancer, preparing for the future, and palliative and supportive care services. CONCLUSIONS: The present paper describes the development of a group psychoeducational intervention to address the informational and supportive care needs of people affected by pancreatic cancer. Consideration of implementation science during intervention development efforts can optimize uptake and sustainability in the clinical setting. Our approach may be utilized as a framework for the design and implementation of similar initiatives to support people affected by diseases with limited prognoses.

Characterizing death acceptance among patients with cancer.

OBJECTIVE: Death acceptance may indicate positive adaptation in cancer patients. Little is known about what characterizes patients with different levels of death acceptance or its impact on psychological distress. We aimed to broaden the understanding of death acceptance by exploring associated demographic, medical, and psychological characteristics. METHODS: At baseline, we studied 307 mixed cancer patients attending the University Cancer Center Hamburg and a specialized lung cancer center (age M = 59.6, 69% female, 69% advanced cancer). At 1-year follow-up, 153 patients participated. We assessed death acceptance using the validated Life Attitude Profile-Revised. Patients further completed the Memorial Symptom Assessment Scale, the Demoralization Scale, the Patient Health Questionnaire, and the Generalized Anxiety Disorder Questionnaire. Statistical analyses included multinomial and hierarchical regression analyses. RESULTS: At baseline, mean death acceptance was 4.33 (standard deviation [SD] = 1.3, range 1-7). There was no change to follow-up (P = 0.26). When all variables were entered simultaneously, patients who experienced high death acceptance were more likely to be older (odds ratio [OR] = 1.04; 95% confidence interval [CI], 1.01-1.07), male (OR = 3.59; 95% CI, 1.35-9.56), widowed (OR = 3.24; 95% CI, 1.01-10.41), and diagnosed with stage IV (OR = 2.44; 95% CI, 1.27-4.71). They were less likely to be diagnosed with lung cancer (OR = 0.20; 95% CI, 0.07-0.58), and their death acceptance was lower with every month since diagnosis (OR = 0.99; 95% CI, 0.98-0.99). High death acceptance predicted lower demoralization and anxiety at follow-up but not depression. CONCLUSIONS: High death acceptance was adaptive. It predicted lower existential distress and anxiety after 1 year. Advanced cancer did not preclude death acceptance, supporting the exploration of death-related concerns in psychosocial interventions.

Mentalization in CALM psychotherapy sessions: Helping patients engage with alternative perspectives at the end of life.

OBJECTIVE: To identify how therapists invite patients with advanced cancer to engage with alternative perspectives about their illness trajectory and their end of life. METHODS: Sequences of talk in which a therapist introduced a patient to alternative perspectives, were transcribed and analysed using the method of conversation analysis. RESULTS: The analysis identifies one subtle way a patient is invited to consider an alternative perspective relating to their disease progression. Meaning expansion enquiries invite the patient to expand on the meaning of an utterance and in doing so, implicitly problematize the singularity of the patient's assumptions, without directly challenging them. The questions work as preliminary moves, providing the patient with the opportunity to expand on their assumptions. This enables the therapist to subsequently present an alternative perspective in a way that incorporates the patient's expanded perspective. CONCLUSION: The analysis reveals a skilful way in which therapists can cautiously and collaboratively introduce a patient to alternative perspectives concerning end-of-life, without invalidating the patient's perspective in this particularly delicate context. PRACTICE IMPLICATIONS: Whilst mentalization is considered an important therapeutic process, the present study reveals precisely how this phenomenon can be enacted in therapy and within the particularly challenging context of end-of-life.

Managing Cancer And Living Meaningfully (CALM): randomised feasibility trial in patients with advanced cancer.

BACKGROUND: Managing Cancer And Living Meaningfully (CALM) is a brief individual psychotherapy for patients with advanced cancer. In an intervention-only phase 2a trial, CALM showed promising results, leading to the present 2b pilot, which introduces procedures for randomisation and improved rigour in preparation for a phase 3 randomised controlled trial (RCT). AIMS: To test trial methodology and assess feasibility of a confirmatory RCT. DESIGN: A parallel-arm RCT (intervention vs usual care) with 3 and 6-month follow-ups. Assessment of feasibility included rates of consent, randomisation, attrition, intervention non-compliance and usual care contamination. PRIMARY OUTCOME: depressive symptoms (Patient Health Questionnaire-9; PHQ-9). SECONDARY OUTCOMES: major depressive disorder (MDD), generalised anxiety, death anxiety, spiritual well-being, attachment anxiety and avoidance, self-esteem, experiential avoidance, quality of life and post-traumatic growth. Bayesian conjugate analysis was used in this low-powered setting. SETTING/PARTICIPANTS: 60 adult patients with advanced cancer from the Princess Margaret Cancer Centre. RESULTS: Rate of consent was 32%, randomisation 78%, attrition 25%, non-compliance 37% and contamination 17%. There was support for potential treatment effects on: PHQ-9, OR=1.48, 95% Credible Interval (CRI.95) (0.65, 3.38); MDD, OR=1.56, CRI.95 (0.50, 4.84); attachment anxiety, OR=1.72, CRI.95 (0.73, 4.03); and attachment avoidance, OR=1.58, CRI.95 (0.67, 3.71). There was no support for effects on the seven remaining secondary outcomes. CONCLUSIONS: A phase 3 CALM RCT is feasible and should aim to detect effect sizes of d=0.40, with greater attention to issues of compliance and contamination. TRIAL REGISTRATION NUMBER: NCT02353546.

Traumatic stress in patients with acute leukemia: A prospective cohort study.

OBJECTIVE: Acute leukemia (AL) is associated with an immediate threat to life, an unpredictable clinical course, and substantial physical suffering. Traumatic stress symptoms that may meet criteria for acute stress disorder (ASD) may be common and disabling in this context, but have received little clinical attention. We investigated the incidence over time and risk factors for traumatic stress symptoms and ASD in the 3 months following diagnosis or relapse of AL. METHODS: Individuals with AL were recruited at a tertiary cancer center in Canada within one month of diagnosis or relapse. Participants (N = 230) completed self-report measures, including the Stanford Acute Stress Reaction Questionnaire, at baseline and monthly over 3 months. The incidence of traumatic stress symptoms over time was examined, and a generalized logistic model was used to identify factors associated with ASD. RESULTS: Participants were 60% male, with a mean age of 48.9 ± 15.2 years. Symptoms of ASD were identified on ≥1 assessment over the study period in 24.4% of participants at baseline and in an additional 12.6% at a subsequent follow-up. Of these, 55.3% reported symptoms on ≥2 assessments. ASD was associated with having young children, being unmarried, acute lymphocytic leukemia, and greater physical symptom burden. Persistent or recurrent ASD was associated with female sex, acute lymphocytic leukemia, greater attachment anxiety, less spiritual well-being, and less satisfactory patient-clinician communication. CONCLUSIONS: Symptoms of ASD are common and often persist or recur following diagnosis or relapse of AL. Research is urgently needed to determine the impact of interventions to prevent and treat psychological distress in this population.

Death-Related Anxiety in Patients With Advanced Cancer: Validation of the German Version of the Death and Dying Distress Scale.

CONTEXT: Distress and anxiety about issues related to death and dying is commonly experienced in patients with advanced disease and a limited life expectancy. OBJECTIVES: To evaluate the psychometric properties of the German version of the Death and Dying Distress Scale (DADDS-G) in advanced cancer patients. METHODS: We recruited advanced patients with mixed tumor entities (Union for International Cancer Control [UICC] Stage III/IV) treated in two German University Medical Centers during their outpatient treatment. After testing a preliminary version of the state-of-the-art translated original Death and Dying Distress Scale, we analyzed the psychometric properties of the shortened nine-item adapted DADDS-G using validated instruments measuring distress, anxiety, depression, fear of progression, and quality of life. RESULTS: We obtained complete questionnaires from 77 of 93 patients with advanced cancer (response rate: 83%). Participants were mostly married or cohabiting (75%), well-educated, and both sexes were almost equally represented (52% men; mean age 58 years, SD = 12). The total mean DADDS-G score was 13.3 (SD = 8.5). Patients reported to be most distressed by the feeling of being a burden to others. The exploratory factor analysis led to one factor that accounted for more than 59% of the variance. The DADDS-G's internal consistency was excellent with Cronbach alpha = 0.91. The confirmatory factor analysis demonstrated a very good model fit. Death-related anxiety was significantly associated with distress, depression, anxiety, fear of progression, and lower quality of life (P < 0.001). CONCLUSION: Results provide further evidence that the DADDS-G is a valid and reliable instrument of high clinical relevance for use in patients with advanced cancer.

The meaning of self-reported death anxiety in advanced cancer.

BACKGROUND: Death anxiety is important but understudied in palliative care. New self-report measurements have been developed, but their interpretation and clinical utility may not be evident. AIM: To inform our understanding of death anxiety in patients with advanced cancer by exploring the relationship between this self-reported symptom and its clinical presentation. DESIGN: Participants were part of a psychotherapy trial in advanced cancer. First therapy session transcripts were analyzed using interpretive description in patients reporting low, moderate, and high death anxiety on the Death and Dying Distress Scale (DADDS). SETTING/PARTICIPANTS: A total of 16 participants (10 women and 6 men) with advanced or metastatic cancer were sampled from the Princess Margaret Cancer Centre, Toronto, Canada. Six participants reported low death anxiety scores (Death and Dying Distress Scale: 0-19), five moderate (Death and Dying Distress Scale: 20-50), and five high (Death and Dying Distress Scale: 51-75). RESULTS: The low death anxiety group exhibited psychological readiness for death, or contrastingly, non-reflectiveness about death. The moderate group recognized the imminence of mortality, which impacted treatment decisions and future plans. Prior experience with death was discussed as raising the salience of mortality. The high group felt dominated by powerful emotions and could not make sense of their situation. Their distress was exacerbated by substantial relational concerns. CONCLUSION: Self-reported death anxiety is affected by the awareness and ability to reflect on mortality. Death and Dying Distress Scale scores may facilitate exploration of this symptom as part of a clinical assessment and may serve to guide treatment approaches. Greater attention to death anxiety is consistent with and recommended by contemporary approaches to palliative care.

Depression and hopelessness in patients with acute leukemia: the psychological impact of an acute and life-threatening disorder.

OBJECTIVE: Acute leukemia (AL) is a life-threatening cancer associated with substantial morbidity and mortality, particularly in older adults. Given that there has been little research on the psychological impact of such malignancies with acute onset, we assessed the prevalence and correlates of depression and hopelessness in patients with AL. METHODS: Three hundred forty-one participants were recruited within 1 month of diagnosis or relapse and completed the Beck Depression Inventory-II (BDI-II), Beck Hopelessness Scale (BHS), Memorial Symptom Assessment Scale, and other psychosocial measures. Multivariate regression analyses identified correlates of depression and hopelessness. RESULTS: 17.8% reported clinically significant depressive symptoms (BDI-II ≥ 15), 40.4% of which were in the moderate-severe range (BDI-II ≥ 20). 8.5% reported significant symptoms of hopelessness (BHS ≥ 8). Depression was associated with greater physical symptom burden (adjusted R(2) = 48.4%), while hopelessness was associated with older age and lower self-esteem (adjusted R(2) = 45.4%). Both were associated with poorer spiritual well-being. CONCLUSIONS: Clinically significant depressive symptoms were common early in the course of AL and related to physical symptom burden. Hopelessness was less common and associated with older age and lower self-esteem. The results suggest that whereas depression in AL may be related to disease burden, the preservation of hope may be linked to individual resilience, life stage, and realistic prognosis.Copyright © 2015 John Wiley & Sons, Ltd.

Managing Cancer And Living Meaningfully: study protocol for a randomized controlled trial.

BACKGROUND: We have developed a novel and brief semi-structured psychotherapeutic intervention for patients with advanced or metastatic cancer, called Managing Cancer And Living Meaningfully. We describe here the methodology of a randomized controlled trial to test the efficacy of this treatment to alleviate distress and promote well-being in this population. METHODS/DESIGN: The study is an unblinded randomized controlled trial with 2 conditions (intervention plus usual care versus usual care alone) and assessments at baseline, 3 and 6 months. The site is the Princess Margaret Cancer Centre, part of the University Health Network, in Toronto, Canada. Eligibility criteria include: ≥ 18 years of age; English fluency; no cognitive impairment; and diagnosis of advanced cancer. The 3-6 session intervention is manualized and allows for flexibility to meet individual patients' needs. It is delivered over a 3-6 month period and provides reflective space for patients (and their primary caregivers) to address 4 main domains: symptom management and communication with health care providers; changes in self and relations with close others; sense of meaning and purpose; and the future and mortality. Usual care at the Princess Margaret Cancer Centre includes distress screening and referral as required to in-hospital psychosocial and palliative care services. The primary outcome is frequency of depressive symptoms and the primary endpoint is at 3 months. Secondary outcomes include diagnosis of major or minor depression, generalized anxiety, death anxiety, spiritual well-being, quality of life, demoralization, attachment security, posttraumatic growth, communication with partners, and satisfaction with clinical interactions. DISCUSSION: Managing Cancer And Living Meaningfully has the potential to relieve distress and promote psychological well-being in patients with advanced cancer and their primary caregivers. This trial is being conducted to determine its benefit and inform its dissemination. The intervention has cross-national relevance and training workshops have been held thus far with clinicians from North and South America, Europe, the Middle East, Asia and Africa. TRIAL REGISTRATION: ClinicalTrials.gov NCT01506492 4 January 2012.

Efficacy of a brief manualized intervention Managing Cancer and Living Meaningfully (CALM) adapted to German cancer care settings: study protocol for a randomized controlled trial.

BACKGROUND: Although psycho-oncological interventions have been shown to significantly reduce symptoms of anxiety and depression and enhance quality of life, a substantial number of patients with advanced cancer do not receive psycho-oncological interventions tailored to their individual situation. Given the lack of reliable data on the efficacy of psycho-oncological interventions in palliative care settings, we aim to examine the efficacy of a brief, manualized individual psychotherapy for patients with advanced cancer: Managing Cancer and Living Meaningfully (CALM). CALM aims to reduce depression and death anxiety, to strengthen communication with health care providers, and to enhance hope and meaning in life. We adapted the intervention for German cancer care settings. METHODS/DESIGN: We use a single-blinded randomized-controlled trial design with two treatment conditions: intervention group (IG, CALM) and control group (CG). Patients in the CG receive a usual non-manualized supportive psycho-oncological intervention (SPI). Patients are randomized between the IG and CG and assessed at baseline (t0), after three (t1) and after 6 months (t2). We include patients with a malignant solid tumor who have tumor stages of III or IV (UICC classification). Patients who are included in the study are at least 18 years old, speak German fluently, score greater than or equal to nine on the PHQ-9 or/and greater than or equal to five on the Distress Thermometer. It is further necessary that there is no evidence of severe cognitive impairments. We measure depression, anxiety, distress, quality of life, demoralization, symptom distress, fatigue as well as spiritual well-being, posttraumatic growth and close relationship experiences using validated questionnaires. We hypothesize that patients in the IG will show a significantly lower level of depression 6 months after baseline compared to patients in the CG. We further hypothesize a significant reduction in anxiety and fatigue as well as significant improvements in psychological and spiritual well-being, meaning and post-traumatic growth in the IG compared to CG 6 months after baseline. DISCUSSION: Our study will contribute important statistical evidence on whether CALM can reduce depression and existential distress in a German sample of advanced and highly distressed cancer patients. TRIAL REGISTRATION: ClinicalTrials.gov NCT02051660.