Search

Abstract Background Little is known about the effect of ethnicity on drug treatment in patients with an acute manic episode. The aim of this study is to determine whether ethnicity moderates the response to drug treatment in patients with an acute manic episode, and whether this moderation is independent of potential confounders. Methods We analysed ten short-term placebo-controlled registration trials of atypical antipsychotics and anticonvulsive mood stabilizers in patients with an acute manic episode (n = 2199). A one-step random effects individual patient data meta-analysis (IPD) was applied to establish the moderating effect of ethnicity on symptom improvement on the Young Mania Rating Scale (Y)MRS and on response defined as 50% (Y)MRS symptom reduction. These analyses were corrected for baseline severity, age, and gender. A two-step IPD comparing these outcomes between White, Black and Asian patients. Additionally, a conventional meta-analysis was performed to determine the effect size of drug treatment separately for these ethnic groups. Results In the complete dataset, 60.4% of the patients was White, 8.0% was Black, 12.7% was Asian, 33.7% was of other ethnicities. Ethnicity did not significantly moderate the efficacy of drug treatment: pooled beta-coefficient (β) for the interaction between treatment and the ethnicities White, Black and Asian, varying from 0.889 to 0.899 with overlapping confidence-intervals ranging from 2.356 to 2.430 in the main analysis. The drug treatment effects were significant in all three analysable ethnicity groups compared to placebo. Discussion In White,Black, and Asian patients with an acute manic episode drug treatment is equally effective.

Abstract Background Women with migraine, especially with aura (MA), have a higher risk of white matter hyperintensities (WMH) and ischemic stroke. We aimed to assess differences in stroke etiology between women with and without migraine and the impact of migraine on WMH volume in women with stroke. Methods We included women aged 40–60 years with a history of ischemic stroke, migraine or both. Stroke etiology was categorized using the TOAST criteria. WMH volume was measured using 3D-FLAIR images. Presence or absence of cerebellar WMH was scored. We used regression analysis to assess differences between groups, with adjustments for age, BMI, hypertension and smoking status. Results We included 55 women with stroke, 55 with stroke and migraine, and 38 with MA. Women with stroke more often had a history of smoking than those with stroke and migraine (74% vs. 46%, p = 0.004). Stroke of undetermined origin was more common in women with both conditions than with stroke alone (49% vs. 27%, p = 0.019). Periventricular WMH volumes were higher in women with stroke with migraine than in those with MA alone (0.55mL vs. 0.42mL, B = 0.21, 95%CI = 0.01–0.41, p = 0.040). There were no differences in deep WMH volume and cerebellar WMH between groups. Importantly, the addition of migraine did not affect WMH volume in women who had experienced stroke. Conclusion Women with both stroke and migraine more often had undetermined etiology of stroke compared to women with stroke alone, and in women with stroke alone smoking was a more prevalent risk factor. Migraine did not contribute to increased WMH volume in women with stroke.

Abstract We propose the addition of usability validation to the extended V3 framework, now “V3+”, and describe a pragmatic approach to ensuring that sensor-based digital health technologies can be used optimally at scale by diverse users. Alongside the original V3 components (verification; analytical validation; clinical validation), usability validation will ensure user-centricity of digital measurement tools, paving the way for more inclusive, reliable, and trustworthy digital measures within clinical research and clinical care.

Abstract Background Postcardiotomy cardiogenic shock (PCCS) in cardiac surgery is associated with a high rate of morbidity and mortality. Beside other therapeutic measures (e.g. intraaortic balloon pump (IABP)), extracorporeal life support is being increasingly used in this particular form of shock. Objectives of this meta-analysis were to determine mortality and complications of extracorporeal life support treatment (ECLS) in cardiac surgery patients, and if outcomes were influenced by a preexisting cardiovascular risk profile. Methods MEDLINE and EMBASE were searched for studies in English, published between January 1st 2000 and January 16th 2023, reporting mortality and morbidity in patients aged ≥ 18 treated with ECLS for PCCS. Supplementary data were requested from the respective corresponding authors. Outcomes were weaning from extracorporeal life support, hospital survival and complications. Results Two thousand, seven hundred seventy-four papers were screened, of which 132 full text articles were assessed for suitability. 70 remaining studies were included for further evaluation and data analysis. Five studies could be included in the final analysis since the corresponding authors provided additional necessary information. Successful weaning from extracorporeal life support was accomplished in 52.8% (30.8%—57.4%) and 31.1% were discharged alive (mortality of 25.0 – 56.2% after weaning). 95.1% of all treated patients suffered from at least one complication. Diabetes mellitus and obesity seem to be independent risk factors for poor outcome. Conclusions Extracorporeal life support for PCCS is associated with a substantial mortality and complication rate. Diabetes mellitus and obesity seem to be independent risk factors. Therefore, until future work has elucidated which patients benefit at all, the risks of ECLS-treatment must be critically weighed up against a possible benefit.

Abstract Background Fibroblast activation protein (FAP) is an attractive target for cancer theranostics. Although FAP-targeted nuclear imaging demonstrated promising clinical results, only sub-optimal results are reported for targeted radionuclide therapy (TRT). Preclinical research is crucial in selecting promising FAP-targeted radiopharmaceuticals and for obtaining an increased understanding of factors essential for FAP-TRT improvement. FAP is mainly expressed by cancer-associated fibroblasts in the tumor stroma and less on cancer cells themselves. Therefore, other (complex) factors impact FAP-TRT efficacy compared to currently clinically applied TRT strategies. For accurate evaluation of these aspects, selection of a representative preclinical model is important. Currently mainly human cancer cell lines transduced to (over)express FAP are applied, lacking clinical representation. It is unclear how these and more physiological FAP-expressing models compare to each other, and whether/how the model influences the study outcome. We aimed to address this by comparing FAP tracer behavior in FAP-transduced HT1080-huFAP and HEK293-huFAP cells, and endogenous FAP-expressing U-87 MG cancer cells and PS-1 pancreatic stellate cells. [111In]In-FAPI-46 and a fluorescent FAP-targeted tracer (RTX-1370S) were used to compare tracer binding/uptake and localization in vitro and ex vivo. Additionally, FAP expression was determined with RT-qPCR and anti-FAP IHC. Results Although FAP expression was highest in HEK293-huFAP cells and cell line derived xenografts, this did not result in the highest tracer uptake. [111In]In-FAPI-46 uptake was highest in HT1080-huFAP, closely followed by HEK293-huFAP, and a 6-10-fold lower uptake for U-87 MG and PS-1 cells. However, ex vivo U-87 MG xenografts only showed a 2-fold lower binding compared to HT1080-huFAP and HEK293-huFAP xenografts, mainly because the cell line attracts murine fibroblasts as demonstrated in our RT-qPCR and IHC studies. Conclusions The interaction between FAP and FAP-targeted tracers differs between models, indicating the need for appropriate model selection and that comparing results across studies using different models is difficult.

NanoBioAccumulate is a free-to-use web-based tool hosted on the Enalos DIAGONAL Cloud Platform (https://www.enaloscloud.novamechanics.com/diagonal/pbpk/) that provides users with the capability to model and predict the uptake and bioaccumulation of nanomaterials (NMs) by soil and aquatic invertebrates using two common first-order one-compartment biokinetic models. NanoBioAccumulate offers an approach for comprehensively analyzing the kinetics of different forms of NMs via a nonlinear fitting feature, integrating them with environmental fate models, and considering important physiological processes. NanoBioAccumulate overcomes the constraint of requiring prior knowledge of kinetic rate constants associated with the biokinetic models and eliminates the need for external statistical analysis software as it quantifies the kinetic rate constants and other constants through the application of nonlinear regression, using user-provided experimental data. Furthermore, NanoBioAccumulate incorporates statistical analysis measures like the adjusted R-squared and the bias-corrected Akaike information criterion, allowing for assessment of the goodness-of-fit of the two different biokinetic models, assisting in the identification of the best-performing model for a specific nanoform and its uptake kinetics by a specific invertebrate. The tool also includes model scenarios, retrieved from literature, which involve examining the exposure of soil and aquatic invertebrates to various types of NMs such as TiO2, SiO2, C60, graphene, graphene oxide (GO), Au, Ag and its ionic control AgNO3. These model scenarios aim to enhance understanding of the uptake and elimination rates exhibited by different NM-species. NanoBioAccumulate features advanced integration capabilities, enabled by an extensive Application Programming Interface (API). This functionality promotes efficient data exchange and interoperability with other software and web applications, significantly expanding its utility in research, regulatory risk assessment and environmental surveillance and monitoring contexts. The inclusion of a user-friendly Graphical User Interface (GUI) in NanoBioAccumulate greatly improves the overall user experience by simplifying complex tasks and eliminating the need for programming proficiency, thereby expanding the tool's applicability to a diverse range of users across various fields such as environmental research, monitoring, and regulation.

Abstract Background Persons who migrate for economic reasons, along with asylum seekers and refugees, face multiple personal experiences and societal inequalities that increase the risk of mental health problems and substance dependency, compounded by intersectional social and economic vulnerabilities. The precarious situation and limited access to care of persons with a migration background who use drugs (PMWUD) in Europe raises concern. Therefore, this qualitative study explores the challenges and support needs of a sample of PMWUD in vulnerable situations living in Amsterdam, Athens, Berlin and Paris. Methods This study employed a community-based participatory approach. Through semi-structured interviews with PMWUD (n = 99), we identified (service) needs of a diversity of PMWUD in Europe. Participants were recruited through a combination of community gatekeepers, venue-based sampling, and snowball sampling. Trained community researchers conducted the interviews, which focused on participants’ living situation, substance use, physical and mental health, and employment opportunities. Results Despite substantial heterogeneity among the PMWUD, several common themes emerged across all groups. Participants frequently mentioned early childhood adversity, limited social networks leading to loneliness, medical, psychological, and substance use issues, histories of personal violence or poverty, homelessness, lack of necessary documents for health care, social security, and employment, and encounters with the criminal justice system. These intertwined and mutually reinforcing factors simultaneously functioned as barriers to care and support, alongside other barriers such as linguistic and cultural differences, and stigma and discrimination. Due to social exclusion, migration, and substance dependence, participants had limited reliable social networks. Therefore, they often had to rely on accessible and low-threshold services. Harm reduction services played a significant role in providing support to PMWUD. Most PMWUD indicated that basic needs for hygiene and food were met thanks to local organizations. Differences in housing opportunities and access to harm reduction services were identified in each city. Conclusion Structural barriers toward treatment and care, often related to administrative requirements, stand in the way of appropriate care for PMWUD. Linguistically and culturally sensitive outreach activities with limited practical requirements could break down social and treatment barriers.

Abstract Successful implementation of remote monitoring of vital signs outside of the hospital setting hinges on addressing three crucial unmet needs: longer-term wear, skin comfort and signal quality. Earlier, we developed a Health Patch research platform that uses self-adhesive dry electrodes to measure vital digital biomarkers. Here, we report on the analytical validation for heart rate, heart rate variability and respiration rate. Study design included n = 25 adult participants with data acquisition during a 30-minute exercise protocol involving rest, squats, slow, and fast cycling. The Shimmer3 ECG Unit and Cosmed K5, were reference devices. Data analysis showed good agreement in heart rate and marginal agreement in respiratory rate, with lower agreement towards higher respiratory rates. The Lin’s concordance coefficient was 0.98 for heart rate and 0.56 for respiratory rate. Heart rate variability (RMSSD) had a coefficient of 0.85. Participants generally expressed a positive experience with the technology, with some minor irritation from the medical adhesive. The results highlighted potential of this technology for short-to-medium term clinical use for cardiorespiratory health, due to its reliability, accuracy, and compact design. Such technology could become instrumental for remote monitoring providing healthcare professionals with continuous data, remote assessment and enhancing patient outcomes in cardiorespiratory health management.

Claims of AI outperforming medical practitioners are under scrutiny, as the evidence supporting many of these claims is not convincing or transparently reported. These claims often lack specificity, contextualization, and empirical grounding. In this comment, we offer constructive ethical guidance that can benefit authors, journal editors, and peer reviewers when reporting and evaluating findings in studies comparing AI to physician performance. The guidance provided here forms an essential addition to current reporting guidelines for healthcare studies using machine learning.

Abstract Children learn about art by actively engaging with their surroundings. This makes museums potentially rich environments for learning and development. Yet, the descriptions of paintings on show are usually written for adults rather than younger visitors. This study uses mobile eye tracking to examine how painting descriptions tailored for children influence their eye movements when viewing paintings at the Rijksmuseum - the national museum of The Netherlands. Our findings underscore the importance of adapting information specifically for children, rather than simply providing them with adult-oriented museum materials. Children who received information tailored to their developmental level showed increased glance durations to areas highlighted in the descriptions. Strikingly, the behavior of children provided with painting descriptions intended for adults was no different from their behavior when they received no information at all.

Digital biomarkers are quantifiable and objective indicators of a person's physiological function, behavioral state or treatment response, that can be captured using connected sensor technologies such as wearable devices and mobile apps. We envision that continuous and 24-h monitoring of the underlying physiological and behavioral processes through digital biomarkers can enhance early diagnostics, disease management, and self-care of cardiometabolic diseases. Cardiometabolic diseases, which include a combination of cardiovascular and metabolic disorders, represent an emerging global health threat. The prevention potential of cardiometabolic diseases is around 80%, indicating a promising role for interventions in the lifestyle and/or the environmental context. Disruption of sleep and circadian rhythms are increasingly recognized as risk factors for cardiometabolic disease. Digital biomarkers can be used to measure around the clock, that is, day and night, to quantify not only sleep patterns but also diurnal fluctuations of certain biomarkers and processes. In this way, digital biomarkers can support the delivery of optimal timed medical care. Night-time cardiometabolic patterns, such as blood pressure dipping, are predictive of cardiometabolic health outcomes. In addition, the sleep period provides an opportunity for digital cardiometabolic health monitoring with relatively low influence of artifacts, such as physical activity and eating. Digital biomarkers that utilize sleep as a window of health can be used during daily life to enable early diagnosis of cardiometabolic diseases, facilitate remote patient monitoring, and support self-management in people with cardiometabolic diseases. This review describes the influence of sleep and circadian rhythms on cardiometabolic disease and highlights the state-of-the-art sleep and circadian digital biomarkers which could be of benefit in the prevention of cardiometabolic disease.

The extensive use of antibiotics has led to their frequent detection as residues in the environment. However, monitoring of their levels in groundwater and the associated ecological and health risks remains limited, and the impact of river pollution on groundwater is still unclear. This study focused on the highly urbanized Maozhou River and its groundwater. Forty-five antibiotics and microbial community composition were analyzed by high-resolution LC-MS/MS and 16S rRNA gene sequencing, respectively. These endpoints were measured in sediment, surface- and groundwater sampled during wet and dry seasons, while isolation and resistance profiling of Escherichia coli was performed in groundwater. This study aimed to assess the ecological and health risks posed by antibiotics in the Maozhou River and its groundwater, to assess the prevalence and type of antimicrobial resistance in Escherichia coli, and to trace the sources of antibiotic resistance genes (ARGs) in groundwater. Multiple antibiotics detected in the river and sediment were predicted to pose high risks to algae growth and bacterial resistance selection. In groundwater, the antibiotics erythromycin and norfloxacin were predicted to pose a medium risk to algae and a low risk towards bacterial resistance. Furthermore, significant positive correlations were observed between several predominant bacterial phyla in the river and groundwater and the detected antibiotics, suggesting a possible effect of local antibiotic residues on bacterial community composition. Antimicrobial susceptibility testing of 76 Escherichia coli isolates revealed 74 % exhibited resistance to at least one tested antibiotic and 7.9 % exhibiting multidrug resistance, which was confirmed by ARG-targeted PCR analysis. SourceTracker analysis of ARGs in groundwater indicated that ARG contamination in shallow groundwater was primarily from river sediments, while contamination in deeper groundwater originated mainly from river water. The results emphasize the need to address river pollution, as it directly impacts groundwater quality, particularly in areas with severe antibiotic contamination.

BackgroundThe dysregulated immune response during sepsis involves endothelial injury, which may be augmented by infusion of clear fluids such as crystalloids. Plasma has been suggested as an alternative resuscitation fluid but it is unclear whether previously observed benefits were due to the type of fluid, or due to less volume required to restore tissue perfusion. We hypothesized that resuscitation with plasma reduces endothelial injury, inflammation, and organ injury compared to similar and higher volumes of crystalloids in a rat pneumosepsis model.MethodsRats were intratracheally inoculated with Streptococcus Pneumoniae to induce pneumosepsis. Twenty-four hours after inoculation, animals were randomized to 4 groups: healthy controls (non-resuscitated, n = 6), 10 ml/kg/hr (standard-volume, n = 11) crystalloid resuscitation, 3.33 ml/kg/hr (low-volume, n = 11) crystalloid resuscitation or 3.33 ml/kg/hr plasma resuscitation (n = 11). Plasma markers of inflammation and endothelial injury were measured. Organs were harvested for histology and wet-to-dry weight ratio determination.ResultsInoculated animals developed pneumosepsis, with lower mean arterial pressures (p ConclusionPlasma resuscitation modestly reduces endothelial injury compared to crystalloid resuscitation. This effect might be attributed to decreased resuscitation volumes rather than the type of fluid.