Informing the structure of executive function in children: a meta-analysis of functional neuroimaging data

The structure of executive function (EF) has been the focus of much debate for decades. What is more, the complexity and diversity provided by the developmental period only adds to this contention. The development of executive function plays an integral part in the expression of children's behavioral, cognitive, social, and emotional capabilities. Understanding how these processes are constructed during development allows for effective measurement of EF in this population. This meta-analysis aims to contribute to a better understanding of the structure of executive function in children. A coordinate-based meta-analysis was conducted (using BrainMap GingerALE 2.3), which incorporated studies administering functional magnetic resonance imaging (fMRI) during inhibition, switching, and working memory updating tasks in typical children (aged 6–18 years). The neural activation common across all executive tasks was compared to that shared by tasks pertaining only to inhibition, switching or updating, which are commonly considered to be fundamental executive processes. Results support the existence of partially separable but partially overlapping inhibition, switching, and updating executive processes at a neural level, in children over 6 years. Further, the shared neural activation across all tasks (associated with a proposed “unitary” component of executive function) overlapped to different degrees with the activation associated with each individual executive process. These findings provide evidence to support the suggestion that one of the most influential structural models of executive functioning in adults can also be applied to children of this age. However, the findings also call for careful consideration and measurement of both specific executive processes, and unitary executive function in this population. Furthermore, a need is highlighted for a new systematic developmental model, which captures the integrative nature of executive function in children

Factors that affect quality of life for older people with head and neck cancer: A systematic review

Purpose: Quality of life is a critical aspect in the management of older head and neck cancer patients. It needs to be considered alongside survival benefit, treatment burden, and longer-term outcomes. The purpose was to undertake a systematic review of empirical peer-reviewed studies with a primary focus on factors impacting quality of life for older head and neck cancer patients. Methods: A systematic review, searching 5 electronic databases (PsychoINFO, MEDLINE, CINHAL, Embase, and Scopus) using PRISMA methodology was conducted. Data was appraised using the Newcastle-Ottawa scale and a narrative synthesis performed. Results: Only 10 papers fulfilled the inclusion criteria. Two main themes emerged: 1) Impact of head and neck cancer on quality of life domains and 2) quality of life in treatment decision-making. Conclusions: In an era of progressive personalised care, there is an evident need for more qualitative and quantitative studies focusing on quality of life for older head and neck cancer patients. However, older head and neck cancer patients experience notable differences, especially with poorer physical functioning and greater eating and drinking challenges. Quality of life impacts older patients decision-making, treatment planning and intensifies post-treatment support

Adding 6 months of androgen deprivation therapy to postoperative radiotherapy for prostate cancer: a comparison of short-course versus no androgen deprivation therapy in the RADICALS-HD randomised controlled trial

Background Previous evidence indicates that adjuvant, short-course androgen deprivation therapy (ADT) improves metastasis-free survival when given with primary radiotherapy for intermediate-risk and high-risk localised prostate cancer. However, the value of ADT with postoperative radiotherapy after radical prostatectomy is unclear. Methods RADICALS-HD was an international randomised controlled trial to test the efficacy of ADT used in combination with postoperative radiotherapy for prostate cancer. Key eligibility criteria were indication for radiotherapy after radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to radiotherapy alone (no ADT) or radiotherapy with 6 months of ADT (short-course ADT), using monthly subcutaneous gonadotropin-releasing hormone analogue injections, daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as distant metastasis arising from prostate cancer or death from any cause. Standard survival analysis methods were used, accounting for randomisation stratification factors. The trial had 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 80% to 86% (hazard ratio [HR] 0·67). Analyses followed the intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov, NCT00541047. Findings Between Nov 22, 2007, and June 29, 2015, 1480 patients (median age 66 years [IQR 61–69]) were randomly assigned to receive no ADT (n=737) or short-course ADT (n=743) in addition to postoperative radiotherapy at 121 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 9·0 years (IQR 7·1–10·1), metastasis-free survival events were reported for 268 participants (142 in the no ADT group and 126 in the short-course ADT group; HR 0·886 [95% CI 0·688–1·140], p=0·35). 10-year metastasis-free survival was 79·2% (95% CI 75·4–82·5) in the no ADT group and 80·4% (76·6–83·6) in the short-course ADT group. Toxicity of grade 3 or higher was reported for 121 (17%) of 737 participants in the no ADT group and 100 (14%) of 743 in the short-course ADT group (p=0·15), with no treatment-related deaths. Interpretation Metastatic disease is uncommon following postoperative bed radiotherapy after radical prostatectomy. Adding 6 months of ADT to this radiotherapy did not improve metastasis-free survival compared with no ADT. These findings do not support the use of short-course ADT with postoperative radiotherapy in this patient population

Duration of androgen deprivation therapy with postoperative radiotherapy for prostate cancer: a comparison of long-course versus short-course androgen deprivation therapy in the RADICALS-HD randomised trial

Background Previous evidence supports androgen deprivation therapy (ADT) with primary radiotherapy as initial treatment for intermediate-risk and high-risk localised prostate cancer. However, the use and optimal duration of ADT with postoperative radiotherapy after radical prostatectomy remains uncertain. Methods RADICALS-HD was a randomised controlled trial of ADT duration within the RADICALS protocol. Here, we report on the comparison of short-course versus long-course ADT. Key eligibility criteria were indication for radiotherapy after previous radical prostatectomy for prostate cancer, prostate-specific antigen less than 5 ng/mL, absence of metastatic disease, and written consent. Participants were randomly assigned (1:1) to add 6 months of ADT (short-course ADT) or 24 months of ADT (long-course ADT) to radiotherapy, using subcutaneous gonadotrophin-releasing hormone analogue (monthly in the short-course ADT group and 3-monthly in the long-course ADT group), daily oral bicalutamide monotherapy 150 mg, or monthly subcutaneous degarelix. Randomisation was done centrally through minimisation with a random element, stratified by Gleason score, positive margins, radiotherapy timing, planned radiotherapy schedule, and planned type of ADT, in a computerised system. The allocated treatment was not masked. The primary outcome measure was metastasis-free survival, defined as metastasis arising from prostate cancer or death from any cause. The comparison had more than 80% power with two-sided α of 5% to detect an absolute increase in 10-year metastasis-free survival from 75% to 81% (hazard ratio [HR] 0·72). Standard time-to-event analyses were used. Analyses followed intention-to-treat principle. The trial is registered with the ISRCTN registry, ISRCTN40814031, and ClinicalTrials.gov , NCT00541047 . Findings Between Jan 30, 2008, and July 7, 2015, 1523 patients (median age 65 years, IQR 60–69) were randomly assigned to receive short-course ADT (n=761) or long-course ADT (n=762) in addition to postoperative radiotherapy at 138 centres in Canada, Denmark, Ireland, and the UK. With a median follow-up of 8·9 years (7·0–10·0), 313 metastasis-free survival events were reported overall (174 in the short-course ADT group and 139 in the long-course ADT group; HR 0·773 [95% CI 0·612–0·975]; p=0·029). 10-year metastasis-free survival was 71·9% (95% CI 67·6–75·7) in the short-course ADT group and 78·1% (74·2–81·5) in the long-course ADT group. Toxicity of grade 3 or higher was reported for 105 (14%) of 753 participants in the short-course ADT group and 142 (19%) of 757 participants in the long-course ADT group (p=0·025), with no treatment-related deaths. Interpretation Compared with adding 6 months of ADT, adding 24 months of ADT improved metastasis-free survival in people receiving postoperative radiotherapy. For individuals who can accept the additional duration of adverse effects, long-course ADT should be offered with postoperative radiotherapy. Funding Cancer Research UK, UK Research and Innovation (formerly Medical Research Council), and Canadian Cancer Society

Interim 2023/24 influenza A vaccine effectiveness: VEBIS European primary care and hospital multicentre studies, September 2023 to January 2024

Influenza A viruses circulated in Europe from September 2023 to January 2024, with influenza A(H1N1)pdm09 predominance. We provide interim 2023/24 influenza vaccine effectiveness (IVE) estimates from two European studies, covering 10 countries across primary care (EU-PC) and hospital (EU-H) settings. Interim IVE was higher against A(H1N1)pdm09 than A(H3N2): EU-PC influenza A(H1N1)pdm09 IVE was 53% (95% CI: 41 to 63) and 30% (95% CI: -3 to 54) against influenza A(H3N2). For EU-H, these were 44% (95% CI: 30 to 55) and 14% (95% CI: -32 to 43), respectively.The ‘Vaccine Effectiveness, Burden and Impact Studies’ (VEBIS) is a project of the European Centre for Disease Prevention and Control (ECDC) run under the framework contract No. ECDC/2021/019 (EU-PC) and ECDC/2021/016 (EU-H).S

Utility estimation in chronic obstructive pulmonary disease: a preference for change?

Economic evaluations of chronic obstructive pulmonary disease (COPD) incorporate utilities through multi-attribute utility (MAU) measures, most commonly the EQ-5D, to report health-related quality-of-life (HR-QOL) changes or differences. Questions have been raised about the sensitivity of these measures in COPD. Limitations in detecting adequate patient-level changes in HR-QOL over time in stable and exacerbation states compared with disease-specific instruments could also result in underestimation of known treatment benefits. The purpose of this article was to present and discuss the empirical evidence on the validity of generic MAU measures within the COPD population. We built upon a previously conducted validation review for the period 1997-2007 that used 'respiratory disease' and 'EQ-5D' as keywords. For this discussion, PubMed and EMBASE databases were searched for articles in English from 1988 to August 2009, using similar search words. Based on the performance of MAU measures in COPD and exacerbations, they appear to have limited discriminatory ability, particularly between moderate and severe COPD, despite known differences in HR-QOL. Sensitivity to clinically relevant change in stable COPD over time due to treatment also appears limited. Current research suggests adequate sensitivity regarding detecting the onset and resolution of an exacerbation; however, sensitivity is limited in the short term, such as daily changes in health status. The evidence suggests responsiveness of MAU measures may be restricted to large within-patient change, which leads to difficulties in evaluating the subtle but important impact of exacerbations. Studies presenting alternative methods of deriving COPD-related utilities are also discussed. Overall, the insensitivities of generic MAU measures in COPD can lead to biased cost-effectiveness analyses and ill-informed economic decisions. Alternative measures such as condition-specific preference-based measures may be used in circumstances where more sensitivity is needed. The trade-off allows relevant and sensitive matters most important to patients to be evaluated; however inevitable gaps such as those related to adverse events are not considered