Search Results (3,051)

Catheter ablation is the cornerstone of rhythm control in atrial fibrillation (AF), yet recurrence remains common, and obesity is among the most consistently implicated modifiable risk factors. Weight reduction and metabolic pharmacotherapy are increasingly used in the periprocedural period, but whether they act through a shared pathway has not been systematically examined. This narrative review compares the two approaches and asks whether metabolic agents confer protection beyond weight loss itself. Three observations argue that they do not act identically. First, the benefit of weight reduction is dose-dependent yet contingent on delivery: a structured, physician-led risk-factor program reduced 12-month arrhythmia recurrence (risk ratio 0.53), whereas nurse-led care that improved guideline adherence without structured delivery did not alter the primary endpoint. Second, sodium-glucose cotransporter 2 inhibitors (SGLT2i) have been associated with reduced recurrence across BMI strata despite producing only modest weight loss; notably, a randomized trial in patients without cardiovascular or metabolic comorbidity showed no additional benefit, whereas benefit was observed in patients with type 2 diabetes and heart failure. Third, glucagon-like peptide-1 receptor agonists (GLP-1RA) achieve greater weight loss but yield inconsistent recurrence data, and Mendelian randomization suggests their cardiometabolic benefit is largely BMI-mediated, whereas that of SGLT2i is weight-independent. Together, these observations are consistent with a working hypothesis of two partly distinct atrial substrates—an obesity-related substrate responsive to weight reduction, and a metabolic-inflammatory substrate that may respond to SGLT2i predominantly when metabolic comorbidity is present. This framework is hypothesis-generating: it rests on indirect, cross-study comparisons and has not been tested by formal mediation analysis. If confirmed, it would imply that the two interventions are complementary rather than interchangeable. Full article

Introduction. Statins’ established cardiovascular benefits are often undermined by hepatic adverse effects in obese diabetic patients with suspected non-alcoholic fatty liver disease. We evaluated whether cannabis plant treatment is a safe and effective alternative to atorvastatin in a metabolically challenged rodent model. Methods. Fourteen obese and diabetic Wistar rats received either atorvastatin for 30 days or cannabis plant extract for 30 days. Main outcome: lipid profile; secondary outcomes: renal function, glycemia and endothelial health assessed through atherogenic indices. Safety was assessed using plasma liver enzyme concentrations. Results. Baseline biochemical profiles were similar between groups. Atorvastatin increased HDL-Col more than cannabis plant (MD: 44.3; IQR [33, 57.5] mg/dL, Hedges’ g 2.713 vs. MD: 14.3; IQR [14, 17] mg/dL, Hedges’ g 5.049), and cannabis plant did not change LDL-Col. Atherogenic index of plasma and Castelli Risk Index 1 improved with both interventions, more so with atorvastatin. Liver enzymes increased with atorvastatin (ALAT, MD: 15.9; IQR [12.5, 19.5] U/L; ASAT, MD: 33; IQR [26.5, 38] U/L) but remained virtually unchanged with cannabis. Serum creatinine increased with cannabis plant, with moderate effect size (Hedges’ g 0.798), but negligibly with statins (Hedges’ g 0.122). Conclusions. Cannabis plant extract modestly improved the lipid profile and atherogenic indices, with differences often not exceeding the change in control groups. Despite apparent liver safety, the undesired renal and neurological consequences limit applicability in humans. Further studies should prioritize addiction development and renal function. Full article

Background/Objectives: Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder caused by recurrent upper-airway collapse during sleep, leading to intermittent hypoxia, sleep fragmentation, and excessive daytime sleepiness. Although continuous positive airway pressure (CPAP) remains the first-line therapy, long-term adherence is often suboptimal, underscoring the need for more tolerable and flexible treatment options. This review aims to summarize the pathophysiological rationale for pharmacotherapy in OSA and to discuss recent developments in drug-based interventions. Methods: We conducted a narrative review of the literature on pharmacological interventions for OSA, with a systematic search of PubMed, Embase, Cochrane Library, and ClinicalTrials.gov up to 4 August 2026. We included randomised controlled trials, observational studies, meta-analyses, and mechanistic human or animal studies that reported relevant sleep and respiratory outcomes, and graded evidence according to the principles of GRADE framework. Results: Several drug classes have shown promise: agents that increase upper-airway dilator muscle activity, respiratory stabilizers that reduce loop gain, medications that raise the arousal threshold, topical anti-inflammatory drugs for mucosal edema, and systemic metabolic modulators such as glucagon-like peptide-1 receptor agonists and dual incretin receptor agonists. Emerging strategies, including gene therapy directed at the hypoglossal motor system, are also under investigation at the preclinical stage. Moreover, combining pharmacotherapy with CPAP or other devices can produce synergistic benefits, enabling lower device pressures and enhanced patient comfort. Conclusions: Pharmacotherapy for OSA is progressively moving from exploratory research towards targeted, phenotype-driven personalized treatment. Future studies should focus on robust patient phenotyping, multi-mechanistic combination regimens, and long-term clinical outcome evaluations to facilitate the integration of drug-based therapies into routine OSA management, particularly in specific subgroups such as those with COMISA. Full article

In 1994, leptin was identified as a hormone that signals the brain to reduce food intake and increase energy expenditure. Leptin was initially considered a breakthrough therapy for obesity. This was largely based on animal studies, showing that leptin reversed obesity in individuals with congenital leptin deficiency and normal leptin receptor sensitivity. However, due to leptin resistance, leptin therapy failed to reduce weight in common human obesity. Consequently, interest in leptin waned for many years. However, recent studies in animal models of common obesity show that combining leptin with other weight-loss-stimulating agents, can restore hypothalamic leptin sensitivity and induce a greater reduction of body weight than after single drug treatment. Moreover, after initially reducing weight by combination therapy, leptin monotherapy proved enough to maintain reduced body weight. The strongest evidence for restoring leptin’s weight-lowering actions in common obesity to date comes from mouse studies in which leptin was combined with other pharmacotherapies. However, it is unclear at this moment whether this strategy also can be used to treat common human obesity successfully. Overcoming leptin resistance, by combining leptin with other pharmacotherapies, is a promising strategy that needs to be further investigated in humans with obesity. Full article

Atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of morbidity and mortality worldwide, driven by complex interactions among dyslipidemia, chronic inflammation, insulin resistance, endothelial dysfunction, and gut microbiome-derived metabolites. This review synthesizes mechanistic and clinical evidence on non-pharmacological strategies that modulate these pathways and contribute to ASCVD risk reduction. Dietary patterns such as Mediterranean, DASH, and plant-based diets improve lipid metabolism, attenuate inflammation, and enhance endothelial function. Chrononutrition approaches, including time-restricted feeding and structured fasting protocols, influence circadian regulation of glucose and lipid homeostasis. Circadian misalignment—including irregular sleep timing, shift work, and disrupted feeding–fasting cycles—independently contributes to ASCVD through impaired glucose tolerance, dyslipidemia, endothelial dysfunction, and systemic inflammation. Modulation of the gut microbiome, particularly through increased short-chain fatty acid production and reduced TMAO formation, provides additional cardiometabolic benefits. Key nutraceuticals—phytosterols, omega-3 fatty acids, and berberine—demonstrate clinically meaningful effects through micellar competition, inflammation-resolving lipid mediators, and AMPK activation, respectively. When combined with evidence-based pharmacotherapy, these interventions exert synergistic effects on cardiometabolic risk factors. This integrative biomedical framework highlights the importance of combining lifestyle, metabolic, microbiome-targeted, and nutraceutical strategies for comprehensive ASCVD prevention. Full article

Background/Objectives: The aim of the present study was to investigate the mechanisms in Parkinson’s disease (PD), a progressive neurodegenerative disorder characterized by loss of dopaminergic neurons, aggregation of α-synuclein, mitochondrial dysfunction, oxidative stress, neuroinflammation, gut dysbiosis, and blood–brain barrier (BBB) impairment. Although there are several approved therapies that have been developed, their aqueous solubility, oral bioavailability, first-pass metabolism, and inability to penetrate the BBB make them less effective over time. This review is intended to critically analyze the potential of self-nanoemulsifying drug delivery systems (SNEDDSs) as a pathogenesis-related approach to enhance the delivery and therapeutic activity of repurposed drugs and conventional drugs for PD. Methods: A comprehensive literature search was conducted to address the pathogenic mechanisms of PD, the deficiencies of current pharmacotherapy, recent developments in SNEDDS formulation strategies and their application in improving oral bioavailability, lymphatic transport, BBB penetration and targeted brain delivery. A special focus was dedicated to drug repurposing, functionalized SNEDDSs, PEGylation, and gut–brain axis modulation. Results: SNEDDSs significantly enhance the water solubility, stability, intestinal absorption and systemic exposure of poorly water-soluble therapeutic agents and, to a certain extent, lymphatic uptake to avoid first-pass metabolism. These systems include improved brain delivery, decreased pharmacokinetic variability, and prolonged drug levels within the therapeutic range. Moreover, SNEDDSs can be used to deliver multiple molecules that are found to be neuroprotective, antioxidant, anti-inflammatory and probiotic, all at once, which can act on multiple pathogenic mechanisms associated with PD. Functionalized and PEGylated SNEDDSs add further to formulation stability, extend systemic circulation and increase efficiency of brain targeting. Conclusions: SNEDDSs are a promising translational nanomedicine platform for enhancing the effectiveness of conventional and repurposed therapeutics in PD, which address key pharmacokinetic and biological challenges. The next generation of oral therapies with targeted surface engineering, precision drug repurposing and clinical validation will be expected to bring about a faster advancement of drugs that can alter the course of disease rather than giving only symptomatic relief. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are transforming obesity management, yet landmark trials often incompletely measure and report a central mediator of response: dietary intake. Because GLP-1RAs promote weight loss primarily by suppressing appetite and reducing energy consumption, capturing changes in dietary intake is essential to interpreting efficacy, safety, and translation into clinical care. This perspective argues that failure to measure and report comprehensive dietary intake raises concerns under four core bioethical principles. It undermines autonomy by limiting evidence for shared decision-making across the treatment continuum. It challenges non-maleficence because inadequate energy, protein, and micronutrient intake may contribute to lean mass loss and nutrient deficiencies, particularly in vulnerable populations. It weakens beneficence because failing to report a measurable mediator diminishes the scientific value of research requiring substantial investment and participant burden. It raises justice concerns because the equitable distribution of assessment burden and access to resulting nutritional care cannot be evaluated without transparent reporting. To meet the ethical and scientific obligations of clinical research, future trials should preregister dietary intake as a key secondary or safety endpoint. Investigators should report total energy, macronutrient, and micronutrient distribution at baseline and serial follow-up alongside dietary assessment methods, food composition databases, and assessor training. Journal editors, funders, and regulatory bodies should support development of consensus-based, nutrition-specific reporting recommendations aligned with CONSORT principles and encourage preregistration of dietary trial endpoints. Registered dietitian nutritionists should be prospectively integrated into GLP-1RA trial teams from design through data interpretation. Advancing the standard of obesity care requires that the research community look beyond the scale and ground clinical translation in the nutritional context in which pharmacotherapy operates. Full article

Background/Objectives: GLP-1 receptor agonists are an established component of obesity treatment that should complement nutritional and lifestyle interventions. Social media narratives may shape public understanding and acceptance of these therapies. This study examined whether exposure to GLP-1-related narratives and their perceived credibility were associated with perceptions of obesity pharmacotherapy. Methods: An anonymous cross-sectional online survey was conducted among Polish-speaking adults aged ≥ 18 years who used social media at least weekly and reported exposure to GLP-1-related content within the preceding 3 months. Five exploratory composite scores assessed narrative exposure, perceived credibility, perceptions of communication, attitudes toward obesity pharmacotherapy, and GLP-1 treatment evaluation. Associations were examined using univariable and multivariable linear regression. Results: The final sample comprised 279 participants (84.6% women; mean age, 38.14 ± 8.58 years). In adjusted models, greater perceived narrative credibility was associated with less favorable GLP-1 treatment evaluations (B = −0.311, 95% CI: −0.359 to −0.263; p < 0.001) and greater endorsement of negative pharmacotherapy-related statements (B = 0.401, 95% CI: 0.350 to 0.453; p < 0.001). Greater narrative exposure was associated with more favorable GLP-1 treatment evaluations (B = 0.072, 95% CI: 0.026 to 0.118; p = 0.002) and more negative perceptions of social media communication (B = 0.235, 95% CI: 0.161 to 0.309; p < 0.001). Conclusions: Greater perceived credibility of GLP-1-related narratives was associated with less favorable perceptions of obesity pharmacotherapy, but the cross-sectional design precludes conclusions about direction or causality. The findings highlight the importance of evidence-based communication that supports critical evaluation of treatment-related claims and presents pharmacotherapy, nutrition, and lifestyle support as complementary components of comprehensive obesity care. Full article

Background/Objectives: Liver cirrhosis (LC) is a major cause of morbidity and mortality requiring continuous monitoring and early recognition of clinical deterioration. Home telemonitoring is increasingly considered a supportive strategy for outpatient hepatology care; however, patient acceptance remains insufficiently characterized in Eastern Europe, and no validated instrument currently exists for this population. This study aimed to develop and provide the initial psychometric validation of a Technology Acceptance Model (TAM)-based questionnaire assessing acceptance of home telemonitoring among patients with LC. Methods: In this prospective cross-sectional study, 130 adult patients with LC (Child–Pugh A/B/C) were enrolled. A 25-item questionnaire, including 13 Likert-scale items mapped to Perceived Usefulness (PU), Perceived Ease of Use (PEU), and Intention to Use (ITU), was administered under supervision. Psychometric evaluation included internal consistency, exploratory and confirmatory factor analyses, structural equation modelling (SEM), convergent and discriminant validity, and known-groups validity. Results: Internal consistency was excellent (Cronbach’s α = 0.934; McDonald’s ω = 0.950). EFA identified a 2-factor structure explaining 77.9% of the variance, whereas CFA supported the theoretically driven 3-factor TAM, which showed improved incremental fit (CFI = 0.927; TLI = 0.908) and was retained on theoretical grounds. SEM confirmed the TAM pathway, with PU strongly predicting ITU (β = 0.823, p < 0.001), whereas PEU significantly influenced PU (β = 0.343, p < 0.001) but not ITU directly. The model explained 69.5% of the variance in ITU. Known-groups validity was supported across digital access, IT comfort, education level, and disease severity. Patients with advanced cirrhosis and lower digital confidence showed lower acceptance scores. Conclusions: The proposed 13-item Likert scale demonstrated good initial psychometric performance and may represent a useful tool for assessing telemonitoring acceptance and readiness for digital monitoring among patients with LC. Pending further multicentre validation and assessment of predictive validity, the instrument may support identification of patients requiring additional support for successful telemonitoring adoption. Full article

Background: Trigeminal neuralgia associated with multiple sclerosis (TN-MS) is a secondary facial pain syndrome whose clinical and therapeutic features differ substantially from those of classical TN. Although the literature comparing treatment outcomes between TN-MS and classical TN is relatively abundant, evidence on the impact of treatment on quality of life in TN-MS is scarce. In patients with MS—already vulnerable owing to the course of their disease and the burden of its treatments—therapeutic success cannot be defined by pain scales alone, because even modest analgesic improvement and, in particular, a reduction in medication burden may represent meaningful gains. This review aims to reappraise the therapeutic goals in TN-MS. Methods: We provide a critical narrative review of the evidence, explicitly distinguishing direct evidence from indirect evidence extrapolated from the MS and classical-TN literature, across medical therapy, percutaneous procedures, stereotactic radiosurgery, and microvascular decompression (MVD). Results: First-line pharmacotherapy remains standard but is largely extrapolated from classical TN, and tolerability is frequently limited by sedative and motor adverse effects in already polymedicated patients. Percutaneous procedures and radiosurgery provide clinically meaningful relief in selected patients, but recurrence is common and patient-centered outcomes are poorly documented. Surgical exploration of the cerebellopontine angle—including MVD, neurolysis, and combined techniques—should not be categorically excluded on the basis of an MS diagnosis in carefully selected patients, although outcomes are generally less favorable than in classical TN and the direct evidence is limited and vulnerable to selection bias. Conclusions: Future studies should assess treatment impact on additional outcomes such as medication burden, quality of life, fatigue, cognition, and functional status. Full article

Background: Australia has experienced high rates of antibiotic shortages, yet little is known about how Australian pharmacists experience and manage them. This study aimed to explore Australian community and hospital pharmacists’ experiences of antibiotic shortages, including their perceived clinical impact and approaches to managing shortages. Methods: An exploratory qualitative study using semi-structured interviews was conducted with Australian community and hospital pharmacists between May and August 2024. Participants were recruited via convenience sampling through professional networks and social media. Interviews were audio-recorded, transcribed verbatim, and analysed thematically using an inductive–deductive approach, with coding performed independently by two researchers. Results: Fifteen interviews were conducted before data saturation was reached. Sixty percent of participants were female, 67% worked in hospital settings, and pharmacists were located across five Australian states. Four overarching themes were identified: factors driving shortages, communication and collaboration, impact of shortages, and mitigation and prevention. Pharmacists described antibiotic shortages as frequent and unpredictable, attributing them to supply-chain vulnerabilities, limited manufacturing, and market competition. Shortages were reported to affect treatment choice, contribute to antimicrobial resistance concerns, increase pharmacist workload and stress, and negatively affect patients. Pharmacists used strategies such as stock management, collaboration, and importing alternatives, but felt that lasting solutions required coordinated national action. Conclusions: Australian pharmacists perceive antibiotic shortages as a complex challenge affecting patient care, antimicrobial stewardship, workload, and healthcare efficiency. While pharmacists have developed reactive strategies to manage shortages, stronger communication, collaboration, and national policy coordination, alongside improved supply-chain resilience, are needed to reduce the impact of future shortages. Full article

Brain tumor (BT) patients can experience neurological complications as a result of the disease itself or after exposure to anticancer treatment. It is already known that BT patients have a poor survival and quality of life due to tumor progression, but also to various complications. The neurological complications may represent obstacles in patient management and require multidisciplinary collaboration. Although new methods of surgery, radiation therapy and pharmacotherapy have been designed in the last few years in order to prevent, mitigate, or manage the adverse effects of classical therapies, the overall survival of patients with BTs, especially glioblastoma (GB), remain poor. In this review we provide an overview of the most commo022328n neurological complications of BTs, as well as tumor therapies. We present what is already known on the topic but also the newest clinical data, and the results of clinical trials from the last few years. We also make a summary of the strategies capable of managing or even preventing these adverse effects. Full article

Obesity is a complex, multifactorial chronic disease characterized by excessive and/or aberrant adiposity that requires interventions beyond conventional calorie-restriction models. Current clinical guidelines converge on behavioral modification, encompassing nutritional therapy, physical activity, stress reduction, and sleep improvement, as the cornerstone of obesity management, with psychological therapy, pharmacotherapy, and bariatric procedures as adjunctive or escalating options. While traditional “one-size-fits-all” dietary approaches frequently yield suboptimal long-term outcomes, precision nutrition has emerged as a promising strategy for individualized obesity care. This review critically appraises the evidence underlying each pillar of precision nutrition: genetic profiling shows clear utility in monogenic obesity but variable benefit when diet is matched to common polygenic variants; microbiome-targeted studies reveal that the Bacillota to Bacteroidota ratio shows inconsistent associations with obesity across studies, with genus-level and functional alterations offering more reproducible targets; and metabolomic profiling of postprandial glycemic responses has progressed from foundational predictive algorithms to large-scale clinical validation. It also highlights chrono-nutrition, the alignment of food timing with individual chronotype, as an emerging pillar of personalization. Beyond dietary composition, the review addresses how personalized nutrition can mitigate the adverse effects of incretin-based pharmacotherapy and discusses how artificial intelligence can integrate multi-omics and behavioral data into real-time dietary guidance. Future clinical implementation will require overcoming challenges related to data integration, predictive accuracy, and accessibility, paving the way for more effective, evidence-based obesity management. Full article

Objectives: The aim of this study was to determine whether direct evidence shows that contemporary guideline-directed heart failure (HF) pharmacotherapies influence cardiac remodeling through hydrogen sulfide (H₂S) signaling, and to define the resulting evidence gap. Design: A systematic review was conducted according to PRISMA 2020. Registration: PROSPERO CRD420251238589. Data Sources: MEDLINE (PubMed), Web of Science, Scopus, and the Cochrane Library; searches were initiated in March 2025, covered publications from January 2007 onward, and were last updated in November 2025. Eligibility Criteria: Primary studies had to include (A) an HF or cardiac-remodeling model, (B) an HF-relevant pharmacological intervention, (C) direct assessment or manipulation of H₂S biology, and (D) at least one cardiac-remodeling endpoint. Results: Of the 40,796 unique records screened, 50 reports underwent full-text assessment and 14 unique studies were included. No study demonstrated that the remodeling benefits of ACE inhibitors, ARBs, ARNIs, beta-blockers, MRAs, hydralazine/isosorbide dinitrate, or SGLT2 inhibitors are mediated by endogenous H₂S signaling. Doiron et al. evaluated empagliflozin with or without the H₂S donor SG1002 in experimental HFpEF; the combination improved several outcomes beyond empagliflozin alone, but this adjunctive design does not establish H₂S mediation of empagliflozin action. Most eligible evidence concerned exogenous H₂S donors in animal models and reported improvements in fibrosis, hypertrophy, oxidative stress, mitochondrial injury, and cardiac function. The overall certainty was low because of preclinical predominance, heterogeneous models and H₂S assays, donor-specific pharmacology, and incompletely reported randomization and blinding. Conclusions: The principal finding is negative but clinically important: direct evidence that H₂S mediates established HF pharmacotherapy is currently absent. H₂S remains a promising experimental therapeutic candidate rather than an established shared mechanism or clinically validated treatment target. Full article