340880 research outputs found
Sort by
Real-world studies in psychiatry:insights into antipsychotic-associated breast cancer risk and their broader implications
No full textReal-world studies provide valuable insights into long-term outcomes across diverse populations. Here, we contextualise recent findings on the association between antipsychotic use and breast cancer risk in women with schizophrenia. We discuss clinical implications and the strengths and limitations of real-world studies in psychiatry. We conclude with future perspectives
The fate of thiopurine metabolites after switching to low-dose thiopurine with allopurinol or thioguanine in IBD patients:A retrospective analysis
No full textAims: Shunting (hypermethylating) thiopurine metabolism, characterized by excessive 6-MMPR production and (sub)therapeutic 6-TGN levels, poses a significant challenge in the treatment of inflammatory bowel disease (IBD). This study evaluates the metabolic outcomes of switching to low-dose thiopurine with allopurinol (LDTA) or thioguanine (TG) in IBD patients with shunting metabolism. Methods: This retrospective study analysed demographic data, thiopurine metabolite profiles, and adverse event rates in shunting IBD patients before and after switching to LDTA or TG therapy. Metabolite variability was assessed by examining alterations in 6-MMPR and 6-TGN levels and their correlation before and after therapy switch. Results: Both therapies significantly reduced toxic 6-MMPR levels, with 100% of patients achieving non-toxic levels (6-MMPR-level below 7000 pmol/8 × 10E8 RBC) post-therapy. For TG, 93% of patients attained non-toxic 6-TGN levels (6-TGN < 1000 pmol/8 × 10E8 RBC). In contrast, LDTA showed greater variability in 6-TGN outcomes, with 50% of patients reaching therapeutic levels, 31% remaining subtherapeutic, and 19% within toxic range. The slope for LDTA was significantly positive (1.044, R 2 = 0.4515, P = 0.004), reflecting proportional increases in 6-TGN levels. Conclusions: Switching to LDTA or TG therapy in shunting IBD patients resulted in favourable alterations in thiopurine metabolism. However, LDTA appears to have a slightly less favourable metabolite profile, with some residual 6-MMPR formation and fewer patients achieving normal 6-TGN levels compared to TG. Given the challenges associated with achieving optimal thiopurine metabolite levels with LDTA and the need for closer monitoring of 6-TGN levels, TG appears a more suitable option for thiopurine shunting IBD patients.</p
Authors' response:A personalized approach is essential for enhancing the clinical relevance of exercise prehabilitation
No full textPTSD and epigenetic aging:a longitudinal meta-analysis
No full textBackground Posttraumatic stress disorder (PTSD) has been associated with advanced epigenetic age cross-sectionally, but the association between these variables over time is unclear. This study conducted meta-analyses to test whether new-onset PTSD diagnosis and changes in PTSD symptom severity over time were associated with changes in two metrics of epigenetic aging over two time points.Methods We conducted meta-analyses of the association between change in PTSD diagnosis and symptom severity and change in epigenetic age acceleration/deceleration (age-adjusted DNA methylation age residuals as per the Horvath and GrimAge metrics) using data from 7 military and civilian cohorts participating in the Psychiatric Genomics Consortium PTSD Epigenetics Workgroup (total N = 1,367).Results Meta-analysis revealed that the interaction between Time 1 (T1) Horvath age residuals and new-onset PTSD over time was significantly associated with Horvath age residuals at T2 (meta beta = 0.16, meta p = 0.02, p-adj = 0.03). The interaction between T1 Horvath age residuals and changes in PTSD symptom severity over time was significantly related to Horvath age residuals at T2 (meta beta = 0.24, meta p = 0.05). No associations were observed for GrimAge residuals.Conclusions Results indicated that individuals who developed new-onset PTSD or showed increased PTSD symptom severity over time evidenced greater epigenetic age acceleration at follow-up than would be expected based on baseline age acceleration. This suggests that PTSD may accelerate biological aging over time and highlights the need for intervention studies to determine if PTSD treatment has a beneficial effect on the aging methylome
Acceptability and feasibility of a mobile electronic medical record system for community-based antiretroviral therapy in Lilongwe, Malawi:A rapid qualitative analysis
No full textBackground Mobile health (mHealth) is reshaping healthcare delivery, especially in HIV management. The World Health Organization advocates for mHealth to provide healthcare workers (HCWs) with real-time data, enhancing client care. However, in Malawi's Lighthouse Trust antiretroviral therapy (ART) clinic, the nurse-led community-based ART (NCAP) program faces hurdles with data management due to lack of access to electronic medical records systems (EMRS) in the community setting. EMRS are not typically available in differentiated service delivery settings where reliable power and internet are often unavailable. We used human-centered design (HCD) processes to create a mobile EMRS prototype, the Community-based ART Retention and Suppression (CARES) app. CARES aims to simplify workflow for HCWs and improve client care. As part of prototype testing, we explore CARES' feasibility and acceptability from the perspective of NCAP HCWs.Methods We conducted in-depth interviews among 15 NCAP HCWs. We used a rapid qualitative analysis approach guided by the Technology Acceptance Models (TAM1 and TAM2). The study complied with the Consolidated Criteria for Reporting Qualitative Research (COREQ).Results HCWs demonstrated high perceived usefulness for the CARES app to improve healthcare delivery and data management, both of which could facilitate continued and effective use. However, challenges such as app performance, data integration, and system navigation were significant barriers to ease of use, reducing acceptance and current feasibility of scale-up. Despite challenges, HCWs remained optimistic about CARES' potential to enhance NCAP clinical decision-making and data flow in future, likely reflecting organizational expectations for CARES optimization. Beyond the TAM framework, additional themes of consistent staff engagement and considerations for sustainability were identified as critical factors for long-term success. HCWs emphasized the need for continuous training and stakeholder engagement, improved infrastructure, data security protections, and establishing the CARES app and EMRS integration to facilitate CARES' sustained expansion.Conclusion The study findings underscore the importance of HCD for mHealth buy-in. As HCWs were invested in CARES success, they remained optimistic that the app could enhance NCAP services if user experience and app performance improved. Incorporation of HCW feedback could help deliver the promise of CARES, current and future
The Decisive Role of Confinement in Enhancing or Suppressing Self-Nucleation in Polyethylene-Containing Block Copolymers
No full textThe influence of confinement on the self-nucleation behavior of crystallizable polyethylene (PE) and poly(ethylene oxide) (PEO) blocks in block copolymers of different architectures is studied by differential scanning calorimetry. The amorphous blocks, polystyrene (PS) and poly(methyl methacrylate) (PMMA), with high glass transition temperatures, create glassy matrices that confine crystallization in the microphase-segregated block copolymers. For diblock copolymers (PS-b-PE, PMMA-b-PE), the PE blocks exhibit stronger melt memory than neat PE, as moderate confinement favors the preservation of the conformations adopted in the crystalline regions. However, when both ends of the PE block are tethered to glassy blocks, in PS-b-PE-b-PS and PS-b-PE-b-PMMA, melt memory and self-nucleation completely vanish as the confinement degree increases. In PS-b-PE-b-PEO triblock terpolymers, the self-nucleation of the PE block is hindered even at very low temperatures, where annealing is dominant. The PEO block undergoes a complex fractionated crystallization where self-nucleation disappears in the isolated, highly confined microdomains. SSA (successive self-nucleation and annealing) thermal fractionation results are similar for PE homopolymer and PE blocks (i.e., hydrogenated polybutadiene), resulting from molecular defects caused by branching. These results indicate that the melt memory of confined crystallizable blocks can be triggered by moderate confinement but is completely suppressed when confinement is too strong
The effect of compulsory education on non-cognitive skills:Evidence from low-and middle-income countries
No full textPersonality traits, preferences, and attitudes significantly influence labor market outcomes, and these non-cognitive skills are shaped by the social environment. While curriculum interventions can impact these skills, the effect of compulsory education on non-cognitive skills is less well understood. This study investigates the impact of extending compulsory education by examining educational reforms in four low-and middle-income countries. Utilizing cross-sectional data from the World Bank's 2012/2013 initiative, we analyze the within-country variation in compulsory education years. Our findings indicate that increased compulsory education decreases emotional stability, grit, hostile attribution bias, patience, and willingness to take risks, while enhancing openness to experience and alternative solution or consequential thinking
Safety and efficacy of amiodarone and dronedarone for early rhythm control in EAST-AFNET 4
No full textAims: Concerns exist about the safety of amiodarone and dronedarone. We assessed the long-term outcome of both drugs for early rhythm control (ERC) in the EAST-AFNET 4 trial. Methods and Results: Patients randomized for ERC and treated with amiodarone or dronedarone were compared to other ERC-therapies. Patients receiving amiodarone or dronedarone at initial therapy (n = 653/1395) were older with more comorbidities and less paroxysmal atrial fibrillation (AF, 29%) compared to patients never receiving amiodarone or dronedarone (Amiodarone/Dronedarone never, 43% paroxysmal AF). Patients treated with amiodarone had more often heart failure (HF, 42%) and persistent AF (40%) compared to patients treated with dronedarone (16% HF, 15% persistent AF) and Amiodarone/Dronedarone never (25% HF, 22% persistent AF). 115/398 amiodarone-treated patients (6.7/100 patient-years) and 51/255 dronedarone-treated patients (4.2/100 patient-years) experienced a primary efficacy outcome (cardiovascular death, stroke, HF-hospitalization or acute coronary syndrome), while 98/398 (5.3/100 patient-years) and 43/255 (3.4/100 patient-years) experienced a primary safety outcome (death, stroke or serious adverse events related to rhythm-control therapy). Serious adverse events related to drug therapy were similar for amiodarone (1.4/100 patient-years), dronedarone (1.2/100 patient-years), and other ERC (0.8/100 patient-years). Dronedarone (hazard ratio (HR) 0.5; CI 0.28–0.91), age (HR 1.05; CI 1.03–1.07), coronary artery disease (HR 1.84; CI 1.38–2.46) and stable HF (HR 1.66; CI 1.28–2.16) were associated with efficacy outcome upon multivariate Cox regression. Age (HR 1.07; CI 1.05–1.09) and left ventricular hypertrophy (HR 1.94; CI 1.13–3.32) were associated with safety outcome. Conclusion: Early rhythm control using amiodarone or dronedarone rarely led to drug-related serious adverse events in EAST-AFNET 4. Clinical Trial Registration: ISRCTN04708680, NCT01288352, EudraCT2010-021258-20.</p
Geospatial Framework for Assessing the Suitability and Demand for Agricultural Digital Solutions in Europe:A Tool for Informed Decision-Making
No full textThis study introduces a geospatial comprehensive methodological system aimed at evaluating the suitability and need for agricultural digital solutions (ADSs) across Europe. This system integrates a diverse range of factors, including geophysical characteristics, climate patterns, and socioeconomic conditions, evaluated at regional- and farm-specific levels. By leveraging open-source Earth observations and socioeconomic data, we develop multiple performance, environmental, and socioeconomic similarity indexes that compare regions based on shared characteristics, such as soil quality, climate, and socioeconomic factors. Using advanced statistical and multi-criteria analysis tools, these indexes are tailored to different stages of agricultural production, enabling region-specific assessments that identify and prioritize the needs for digital solutions across Europe. The results indicate that the developed indexes effectively categorize regions based on comparable characteristics, facilitating the targeted recommendation of ADSs. Additionally, a connectivity performance index is created to assess the local deployment model of agricultural digital solutions (cloud, edge, or mixed), ensuring that the recommendations for technological implementation are feasible and effective given the local connectivity conditions
Political Ecologies of Storage for the 21st Century
No full textNew resource storage arrangements are proliferating rapidly both in terms of physical infrastructures—for the storage of things like “clean” energy, nuclear waste, carbon dioxide, fresh water, and data—and as part of a set of discursive moves that reinforce a vision of a near future world in which problems of climate change mitigation and adaptation in particular (but also issues like energy security, water security, industry growth, etc.) are solved through eco-modernist techno-fixes. This Symposium sketches the contours of a framework we term political ecologies of storage. In doing so, we treat storage as both a potent imaginary and a concrete arrangement of infrastructures and (lively) materials, developing storage as a critical analytic for examining a diverse range of resource configurations. The political ecology of storage highlights the ways in which different storage arrangements are both conditions and consequences of specific political economic dynamics, while at the same time inextricable from multi-scalar physical environments in which they are embedded.</p