Search Results (677)

Inflammatory Bowel Diseases (IBDs) are complex, multifactorial disorders with no known cure, necessitating lifelong care and often leading to surgical interventions. This ongoing healthcare requirement, coupled with the increased use of biological drugs and rising disease prevalence, significantly increases the financial burden on the healthcare systems. Thus, a number of novel technological approaches have emerged in order to face some of the pivotal questions still associated with IBD. In navigating the intricate landscape of IBD, biosensors act as indispensable allies, bridging the gap between traditional diagnostic methods and the evolving demands of precision medicine. Continuous progress in biosensor technology holds the key to transformative breakthroughs in IBD management, offering more effective and patient-centric healthcare solutions considering the One Health Approach. Here, we will delve into the landscape of biomarkers utilized in the diagnosis, monitoring, and management of IBD. From well-established serological and fecal markers to emerging genetic and epigenetic markers, we will explore the role of these biomarkers in aiding clinical decision-making and predicting treatment response. Additionally, we will discuss the potential of novel biomarkers currently under investigation to further refine disease stratification and personalized therapeutic approaches in IBD. By elucidating the utility of biosensors across the spectrum of IBD care, we aim to highlight their importance as valuable tools in optimizing patient outcomes and reducing healthcare costs. Full article

Background/Objectives: This study compared overall survival (OS) associated with common real-world treatment sequences in patients with chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) in the United States. Methods: Utilizing the nationwide Flatiron Health electronic health record-derived de-identified database, adult CLL/SLL patients who initiated systemic therapy (JAN2016-NOV2023) and received at least two lines of therapy (LoTs) were analyzed. Treatment regimens were categorized based on drug class, and most frequent (n ≥ 50) sequences (first LoT followed by [→] second LoT) were compared. OS from initiation of the first LoT was compared using multivariable Cox proportional hazard models, and adjusted hazard ratios with 95% CIs were reported. Results: Among 2354 eligible patients, n = 1711 (73%) received the 16 most frequent treatment sequences. Sequencing chemoimmunotherapy (CIT) → CIT (HR: 2.29 [1.23–4.28]), anti-CD20 monoclonal antibody (anti-CD20mab) monotherapy → CIT (1.95 [1.03–3.69]), and covalent Bruton tyrosine kinase inhibitor (cBTKi) monotherapy → anti-CD20mab monotherapy (2.00 [1.07–3.74]) were associated with worse OS compared to patients treated with cBTKi monotherapy → B-cell lymphoma 2 inhibitors (BCL2i) + anti-CD20mab (reference). Conclusions: OS associated with other sequences were not significantly different from the reference sequence in adjusted analyses, suggesting a lack of evidence for the optimal standard of care for sequencing the first two LoTs in real-world settings. Future research should reassess sequencing outcomes as novel treatments become adopted into clinical practice. Full article

Background: Hypertension is a serious global health issue affecting over one billion adults and leading to severe complications if left unmanaged. Despite medical advancements, only a fraction of patients effectively have their hypertension under control. Among the factors that hinder adherence to hypertensive drugs are the debilitating side effects of the drugs. The lack of adherence results in poorer patient outcomes as patients opt to live with their condition, instead of having to deal with the side effects. Hence, there is a need to discover new hypertension drug molecules with better side effects to increase patient treatment options. To this end, computational methods such as artificial intelligence (AI) have become an exciting option for modern drug discovery. AI-based computational drug discovery methods generate numerous new lead antihypertensive drug molecules. However, predicting their potential side effects remains a significant challenge because of the complexity of biological interactions and limited data on these molecules. Methods: This paper presents a machine learning approach to predict the potential side effects of computationally synthesised antihypertensive drug molecules based on their molecular properties, particularly functional groups. We curated a dataset combining information from the SIDER 4.1 and ChEMBL databases, enriched with molecular descriptors (logP, PSA, HBD, HBA) using RDKit. Results: Gradient Boosting gave the most stable generalisation, with a weighted F1 of 0.80, and AUC-ROC of 0.62 on the independent test set. SHAP analysis over the cross-validation folds showed polar surface area and logP contributing the largest global impact, followed by hydrogen bond counts. Conclusions: Functional group patterns, augmented with key ADMET descriptors, offer a first-pass screen for identifying side-effect risks in AI-designed antihypertensive leads. Full article

Background: Chronic Kidney Disease (CKD) is a major global health issue, with diabetes being its primary cause and cardiovascular disease contributing significantly to patient mortality. Recently, two classes of medications—sodium–glucose cotransporter 2 inhibitors (SGLT2i) and glucagon-like peptide-1 receptor agonists (GLP-1 RAs)—have shown promise in protecting both kidney and heart health beyond their effects on blood sugar control. Methods: We conducted a narrative review summarizing the findings of different clinical trials and mechanistic studies evaluating the effect of SGLT2i and GLP-1 RAs on kidney function, cardiovascular outcomes, and overall disease progression in patients with CKD and DKD. Results: SGLT2i significantly mitigate kidney injury by restoring tubuloglomerular feedback, reducing intraglomerular hypertension, and attenuating inflammation, fibrosis, and oxidative stress. GLP-1 RAs complement these effects by enhancing endothelial function, promoting weight and blood pressure control, and exerting direct anti-inflammatory and anti-fibrotic actions on renal tissues. Landmark trials—CREDENCE, DAPA-CKD, and EMPA-KIDNEY—demonstrate that SGLT2i reduce the risk of kidney failure and renal or cardiovascular death by 25–40% in both diabetic and non-diabetic CKD populations. Likewise, trials such as LEADER, SUSTAIN, and AWARD-7 confirm that GLP-1 RAs slow renal function decline and improve cardiovascular outcomes. Early evidence suggests that using both drugs together may offer even greater benefits through multiple mechanisms. Conclusions: SGLT2i and GLP-1 RAs have redefined the therapeutic landscape of CKD by offering organ-protective benefits that extend beyond glycemic control. Whether used individually or in combination, these agents represent a paradigm shift toward integrated cardiorenal-metabolic care. A deeper understanding of their mechanisms and clinical utility in both diabetic and non-diabetic populations can inform evidence-based strategies to slow disease progression, reduce cardiovascular risk, and improve long-term patient outcomes in CKD. Full article

The designs of clinical trials of drugs for rare diseases are challenged by health technology assessment organisations and payers. Phase II pivotal studies, single-arm or open-label designs, the extensive use of non-final endpoints, and the limited use of patient-reported outcomes (PROs) are the main points of contention. The evidence on the actual design of these trials is limited, but corroborates the concerns of the above. Our aim is to scrutinise whether the design of pivotal studies of drugs for rare diseases to be launched into the Italian market by 2026 present similar issues. The drugs and the relevant pivotal studies were retrieved from Biomedtracker and US and European clinical trial databases. We identified 154 new drugs for rare diseases. Single-arm designs account for 36% of trials. Almost 50% of randomised control trials (RCTs) are designed using an active comparator and 61% are double-blinded. Primary endpoints are mostly (82%) surrogate. A total of 59% of studies include PROs. Our findings were partially expected (e.g., extensive use of surrogate endpoints) and partially not (e.g., RCTs and an active comparator), considering previous studies on the same topic. Having more head-to-head studies may reduce uncertainty concerning evidence at market launch, but different issues persist, including the still limited role of PROs. Full article

Objective: Pulmonary arterial hypertension (PAH) is a progressive and life-threatening disease. Adverse events (AEs) related to its drug treatment seriously damaged the patient’s health. This study aims to clarify the causal relationship between PAH drugs and these AEs by combining pharmacovigilance signal detection with the Bayesian causal network model. Methods: Patient data were obtained from the U.S. Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS), covering reports from 2013 to 2023. In accordance with standard pharmacovigilance methodologies, disproportionality analysis was performed to detect signals. Target drugs were selected based on the following criteria: number of reports (a) ≥ 3, proportional reporting ratio (PRR) ≥ 2, and chi-square (χ²) ≥ 4. Bayesian causal network models were then constructed to estimate causal relationships. The do-calculus and adjustment formula were applied to calculate the causal effects between drugs and AEs. Results: Signal detection revealed that Ambrisentan, Bosentan, and Iloprost were associated with serious AEs, including death, dyspnea, pneumonia, and edema. For Ambrisentan, the top-ranked adverse drug events (ADEs) based on average causal effect (ACE) were peripheral swelling (ACE = 0.032) and anemia (ACE = 0.021). For Iloprost, the most prominent ADE was hyperthyroidism (ACE = 0.048). Conclusions: This study quantifies causal drug–event relationships in PAH using Bayesian causal networks. The findings offer valuable evidence regarding the clinical safety of PAH medications, thereby improving patient health outcomes. Full article

Background/Objectives: Tuberculosis (TB) remains a major public health challenge in Davao City, Philippines, with persistent issues in both disease burden and treatment outcomes. Understanding the risk factors for TB and its unsuccessful treatment is essential for guiding effective interventions. This study aimed to evaluate the association of sociodemographic and clinical factors with TB occurrence and to identify predictors of unsuccessful TB treatment outcomes among patients in Davao City. Methods: A retrospective cohort study was conducted using data from 521 patients diagnosed with drug-susceptible TB at Davao Chest Center between January 2021 and May 2024. The sociodemographic and clinical profiles of the patients were described using descriptive statistics. Chi-square tests were used to assess the associations between sociodemographic and clinical variables with TB risk and treatment outcomes. Results: The patient cohort was predominantly aged 31–50 years (n = 201, 38.58%), male (n = 284, 54.51%), and married (n = 285, 54.70%), with most residing in Districts I and II (n = 98, 38% each), and had no previous TB treatment (n = 344, 66.03%). Among the 456 patients assessed for comorbidities, 56.14% (n = 256) had at least one comorbidity. Evaluation of the risk factors for TB occurrence among the study population revealed that comorbidity status was not significantly associated with an increased risk of TB diagnosis (p = 0.682). However, among patients diagnosed with TB, the presence of comorbidities was significantly associated with unsuccessful treatment outcomes (p = 0.003). Conclusions: Although sociodemographic factors did not significantly influence TB risk or treatment outcomes, the presence of comorbidities was a significant predictor of unsuccessful TB treatment. These findings highlight the importance of integrating comorbidity management with TB care to improve treatment success in high-burden urban settings. Full article

Background: Prematurely born newborns with low birth weight constitute a group of patients who require special care from the first days of life. Prematurity and low birth weight affect about 13.4 million infants. Risk factors include placental disorders but also factors related to the mother, such as smoking, alcohol drinking, drug use, malnutrition, or certain diseases. It is imperative to educate women of reproductive age (15–49) about the basic factors influencing embryonic development, such as oral health, diet, medicine intake, and harmful habits. Even though most women are aware of the negative impact of harmful habits on the fetus, still too little attention is paid to oral health in pregnant women. Poor oral health may influence the well-being of the future mother, as well as of the child. Therefore, women of reproductive age and those who are pregnant must have adequate knowledge on this subject. The aim of this study was to assess the knowledge of Polish women of reproductive age (15–49) regarding oral health during pregnancy, including the impact of dental treatment, oral hygiene, and maternal oral conditions on pregnancy outcomes and the health of the newborn. Materials and Methods: This was a cross-sectional study of 508 women, in the reproductive age, whose age ranged from 18 to 49 years old. The surveys were conducted from April 2020 to November 2020. The questionnaire was originally developed based on the available literature and consisted of seven sections: basic information, general health and habits, pregnancy status and dental care, knowledge of treatment options during pregnancy, oral health status and its association with the risk of preterm birth, prematurity and the child’s oral health, and breastfeeding and oral development. Results: After excluding incomplete questionnaires, a total of 499 questionnaires were included in the analysis. Women participating in the study had a fairly good understanding of the impact of oral health on the fetus and the role of breastfeeding in the development of the stomatognathic system (from 50% to 70% correct answers). However, even though most respondents had completed higher education (344/68.94%), their knowledge of oral health, preterm birth, and low birth weight was very limited (including the impact of inflammation on the intrauterine development of the child or bacteria and transfer across the placenta). In these sections, the percentage of correct answers ranged from less than 20% to 50%. When analyzing knowledge by age, education, number of births, and place of residence, the highest levels of knowledge were observed among respondents with higher education, particularly those aged 27–32. Conclusions: Respondents had a fairly good understanding of the general impact of oral health during pregnancy and recognition of the importance of breastfeeding for infants. However, their knowledge about the impact of bacteria and inflammation in the mother’s oral cavity on prematurity and low birth weight was limited. Therefore, educating women of reproductive age and pregnant women on this topic is essential, as it may help reduce the adverse consequences of prematurity. Full article

Obesity is a chronic, relapsing disease with multifactorial origins and significant global health implications. Historically, bariatric surgery has been the most effective intervention for achieving sustained weight loss and metabolic improvement, especially in individuals with moderate to severe obesity. However, the therapeutic landscape is rapidly evolving. Recent advances in pharmacotherapy—including GLP-1 receptor agonists, dual and triple incretin agonists, and amylin-based combination therapies—have demonstrated unprecedented efficacy, with some agents inducing 15–25% weight loss, approaching outcomes once exclusive to surgical intervention. These developments challenge the continued applicability of existing bariatric surgery criteria, which were established in an era of limited medical alternatives. In this narrative review, we examine the evolution of surgical eligibility thresholds and critically assess the potential role of novel pharmacotherapies in redefining treatment algorithms. By comparing the efficacy, safety, metabolic benefits, and cost-effectiveness of surgery versus next-generation drugs, we explore whether a more stepwise, pharmacotherapy-first approach may now be justified, particularly in patients with BMI 30–40 kg/m². We also discuss future directions in obesity management, including personalized treatment strategies, perioperative drug use, and the integration of pharmacologic agents into long-term care pathways. As the field advances, a paradigm shift toward individualized, minimally invasive interventions appears inevitable—necessitating a timely re-evaluation of current bariatric surgery guidelines to reflect the expanding potential of medical therapy. Full article

The increasing prevalence of chronic kidney disease (CKD) and end-stage kidney disease (ESKD) has led to a growing demand for kidney transplantation (KTx). Identifying risk factors that enable improved allograft survival through novel therapeutic agents, advanced biomarkers, and artificial intelligence (AI)-driven data integration are critical to addressing this challenge. Drugs, such as SGLT2 inhibitors and finerenone, have demonstrated improved outcomes in patients but lack comprehensive long-term evidence in KTx patients. The use of biomarkers, including circulating cytokines and transcriptomics, coupled with AI, could enhance early detection and personalized treatment strategies. Addressing patient self-management and addressing health access disparities may be more achievable using technologies used at home rather than traditional models of healthcare and thus lead to increased transplant success, both in terms of transplantation rates and allograft longevity. Full article

Background and Objectives: Alcoholic hepatitis (AH) is a growing public health concern with its rising incidence and its contribution to nearly half of all cirrhosis-related deaths in the United States. In this systematic review, we aimed to comprehensively evaluate the current evidence and trials on the use of anti-interleukin-1 (anti-IL-1) drugs in patients with AH, assessing their efficacy and adverse events compared to routinely prescribed drugs like corticosteroids. Materials and Methods: A comprehensive literature search was conducted across five databases to identify randomized controlled trials (RCTs) evaluating the role of anti-IL-1 agents like canakinumab and anakinra among patients diagnosed with AH. Data was extracted and pooled in the form of mean and standard deviation for continuous variables and event and total for dichotomous variables. Results: Three RCTs were included for quantitative synthesis, encompassing 307 patients. Using canakinumab, 58% of patients showed improvement in histology. Prednisolone was associated with higher 90-day survival (90% vs. 70%; hazard ratio for death = 0.34, 95% CI 0.14–0.83, p = 0.018) and transplant-free survival. Overall, a higher incidence of acute kidney injury and new-onset cardiac disorders was noted in the anti-IL-1 arm when compared to placebo. Conclusions: This study concludes the lack of efficacy of anti-IL-1 agents in causing improvement in patient outcomes when compared to standard therapies. A higher incidence of adverse events was also noted in the anti-IL-1 arm. These results emphasize the need for future clinical trials to evaluate the use of anti-IL-1 agents in AH objectively. Full article

Tuberculosis (TB) and undernutrition are intricately linked, significantly impacting health outcomes. However, nutritional support for TB patients is not systematically implemented in Lao People’s Democratic Republic (Lao PDR). This study evaluated the effects of nutritional counselling and support on nutritional recovery and TB treatment outcomes. A longitudinal study involved 297 individuals with drug-susceptible TB, 39.4% of whom had a body mass index (BMI) below 18.5 kg/m². Participants were divided into an observation group and an intervention group, the latter receiving nutritional support. Nutritional support included ready-to-use therapeutic food and therapeutic milk products, tailored to patients’ nutritional status. Data collection was conducted at four intervals during treatment. By the end of treatment, 84.3% of participants improved their nutritional status to a BMI of 18.5 kg/m² or higher. The intervention group showed early nutritional recovery, particularly during the intensive phase of TB treatment, although the p-value (p = 0.067) should be interpreted with caution. The overall treatment success rate was high at 90.6%, with no significant difference between groups. Factors associated with treatment success included age under 45, HIV-negative status, a BMI of 18.5 kg/m² or higher, and clinically diagnosed pulmonary TB. Further assessment is required for the operational feasibility to provide systematic nutritional assessment and counselling for people with TB in Lao PDR. Full article

Background and Objectives: The worldwide shift toward psychiatric deinstitutionalization has aimed to enhance patient autonomy, social integration, and overall quality of life. However, limited studies have examined how concurrent substance use—particularly alcohol, marijuana, and inhalable drugs—affects clinical outcomes in these populations. This study aimed to evaluate psychiatric patients with varying degrees of institutionalization and investigate whether substance use complicates or exacerbates treatment outcomes. We hypothesized that individuals using substances would demonstrate worse psychosocial functioning, higher healthcare costs, and increased readmission rates. Methods: We performed a cross-sectional study of 95 participants recruited from long-term care facilities. Participants completed the SF-36 survey validated in Romanian. Financial data were collected to gauge direct and indirect healthcare expenditures. Results: Results indicated that 34.7% of participants reported alcohol use, 12.6% used marijuana, and 9.5% used inhalable substances. Substance-using patients experienced higher mean hospitalization costs of approximately USD 3251.8, compared to non-users (USD 2743.6, p = 0.032). Quality-of-life scores were significantly lower among substance users (mean SF-36 score 58.4 vs. 66.7, p = 0.027). Rates of relapse and readmission were also notably higher in the substance-using cohort (42.1%) relative to non-users (29.8%, p = 0.041). Conclusions: To our knowledge, this is the first Romanian study—and one of only a handful in Europe—to quantify how specific substance-use profiles simultaneously alter quality of life and direct healthcare costs in a deinstitutionalized psychiatric population. Our findings highlight the need for integrated interventions targeting both mental health and substance abuse. Full article

Hepatitis C is an infectious liver disease which contributes to an estimated 400,000 deaths each year. The disease is caused by the hepatitis C virus (HCV) and is spread by direct blood contact between infected and susceptible individuals. While the magnitude of its impact on human populations has prompted a growing body of scientific work, the current epidemiological models of HCV transmission among injecting drug users treat risk behaviors as fixed parameters rather than as outcomes of a dynamic, decision-making process. Our study addresses this gap by constructing a game-theoretic model to investigate the implications of voluntary participation in clean needle exchange programs on the spread of HCV among this high-risk population. Individual drug users weigh the (perceived) cost of clean equipment usage relative to the (perceived) cost of infection, as well as the strategies adopted by the rest of the population, and look for a selfishly optimal level of protection. We find that the spread of HCV in this population can theoretically be eliminated if individuals use sterile equipment approximately two-thirds of the time. Achieving this level of compliance, however, requires that the real and perceived costs of obtaining sterile equipment are essentially zero. Our study demonstrates a robust method for integrating game theory with epidemiological models to analyze voluntary health interventions. It provides a quantitative justification for public health policies that eliminate all barriers—both monetary and social—to comprehensive harm-reduction services. Full article

Polycystic ovary syndrome (PCOS) is an endocrine disorder prevalent in women of reproductive age, often requiring complex pharmacological management. The heterogeneity of the syndrome and the use of on- and off-label therapeutic agents—ranging from insulin sensitizers and ovulation inducers to oral contraceptives and herbal supplements—pose significant challenges, including adverse effects, drug interactions, and poor adherence. This narrative review explores the role of pharmacists in identifying and mitigating drug-related problems (DRPs) associated with PCOS therapy. Through thematic synthesis of the current literature, the study highlights common DRPs such as suboptimal drug selection, inappropriate dosing, prolonged therapy duration, and treatment-related safety concerns. It underscores the value of pharmacists’ interventions in enhancing medication adherence, optimizing therapeutic regimens, providing patient education, and monitoring adverse events. A structured, patient-level pharmaceutical care model is proposed, emphasizing personalized assessment, interdisciplinary collaboration, and continuous follow-up. The integration of clinical pharmacists into PCOS care teams has the potential to improve treatment effectiveness, patient satisfaction, and long-term health outcomes. Pharmacists’ contributions are especially critical given the widespread use of off-label therapies and supplements with variable evidence of benefit. Tailored pharmaceutical care can thus bridge the existing gaps in PCOS management and enhance the quality of life for the affected individuals. Full article