Quality of Life of Caregivers of Older Patients with Advanced Cancer

OBJECTIVES: To evaluate the relationships between aging-related domains captured by geriatric assessment (GA) for older patients with advanced cancer and caregivers’ emotional health and quality of life (QOL). DESIGN: In this cross sectional study of baseline data from a nationwide investigation of older patients and their caregivers, patients completed a GA that included validated tests to evaluate eight domains of health (eg, function, cognition). SETTING: Thirty-one community oncology practices throughout the United States. PARTICIPANTS: Enrolled patients were aged 70 and older, had one or more GA domain impaired, and had an incurable solid tumor malignancy or lymphoma. Each could choose one caregiver to enroll. MEASUREMENTS: Caregivers completed the Generalized Anxiety Disorder-7, Distress Thermometer, Patient Health Questionnaire-2 (depression), and Short Form Health Survey-12 (SF-12 for QOL). Separate multivariate linear or logistic regression models were used to examine the association of the number and type of patient GA impairments with caregiver outcomes, controlling for patient and caregiver covariates. RESULTS: A total of 541 patients were enrolled, 414 with a caregiver. Almost half (43.5%) of the caregivers screened positive for distress, 24.4% for anxiety, and 18.9% for depression. Higher numbers of patient GA domain impairments were associated with caregiver depression (adjusted odds ratio [aOR] = 1.29; P <.001], caregiver physical health on SF-12 (regression coefficient [β] = −1.24; P <.001), and overall caregiver QOL (β = −1.14; P <.01). Impaired patient function was associated with lower caregiver QOL (β = −4.11; P <.001). Impaired patient nutrition was associated with caregiver depression (aOR = 2.08; P <.01). Lower caregiver age, caregiver comorbidity, and patient distress were also associated with worse caregiver outcomes. CONCLUSION: Patient GA impairments were associated with poorer emotional health and lower QOL of caregivers

Anti-GD2 CAR-NKT cells in relapsed or refractory neuroblastoma: updated phase 1 trial interim results

Vα24-invariant natural killer T cells (NKTs) have anti-tumor properties that can be enhanced by chimeric antigen receptors (CARs). Here we report updated interim results from the first-in-human phase 1 evaluation of autologous NKTs co-expressing a GD2-specific CAR with interleukin 15 (IL15) (GD2-CAR.15) in 12 children with neuroblastoma (NB). The primary objectives were safety and determination of maximum tolerated dose (MTD). The anti-tumor activity of GD2-CAR.15 NKTs was assessed as a secondary objective. Immune response evaluation was an additional objective. No dose-limiting toxicities occurred; one patient experienced grade 2 cytokine release syndrome that was resolved by tocilizumab. The MTD was not reached. The objective response rate was 25% (3/12), including two partial responses and one complete response. The frequency of CD62L+NKTs in products correlated with CAR-NKT expansion in patients and was higher in responders (n = 5; objective response or stable disease with reduction in tumor burden) than non-responders (n = 7). BTG1 (BTG anti-proliferation factor 1) expression was upregulated in peripheral GD2-CAR.15 NKTs and is a key driver of hyporesponsiveness in exhausted NKT and T cells. GD2-CAR.15 NKTs with BTG1 knockdown eliminated metastatic NB in a mouse model. We conclude that GD2-CAR.15 NKTs are safe and can mediate objective responses in patients with NB. Additionally, their anti-tumor activity may be enhanced by targeting BTG1. ClinicalTrials.gov registration: NCT03294954

School-based prevention for adolescent Internet addiction: prevention is the key. A systematic literature review

Adolescents’ media use represents a normative need for information, communication, recreation and functionality, yet problematic Internet use has increased. Given the arguably alarming prevalence rates worldwide and the increasingly problematic use of gaming and social media, the need for an integration of prevention efforts appears to be timely. The aim of this systematic literature review is (i) to identify school-based prevention programmes or protocols for Internet Addiction targeting adolescents within the school context and to examine the programmes’ effectiveness, and (ii) to highlight strengths, limitations, and best practices to inform the design of new initiatives, by capitalizing on these studies’ recommendations. The findings of the reviewed studies to date presented mixed outcomes and are in need of further empirical evidence. The current review identified the following needs to be addressed in future designs to: (i) define the clinical status of Internet Addiction more precisely, (ii) use more current psychometrically robust assessment tools for the measurement of effectiveness (based on the most recent empirical developments), (iii) reconsider the main outcome of Internet time reduction as it appears to be problematic, (iv) build methodologically sound evidence-based prevention programmes, (v) focus on skill enhancement and the use of protective and harm-reducing factors, and (vi) include IA as one of the risk behaviours in multi-risk behaviour interventions. These appear to be crucial factors in addressing future research designs and the formulation of new prevention initiatives. Validated findings could then inform promising strategies for IA and gaming prevention in public policy and education

RANTES/CCL5 and risk for coronary events: Results from the MONICA/KORA Augsburg case-cohort, Athero-express and CARDIoGRAM studies

Background: The chemokine RANTES (regulated on activation, normal T-cell expressed and secreted)/CCL5 is involved in the pathogenesis of cardiovascular disease in mice, whereas less is known in humans. We hypothesised that its relevance for atherosclerosis should be reflected by associations between CCL5 gene variants, RANTES serum concentrations and protein levels in atherosclerotic plaques and risk for coronary events. Methods and Findings: We conducted a case-cohort study within the population-based MONICA/KORA Augsburg studies. Baseline RANTES serum levels were measured in 363 individuals with incident coronary events and 1,908 non-cases (mean follow-up: 10.2±

Short-term calorie restriction enhances adult hippocampal neurogenesis and remote fear memory in a Ghsr-dependent manner

The beneficial effects of calorie restriction (CR) have been described at both organismal and cellular levels in multiple organs. However, our understanding of the causal mediators of such hormesis is poorly understood, particularly in the context of higher brain function. Here, we show that the receptor for the orexigenic hormone acyl-ghrelin, the growth hormone secretagogue receptor (Ghsr), is enriched in the neurogenic niche of the hippocampal dentate gyrus (DG). Acute elevation of acyl-ghrelin levels by injection or by overnight CR, increased DG levels of the neurogenic transcription factor, Egr-1. Two weeks of CR increased the subsequent number of mature newborn neurons in the DG of adult wild-type but not Ghsr−/− mice. CR wild-type mice also showed improved remote contextual fear memory. Our findings suggest that Ghsr mediates the beneficial effects of CR on enhancing adult hippocampal neurogenesis and memory

The performance of the jet trigger for the ATLAS detector during 2011 data taking

The performance of the jet trigger for the ATLAS detector at the LHC during the 2011 data taking period is described. During 2011 the LHC provided proton–proton collisions with a centre-of-mass energy of 7 TeV and heavy ion collisions with a 2.76 TeV per nucleon–nucleon collision energy. The ATLAS trigger is a three level system designed to reduce the rate of events from the 40 MHz nominal maximum bunch crossing rate to the approximate 400 Hz which can be written to offline storage. The ATLAS jet trigger is the primary means for the online selection of events containing jets. Events are accepted by the trigger if they contain one or more jets above some transverse energy threshold. During 2011 data taking the jet trigger was fully efficient for jets with transverse energy above 25 GeV for triggers seeded randomly at Level 1. For triggers which require a jet to be identified at each of the three trigger levels, full efficiency is reached for offline jets with transverse energy above 60 GeV. Jets reconstructed in the final trigger level and corresponding to offline jets with transverse energy greater than 60 GeV, are reconstructed with a resolution in transverse energy with respect to offline jets, of better than 4 % in the central region and better than 2.5 % in the forward direction

Geographical and temporal distribution of SARS-CoV-2 clades in the WHO European Region, January to June 2020

We show the distribution of SARS-CoV-2 genetic clades over time and between countries and outline potential genomic surveillance objectives. We applied three available genomic nomenclature systems for SARS-CoV-2 to all sequence data from the WHO European Region available during the COVID-19 pandemic until 10 July 2020. We highlight the importance of real-time sequencing and data dissemination in a pandemic situation. We provide a comparison of the nomenclatures and lay a foundation for future European genomic surveillance of SARS-CoV-2.Peer reviewe

The impact of a large-scale quality improvement programme on work engagement: preliminary results from a national cross-sectional-survey of the 'Productive Ward'

Background: Quality improvement (QI) Programmes, like the Productive Ward: Releasing-time-to-care initiative, aim to 'engage' and 'empower' ward teams to actively participate, innovate and lead quality improvement at the front line. However, little is known about the relationship and impact that QI work has on the 'engagement' of the clinical teams who participate and vice-versa. Objective: This paper explores and examines the impact of a large-scale QI programme, the Productive Ward, on the 'work engagement' of the nurses and ward teams involved. Design/methods: Using the Utrecht Work Engagement Scale (UWES), we surveyed, measured and analysed work engagement in a representative test group of hospital-based ward teams who had recently commenced the latest phase of the national 'Productive Ward' initiative in Ireland and compared them to a control group of similar size and matched (as far as is possible) on variables such as ward size, employment grade and clinical specialty area. Results: 338 individual datasets were recorded, n=. 180 (53.6) from the Productive Ward group, and n=. 158 (46.4) from the control group; the overall response rate was 67, and did not differ significantly between the Productive Ward and control groups. The work engagement mean score (±standard deviation) in the Productive group was 4.33(±0.88), and 4.07(±1.06) in the control group, representing a modest but statistically significant between-group difference (. p=. 0.013, independent samples t-test). Similarly modest differences were observed in all three dimensions of the work engagement construct. Employment grade and the clinical specialty area were also significantly related to the work engagement score (. p<. 0.001, general linear model) and (for the most part), to its components, with both clerical and nurse manager grades, and the elderly specialist areas, exhibiting substantially higher scores. Conclusions: The findings demonstrate how QI activities, like those integral to the Productive Ward programme, appear to positively impact on the work engagement (the vigour, absorption and dedication) of ward-based teams. The use and suitability of the UWES as an appropriate measure of 'engagement' in QI interventions was confirmed. The engagement of nurses and front-line clinical teams is a major component of creating, developing and sustaining a culture of improvement. © 2014 The Authors