Men considering the prostate specific antigen (PSA) test for prostate cancer, an increasingly common male cancer, are encouraged to make informed decisions, as the test is limited in its accuracy and ...the natural history of the condition is poorly understood. The Web-based PSA decision aid, Prosdex, was developed as part of the UK Prostate Cancer Risk Management Programme in order to help men make such informed decisions.
The aim of this study was to evaluate the effect of the Web-based PSA decision aid, Prosdex, on informed decision making.
A Web-based randomized controlled trial was conducted in South Wales, United Kingdom. Men aged 50 to 75 who had not previously had a PSA test were randomly allocated to two intervention and two control groups. Participants in the intervention groups either viewed Prosdex or were given a paper version of the text. The main outcome measures were the three components of informed decision making: (1) knowledge of prostate cancer and PSA, (2) attitude toward PSA testing, (3) behavior using a proxy measure, intention to undergo PSA testing. Decisional conflict and anxiety were also measured as was uptake of the PSA test. Outcomes were measured by means of an online questionnaire for the Prosdex group, the paper version group, and one of two control groups. Six months later, PSA test uptake was ascertained from general practitioners' records, and the online questionnaire was repeated. Results are reported in terms of the Mann-Whitney U-statistic divided by the product of the two sample sizes (U/mm), line of no effect 0.50.
Participants were 514 men. Compared with the control group that completed the initial online questionnaire, men in the Prosdex group had increased knowledge about the PSA test and prostate cancer (U/mn 0.70; 95% CI 0.62 - 0.76); less favourable attitudes to PSA testing (U/mn 0.39, 95% CI 0.31 - 0.47); were less likely to undergo PSA testing (U/mn 0.40, 95% CI 0.32 - 0.48); and had less decisional conflict (U/mn 0.32, 95% CI 0.25 - 0.40); while anxiety level did not differ (U/mn 0.50, 95% CI 0.42 - 0.58). For these outcomes there were no significant differences between men in the Prosdex group and the paper version group. However, in the Prosdex group, increased knowledge was associated with a less favourable attitude toward testing (Spearman rank correlation rho = -0.49, P < .001) and lower intention to undergo testing (rho = -0.27, P = .02). After six months, PSA test uptake was lower in the Prosdex group than in the paper version and the questionnaire control group (P = .014). Test uptake was also lower in the control group that did not complete a questionnaire than in the control group that did, suggesting a possible Hawthorne effect of the questionnaire in favour of PSA testing.
Exposure to Prosdex was associated with improved knowledge about the PSA test and prostate cancer. Men who had a high level of knowledge had a less favourable attitude toward and were less likely to undergo PSA testing. Prosdex appears to promote informed decision making regarding the PSA test.
ISRCTN48473735; http://www.controlled-trials.com/ISRCTN48473735 (Archived by WebCite at http://www.webcitation.org/5r1TLQ5nK).
BackgroundPreventing mental health problems in early adolescence is a priority. School-based mindfulness training (SBMT) is an approach with mixed evidence.ObjectivesTo explore for whom SBMT ...does/does not work and what influences outcomes.MethodsThe My Resilience in Adolescence was a parallel-group, cluster randomised controlled trial (K=84 secondary schools; n=8376 students, age: 11–13) recruiting schools that provided standard social–emotional learning. Schools were randomised 1:1 to continue this provision (control/teaching as usual (TAU)), and/or to offer SBMT (‘.b’ (intervention)). Risk of depression, social–emotional–behavioural functioning and well-being were measured at baseline, preintervention, post intervention and 1 year follow-up. Hypothesised moderators, implementation factors and mediators were analysed using mixed effects linear regressions, instrumental variable methods and path analysis.FindingsSBMT versus TAU resulted in worse scores on risk of depression and well-being in students at risk of mental health problems both at post intervention and 1-year follow-up, but differences were small and not clinically relevant. Higher dose and reach were associated with worse social–emotional–behavioural functioning at postintervention. No implementation factors were associated with outcomes at 1-year follow-up. Pregains−postgains in mindfulness skills and executive function predicted better outcomes at 1-year follow-up, but the SBMT was unsuccessful to teach these skills with clinical relevance.SBMT as delivered in this trial is not indicated as a universal intervention. Moreover, it may be contraindicated for students with existing/emerging mental health symptoms.Clinical implicationsUniversal SBMT is not recommended in this format in early adolescence. Future research should explore social−emotional learning programmes adapted to the unique needs of young people.
Although several cancer immunotherapy strategies are based on the use of analog peptides and on the modulation of the TCR affinity of adoptively transferred T cells, it remains unclear whether ...tumor-specific T cell activation by strong and weak TCR stimuli evoke different Ca(2+) signatures from the Ca(2+) intracellular stores and whether the amplitude of Ca(2+) release from the endoplasmic reticulum (ER) can be further modulated by coreceptor binding to peptide/MHC. In this study, we combined functional, structural, and kinetic measurements to correlate the intensity of Ca(2+) signals triggered by the stimulation of the 1G4 T cell clone specific to the tumor epitope NY-ESO-1(157-165). Two analogs of the NY-ESO-1(157-165) peptide, having similar affinity to HLA-A2 molecules, but a 6-fold difference in binding affinity for the 1G4 TCR, resulted in different Ca(2+) signals and T cell activation. 1G4 stimulation by the stronger stimulus emptied the ER of stored Ca(2+), even in the absence of CD8 binding, resulting in sustained Ca(2+) influx. In contrast, the weaker stimulus induced only partial emptying of stored Ca(2+), resulting in significantly diminished and oscillatory Ca(2+) signals, which were enhanced by CD8 binding. Our data define the range of TCR/peptide MHC affinities required to induce depletion of Ca(2+) from intracellular stores and provide insights into the ability of T cells to tailor the use of the CD8 coreceptor to enhance Ca(2+) release from the ER. This, in turn, modulates Ca(2+) influx from the extracellular environment, ultimately controlling T cell activation.
Creative outputs engage the public and can be used to share research. This paper reports on public engagement activities that were part of the research project Dementia and Imagination (D&I). We ...found that artwork and creative activities effectively engaged a range of audiences and challenged negative ideas about dementia. For the project team, public engagement developed relationships with collaborators and connected the research to different community settings, influencing future programmes of work. Further work could explore public engagement in diverse settings to assess which approaches are effective in maximising research value and wider community benefit.
The effectiveness of anti-obesity medications for children and adolescents is unclear.
To update the evidence on the benefits and harms of anti-obesity medication.
Cochrane CENTRAL, MEDLINE, ...ClinicalTrials.gov and WHO ICTRP (1/1/16-17/3/23).
Randomized controlled trials ≥6 months in people <19 years living with obesity.
Screening, data extraction and quality assessment conducted in duplicate, independently.
Body mass index (BMI): 95th percentile BMI, adverse events and quality of life.
Thirty-five trials (N = 4331), follow-up: 6-24 months; age: 8.8-16.3 years; BMI: 26.2-41.7 kg/m
. Moderate certainty evidence demonstrated a -1.71 (95% confidence interval CI: -2.27 to -1.14)-unit BMI reduction, ranging from -0.8 to -5.9 units between individual drugs with semaglutide producing the largest reduction of -5.88 kg/m
(95% CI: -6.99 to -4.77, N = 201). Drug type explained ~44% of heterogeneity. Low certainty evidence demonstrated reduction in 95th percentile BMI: -11.88 percentage points (95% CI: -18.43 to -5.30, N = 668). Serious adverse events and study discontinuation due to adverse events did not differ between medications and comparators, but medication dose adjustments were higher compared to comparator (10.6% vs 1.7%; RR = 3.74 95% CI: 1.51 to 9.26, I
= 15%), regardless of approval status. There was a trend towards improved quality of life. Evidence gaps exist for children, psychosocial outcomes, comorbidities and weight loss maintenance.
Anti-obesity medications in addition to behaviour change improve BMI but may require dose adjustment, with 1 in 100 adolescents experiencing a serious adverse event.
Abstract
Background
Cancer and dementia are common in older people and management of the conditions as comorbidities can be challenging, yet little is known about the size or characteristics of this ...group. We aimed to estimate the prevalence, characteristics and general practice resource usage of people living with both conditions in England.
Methods
Anonymised electronic healthcare records from 391 National Health Service general practices across England using the TPP SystmOne general practice system were obtained from ResearchOne. Data included demographic and clinical characteristics, and general practice healthcare useage (appointments, prescriptions, referrals and secondary care contacts) for people aged 50 and over with a cancer and/or dementia diagnosis consistent with the Quality and Outcomes Framework between 2005 and 2016. Multi-level negative binomial regression was used to analyse the association between having cancer and/or dementia and the number of general practice appointments.
Results
Data from 162,371 people with cancer and/or dementia were analysed; 3616 (2.2%) people were identified as having comorbid cancer and dementia. Of people with cancer, 3.1% also had dementia, rising to 7.5% (1 in 13 people) in those aged 75 and over. Fewer people with both conditions were female (50.7%) compared to those with dementia alone (65.6%) and those with comorbid cancer and dementia were older than those with cancer alone mean ages 83 (sd = 7), 69 (sd = 12) respectively. Those with both conditions were less likely to have lung cancer than those with cancer alone (7.5% vs. 10.3%) but more likely to have prostate cancer (20.9% vs. 15.8%). Additional comorbidities were more prevalent for those with both conditions than those with cancer or dementia alone (68.4% vs. 50.2% vs. 54.0%). In the year following the first record of either condition, people with cancer and dementia had 9% more general practice appointments (IRR:1.09, 95% CI:1.01–1.17) than those with cancer alone and 37% more appointments than those with dementia alone (IRR: 1.37, 95% CI: 1.28–1.47).
Conclusions
A significant number of people are living with comorbid cancer and dementia in England. This group have additional comorbidity and higher general practice usage than those with cancer/dementia alone. The needs of this group should be considered in future general practice care planning and research.
Knickpoint evolution in a supraglacial stream Kamintzis, J. E.; Irvine-Fynn, T. D. L.; Holt, T. O. ...
Geografiska annaler. Series A, Physical geography,
20/4/3/, Letnik:
101, Številka:
2
Journal Article
Recenzirano
Odprti dostop
Despite numerous studies of knickpoints in bedrock and alluvial channels, no detailed description of knickpoint change on ice has been reported to date. This paper presents the first investigation of ...knickpoint evolution within a supraglacial stream. Repeat longitudinal profile surveys of a knickpoint on Vadrec del Forno, Switzerland reveal a step height increase of 115 mm and upstream migration of 0.26 m over three days during the 2017 ablation season. Rates and magnitudes of erosion vary spatially across the knickpoint in relation to differing discharge regimes. At high discharges (∼0.013 m
3
s
−1
), erosion is focused at the step base; at low discharges (∼0.003 m
3
s
−1
), erosion is focused on the reach upstream of the knickpoint, at the step lip and the step-riser face. This results in replacement of knickpoint morphology, driven by frictional thermal erosion and hydraulic action. Pool formation further influences step morphology, inducing secondary circulation and increased melt at the base of the step-riser, causing steepening. Results highlight the complexities of water flow over knickpoints, demonstrating that the stream power law does not accurately characterise changing knickpoint morphology or predict retreat rates. Although morphological similarities have been reported between supraglacial and bedrock/alluvial channels, knickpoints in non-ice-walled channels will not necessarily respond to discharge similarly to those on ice due to the different erosional processes involved.
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