Online mindfulness-based cognitive therapy for fatigue in patients with sarcoidosis (TIRED): a randomised controlled trial

Background: Sarcoidosis-associated fatigue is highly prevalent and is often reported as the most burdensome symptom of sarcoidosis. Management of fatigue is challenging, and evidence-based therapies are lacking. In this TIRED trial, we aimed to assess the effects of a 12-week online mindfulness-based cognitive therapy (eMBCT) on fatigue. Methods: This study was a prospective, open-label, multicentre randomised controlled trial, conducted at three centres in the Netherlands. Eligible patients were 18 years or older, had stable sarcoidosis, and a score of more than 21 points on the Fatigue Assessment Scale (FAS). Patients were randomised into either the eMBCT or the control group. Participants completed patient-reported outcome measures at baseline, after intervention (T1), and 12 weeks after completion of eMBCT (T2). The primary outcome was the change in FAS score at T1 in the eMBCT group compared with the control group, assessed with the independent students' t test in all patients who started the study. Secondary outcomes included within-group difference in FAS score at T1 and T2, between-group difference in FAS score at T2, and changes in the Hospital Anxiety and Depression Scale, the Freiburg Mindfulness Inventory–Short Form, and the Kings Sarcoidosis Questionnaire. The study was registered at the Netherlands Trial Register, NL7816. Findings: Between June 5, 2019, and Oct 28, 2021, 99 patients were randomly assigned to the eMBCT (n=52) or the control (n=47) groups. Six patients withdrew consent after psychological screening before the start of eMBCT. Baseline FAS score was similar in both groups (34·57 [SD 6·07] for 46 patients in the eMBCT group and 35·51 [4·65] for 47 patients in the control group). Mean change in FAS score at T1 was –4·53 (SD 5·77; p<0·0001) in the eMBCT group and –1·28 (3·80; p=0·026) in the control group (between-group difference 3·26 [95% CI 1·18 to 5·33; p=0·0025]). Furthermore, the eMBCT group had a significant improvement in anxiety (mean between-group difference 1·69, 95% CI 0·22–3·16; p=0·025), depressive symptoms (1·52, 0·08–2·95; p=0·039), mindfulness (3·1, 0·70–5·49; p=0·022), and general health status (6·28, 2·51–10·06; p=0·002) at T1, compared with the control group. Interpretation: 12 week eMBCT improves fatigue, anxiety, depression, mindfulness, and health status in patients with sarcoidosis-associated fatigue. Funding: Dutch Sarcoidosis Patient Association (Sarcoidose.nl). Translation: For the Dutch translation of the summary see Supplementary Materials section

Ruby's Mission: Towards an Applied Gaming Intervention for reducing Loneliness of Children with Chronic Illness

Children with a chronic disease, such as cystic fibrosis or juvenile arthritis, often face obstacles that can have a negative impact on children's physical, social-emotional and cognitive development, beyond the actual illness itself. Children with chronic conditions are, on average, lonelier than their peers without such conditions. Feelings of loneliness in children and adolescents have been associated with a wide range of negative outcomes, including school drop-out, depressive symptoms, social anxiety, suicide ideation, low self-esteem, eating disorders, and sleep problems. As such, the present investigation sets out to reduce these feelings of loneliness for children with chronic conditions, and aims to do so by the structured design of an applied gaming intervention. Specifically, the present paper contributes (1) a literature-based understanding on training socioemotional skills as a novel means to reduce feelings of loneliness in chronically ill children, (2) intervention objectives that are aligned to this goal, and (3) a structured proposal for design guidelines that implement the intervention objectives into gRuby's Mission'; an applied gaming intervention for reducing loneliness of children with chronic illness

Game mechanics in eHealth interventions promoting self-management in young people with chronic diseases: a protocol for a systematic review and meta-analyses from the eHealth Junior Consortium

INTRODUCTION: Young people (aged 10-25 years) with chronic diseases are vulnerable to have reduced social participation and quality of life. It is important to empower young people to engage in their chronic diseases self-management. In comparison with traditional face-to-face care, interventions delivered through the internet and related technologies (eHealth) are less stigmatising and more accessible. Gamified eHealth self-management interventions may be particularly promising for young people. This systematic review aims at identifying (1) the game mechanics that have been implemented in eHealth interventions to support young people's self-management of their chronic (somatic or psychiatric) diseases, (2) the investigators' rationale for implementing such game mechanics and, if possible, (3) the effects of these interventions. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement guidelines will be followed. A systematic search of the literature will be conducted in Embase, Psycinfo and Web of Science from inception until 30 August 2022. Studies will be eligible if focused on (1) young people (aged 10-25 years) with chronic diseases and (2) describing gamified eHealth self-management interventions. When possible, the effects of the gamified interventions will be compared with non-gamified interventions or care-as-usual. Primary quantitative, qualitative or mixed-method studies written in English will be included. Two independent reviewers will (1) select studies, (2) extract and summarise the implemented game mechanics as well as the characteristics of the intervention and study, (3) evaluate their methodological quality and (4) synthesise the evidence. The reviewers will reach a consensus through discussion, and if required, a third researcher will be consulted. ETHICS AND DISSEMINATION: As systematic reviews use publicly available data, no formal ethical review and approval are needed. Findings will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders including patient organisations via the eHealth Junior Consortium. PROSPERO REGISTRATION NUMBER: CRD42021293037

Game mechanics in eHealth interventions promoting self-management in young people with chronic diseases: a protocol for a systematic review and meta-analyses from the eHealth Junior Consortium

INTRODUCTION: Young people (aged 10-25 years) with chronic diseases are vulnerable to have reduced social participation and quality of life. It is important to empower young people to engage in their chronic diseases self-management. In comparison with traditional face-to-face care, interventions delivered through the internet and related technologies (eHealth) are less stigmatising and more accessible. Gamified eHealth self-management interventions may be particularly promising for young people. This systematic review aims at identifying (1) the game mechanics that have been implemented in eHealth interventions to support young people's self-management of their chronic (somatic or psychiatric) diseases, (2) the investigators' rationale for implementing such game mechanics and, if possible, (3) the effects of these interventions. METHODS AND ANALYSIS: The Preferred Reporting Items for Systematic reviews and Meta-Analysis statement guidelines will be followed. A systematic search of the literature will be conducted in Embase, Psycinfo and Web of Science from inception until 30 August 2022. Studies will be eligible if focused on (1) young people (aged 10-25 years) with chronic diseases and (2) describing gamified eHealth self-management interventions. When possible, the effects of the gamified interventions will be compared with non-gamified interventions or care-as-usual. Primary quantitative, qualitative or mixed-method studies written in English will be included. Two independent reviewers will (1) select studies, (2) extract and summarise the implemented game mechanics as well as the characteristics of the intervention and study, (3) evaluate their methodological quality and (4) synthesise the evidence. The reviewers will reach a consensus through discussion, and if required, a third researcher will be consulted. ETHICS AND DISSEMINATION: As systematic reviews use publicly available data, no formal ethical review and approval are needed. Findings will be published in peer-reviewed journals, presented at conferences and communicated to relevant stakeholders including patient organisations via the eHealth Junior Consortium. PROSPERO REGISTRATION NUMBER: CRD42021293037.Design Aesthetic

Ten-year follow-up of the observational RASTER study, prospective evaluation of the 70-gene signature in ER-positive, HER2-negative, node-negative, early breast cancer

Introduction: Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited. Methods: In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint). The results were provided to their treating physician to be incorporated in the decision-making on adjuvant systemic therapy. Here, we report the long-term outcome of the 310 patients with ER-positive, HER2-negative tumours by clinical and genomic risk categories at a median follow-up of 10.3 years. Results: Among the clinically high-risk patients, 45 (49%) were classified as genomically low risk. In this subgroup, at 10 years, distant recurrence free interval (DRFI) was similar between patients treated with (95.7% [95% CI 87.7–100]) and without (95.5% [95% CI 87.1–100]) chemotherapy. Within the group of clinically low-risk patients, 56 (26%) were classified as genomically high risk. Within the clinically low-risk group, beyond 5 years, a difference emerged between the genomically high- and low-risk subgroup resulting in a 10-year DRFI of 84.3% (95% CI 74.8–95.0) and 93.4% (95% CI 89.5–97.5), respectively. Interestingly, genomic ultralow-risk patients have a 10-year DRFI of 96.7% (95% CI 90.5–100), largely (79%) without systemic therapy. Conclusions: These data confirm that clinically high-risk, genomically low-risk tumours have an excellent outcome in the real-world setting of shared decision-making. Together with the updated results of the MINDACT trial, these data support the use of the MammaPrint, in ER-positive, HER2-negative, node-negative, clinically high-risk breast cancer patients

Ten-year follow-up of the observational RASTER study, prospective evaluation of the 70-gene signature in ER-positive, HER2-negative, node-negative, early breast cancer

Introduction: Prognostic gene expression signatures can be used in combination with classical clinicopathological factors to guide adjuvant chemotherapy decisions in ER-positive, HER2-negative breast cancer. However, long-term outcome data after introduction of genomic testing in the treatment decision-making process are limited. Methods: In the prospective RASTER study, the tumours of 427 patients with cTanyN0M0 breast cancer were tested to assess the 70-gene signature (MammaPrint). The results were provided to their treating physician to be incorporated in the decision-making on adjuvant systemic therapy. Here, we report the long-term outcome of the 310 patients with ER-positive, HER2-negative tumours by clinical and genomic risk categories at a median follow-up of 10.3 years. Results: Among the clinically high-risk patients, 45 (49%) were classified as genomically low risk. In this subgroup, at 10 years, distant recurrence free interval (DRFI) was similar between patients treated with (95.7% [95% CI 87.7–100]) and without (95.5% [95% CI 87.1–100]) chemotherapy. Within the group of clinically low-risk patients, 56 (26%) were classified as genomically high risk. Within the clinically low-risk group, beyond 5 years, a difference emerged between the genomically high- and low-risk subgroup resulting in a 10-year DRFI of 84.3% (95% CI 74.8–95.0) and 93.4% (95% CI 89.5–97.5), respectively. Interestingly, genomic ultralow-risk patients have a 10-year DRFI of 96.7% (95% CI 90.5–100), largely (79%) without systemic therapy. Conclusions: These data confirm that clinically high-risk, genomically low-risk tumours have an excellent outcome in the real-world setting of shared decision-making. Together with the updated results of the MINDACT trial, these data support the use of the MammaPrint, in ER-positive, HER2-negative, node-negative, clinically high-risk breast cancer patients. Registry: ISRCTN7191791

Comparison of the sentinel node procedure between patients with multifocal and unifocal breast cancer in the EORTC 10981-22023 AMAROS Trial:Identification rate and nodal outcome

<p>Introduction: Multifocal breast cancer is associated with a higher risk of nodal involvement compared to unifocal breast cancer and the drainage pattern from multifocal localisations may be different. For this reason, the value of the sentinel node biopsy ( SNB) procedure for this indication is debated. The aim of the current analysis was to evaluate the sentinel node identification rate and nodal involvement in patients with a multifocal tumour in the EORTC 10981-22023 AMAROS trial.</p><p>Patients and Methods: From the first 4000 registered patients, 342 were identified with a multifocal tumour on histological examination and compared to a randomly selected control group of 684 patients with a unifocal tumour. The outcome of the SNB was assessed.</p><p>Results: The sentinel node was identified in 96% of the patients with a multifocal tumour and in 98% of those with unifocal disease. In the multifocal group, 51% had a metastasis in the sentinel node compared to 28% in the unifocal group; and further nodal involvement after a positive sentinel node was found in 40% (38/95) and 39% (39/101) respectively.</p><p>Conclusion: In this prospective international multicentre study, the 96% detection rate indicates that the SNB procedure can be highly effective in patients with a multifocal tumour. Though the tumour-positive rate of the sentinel node was twice as high in the multifocal group compared to the unifocal group, further nodal involvement after a positive sentinel node was similar in both groups. This suggests that the SNB procedure is safe in patients with multifocal breast cancer. (C) 2013 Elsevier Ltd. All rights reserved.</p>

Radiotherapy or Surgery of the Axilla After a Positive Sentinel Node in Breast Cancer: 10-Year Results of the Randomized Controlled EORTC 10981-22023 AMAROS Trial

PURPOSE: The European Organisation for Research and Treatment of Cancer 10981-22023 AMAROS trial evaluated axillary lymph node dissection (ALND) versus axillary radiotherapy (ART) in patients with cT1-2, node-negative breast cancer and a positive sentinel node (SN) biopsy. At 5 years, both modalities showed excellent and comparable axillary control, with significantly less morbidity after ART. We now report the preplanned 10-year analysis of the axillary recurrence rate (ARR), overall survival (OS), and disease-free survival (DFS), and an updated 5-year analysis of morbidity and quality of life. METHODS: In this open-label multicenter phase III noninferiority trial, 4,806 patients underwent SN biopsy; 1,425 were node-positive and randomly assigned to either ALND (n = 744) or ART (n = 681). RESULTS: Per intention-to-treat analysis, 10-year ARR cumulative incidence was 0.93% (95% CI, 0.18 to 1.68; seven events) after ALND and 1.82% (95% CI, 0.74 to 2.94; 11 events) after ART (hazard ratio [HR], 1.71; 95% CI, 0.67 to 4.39). There were no differences in OS (HR, 1.17; 95% CI, 0.89 to 1.52) or DFS (HR, 1.19; 95% CI, 0.97 to 1.46). ALND was associated with a higher lymphedema rate in updated 5-year analyses (24.5% v 11.9%; P < .001). Quality-of-life scales did not differ by treatment through 5 years. Exploratory analysis showed a 10-year cumulative incidence of second primary cancers of 12.1% (95% CI, 9.6 to 14.9) after ART and 8.3% (95% CI, 6.3 to 10.7) after ALND. CONCLUSION: This 10-year analysis confirms a low ARR after both ART and ALND with no difference in OS, DFS, and locoregional control. Considering less arm morbidity, ART is preferred over ALND for patients with SN-positive cT1-2 breast cancer