Search Results (13,834)

Due to the rising prevalence of polypharmacy, pharmacists face more challenges in ensuring patient safety and optimizing medication management. This paper introduces PharmiTech, a Clinical Decision Support System that leverages Artificial Intelligence (AI) to tackle the growing need for efficient tools to assist pharmacists. The primary focus of the tool is to identify possible herb-drug interactions and instances of prescription drug abuse, combining an expert knowledge base with a supervised classification model and providing user-friendly alerts to pharmacists. To demonstrate the capabilities of the developed tool, this paper presents its functionalities through a case study involving simulated scenarios using de-identified information to maintain the confidentiality of real patients’ personal data. Tested in Portuguese pharmacies, PharmiTech enhances pharmaceutical care, safeguards patient data, and aids pharmacists in informed decision-making, making it a valuable resource for healthcare professionals. Full article

Rift Valley fever (RVF) is a mosquito-borne viral disease that primarily affects animals, especially ruminants, but has the capacity to infect humans and result in outbreaks. Infection with the causative agent, RVF virus (RVFV), causes severe disease in domestic animals, especially sheep, resulting in fever, anorexia, immobility, abortion, and high morbidity and mortality rates in neonate animals. Humans become infected through exposure to infected animals and, less frequently, directly via a mosquito bite. A greater awareness of RVFV and its epidemic potential has resulted in increased investment in the development of interventions, especially vaccines. There is currently no substitute for the use of animal models in order to evaluate these vaccines. As outbreaks of RVF disease are difficult to predict or model, conducting Phase III clinical trials will likely not be feasible. Therefore, representative animal model systems are essential for establishing efficacy data to support licensure. Nonhuman primate (NHP) species are often chosen due to their closeness to humans, reflecting similar susceptibility and disease kinetics. This review covers the use of NHP models in RVFV research, with much of the work having been conducted in rhesus macaques and common marmosets. The future direction of RVF work conducted in NHP is discussed in anticipation of the importance of it being a key element in the development and approval of a human vaccine. Full article

With profound effects on patient care, the role of artificial intelligence (AI) in radiomics has become a disruptive force in contemporary medicine. Radiomics, the quantitative feature extraction and analysis from medical images, offers useful imaging biomarkers that can reveal important information about the nature of diseases, how well patients respond to treatment and patient outcomes. The use of AI techniques in radiomics, such as machine learning and deep learning, has made it possible to create sophisticated computer-aided diagnostic systems, predictive models, and decision support tools. The many uses of AI in radiomics are examined in this review, encompassing its involvement of quantitative feature extraction from medical images, the machine learning, deep learning and computer-aided diagnostic (CAD) systems approaches in radiomics, and the effect of radiomics and AI on improving workflow automation and efficiency, optimize clinical trials and patient stratification. This review also covers the predictive modeling improvement by machine learning in radiomics, the multimodal integration and enhanced deep learning architectures, and the regulatory and clinical adoption considerations for radiomics-based CAD. Particular emphasis is given to the enormous potential for enhancing diagnosis precision, treatment personalization, and overall patient outcomes. Full article

Background: The application of normo- and hyperbaric O₂ is a common therapy option in various disease patterns. Thereby, the applied O₂ affects the whole body, including the blood and its components. This study investigates influences of pressure and oxygen fraction on human blood plasma, nutrient media, and the functions of neutrophil granulocytes (PMNs). Methods: Neutrophil migration, reactive oxygen species (ROS) production, and NETosis were examined by live cell imaging. The treatment of various matrices (Roswell Park Memorial Institute 1640 medium, Dulbecco’s Modified Eagle’s Medium, H₂O, human plasma, and isolated PMNs) with hyperbaric oxygen (HBO) was performed. In addition, the expression of different neutrophil surface epitopes (CD11b, CD62L, CD66b) and the oxidative burst were investigated by flow cytometry (FACS). The application of cold atmospheric plasma (CAP) to normoxic and normobaric culture media served as a positive control. Soluble reaction products such as H₂O₂, reactive nitrogen species (RNS: NO₂⁻ and NO₃⁻), and ROS-dependent dihydrorhodamine oxidation were quantified by fluoro- and colorimetric assay kits. Results: Under normobaric normoxia, PMNs migrate slower and shorter in comparison with normobaric hyper- or hypoxic conditions and hyperbaric hyperoxia. The pressure component has less effect on the migration behavior of PMNs than the O₂ concentration. Individual PMN cells produce prolonged ROS at normoxic conditions. PMNs showed increased expression of CD11b in normobaric normoxia, lower expression of CD62L in normobaric normoxia, and lower expression of CD66b after HBO and CAP treatment. Treatment with CAP increased the amount of ROS and RNS in common culture media. Conclusions: Hyperbaric and normobaric O₂ influences neutrophil functionality and surface epitopes in a measurable way, which may have an impact on disorders with neutrophil involvement. In the context of hyperbaric experiments, especially high amounts of H₂O₂ in RPMI after hyperbaric oxygen should be taken into account. Therefore, our data support a critical indication for the use of normobaric and hyperbaric oxygen and conscientious and careful handling of oxygen in everyday clinical practice. Full article

Long COVID affects millions of people worldwide and has emerged as a major health consequence of the COVID-19 pandemic. While quantitative studies have helped paint a picture of ongoing symptomatology, there are very few longitudinal qualitative studies that present patients’ perspectives about the significant and persistent impact Long COVID has on their daily lives. To address this gap, we conducted semi-structured qualitative interviews with nine Long COVID patients about 15 months after we performed an initial set of interviews with those patients who were seeking care at a Long COVID specialty clinic. Most patients that we re-interviewed reported having lingering symptoms that continue to impact their lives. Many described suffering with mental health issues, particularly depression and anxiety. Others described financial stress. Most reported not yet being able to return to their pre-COVID level of health and well-being. Our work demonstrates the ongoing need to study Long COVID and provide robust social support, mental health resources, and healthcare focused on symptom relief. Full article

Background and objective: Colorectal cancer (CRC) is the leading cause of mortality in Spain, with screening programs, such as the faecal occult blood test and colonoscopy, having shown effectiveness in reducing CRC incidence and mortality. Despite these advancements, CRC screening uptake remains low in Spain, highlighting the need for studies comparing outcomes between screening-diagnosed and symptom-diagnosed patients to better understand the impact on overall survival and to quantify the clinical benefit in prognosis at diagnosis and at the end of follow-up. Methods: We conducted a retrospective cohort study with the following objectives: to compare stage at diagnosis, all-cause mortality, and disease-specific mortality among people diagnosed with CRC based on screening and based on symptoms; to identify the risk factors associated with mortality in this population; and to evaluate the effectiveness of screening on survival and early detection. Our study included people diagnosed with CRC in the public hospital of Elda (Spain) from 2014 to 2018; follow-up was until 2023 or death. Our primary outcome was all-cause mortality, which we analysed using Kaplan–Meier curves. We also investigated CRC-specific mortality and other-cause mortality. Results: Our sample included 315 people (186 with symptom-based diagnoses, 129 with screening-based diagnoses). The mean length of follow-up was 62.8 months. The screening group had a higher prevalence of a family history of CRC (p = 0.008), a distal tumour location (p = 0.002), and a cancer stage of 0 or I (p < 0.001). The symptoms group had a higher prevalence of a proximal CRC (p = 0.002), other chronic diseases (p < 0.001), and stages II, III, and IV (p < 0.001). Two variables were associated with mortality: stage IV at diagnosis and previous cancers. People with a symptom-based diagnosis had a higher prevalence of stage IV at diagnosis and a higher cumulative incidence of CRC mortality and all-cause mortality at the end of follow-up (p < 0.05). The Kaplan–Meier curves also showed a higher rate of all-cause mortality in the symptoms group throughout the follow-up. Conclusion: CRC screening enables an earlier diagnosis and improves survival. These findings support public health policies that promote accessible and effective screening. Full article

Oxidative stress frequently contributes to intestinal barrier injury in animals and humans. It was reported that both Selenomethionine (SeMet) and allicin exhibit protective effects against a range of diseases caused by oxidative stress. This study aimed to investigate the synergistic antioxidant effects and underlying mechanisms of SeMet and allicin on a H₂O₂-induced intestinal barrier injury model using IPEC-J2 cells and mice. The results showed that H₂O₂ induced severe oxidative stress, including a decrease in cell viability, antioxidant level, migration capacity, and cell integrity. SeMet and allicin exhibited significant synergistic anti-oxidative effects on intestinal epithelial cells. The combined use of SeMet and allicin increased SOD activity, GSH content, and GSH/GSSG ratio while decreasing MDA, NO, and ROS content levels. Furthermore, we found that SeMet and allicin synergistically activated the nuclear factor erythroid-related factor 2 (Nrf2)-NAD(P)H dehydrogenase [quinone] 1 (NQO1) signaling pathway and down-regulated endoplasmic reticulum stress (ER stress)-related proteins. However, the synergistic antioxidative and intestinal barrier protective effects of SeMet and allicin were abolished by Nrf2 inhibitor ML385 in vitro and in vivo. In conclusion, SeMet and allicin synergistically attenuate intestinal barrier injury induced by excessively oxidative stress through the activation of the Nrf2 signaling pathway and inhibition ER stress. These findings support that the combined use of SeMet and allicin could enhance antioxidative properties and alleviate intestinal injury in further clinical practice. Full article

Newborn screening for sickle cell disease (SCD) is sparse in sub-Saharan Africa. The leadership of the Aminu Kano Teaching Hospital (AKTH) in Kano, Nigeria, with the support of local religious authorities, established a groundbreaking SCD newborn screening program that has become the standard of care for pregnant women and their newborns. Our program includes (1) prenatal genetic counseling for all pregnant women in the antenatal clinic, (2) newborn screening, (3) postnatal genetic counseling for parents of newborns diagnosed with SCD and SCT, and (4) referral of newborns with SCD for follow-up in the SCD Comprehensive Care Clinic by 3 months of age. From September 2020 to December 2023, the team screened 7530 infants for SCD at the AKTH, identifying 126 (1.7%) infants with SCD and 1546 (20.5%) with SCT. Of these, 93 (73.8%) newborns with SCD received individualized genetic counseling, and 43 (46%) were referred to the SCD Comprehensive Care Clinic before 3 months. Group genetic counseling was provided to the parents of 778 (50.3%) of newborns identified with SCT. The SCD newborn screening at the AKTH is now standard care, indicating the viability of sustaining an SCD newborn screening program that provides pre- and postnatal genetic counseling and comprehensive SCD care within a low-income setting. Full article

Accurate diagnosis of dementia subtypes is crucial for optimizing treatment planning and enhancing caregiving strategies. To date, the accuracy of classifying Alzheimer’s disease (AD) and frontotemporal dementia (FTD) using electroencephalogram (EEG) data has been lower than that of distinguishing individuals with these diseases from healthy elderly controls (HCs). This limitation has impeded the feasibility of a cost-effective differential diagnosis for the two subtypes in clinical settings. This study addressed this issue by quantifying communication between electrode pairs in EEG data, along with demographic information, as features to train machine learning (support vector machine) models. Our focus was on refining the feature set specifically for AD-FTD classification. Using our initial feature set, we achieved classification accuracies of 76.9% for AD-HC, 90.4% for FTD-HC, and 91.5% for AD-FTD. Notably, feature importance analyses revealed that the features influencing AD-HC classification are unnecessary for distinguishing between AD and FTD. Eliminating these unnecessary features improved the classification accuracy of AD-FTD to 96.6%. We concluded that communication between electrode pairs specifically involved in the neurological pathology of FTD, but not AD, enables highly accurate EEG-based AD-FTD classification. Full article

Heterogeneity of outcomes across different clinical trial study sites is often inevitable. Understanding how outcomes differ by site is important for planning future programs and studies. We examined the extent of heterogeneity of hepatitis C virus (HCV) treatment cascade outcomes among persons who inject drugs (PWIDs) across sixteen clinical sites utilized in the HERO Study—a pragmatic randomized trial of HCV treatment support. Treatment cascade outcomes included averages of overall treatment adherence and proportions of treatment initiation, treatment completion, sustained virologic response (SVR) test completion, and SVR achievement. The HERO study utilized 16 clinical sites across the United States (US): eight opioid treatment programs (OTPs) and eight community health centers (CHCs). Variability of the outcomes across the 16 clinical sites was assessed using ranges and intraclass correlation coefficients (ICC) estimated from mixed-effects linear or logistic regression models. Treatment initiation was analyzed in the intention-to-treat (ITT) sample (N = 755); treatment completion, adherence, and SVR test completion in the modified ITT (mITT) sample, which is the sample that initiated treatment (N = 623); and SVR achievement in the mITT and per-protocol (PP, N = 501) samples. Across the 16 clinical sites, the range observed in the averages of overall treatment adherence was from 68% to 81% [ICC = 0.026 (0.005, 0.054)], and the ranges of proportions observed were from 68% to 96% for treatment initiation [ICC (95% CI) = 0.086 (0.051, 0.155)], 60% to 100% for treatment completion [ICC = 0.049 (0.008, 0.215)], 54% to 95% for SVR test completion [ICC = 0.096 (0.006, 0.177)], 46% to 90% for SVR achievement in the mITT sample [ICC = 0.070 (0.014, 0.122)], and 76% to 100% for SVR achievement in the PP sample [ICC = 0.143 (0.021, 0.422)]. The variability of the outcomes across 16 US sites treating HCV among PWIDs appears to be substantial in view of the ranges and ICC values of the outcomes. It is imperative to develop tailored interventions to target the sources of variability and reduce barriers at the patient, provider, clinic, and state policy levels to facilitate more equitable access to HCV treatment and reduce heterogeneity in treatment outcomes. Full article

Background: Multiple sclerosis is a chronic, inflammatory, neurodegenerative autoimmune disease caused by myelin loss in the central nervous system, which leads to motor and non-motor problems. The main objective of this study was to explore whether an immersive virtual reality (IVR) exercise programme would be feasible as a form of physical therapy for people with MS (pwMS). Methods: 18 participants (13 women; 45.06 years) were assigned to an experimental group (EG, n = 8) and a control group (CG, n = 10). The EG took part in a twice-weekly IVR exergame physical therapy programme—ExeRVIEM programme. A randomised, single-blind clinical trial was conducted and was registered in clinicaltrials (NCT05870254). Results: The intervention was feasible and safe. The participants completed the programme with no adverse effects (no symptoms on the Simulator Sickness Questionnaire), high usability (System Usability Scale 90.31%), and outstandingly positive post-game experiences (Game Experience Questionnaire 3.10/4). In addition, the GE significantly improved several of their functional capacities: increased lower limb strength (Five Times Sit-to-Stand Test p = 0.042), improved functional mobility, and reduced fall risk (Timed Up and Go Test-simple p = 0.009; Timed Up and Go Test-cognitive p = 0.003). There were no statistically significant differences between the groups. Conclusions: The findings support that the use of exergames and IVR as physical therapy in pwMS is feasible and safe. Furthermore, there is the suggestion of possible benefits to participants’ functional abilities, all of which position IVR as a promising tool for the rehabilitation of this neurodegenerative pathology affecting young adults. Full article

Background: Neck reflex points (NRPs) are 2 × 6 potentially tender areas of the neck, denominated NRP-C0 to NRP-C7. They are different from muscular trigger points and become tender in response to chronic trigeminal irritation. NRP examination has a high inter-rater reproducibility. We investigated the prevalence of NRPs in two populations to investigate their usefulness as a clinical test for trigeminal irritation. Methods: In total, 165 patients with chronic pain and 431 students were examined for NRP tenderness using a three-level pain scale: absent pain (PI = 0), mild tenderness (PI = 1), or marked tenderness (PI = 2). Results: In patients, we found more tender NRPs than in the student group (p < 0.001), and on the left side, more tender NRPs were found in NRP-C0–C4. Left and right NRPs appeared independently (kappa 0.1–0.4), except for NRP-C7 (kappa 0.55). Females had more tender NRPs (p < 0.001). Tenderness was independent of age, BMI, and pre-existing diseases. Conclusions: NRP tenderness occurs more frequently in patients than in students, independent from potential covariates. Our results, together with previous findings, support the use of NRP examination as a clinical test for chronic silent inflammation of the trigeminal region. These data provide a base for further studies investigating correlations of NRPs with clinical findings. Full article

Background: The oral cavity is an important but often overlooked reservoir for Staphylococcus aureus. The effective control and prevention of S. aureus colonization and infection in the oral and maxillofacial regions are crucial for public health. Fluoride is widely used in dental care for its remineralization and antibacterial properties. However, its effectiveness against S. aureus has not been thoroughly investigated. Objectives: This study aimed to evaluate the potential of combining sodium fluoride (NaF) with compounds to enhance its antibacterial and antibiofilm effects against S. aureus. Method: We found that a urea derivative significantly enhances the efficacy of fluoride by promoting the retention of fluoride ions within the cells. The synergistic antibacterial and antibiofilm effects of BPU with NaF were confirmed through various assays, including checkerboard assays, time-kill assays, and growth curve analysis. These findings were further supported by additional methods, including transmission electron microscopy (TEM), in silico simulations, and gene overexpression studies. Results: These findings suggest that targeting fluoride ion membrane exporters could enhance antibacterial efficacy. When combined with fluoride, 1,3-Bis [3,5-bis(trifluoromethyl)phenyl]urea (BPU) showed increased effectiveness in inhibiting S. aureus growth and reducing established biofilms. Conclusions: This novel combination represents a promising therapeutic strategy for treating biofilm-associated S. aureus infections, offering a new strategy in oral healthcare. To fully evaluate the clinical potential of this synergistic therapy, further in vivo studies are essential. Full article

Background/Objectives: Schizophrenia (SZ) is a severe psychiatric disorder characterized by a complex interplay of genetic, developmental, and environmental factors that significantly increase the risk of suicidal ideation (SI) and suicide attempts (SAs). This systematic review synthesizes current research on the developmental predictors of SI in individuals with SZ, aiming to delineate the multifactorial etiology of suicide within this population. Methods: A comprehensive search across Medline, PsycINFO, and EMBASE databases identified 23 eligible studies, emphasizing the varied methodological approaches and the global distribution of research efforts. Results: These studies demonstrate a robust association between early life adversities, particularly childhood trauma such as physical neglect, emotional abuse, and sexual abuse, and the increased prevalence of SI and SAs in SZ. This review also highlights the significant genetic factors associated with the development of suicidality in SZ, raising the possibility that polymorphisms in inflammation-related genes and neurodevelopmental abnormalities may influence susceptibility to SI. Notably, family history of psychiatric conditions may exacerbate the risk of SI through both hereditary and environmental mechanisms. Environmental factors, including socioeconomic status and social support, are also implicated, underscoring the role of broader socio-environmental conditions influencing outcomes. Conclusions: This review supports the integration of biopsychosocial models in understanding SI in SZ, advocating for interventions addressing the complex interplay of risk factors and the need for longitudinal studies to elucidate the dynamic interactions between risk factors over time. This comprehensive understanding is crucial for developing targeted preventive strategies and enhancing the clinical management of SZ, aiming to reduce suicidality in this vulnerable population. Full article

Background: Biliary tract cancers (BTCs) are aggressive in nature, often presenting asymptomatically until they are diagnosed at an advanced stage. Surgical resection or liver transplantation are potential curative options. However, a large proportion of patients present with incurable locally advanced or metastatic disease and most of these patients are only eligible for palliative chemotherapy or best supportive care. More recently, targeted therapies have proven beneficial in a molecularly selected subgroup of patients with cholangiocarcinoma who have progressed on previous lines of systemic treatment. However, only a minority of patients with BTCs whose tumours harbour specific molecular alterations can access these therapies. Methods: In relation to ADCs, studies regarding use of antibody–drug conjugates in cancer, particularly in BTCs, were searched in Embase (1974 to 2024) and Ovid MEDLINE(R) (1946 to 2024) to obtain relevant articles. Examples of current clinical trials utilising ADC treatment in BTCs were extracted from the ClinicalTrials.gov trial registry. Conclusions: Overall, this review has highlighted that ADCs have shown encouraging outcomes in cancer therapy, and this should lead to further research including in BTCs, where treatment options are often limited. The promising results observed with ADCs in various cancers underscore their potential as a transformative approach in oncology, warranting continued exploration and development and the need for education on the management of their specific toxicities. By addressing current challenges and optimising ADC design and application, future studies could potentially improve treatment outcomes for patients with BTCs and beyond, potentially in both early and advanced stage settings. Full article