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The PReDicT study showed that predictive algorithm-guided antidepressant treatment reduces anxiety and improves functioning in patients with depression.
Aims
To estimate the costs, outcomes and cost-effectiveness of the PReDicT test compared with treatment as usual (TAU) for primary depression care in five European countries.
Method
Within-trial economic analysis was conducted over 24 weeks from the health/social care and societal perspectives alongside the PReDicT trial (NCT02790970) in France, Germany, The Netherlands, Spain, and the UK, according to Consolidated Health Economic Evaluation Reporting Standards guidelines. We calculated quality-adjusted life-years (QALYs) based on the EQ-5D-5L, capability-weighted life-years based on the Oxford Capabilities Questionnaire – Mental Health (OxCAP-MH) (Germany and UK only), and costs for 2018 (€). Multiple imputation for missing data, multivariable regression for cost and outcome differences, and bootstrapping and sensitivity analyses for uncertainty were conducted.
Results
There were significant outcome improvements (EQ-5D-5L PRedicT: +0.139; TAU: +0.140) and societal cost reductions (PRedicT: −€2589; TAU: −€2602) in both groups (N = 913) between the before and during trial periods. In the UK and Germany (n = 619), the PReDicT group showed significant additional capability well-being gains (OxCAP-MH: +2.127, p = 0.021). Cost-effectiveness probabilities ranged from 46 to 59% at trial level, but exceeded 80% in the UK. Results remained stable across different sensitivity analyses, with societal cost-effectiveness improved for those (self-)employed.
Conclusions
We observed potentially meaningful health and economic benefits of closely monitored antidepressant treatment, as implemented in both treatment and control arms of the PReDicT trial. The PReDicT test itself had some added benefits in improved capabilities and productivity, however, with great uncertainty and country-level variations in cost-effectiveness.
Information about a treatment’s benefits and harms available to a patient often relies on text. However, for many medical conditions, patients must trade off benefits and harms across multiple competing treatments. It remains unknown how to appropriately communicate information on benefits and harms to patients.
Aims
We compared three communication tools using textual information (Cochrane summary of findings table) or increasing combinations of textual and graphical information (Kilim and Vitruvian plots, respectively) to convey the available evidence.
Method
Communication of Benefit–Risk Information, an online randomised controlled trial, is a three-group, parallel, open-label, automated, randomised controlled trial (no. NCT05917639). We recruited participants aged between 18 and 65 years from the general population. Participants were randomly allocated (1:1:1) to one of the three communication tools providing information on competing fictional treatments for social anxiety, and were asked to choose one based on externally provided preferences. The primary outcome was the perceived level of decisional conflict when selecting a treatment (decisional conflict scale (DCS): 0 = best, 100 = worst). Because this was an all-or-nothing, single-visit trial, only those participants providing data contributed to the primary analyses (modified intention to treat).
Results
We recruited 2178 adults between 1 June and 27 November 2023. Vitruvian and Kilim plots outperformed the Cochrane summary of findings table on the primary outcome (adjusted mean difference −10.9, 95% CI −13.5 to −8.2, P < 0.0001 and −9.7, 95% CI −12.4 to −7.1, P < 0.0001), respectively). Results varied by participants’ literacy and numeracy skills, lived experience of the condition of interest, ethnic group, gender assigned at birth and age.
Conclusions
Combining graphical and textual information, as opposed to text only, improved communication and reduced decisional conflict when choosing across multiple competing medical interventions. Organisations involved in disseminating scientific evidence should consider endorsing a combined graphical and textual approach and adopting more intuitive and accessible communication methods. We identified several prognostic factors that should inform the development of future patient decision aids and communication of scientific findings.
Clinical prediction models use individual-level patient data to inform clinical decisions across medicine. However, few are currently used in psychiatry. Here, we examine the opportunities and challenges presented by the new generation of clinical prediction models in psychiatry and consider what it would mean for a model to be ‘good enough’ for clinical use.
People with psychosis have a life expectancy that is reduced by 15 years, mainly owing to preventable physical illnesses of which obesity is a precursor. Obesity is three times more common in individuals with psychosis, and antipsychotics are an important cause. Prediction could individualise obesity treatment, but current models are not fully actionable for individuals.
Aims
To test whether antipsychotic-induced weight increase at 1 year is causally mediated by weight change in the first 12 weeks of treatment, and then develop and internally validate a causal actionable prediction pathway to prevent antipsychotic-induced obesity.
Method
This was a post hoc analysis of a clinical trial of olanzapine versus haloperidol which recruited 263 participants with first-episode psychosis. We conducted two distinct analyses: causal mediation and prediction modelling, within which there were two sequential models (a baseline model to predict 12-week outcome and a 12-week model to predict 1-year outcome), followed by counterfactual prediction. In the first analysis, we used parallel causal mediation analysis to determine the natural direct and indirect and total effects of antipsychotic choice on weight in 97 participants, considering two mediators: weight change from 0 to 12 weeks, and weight change from 12 to 52 weeks. In the second analysis, we first developed a baseline causal actionable prediction model to predict weight gain at 12 weeks in 172 participants and then a 12-week model to predict obesity at 1 year in 97 of the participants. Finally, we demonstrated counterfactual prediction.
Results
Antipsychotic-induced weight gain at 1 year appeared to be causally mediated by weight change during the first 12 weeks of treatment (indirect effect 5.70; 95% CI 2.83 to 8.66). At internal validation, the discrimination c-statistic for the baseline causal actionable prediction model was 0.728 (95% CI 0.661 to 0.801), and the calibration slope was 0.768 (95% CI 0.436 to 1.21). For the 12-week model, the c-statistic was 0.904 (95% CI 0.820 to 0.961), and the calibration slope was 0.601 (95% CI −0.0633 to 1.21). We used the models to predict the counterfactual outcomes of antipsychotic choice and 12-week weight change.
Conclusions
Our results show that it may be early rather than later weight change that causally mediates antipsychotic-induced weight gain at 1 year. They also demonstrate the potential for causal actionable prediction of counterfactuals for true precision medicine, although this is tempered by the feasibility scope of this study and small sample size. Our results are hypothesis-generating and not yet clinically deployable.
Lewin and colleagues’ article in this journal gives a good overview of how artificial intelligence (AI) is contributing to the reshaping of mental healthcare. However, a deeper focus on the synergies between different approaches to AI and its goals is needed. This commentary aims to further consider the unique implications of digital mental health approaches, including predictive, explainable and generative AI, for both research and clinical objectives.
This letter comments on a recent study examining the heterogeneous and sometimes unsustained efficacy of gastric inlet patch (GIP) ablation. To address this clinical puzzle, we propose the conceptual framework of the GIP as a functionally active “foregut microenvironment hub.” Its variable secretory profile (e.g., pepsin, cytokines) likely underlies differences in both symptom generation and treatment response. We argue that advancing therapeutic strategy from the question of “whether to ablate” to “for whom to ablate” is essential. Future approaches should incorporate functional activity assessment of this hub to stratify patients, thereby ushering in an era of precision management for GIP-related symptoms.
Half a century of neuroimaging has transformed our understanding of psychiatric disorders but not our clinical practice. This piece examines why that promise remains unfulfilled and argues that the future lies not in ever newer tools but in rigorous, mechanistically grounded and clinically embedded imaging approaches that bridge brains, behaviours and treatments.
Despite omics technologies gaining traction in clinical settings, particularly in oncology, challenges persist in their widespread adoption due to the pre-requisite robust evidence supporting efficacy and cost-effectiveness. This study aims to explore the experiences of organizations working in the health technology assessment (HTA) field in evaluating omics technologies, with a particular focus on the adoption and application of specific assessment frameworks.
Methods
We conducted a global survey to gather insights into current practices and frameworks used in HTA evaluations of omics technologies.
Results
We gathered responses from thirty-nine participants representing organizations across twenty-nine countries and five continents. Among them, 51 percent (n = 20) reported experience in evaluating omics technologies, including multi-omics tests for early disease detection, biomarker-based cancer diagnostics, and advanced genomic sequencing techniques. Only three organizations employed specific assessment frameworks: the Adelaide Health Technology Assessment Agency in Australia, the Netherlands Cancer Institute, and the Andalusian HTA Agency in Spain. These frameworks address key evaluation aspects such as analytical and clinical validity, clinical and personal utility, organizational impact, and ethical, legal, and social implications of omics technologies.
Discussion
Despite their relevance, the limited adoption of tailored frameworks highlights the need for more structured and context-specific approaches to facilitate the integration of omics technologies into healthcare systems. Collaborative efforts among stakeholders, including patients, healthcare providers, policymakers, and industry representatives, are crucial for devising robust evaluation strategies addressing the complexities of omics technologies comprehensively.
Lived experience – how individuals perceive and interact with their environment – plays a central role in understanding mental health. Yet, insights into this first-person perspective, including subjective thoughts, emotions, and socio-contextual influences, remain limited in current research approaches.
Methods
To address this gap, we developed StreetMind, a scalable, secure, and user-friendly digital citizen science platform grounded in a psycho-sociogeographic framework. The platform collects self-reported data on individuals’ activity spaces through a mobile app and web interface, capturing location visits, travel routes, and daily experiences. These subjective reports are combined with objective real-time health, environmental, and sociocultural data to generate integrated community “footprints.”
Results
Initial usage data (N = 1,010 for location and route entries; N = 509 for daily experiential data) demonstrate the platform’s structural robustness and functional feasibility. StreetMind enables classification of daily experiences by linking personal perceptions with contextual environmental data. This integration facilitates the identification and quantification of key environmental and psychosocial factors associated with mental well-being.
Conclusion
StreetMind offers a novel, data-rich mapping of health–environment interactions by merging individual lived experience with environmental metrics. This approach supports the creation of dynamic “health–environment spaces” and holds promise for informing public health strategies and advancing precision mental health care.
Sex and gender are often overlooked factors in the delivery of mental healthcare, resulting in a gender blindness that ignores the specific needs of women and, in some circumstances, men. A lack of gender-disaggregated data and balanced sex and gender representation in clinical research has led to knowledge gaps in women’s health overall. This article explores the influence of gender bias across a spectrum of conditions where disparities in diagnosis, treatment and research exist, including psychosis, mood disorders, neurodevelopmental disorders, eating disorders and substance use disorders. The influence of female reproductive hormones (oestrogen and progesterone) on symptom onset, presentation and treatment response is also discussed where clinically relevant. Gender-aware approaches to delivering mental healthcare are needed, including trauma-informed care, in order to deliver equitable and effective mental healthcare for all.
Although global knowledge on paediatric cardiomyopathies has advanced, prospective cohort studies from Brazil, particularly those integrating clinical and genetic data, remain limited.
Objective:
To describe the clinical and genetic characteristics of paediatric cardiomyopathy patients and identify mortality predictors in a metropolitan region of Brazil.
Methods:
Prospective observational study of paediatric patients with cardiomyopathies. Clinical data, genetic findings, and survival were analysed using Kaplan–Meier curves.
Results:
A total of 45 cases, male predominance (55.6%), and mean age at diagnosis of 6.5 years. Dilated and hypertrophic cardiomyopathy were the most common (33.3%). The main reason for diagnosis was the investigation of cardiovascular symptoms (60.9%). Genetic investigation occurred in 66.6%, a positivity rate of 60%. Multi-organ/system involvement was significantly associated with a positive genetic result (77.7%, p = 0.017). Mortality was 11.1%; survival was significantly lower in the following conditions: ejection fraction < 30% (p < 0.0001), functional class III/IV (p < 0.0001), heart failure (p = 0.0091), use of three or more cardiovascular medications (p < 0.001), N-Terminal Pro-B-Type natriuretic peptide >1000pg/mL (p = 0.004), and heart transplant indication (p < 0.001).
Conclusion:
These findings provide novel data in Brazil, highlight a high rate of positive genetic test, particularly among patients with systemic involvement and identify key clinical predictors of mortality to guide risk stratification and care.
Molecular biology stands at the vanguard of neurosurgical innovation, providing unprecedented insights into the chemical tapestry that makes up the human body. We trace the historical milestones that revolutionized our understanding of the brain’s molecular framework, spotlighting pivotal breakthroughs from the discovery of DNA’s structure to the sophisticated therapeutic interventions of today. The current neurosurgical landscape is explored through the lens of molecular diagnostics and therapeutics, emphasizing the paradigm shift toward precision medicine, with an emphasis on neurosurgical oncology. Advancements in targeted molecular treatments, personalized vaccines, and the exciting frontier of gene therapy are discussed. Looking to the horizon, we discuss future intersections between the worlds of molecular biology and neurosurgery – an era brimming with the promise of direct personalized and regenerative medicine
Cancer heterogeneity presents a major obstacle to effective drug treatment, emphasizing the need for personalized approaches that can accurately predict drug responses. Advances in high-throughput technologies have driven precision medicine initiatives toward integrating multi-omics data, enabling a more comprehensive understanding of tumor biology. However, integration of diverse omics layers poses challenges for computational modeling, as many traditional machine learning (ML) and statistical methods are not designed to capture complex, high-dimensional and multimodal data. This review examines the studies that integrate multi-omics datasets, aiming to enhance drug response prediction (DRP). Specifically, it outlines the most used omics types and computational approaches – classical ML models, as well as advanced deep learning and multimodal integration frameworks for improving DRP, detailing key methodologies and evaluation metrics, such as area under the dose–response curve, F1 score and mean square error, which assess model performance. By summarizing the integrated omics data, computational methods and challenges encountered, this review provides an in-depth overview of the existing landscape of precision medicine and future directions for advancing drug-response prediction.
The National Institutes of Health All of Us Research Program (All of Us or program) aims to better understand the complexity of diseases, prevention and treatment at the individual level. To accomplish this, one of the program components is to build a longitudinal cohort of one million or more volunteers in the United States and its territories through which clinical, environmental, genetic, and behavioral data are collected. Federally Qualified Health Centers (FQHCs) play a crucial role in enrolling participants in the program and while FQHCs have the dedication, leadership, and wherewithal to operationalize a national longitudinal data collection, their local resources are limited by funding and scope for conducting research. This paper describes the evolution of FQHC research landscape, from building capacity for descriptive, to exploratory operational research, and moving toward biomedical research. As programs such as All of Us continue to ensure that focus on precision medicine is reflected in both data collection and research, continuing to advance the research landscape within health centers is crucial. By developing this capacity, we are developing a research infrastructure that will continue to grow, supporting advancements in precision medicine for improving health outcomes.
Parkinson’s disease (PD) is a complex neurodegenerative disorder that is heterogeneous in both its pathophysiology and clinical presentation. Genetic, imaging and biochemical biomarkers not only provide innovative, objective ways to subtype PD but also offer new insights into the underlying pathophysiology, revealing potential therapeutic targets and improving predictions of clinical phenotype, disease progression and treatment response. In this review, we first summarize the phenotypes linked to key PD genes – such as SNCA, LRRK2, GBA and PRKN – highlighting, for instance, that GBA-PD is often associated with prominent nonmotor features. We then explore studies that have defined new robust subtypes with imaging biomarkers, particularly T1-weighted MRI brain atrophy patterns, and their clinical implications. We also review the role of blood, CSF and urine biomarkers for monitoring disease progression and predicting its presentation in various domains (motor, cognitive, autonomic, psychiatric). These findings could have practical implications by guiding clinicians to individualize symptomatic treatment and helping researchers improve clinical trial design and recruitment, thus bringing us closer to the discovery of effective disease-modifying therapies.
It remains unclear which individuals with subthreshold depression benefit most from psychological intervention, and what long-term effects this has on symptom deterioration, response and remission.
Aims
To synthesise psychological intervention benefits in adults with subthreshold depression up to 2 years, and explore participant-level effect-modifiers.
Method
Randomised trials comparing psychological intervention with inactive control were identified via systematic search. Authors were contacted to obtain individual participant data (IPD), analysed using Bayesian one-stage meta-analysis. Treatment–covariate interactions were added to examine moderators. Hierarchical-additive models were used to explore treatment benefits conditional on baseline Patient Health Questionnaire 9 (PHQ-9) values.
Results
IPD of 10 671 individuals (50 studies) could be included. We found significant effects on depressive symptom severity up to 12 months (standardised mean-difference [s.m.d.] = −0.48 to −0.27). Effects could not be ascertained up to 24 months (s.m.d. = −0.18). Similar findings emerged for 50% symptom reduction (relative risk = 1.27–2.79), reliable improvement (relative risk = 1.38–3.17), deterioration (relative risk = 0.67–0.54) and close-to-symptom-free status (relative risk = 1.41–2.80). Among participant-level moderators, only initial depression and anxiety severity were highly credible (P > 0.99). Predicted treatment benefits decreased with lower symptom severity but remained minimally important even for very mild symptoms (s.m.d. = −0.33 for PHQ-9 = 5).
Conclusions
Psychological intervention reduces the symptom burden in individuals with subthreshold depression up to 1 year, and protects against symptom deterioration. Benefits up to 2 years are less certain. We find strong support for intervention in subthreshold depression, particularly with PHQ-9 scores ≥ 10. For very mild symptoms, scalable treatments could be an attractive option.
Consortia like the Clinical Pharmacogenetic Implementation Consortium (CPIC) and the Dutch Pharmacogenetic Working Group (DPWG) provide clinical guidelines but pharmacogenomics implementation depends on population prevalence of actionable genetic variants and response phenotypes. We analyzed the distribution of actionable genetic variants and clinical recommendations in 14,354 adult Qataris, focusing only genes with guidelines (CYP2C19, CYP2D6, CYP2B6 and CYP3A4). Haplotypes and diplotypes were generated from 490 alleles using whole genome data and metabolizer phenotypes were predicted based on current knowledge. Qatari population predicted to have actionable metabolizer phenotypes of CYP2C19, CYP2B6 and CYP2D6 impacting response to antidepressants were in the range of 1%–58% and for antipsychotics 0.1%–33% based on CYP3A4 and CYP2D6. Fine-grained analysis based on clinical guidelines also revealed that while the Qataris may need prescription of an alternate antidepressant not metabolized by CYP2C19, patients from other populations may just need altering the dosage of tricyclic antidepressants like amitriptyline. Further studies incorporating other factors such as diet, environment and cultural habits alongwith population-specific variants will help in the pharmacogenomics implementation in the Qatari population.