Managing cancer and living meaningfully (CALM):Implementation in Dutch cancer care

Objective: Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands. Methods: In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6 months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6 months. Results: Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p = 0.006), death anxiety (p = 0.008), and anxiety (p = 0.024) was observed over time. Conclusions: This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.</p

Managing cancer and living meaningfully (CALM):Implementation in Dutch cancer care

Objective: Managing Cancer and Living Meaningfully (CALM) is a brief, evidence-based psychotherapy tailored for patients with advanced cancer that has not yet been implemented routinely in Dutch cancer care. The aim of this study was to assess the feasibility, acceptability, sustainability and effectiveness of CALM in different clinical settings in the Netherlands. Methods: In 2019 and 2020 a multi-center, intervention-only study was performed in three Dutch cancer care settings. Professionals were trained to provide CALM under supervision. Patients diagnosed with advanced cancer were included and filled out questionnaires to measure depression (Patient Health Questionnaire-9), death anxiety (Death and Dying Distress Scale), and anxiety (hospital anxiety and depression scale-anxiety) at baseline, 3 and 6 months. The Clinical Evaluation Questionnaire was used to assess acceptability of CALM at 3 and 6 months. Results: Sixty-four patients (55% of the eligible patients) were included in the study and 85% of the included patients received 3 or more CALM sessions. Of the 24 trained therapists, 15 (63%) started providing CALM. Two years post-study, CALM was provided in each center by a total of 19 therapists. On average, patients perceived CALM to be at least somewhat helpful. A significant decrease in severity of depression (p = 0.006), death anxiety (p = 0.008), and anxiety (p = 0.024) was observed over time. Conclusions: This study shows that CALM therapy is feasible, acceptable, and sustainable in three Dutch cancer care settings, although not all predefined feasibility criteria for therapists were met. CALM can be effective in decreasing feelings of depression, anxiety, and death anxiety in patients with advanced cancer.</p

Prospective cohort study of patients with advanced cancer and their relatives on the experienced quality of care and life (eQuiPe study): A study protocol

Background: Palliative care is becoming increasingly important because the number of patients with an incurable disease is growing and their survival is improving. Previous research tells us that early palliative care has the potential to improve quality of life (QoL) in patients with advanced cancer and their relatives. According to limited research on palliative care in the Netherlands, patients with advanced cancer and their relatives find current palliative care suboptimal. The aim of the eQuiPe study is to understand the experienced quality of care (QoC) and QoL of patients with advanced cancer and their relatives to further improve palliative care. Methods: A prospective longitudinal observational cohort study is conducted among patients with advanced cancer and their relatives. Patients and relatives receive a questionnaire every 3 months regarding experienced QoC and QoL during the palliative trajectory. Bereaved relatives receive a final questionnaire 3 to 6 months after the patients' death. Data from questionnaires are linked with detailed clinical data from the Netherlands Cancer Registry (NCR). By means of descriptive statistics we will examine the experienced QoC and QoL in our study population. Differences between subgroups and changes over time will be assessed while adjusting for confounding factors. Discussion: This study will be the first to prospectively and longitudinally explore experienced QoC and QoL in patients with advanced cancer and their relatives simultaneously. This study will provide us with population-based information in patients with advanced cancer and their relatives including changes over time. Results from the study will inform us on how to further improve palliative care. Trial registration: Trial NL6408 (NTR6584). Registered in Netherlands Trial Register on June 30, 2017

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

The risk of COVID-19 death is much greater and age dependent with type I IFN autoantibodies

International audienceSignificance There is growing evidence that preexisting autoantibodies neutralizing type I interferons (IFNs) are strong determinants of life-threatening COVID-19 pneumonia. It is important to estimate their quantitative impact on COVID-19 mortality upon SARS-CoV-2 infection, by age and sex, as both the prevalence of these autoantibodies and the risk of COVID-19 death increase with age and are higher in men. Using an unvaccinated sample of 1,261 deceased patients and 34,159 individuals from the general population, we found that autoantibodies against type I IFNs strongly increased the SARS-CoV-2 infection fatality rate at all ages, in both men and women. Autoantibodies against type I IFNs are strong and common predictors of life-threatening COVID-19. Testing for these autoantibodies should be considered in the general population

Rare predicted loss-of-function variants of type I IFN immunity genes are associated with life-threatening COVID-19

BackgroundWe previously reported that impaired type I IFN activity, due to inborn errors of TLR3- and TLR7-dependent type I interferon (IFN) immunity or to autoantibodies against type I IFN, account for 15-20% of cases of life-threatening COVID-19 in unvaccinated patients. Therefore, the determinants of life-threatening COVID-19 remain to be identified in similar to 80% of cases.MethodsWe report here a genome-wide rare variant burden association analysis in 3269 unvaccinated patients with life-threatening COVID-19, and 1373 unvaccinated SARS-CoV-2-infected individuals without pneumonia. Among the 928 patients tested for autoantibodies against type I IFN, a quarter (234) were positive and were excluded.ResultsNo gene reached genome-wide significance. Under a recessive model, the most significant gene with at-risk variants was TLR7, with an OR of 27.68 (95%CI 1.5-528.7, P=1.1x10(-4)) for biochemically loss-of-function (bLOF) variants. We replicated the enrichment in rare predicted LOF (pLOF) variants at 13 influenza susceptibility loci involved in TLR3-dependent type I IFN immunity (OR=3.70[95%CI 1.3-8.2], P=2.1x10(-4)). This enrichment was further strengthened by (1) adding the recently reported TYK2 and TLR7 COVID-19 loci, particularly under a recessive model (OR=19.65[95%CI 2.1-2635.4], P=3.4x10(-3)), and (2) considering as pLOF branchpoint variants with potentially strong impacts on splicing among the 15 loci (OR=4.40[9%CI 2.3-8.4], P=7.7x10(-8)). Finally, the patients with pLOF/bLOF variants at these 15 loci were significantly younger (mean age [SD]=43.3 [20.3] years) than the other patients (56.0 [17.3] years; P=1.68x10(-5)).ConclusionsRare variants of TLR3- and TLR7-dependent type I IFN immunity genes can underlie life-threatening COVID-19, particularly with recessive inheritance, in patients under 60 years old