Search Results (878)

Background: The efficacy of upadacitinib in patients with Crohn’s disease (CD) has been shown in pivotal randomized controlled trials. However, real-world data is needed to assess its effectiveness and safety in routine clinical care with biologic-experienced patients. This study aimed to evaluate the clinical and endoscopic efficacy, patient-reported outcomes (PROs), and safety of upadacitinib in biologic-experienced patients with CD in a real-world setting. Methods: This prospective bi-centric real-world study enrolled 28 anti-TNF-experienced patients with CD receiving upadacitinib 45 mg daily for 12 weeks (induction), followed by 30 mg daily maintenance through week 52. Primary endpoints included endoscopic response (≥50% SES-CD reduction or ≥2-point decrease from baseline for baseline SES-CD ≤ 4) and clinical remission (Harvey–Bradshaw Index [HBI] ≤ 4). Secondary endpoints included endoscopic remission, clinical response (HBI decrease ≥ 3 points), and quality of life (IBD-Disk). Statistical analysis used the Wilcoxon signed-rank test with 95% confidence intervals (CIs). Results: Median patient age was 37 years; 75% had ≥3 prior biologic failures. Clinical remission rates (HBI) were 59% (95% CI: 41–75%) at week 12, 44% (95% CI: 27–63%) at week 26, and 53% (95% CI: 29–76%) at week 52. Endoscopic response rates were 48% (95% CI: 44–52%) at week 26 and 46% (95% CI: 21–72%) at week 52. Endoscopic remission was achieved in 43% (95% CI: 40–48%) at week 26 and 27% (95% CI: 10–57%) at week 52. Clinical response (HBI) improved progressively from 65% at week 2 to 71% at week 52. Quality of life, as assessed by the IBD-Disk, showed significant improvement: Reduced Disease Burden (defined as a decrease of 70% or a CED-Disk Score of ≤15) was observed in 33% of patients at week 12 and 35% at week 52. Median SES-CD decreased from 9 points (IQR: 6–17) at baseline to 5 points (IQR: 1–12, p = 0.005) at week 52. Adverse events occurred in 11% of patients (4% lymphopenia, 7% skin disease), with no serious adverse events or deaths. Conclusions: Upadacitinib demonstrates significant clinical and endoscopic efficacy in biologic-experienced, anti-TNF-pretreated patients with CD, achieving remission rates comparable to or exceeding those of the pivotal trials despite a highly refractory population (75% with ≥3 prior biologic failures). The favorable safety profile supports upadacitinib as an important therapeutic option in sequential treatment of refractory CD. Full article

Background: Alzheimer’s disease (AD) is a multifactorial neurodegenerative disorder and the leading cause of dementia worldwide. Progressive synaptic dysfunction underlies declines in cognition, daily functioning, and the development of neuropsychiatric syndromes. Neuropsychiatric syndromes that include agitation and aggression affect 40–60% of patients and represent a major source of caregiver burden. Serotonin 5-HT_2B receptor levels are increased in the AD patient brain, and thus, treatment of AD animal models with the selective 5-HT_2B receptor antagonist MW073 in prevention or disease stage paradigms attenuates Aβ- or tau-induced dysfunction. Methods: We investigated the effects of MW073 treatment on the aggressive behavior of Tg2576 mice in a resident–intruder assay. Results: MW073 treatment significantly reduced aggressive behavior in male Tg2576 mice. Conclusions: MW073 efficacy in treating aggression in Tg2576 mice implicates 5-HT_2B receptor-mediated signaling in AD neuropsychiatric symptoms as well as cognitive and behavioral dysfunction. Full article

The COVID-19 pandemic created a natural experiment to assess air quality responses to emission reductions, yet evidence from Latin American coastal industrial cities remains scarce. This study examined how meteorological variability modulated the effects of COVID-19 restrictions on air quality in Ilo, a medium-sized coastal industrial city in southern Peru (~67,000 inhabitants). We analyzed daily concentrations of PM₁₀, PM_2.5, NO₂, O₃, and SO₂ across six pandemic phases (January–December 2020) using multiple linear regression, variance decomposition, and Random Forest models. A health impact assessment translated PM_2.5 changes into cardiovascular mortality estimates using Global Burden of Disease 2021 coefficients. Despite reduced anthropogenic activity, PM_2.5 increased by 34% during early reopening (May–June: 16.9 vs. 12.6 µg/m³ baseline), whereas NO₂ decreased consistently (13–19%), SO₂ declined up to 65%, and O₃ more than doubled (+108%) in austral winter. Variance decomposition revealed that O₃ variability was almost entirely meteorology-driven (98%), while PM_2.5 and NO₂ showed balanced contributions from meteorology and restrictions (~50% each). The PM_2.5 increase corresponded to approximately 3 additional cardiovascular deaths per 100,000 population annually. Coastal meteorology can counteract emission reductions, generating counterintuitive air quality responses and underscoring the need for meteorological normalization in policy evaluation. Full article

Premenstrual syndrome is a common hormone-related condition marked by recurrent physical and affective symptoms that can substantially impair daily functioning. While cyclical ovarian hormone fluctuations are physiological, clinically relevant symptoms occur only in a subset of women, indicating the contribution of individual vulnerability and modifiable environmental factors. In this context, growing attention has been directed toward the role of nutrition. This narrative review synthesizes and critically discusses current evidence on the relationship between dietary factors and premenstrual syndrome, with emphasis on both primary prevention and symptom modulation. Available observational and interventional data suggest that dietary patterns characterized by high intake of ultra-processed foods, refined carbohydrates, and saturated fats are more frequently associated with increased symptom severity, whereas healthier dietary patterns may be linked to a lower symptom burden. Certain micronutrients—including calcium, vitamin D, zinc, iron, and omega-3 fatty acids—have demonstrated potential benefits, although findings remain heterogeneous and methodologically limited. Overall, nutrition emerges as a plausible complementary strategy in premenstrual syndrome management; however, well-designed prospective studies are needed to support robust, evidence-based dietary recommendations. Full article

Background/Objectives: Inpatient falls are widely used patient safety indicators, yet their behavior under periods of large-scale health system stress remains insufficiently understood. This study aimed to evaluate whether risk-adjusted inpatient fall indicators can capture changes in hospital safety performance during such periods, using a prolonged system disruption as an empirical context. The study period was a priori divided into three phases (pre-pandemic, initial pandemic, and later pandemic) according to changes in COVID-19 admission burden and system stress intensity. Methods: We conducted a retrospective observational time-series analysis using daily inpatient fall events and census data from a Japanese acute care hospital between December 2018 and March 2023 (50,140 inpatients; 962 falls). Expected fall rates were estimated using a validated pre-disruption prediction model, and observed/expected (O/E) ratios were calculated to assess risk-adjusted safety performance. Ordinary least squares regression models adjusted for calendar month and seasonal Fourier terms were used to examine temporal associations between fall outcomes and indicators of hospital-level system burden. Results: Both observed and expected fall rates increased during the study period, whereas O/E ratios declined only in the later phase, indicating improvement in risk-adjusted safety performance despite rising intrinsic patient risk. Seasonal patterns in fall outcomes were disrupted during the early phase of system stress but re-emerged over time. Associations between system burden indicators and fall outcomes were most pronounced in the early phase and attenuated in later phases. Conclusions: Risk-adjusted monitoring of inpatient falls provides insight into dynamic changes in hospital safety performance during periods of large-scale system stress and subsequent adaptation. This indicator can also be interpreted as a benchmarking scale for future month-to-month and seasonal safety surveillance beyond crisis contexts. Full article

Devices equipped with the Global Positioning System (GPS) generate massive volumes of trajectory data on a daily basis, imposing substantial computational, network, and storage burdens. Online trajectory simplification reduces redundant points in a streaming manner while preserving essential spatial and temporal characteristics. A representative method in this line of research is Directed acyclic graph-based Online Trajectory Simplification (DOTS). However, DOTS does not preserve stay-related information and can incur high computational cost. To address these limitations, we propose Directed acyclic graph-based Online Trajectory Simplification with Stay Areas (DOTSSA), a fast online simplification method that integrates DOTS with an online stay area detection algorithm (SA). In DOTSSA, SA continuously monitors movement patterns to detect stay areas and segments the incoming trajectory accordingly, after which DOTS is applied to the extracted segments. This approach ensures the preservation of stay areas while reducing computational overhead through localized DAG construction. Experimental evaluations on a real-world dataset show that, compared with DOTS, DOTSSA can reduce compression time, while achieving comparable compression ratios and preserving key trajectory features. Full article

Background: As populations rapidly age, care robots have been proposed as a promising solution, supporting independent living and alleviating care burdens. However, acceptance of care robots among older adults remains limited. This study examined the relative contributions of demographic, health-related, digital competence, and technology-related psychological factors to care robot acceptance among older adults in South Korea. Methods: A cross-sectional survey was conducted with 506 community-dwelling older adults. Hierarchical multiple regression analyses were used to identify predictors of care robot acceptance, sequentially entering demographic characteristics, health-related factors, digital competence, and technology-related psychological variables. Results: Demographic and health-related factors were initially associated with care robot acceptance, but their effects diminished after accounting for digital competence and psychological variables. In the final model, technology-related psychological factors—particularly technology use self-efficacy and technology enthusiasm—were the strongest predictors of acceptance, while most demographic and health variables became non-significant, with the exception of instrumental activities of daily living (IADLs). Conclusions: These findings indicate that psychological readiness and confidence in technology use outweigh demographic or health characteristics in shaping older adults’ acceptance of care robots. Interventions and design strategies that enhance self-efficacy, foster positive engagement, and support functional independence may be critical for promoting the effective and sustainable adoption of care robots in aging societies. Full article

Objective: Homeless individuals are vulnerable, and a high burden of mental health problems is suspected. We aim to identify the prevalence and key predictors of probable depression and anxiety among homeless individuals in Germany during the Coronavirus disease-2019 (COVID-19) pandemic. Study Design: Nationwide multicentre cross-sectional study including clinical, laboratory, and questionnaire-based data on the health of homeless individuals in Germany. Methods: Data were used from the National Survey on the psychiatric and somatic health of homeless individuals during the COVID-19 pandemic. Probable depression and anxiety were determined using the Patient Health Questionnaire 9 and the General Anxiety Disorder 2 questionnaire. Logistic regression analysis was used to identify key predictors of probable depression and anxiety. Results: A high prevalence of probable depression (26.8% [95% CI: 23.2–30.3]) and anxiety (27.2% [95% CI: 23.7–30.7]) was found. Logistic regressions showed both probable depression and anxiety associated with being female (depression: OR 1.80 [95% CI: 1.06–3.03]; anxiety: OR: 1.69 [95% CI: 1.03–2.76]), daily use of any illegal substances (depression: OR 3.20 [95% CI: 1.87–5.49]; anxiety: OR 2.04 [95% CI: 1.21–3.45]), and fear of contracting COVID-19 (little fear, depression: OR: 1.81 [95% CI 1.01–3.23], some fear, anxiety: OR: 2.52 [95% CI: 1.31–4.83]). Probable depression was associated with longer durations of homelessness (OR: 1.004, [95% CI: 1.001–1.007]. Conclusions: Probable depression and anxiety are highly prevalent in homeless individuals throughout. Key predictors may help to identify individuals in need and design targeted interventions. Full article

Public health impacts of non-optimal temperatures and air pollution have received insufficient attention in Southeast Europe, one of the most air-polluted regions in Europe, simultaneously pressured by climate change. This study employed a multimodal approach to characterize the microclimate and air quality and conduct a health impact assessment in the three biggest cities in Bulgaria. Simulation of atmospheric thermo-hydrodynamics and assessment of urban microclimate relied on the Weather Research and Forecasting model. Concentrations of fine particulate matter (PM_2.5) and nitrogen dioxide (NO₂) were calculated with a land-use regression model. Ischemic heart disease (IHD) hospital admissions were linked to daily measurements at background air quality stations. The results showed declining trends in PM_2.5 but persistent levels of NO₂, especially in Sofia and Plovdiv. Distributed lag nonlinear models revealed that, in Sofia and Plovdiv, PM_2.5 was associated with IHD hospitalizations, with a fifth of cases in Sofia attributable to PM_2.5. For NO₂, an increased risk was observed only in Sofia. In Sofia, the risk of IHD was increased at cold temperatures, while both high and low temperatures were associated with IHD in Plovdiv and Varna. Short-term effects were observed in response to heat, while the effects of cold weather took up to several weeks to become apparent. These findings highlight the complexity of exposure–health interactions and emphasize the need for integrated policies addressing traffic emissions, urban design, and disease burden. Full article

Stroke continues to impose an enormous morbidity and mortality burden worldwide. Stroke survivors often incur debilitating consequences that impair motor function, independence in activities of daily living and quality of life. Rehabilitation is a pivotal intervention to minimize disability and promote functional recovery following a stroke. The Internet of Medical Things, a network of connected medical devices, software and health systems that collect, store and analyze health data over the internet, is an emerging resource in neurorehabilitation for stroke survivors. Technologies such as asynchronous transmission to handle intermittent connectivity, edge computing to conserve bandwidth and lengthen device life, functional interoperability across platforms, security mechanisms scalable to resource constraints, and hybrid architectures that combine local processing with cloud synchronization help bridge the digital divide and infrastructure limitations in low-resource environments. This manuscript reviews emerging rehabilitation technologies such as robotic devices, virtual reality, brain–computer interfaces and telerehabilitation in the setting of neurorehabilitation for stroke patients. Full article

Background/Objectives: Branched-chain fatty acids (BCFAs) exhibit a range of biological activities; however, their limited natural abundance and high cost have constrained in vivo research. Lanolin represents a promising source for enriching BCFAs. Nevertheless, the in vivo application, safety, and dose-effect relationship of BCFAs derived from lanolin (BCFAs-DFL) remain unassessed. Methods: In this study, the acute toxicity in C57BL/6J mice was first evaluated for 7 days by a single oral administration of 5000 mg/kg BW of BCFAs-DFL. Subsequently, 40 mice were divided into four groups (control group, low dose of 100 mg/kg BW, medium dose of 300 mg/kg BW, and high dose of 600 mg/kg BW) and were continuously administered by gavage for 28 days to study the effects of BCFAs-DFL on the growth, blood biochemistry, intestinal morphology, and intestinal flora of the mice. Results: In the acute toxicity test, BCFAs-DFL exhibited no lethality or abnormalities in mice, indicating its non-toxic nature. Throughout the 28-day trial, mice in the medium- and high-dose groups experienced a notable decrease in average daily feed intake (p < 0.05), yet their weight gain remained unaffected (p > 0.05). Hemoglobin and hematocrit levels declined in the high-dose group (p < 0.05). Conversely, serum aspartate aminotransferase and total bilirubin levels escalated in the medium- and high-dose groups, while triglycerides and urea nitrogen levels decreased (p < 0.05). The serum’s total antioxidant capacity and immunoglobulin levels (IgA, IgG) rose in proportion to the dosage (p < 0.05). BCFAs-DFL notably enhanced the villus height of the jejunum and ileum in mice (p < 0.05). Gut microbiota analysis indicated no significant impact on overall α and β diversity. Conclusions: The 28-day intervention revealed that BCFAs-DFL can modulate feeding behavior, TG, T-AOC, and immunoglobulin levels in mice. Additionally, it promotes the development of intestinal villi. Based on various indicators, a dosage of 100 mg/kg BW effectively induces beneficial metabolic regulation, such as the reduction of triglycerides, without causing a burden on liver metabolism. This dosage may represent a more suitable application for potential use. Full article

This study aimed to examine the association between physical activity and individuals’ health status, healthcare utilization, socio-demographic characteristics, and health behaviors in a large representative sample from Northern Greece. A cross-sectional study was conducted involving 1227 participants (47.4% males, mean age 49.94 ± 14.87 years) from Thrace, Greece, selected through a two-stage stratified sampling method. According to the Greek version of IPAQ, participants were classified as inactive/insufficiently active, sufficiently and highly active. Data on socio-demographic, lifestyle, and health-related variables were collected through structured interviews. Multivariate logistic regression analysis was performed to determine the independent effect of physical activity on subjects’ characteristics using SPSS ver. 19. Half of the participants (49.8%) were inactive/insufficiently active, 418 participants (34.1%) were sufficiently active, and 198 participants (16.1%) were highly active. In univariate analysis, smoking (p < 0.001), higher coffee consumption (p = 0.002), higher adherence to Mediterranean diet (p < 0.001), napping during the day (p = 0.017) and short sleep duration (p < 0.001) were associated with lower prevalence of high activity. In adjusted analyses, sufficiently active participants had a lower risk for bad self-rated health (aOR = 0.63), hypertension (aOR = 0.41), dyslipidemia (aOR = 0.42), diabetes (aOR = 0.53), obesity (aOR = 0.61), cardiovascular diseases (aOR = 0.43), anxiety (aOR = 0.65), depression (aOR = 0.56), daily sleepiness (aOR = 0.62), poor sleep quality (aOR = 0.71), as well as for primary (aOR = 0.54) and secondary (aOR = 0.40) healthcare utilization compared to inactive participants. Higher-intensity physical activity did not enhance these beneficial effects of sufficient activity on subjects’ characteristics. Physical inactivity significantly compromises health across multiple domains. Promoting even moderate-intensity physical activity may reduce chronic disease burden and healthcare utilization. Full article

Background/Objectives: Apple pomace, a major by-product of juice production, represents both an environmental burden and an underutilized resource. This study aimed to enhance the nutritional value of apple pomace via solid-state fermentation (SSF) to develop a functional feed ingredient and systematically evaluate its effects on growth, metabolism, and intestinal health in weaned piglets. Methods: Apple pomace was fermented using a multi-species consortium (Geotrichum candidum, Saccharomyces cerevisiae, Rhizopus oryzae, Bacillus subtilis, and Trichoderma viride). A total of 180 weaned piglets were fed iso-nitrogenous diets containing 0, 2, 4, 6, 8, or 10% fermented apple pomace for 35 days. Growth performance, serum biochemical and immuno-antioxidant indices, diarrhea incidence, jejunal morphology, and fecal microbiota were analyzed. Results: Dietary fermented apple pomace supplementation showed dose-dependent effects. The 8% fermented apple pomace group exhibited optimal growth performance, with increased average daily gain and feed intake and reduced feed-to-gain ratio (p < 0.05). Serum analysis indicated enhanced protein synthesis, antioxidant capacity (T-AOC, SOD, GSH-Px), and immunoglobulin levels (IgA, IgG, IgM), along with reduced urea nitrogen and oxidative stress marker MDA. This group also had the lowest diarrhea rate, associated with improved jejunal villus morphology. Microbiota analysis revealed that 8% fermented apple pomace effectively increased α-diversity, promoted beneficial bacteria (e.g., lactic acid bacteria and butyrate-producing Clostridium sensu stricto_1), and suppressed pathogens (Escherichia coli, Salmonella, Streptococcus). Conclusions: Multi-species SSF successively enhanced the nutritional profile of apple pomace. Inclusion at 8% showed the most favorable response in terms of growth performance, metabolic profile, and immune–antioxidant status in weaned piglets, mediated through improved intestinal morphology and targeted modulation of the gut microbiota toward a more diverse and beneficial ecosystem. These findings support the high-value, functional utilization of apple pomace as a feed additive in swine nutrition. Full article

Background and Objectives: Behçet’s disease (BD) is a multisystem inflammatory disorder with significant physical, psychological, and social burdens. However, patient-reported outcomes and subjective symptom experiences remain under-recognized in clinical practice. This study aimed to provide a patient-centric analysis of the disease burden, treatment challenges, and unmet needs in BD. Materials and Methods: A multinational cross-sectional study was conducted using a structured questionnaire among 528 BD patients recruited from online support groups and a specialized clinic. The questionnaire gathered information about participants’ backgrounds, medical histories, how symptoms affected them, psychological and social factors, side effects of treatments, and their suggestions for better care. Data were analyzed descriptively. Results: The mean age of the participants was 41.4 years, and 69.3% were male. The most common symptoms that significantly affected daily life were severe fatigue (82.8%), joint pain and swelling (79.0%), and neurological issues (74.1%). Nearly half of patients perceived that fatigue (49.1%) and neurological symptoms (45.1%) were underestimated by healthcare providers. Psychological distress was prevalent, with 74.1% of participants reporting either depression or anxiety. Side effects related to treatment were frequently encountered (56.3%), resulting in treatment discontinuation for 53.4% of the individuals. The main unmet needs identified were fatigue reduction (59.1%), pain management (43.0%), and the minimization of side effects (59.1%). Furthermore, patients expressed a desire for enhanced communication (62.9%), validation of their unobserved symptoms (74.1%), and comprehensive disease education (67.6%). Conclusions: BD imposes a profound multidimensional burden, with a significant disconnect between patient experiences and their perception of clinical recognition. Fatigue, pain, psychological distress, and treatment-related challenges contribute substantially to unmet needs. A patient-centered approach emphasizing communication, symptom validation, and holistic support is essential to improving care and quality of life in BD. Full article

Background. Rheumatoid arthritis (RA) is a chronic autoimmune disease frequently accompanied by cardiovascular, respiratory, skeletal, psychiatric, and neoplastic comorbidities that are associated with higher morbidity and poorer health-related quality of life (HRQoL). This study evaluated the associations between comorbidities and patient-reported physical health, emotional distress, daily functioning, and social relationships in adults with RA and explored patient-reported unmet needs relevant to integrated care. Methods. We conducted a cross-sectional survey among 286 adults with physician-confirmed RA, using a structured questionnaire (ICRA-Q) administered between June and July 2025 via online platforms and in-hospital supervised completion. The survey captured demographics, patient-reported physician-diagnosed comorbidities (current and/or past), perceived disease impact, functional limitations, emotional and social consequences, access to treatment, financial burden, and support needs. Analyses included descriptive statistics, χ² tests, t-tests/ANOVA, effect sizes (Cramer’s V and standardized mean differences), and multivariable logistic regression to explore predictors of high HRQoL impact and high difficulty in disease management. An exploratory classification into high-risk phenotypes was performed using predefined clinical, psychological, and socioeconomic criteria. Results. Most participants (98.6%) reported at least one comorbidity, most commonly hypertension, osteoporosis, and cardiovascular disease. Higher comorbidity burden and depression/anxiety were strongly associated with higher pain, reduced mobility, emotional distress, and financial strain. Exploratory high-risk phenotypes (severe somatic multimorbidity, high psychological vulnerability, high socioeconomic burden, and a composite very high-risk profile) were associated with poorer HRQoL indicators. Younger age, shorter disease duration, and higher perceived social support were associated with lower perceived burden. Conclusions. In this cross-sectional, patient-reported study, comorbidity burden—particularly psychological comorbidity—was strongly associated with poorer HRQoL and greater management difficulty in RA. These findings support the need for multidisciplinary, integrated care pathways; however, subgroup phenotypes should be considered exploratory and require external validation. Full article