An online evidence-based dictionary of common adverse events of antidepressants: a new tool to empower patients and clinicians in their shared decision-making process

Background: Adverse events (AEs) are commonly reported in clinical studies using the Medical Dictionary for Regulatory Activities (MedDRA), an international standard for drug safety monitoring. However, the technical language of MedDRA makes it challenging for patients and clinicians to share understanding and therefore to make shared decisions about medical interventions. In this project, people with lived experience of depression and antidepressant treatment worked with clinicians and researchers to co-design an online dictionary of AEs associated with antidepressants, taking into account its ease of use and applicability to real-world settings. Methods: Through a pre-defined literature search, we identified MedDRA-coded AEs from randomised controlled trials of antidepressants used in the treatment of depression. In collaboration with the McPin Foundation, four co-design workshops with a lived experience advisory panel (LEAP) and one independent focus group (FG) were conducted to produce user-friendly translations of AE terms. Guiding principles for translation were co-designed with McPin/LEAP members and defined before the finalisation of Clinical Codes (CCs, or non-technical terms to represent specific AE concepts). FG results were thematically analysed using the Framework Method. Results: Starting from 522 trials identified by the search, 736 MedDRA-coded AE terms were translated into 187 CCs, which balanced key factors identified as important to the LEAP and FG (namely, breadth, specificity, generalisability, patient-understandability and acceptability). Work with the LEAP showed that a user-friendly language of AEs should aim to mitigate stigma, acknowledge the multiple levels of comprehension in ‘lay’ language and balance the need for semantic accuracy with user-friendliness. Guided by these principles, an online dictionary of AEs was co-designed and made freely available (https://thesymptomglossary.com). The digital tool was perceived by the LEAP and FG as a resource which could feasibly improve antidepressant treatment by facilitating the accurate, meaningful expression of preferences about potential harms through a shared decision-making process. Conclusions: This dictionary was developed in English around AEs from antidepressants in depression but it can be adapted to different languages and cultural contexts, and can also become a model for other interventions and disorders (i.e., antipsychotics in schizophrenia). Co-designed digital resources may improve the patient experience by helping to deliver personalised information on potential benefits and harms in an evidence-based, preference-sensitive way

Do the effects of interventions aimed at the prevention of childhood obesity reduce inequities? A re-analysis of randomized trial data from two Cochrane reviews

Background: Public health attempts to prevent obesity in children and young people should aim to minimize health inequalities. Two Cochrane reviews examining interventions aiming to prevent childhood obesity found that interventions promoting (only) physical activity have a small beneficial effect on BMI for people aged 5–18 years, as do interventions promoting physical activity alongside healthy eating for 5–11 year olds. We examined whether the effectiveness of the interventions included in these reviews differed according to eight factors associated with inequity: place, race/ethnicity, occupation, gender/sex, religion, education, socio-economic status, and social capital (the PROGRESS framework). Methods: We collected data on change in BMI (standardized or unstandardized), subgrouped by baseline measures of PROGRESS factors, for intervention and control groups, from trial authors. We calculated the intervention effect per subgroup (mean difference), then contrasted these to estimate interactions between intervention and the baseline factors. We combined interaction estimates for each factor across trials using meta-analyses. Findings: We collected subgrouped data from 81 trials that took place between 2001 and 2020, involving 84,713 participants. We found no substantial differences in effectiveness of interventions for PROGRESS subgroups in most scenarios. However, in the younger age group (5–11 years), the effect of interventions on standardized BMI appeared to be higher in boys (average difference in mean differences 0.03; 95% CI 0.01 to 0.06; 45 studies, n = 44,740), which was consistent in direction with the BMI effect (average difference in mean differences 0.06 kg/m2; 95% CI −0.02 to 0.13; 31 studies, n = 27,083). Interpretation: Our findings suggest that those responsible for public health can promote these beneficial interventions without major concerns about increasing inequalities but should be mindful that these interventions may work better in boys aged 5–11 years than girls. More data are needed, so we encourage future trialists to perform subgroup analyses on PROGRESS factors. Funding: National Institute for Health and Care Research (NIHR)

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p<0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p<0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p<0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP >5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

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

Evaluating Mock Juror Decision Making

The purpose of this research is to explore the relationships between a defendant’s gender and racial identity on mock juror perceptions of guilt. Participants will read a vignette detailing a homicide and view one of four mock defendant profiles. Afterward, participants will indicate their recommended verdict and sentence length on a scale from 0-100 years for the defendant. This research is intended to reveal whether a defendant's gender identity (i.e., cisgender versus transgender woman) impacts a juror's decision as to their guilt and recommended sentence, and whether that effect depends on the defendant's racial identity (White or Black). Understanding mock juror perceptions of guilt will help mitigate the influence of personal biases on court decisions

Factors associated with effectiveness of interventions to prevent obesity in children:a synthesis of evidence from 204 randomized trials

Introduction: We aim to identify effective characteristics of behaviour change (physical activity and diet) interventions that prevent obesity in children aged 5 to 18 years. Methods: We re-analysed data from two Cochrane systematic reviews published in 2024 using a Bayesian multi-level meta-regression analysis with intervention and trial characteristics coded according to an analytic framework co-developed with stakeholders.Results: We included 204 trials (255 intervention arms) reporting data on BMI, either unstandardized or measured as a z-score (zBMI) or percentile. Interventions were effective on average (MD in zBMI −0.037, 95% credible interval −0.053 to −0.022). The greatest effects were associated with medium term follow-up (9 to &lt;15 months) and older children (12 to 18 years). We found evidence of small beneficial effects for interventions targeting physical activity alone compared with diet alone (difference in MDs −0.227, −0.362 to −0.090) and small unfavorable effects for interventions that involved a change to the structural environment (typically the school food environment) (difference in MDs 0.05, 0.017 to 0.085). Accounting for interactions between covariates, the most effective combination of intervention characteristics was to intervene in the school setting, with an individualized element to delivery, targeting physical activity, using multiple strategies of short duration and high intensity, and involving modification of behaviour through participation in activities. Conclusions: The most effective characteristic to include in a behaviour change intervention to prevent obesity in children aged 5-18 years was targeting of physical activity. This should not be interpreted as evidence that attempts to modify diet are not beneficial. Being physically active and consuming a healthy diet during childhood offer many important benefits beyond contributing to healthy weight and growth. Our findings suggest that interventions to prevent obesity in children should consider increasing their focus on the promotion of physical activity and consider other effective characteristics we identify here.<br/