Search Results (2,438)

Background: Drug–drug interactions (DDIs) may occur when two or more drugs are taken together, leading to undesired side effects or potential synergistic effects. Most clinical effects of drug combinations have not been assessed in clinical trials. Therefore, predicting DDIs can provide better patient management, avoid drug combinations that can negatively affect patient care, and exploit potential synergistic combinations to improve current therapies in women’s healthcare. Methods: A DDI prediction model was built to describe relevant drug combinations affecting reproductive treatments. Approved drug features (chemical structure of drugs, side effects, targets, enzymes, carriers and transporters, pathways, protein–protein interactions, and interaction profile fingerprints) were obtained. A unified predictive score revealed unknown DDIs between reproductive and commonly used drugs and their associated clinical effects on reproductive health. The performance of the prediction model was validated using known DDIs. Results: This prediction model accurately predicted known interactions (AUROC = 0.9876) and identified 2991 new DDIs between 192 drugs used in different female reproductive conditions and other drugs used to treat unrelated conditions. These DDIs included 836 between drugs used for in vitro fertilization. Most new DDIs involved estradiol, acetaminophen, bupivacaine, risperidone, and follitropin. Follitropin, bupivacaine, and gonadorelin had the highest discovery rate (42%, 32%, and 25%, respectively). Some were expected to improve current therapies (n = 23), while others would cause harmful effects (n = 11). We also predicted twelve DDIs between oral contraceptives and HIV drugs that could compromise their efficacy. Conclusions: These results show the importance of DDI studies aimed at identifying those that might compromise or improve their efficacy, which could lead to personalizing female reproductive therapies. Full article

Background: Bipolar disorder (BD) is a chronic and disabling psychiatric condition characterized by recurring episodes of mania, hypomania, and depression. Despite the availability of mood stabilizers, antipsychotics, and antidepressants, long-term management remains challenging due to incomplete symptom control, adverse effects, and high relapse rates. Methods: This paper is a narrative review aimed at synthesizing emerging trends and future directions in the pharmacological treatment of BD. Results: Future pharmacotherapy for BD is likely to shift toward precision medicine, leveraging advances in genetics, biomarkers, and neuroimaging to guide personalized treatment strategies. Novel drug development will also target previously underexplored mechanisms, such as inflammation, mitochondrial dysfunction, circadian rhythm disturbances, and glutamatergic dysregulation. Physiological endophenotypes, such as immune-metabolic profiles, circadian rhythms, and stress reactivity, are emerging as promising translational tools for tailoring treatment and reducing associated somatic comorbidity and mortality. Recognition of the heterogeneous longitudinal trajectories of BD, including chronic mixed states, long depressive episodes, or intermittent manic phases, has underscored the value of clinical staging models to inform both pharmacological strategies and biomarker research. Disrupted circadian rhythms and associated chronotypes further support the development of individualized chronotherapeutic interventions. Emerging chronotherapeutic approaches based on individual biological rhythms, along with innovative monitoring strategies such as saliva-based lithium sensors, are reshaping the future landscape. Anti-inflammatory agents, neurosteroids, and compounds modulating oxidative stress are emerging as promising candidates. Additionally, medications targeting specific biological pathways implicated in bipolar pathophysiology, such as N-methyl-D-aspartate (NMDA) receptor modulators, phosphodiesterase inhibitors, and neuropeptides, are under investigation. Conclusions: Advances in pharmacogenomics will enable clinicians to predict individual responses and tolerability, minimizing trial-and-error prescribing. The future landscape may also incorporate digital therapeutics, combining pharmacotherapy with remote monitoring and data-driven adjustments. Ultimately, integrating innovative drug therapies with personalized approaches has the potential to enhance efficacy, reduce adverse effects, and improve long-term outcomes for individuals with bipolar disorder, ushering in a new era of precision psychiatry. Full article

Orofacial pain encompasses a spectrum of disorders ranging from musculoskeletal disorders, such as myofascial pain, and temporomandibular disorders to neuropathic situations, such as trigeminal neuralgia and painful post-traumatic trigeminal neuropathy, and neurovascular pain such as orofacial migraine and cluster orofacial pain. Each require tailored prophylactic pharmacotherapy, such as carbamazepine, gabapentin, pregabalin, amitriptyline, metoprolol, and topiramate. Yet a substantial subset of patients remains refractory. Botulinum toxin type A (BoNT-A) has demonstrated growing efficacy in the treatment of multiple forms of orofacial pain, which covers the whole range of these disorders. We describe the analgesic properties of BoNT-A for each of the three following orofacial pain disorders: neuropathic, myofascial, and neurovascular. Then, we conclude with a section on the neuromodulatory mechanisms of BoNT-A. This lays the basis for the generation of a hypothesis for the segmental therapeutic action of BoNT-A on the whole range of orofacial pain disorders. In addition, the advantage of BoNT-A for providing a safe sustained effect after a single application for chronic pain prophylaxis is discussed, as opposed to the daily use of current conventional prophylactic medications. Finally, we summarize the clinical applications of BoNT-A for chronic orofacial pain therapy. Full article

Introduction/Objective: Post-bariatric surgery patients require long-term, coordinated care to address complex nutritional, physiological, and behavioral challenges. Personalized smart nutrition, combining individualized dietary strategies with targeted monitoring, has emerged as a valuable direction for optimizing recovery and long-term outcomes. This article examines how traditional medical protocols can be enhanced by digital solutions in a multidisciplinary framework. Methods: The study analyzes current clinical practices, including personalized meal planning, physical rehabilitation, biochemical marker monitoring, and psychological counseling, as applied in post-bariatric care. These established approaches are then analyzed in relation to the NutriMonitCare system, a digital health system developed and tested in a laboratory environment. Used here as an illustrative example, the NutriMonitCare system demonstrates the potential of digital tools to support clinicians through real-time monitoring of dietary intake, activity levels, and physiological parameters. Results: Findings emphasize that medical protocols remain the cornerstone of post-surgical management, while digital tools may provide added value by enhancing data availability, supporting individualized decision making, and reinforcing patient adherence. Systems like the NutriMonitCare system could be integrated into interdisciplinary care models to refine nutrition-focused interventions and improve communication across care teams. However, their clinical utility remains theoretical at this stage and requires further validation. Conclusions: In conclusion, the integration of digital health tools with conventional post-operative care has the potential to advance personalized smart nutrition. Future research should focus on clinical evaluation, real-world testing, and ethical implementation of such technologies into established medical workflows to ensure both efficacy and patient safety. Full article

Medication discrepancies at hospital admission are common and may lead to adverse outcomes. Medication reconciliation is a critical process for minimizing medication discrepancies and medication errors at the time of hospital admission. This study aimed to evaluate the role of clinical pharmacists in identifying pharmacotherapy-related issues upon patient admission in a low-resource setting. A prospective observational study was conducted at a university hospital between 1 March and 31 May 2023. Within 24 h of admission, a clinical pharmacist documented each patient’s pre-admission medication regimen and compared it with the medication history obtained by the admitting physician. Discrepancies and pharmacotherapy problems were subsequently identified. Among 65 patients, pharmacists documented 334 medications versus 189 recorded by physicians (p < 0.01). The clinical pharmacist identified 155 discrepancies, 112 (72.26%) of which were unintentional. The most frequent type was drug omission (91.07%), followed by incorrect dosage (4.46%), incorrect dosing interval (2.68%), and medications with unknown indications (1.79%). Most discrepancies were classified as errors without harm (53.57%), while 41.07% were potentially harmful. These findings underscore the importance of integrating clinical pharmacists into the healthcare team. Their active participation during hospital admission can significantly enhance medication safety and reduce preventable adverse drug events. Full article

Obstructive sleep apnea (OSA) could increase pulmonary artery pressure. However, the clinical consequences vary, mainly depending on comorbidities. Patients with pulmonary hypertension associated with lung diseases (World Health Organization (WHO) Group 3 pulmonary hypertension) are particularly vulnerable increases in pulmonary artery pressure. Managing pulmonary hypertension in this specific patient population presents a considerable challenge. While positive airway pressure therapy for OSA has shown promise in improving pulmonary hemodynamics in patients with obesity hypoventilation syndrome and chronic obstructive pulmonary disease, evidence is lacking for similar improvements in those with other pulmonary diseases and hypoventilation disorders. Furthermore, pulmonary-artery-specific therapies may carry a risk of clinical worsening in this group. Weight management and new pharmacotherapy have together emerged as a crucial intervention, demonstrating benefits for both OSA and pulmonary hemodynamics. We reviewed key studies that provide insights into the influence of OSA on WHO Group 3 pulmonary hypertension and the clinical management of both conditions. Full article

Head and neck squamous cell carcinomas (HNSCCs) represent a heterogeneous group of tumors with a complex molecular profile. Despite therapeutic advances, patient prognosis remains poor, emphasizing the need for more effective treatment strategies. Traditional chemotherapy, with cisplatin and 5-fluorouracil (5-FU), remains the gold standard but is limited by toxicity and tumor resistance. Immunotherapy, particularly immune checkpoint inhibitors targeting programmed cell death protein 1 (PD-1) and its ligand (PD-L1), has improved overall survival, especially in patients with high PD-L1 expression. In parallel, targeted therapies such as poly (ADP-ribose) polymerase 1 (PARP1) inhibitors—which impair DNA repair and increase replication stress—have shown promising activity in HNSCC. Cyclin-dependent kinase (CDK) inhibitors are also under investigation due to their potential to correct dysregulated cell cycle control, a hallmark of HNSCC. This review aims to summarize current and emerging pharmacotherapies for HNSCC, focusing on chemotherapy, immunotherapy, and PARP and CDK inhibitors. It also discusses the evolving role of targeted therapies in improving clinical outcomes. Future research directions include combination therapies, nanotechnology-based delivery systems to enhance treatment specificity, and the development of diagnostic tools such as PARP1-targeted imaging to better guide personalized treatment approaches. Full article

Background and Objectives: The management of type 2 diabetes (T2D) extends beyond glycemic control, requiring a more global strategy that includes optimization of body composition, even more so in the context of sarcopenia and visceral adiposity, as they contribute to poor outcomes. Past reviews have typically been focused on weight reduction or glycemic effectiveness, with limited inclusion of new therapies’ effects on muscle and fat distribution. In addition, the emergence of incretin-based therapies and dual agonists such as tirzepatide requires an updated synthesis of their impacts on body composition. This review attempts to bridge the gap by taking a systematic approach to how current blood-glucose lowering therapies affect lean body mass, fat mass, and the risk of sarcopenia in T2D patients. Materials and Methods: Between January 2015 and March 2025, we conducted a narrative review by searching the PubMed, Scopus, and Web of Science databases for English-language articles. The keywords were combinations of the following: “type 2 diabetes,” “lean body mass,” “fat mass,” “body composition,” “sarcopenia,” “GLP-1 receptor agonists,” “SGLT2 inhibitors,” “tirzepatide,” and “antidiabetic pharmacotherapy.” Reference lists were searched manually as well. The highest precedence was assigned to studies that aimed at adult type 2 diabetic subjects and reported body composition results. Inclusion criteria for studies were: (1) type 2 diabetic mellitus adult patients and (2) reporting measures of body composition (e.g., lean body mass, fat mass, or muscle function). We prioritized randomized controlled trials and large observational studies and excluded mixed diabetic populations, non-pharmacological interventions only, and poor reporting of body composition. Results: Metformin was widely found to be weight-neutral with minimal effects on muscle mass. Insulin therapy, being an anabolic hormone, often leads to fat mass accumulation and increases the risk of sarcopenic obesity. Incretin-based therapies induced substantial weight loss, mostly from fat mass. Notable results were observed in studies with tirzepatide, demonstrating superior reduction not only in fat mass, but also in visceral fat. Sodium-glucose cotransporter 2 inhibitors (SGLT2 inhibitors) promote fat loss but are associated with a small yet significant decrease in lean muscle mass. Conclusions: Blood-glucose lowering therapies demonstrated clinically relevant effects on body composition. Treatment should be personalized, balancing glycemic control, cardiovascular, and renal benefits, together with optimal impact on muscle mass along with glycemic, cardiovascular, and renal benefits. Full article

Background: Depression that is resistant to two or more adequate treatment trials—treatment-resistant depression (TRD)—is a prevalent clinical challenge. Although psychotherapies have been recommended by clinical guidelines as an alternative or adjunctive treatment strategy, the effectiveness of psychotherapy in individuals with TRD has not yet been evaluated through meta-analytic methods, primarily due to a limited number of trials. This highlights the necessity of personalized research targeting this specific population. This systematic review and meta-analysis aimed to summarize the evidence on psychotherapy in treating TRD. Methods: A systematic search was conducted following the Guidelines from Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Articles were included if they quantitatively examined the efficacy of psychotherapy on depression symptoms in individuals diagnosed with depression who had not responded to at least two prior treatments (i.e., pharmacotherapy and/or psychotherapy). Results: A total of 12 studies were included. The quality of evidence was evaluated as being globally moderate. When pooling all psychotherapies, a small-to-moderate, but significant, effect on depressive symptoms was observed compared to the control group (SMD = −0.49, CI = −0.63; −0.34). The observed effect remained unchanged after removing the outlier (SMD = −0.47, CI = −0.62; −0.32). When examining depressive symptoms by type of psychotherapy, Mindfulness-Based Cognitive Therapy (SMD = −0.51, CI = −0.76; −0.25), Cognitive Behavioral Therapy (SMD = −0.53, CI = −0.92; −0.14), and Cognitive Therapy (SMD = −0.51, CI = −1.01; −0.01) showed a moderately significant effect on depressive symptoms compared to the control group. Conclusions: Although this potentially represents the first meta-analysis in this area, the number of studies specifically addressing this complex population remains limited, and the existing literature is still in its early stages. Research focusing on TRD is notably sparse compared to the broader body of work on depression without treatment resistance. Consequently, it was not possible to conduct meta-analyses by type of psychotherapy across all treatment modalities and by type of control group. Due to several study limitations, there is currently limited evidence available about the effectiveness of psychotherapy for TRD, and further trials are needed. Beyond the treatments usually offered for depression, it is possible that TRD requires a personalized medicine approach. Full article

Background/Objectives: In many parts of the world, pharmacists hold the primary responsibility for providing safe and effective pharmacotherapy. A key aspect is the availability of appropriate medicines for each individual patient. When industrially manufactured medicines are unsuitable or unavailable, pharmacists can prepare tailor-made medicines. While this principle applies globally, practices vary between countries. In the Netherlands, the preparation of medicines in pharmacies is well-established and integrated into routine healthcare. This narrative review explores the role and significance of extemporaneous compounding, pharmacy preparations and related product care in the Netherlands. Methods: Pharmacists involved in pharmacy preparations across various professional sectors, including community and hospital pharmacies, central compounding facilities, academia, and the professional pharmacists’ organisation, provided detailed and expert insights based on the literature and policy documents while also sharing their critical perspectives. Results: We present arguments supporting the need for pharmacy preparations and examine their position and role in community and hospital pharmacies in the Netherlands. Additional topics are discussed, including the regulatory and legal framework, outsourcing, quality assurance, standardisation, education, and international context. Specific pharmacy preparation topics, often with a research component and a strong focus on product care, are highlighted, including paediatric dosage forms, swallowing difficulties and feeding tubes, hospital-at-home care, reconstitution of oncolytic drugs and biologicals, total parenteral nutrition (TPN), advanced therapy medicinal products (ATMPs), radiopharmaceuticals and optical tracers, clinical trial medication, robotisation in reconstitution, and patient-centric solid oral dosage forms. Conclusions: The widespread acceptance of pharmacy preparations in the Netherlands is the result of a unique combination of strict adherence to tailored regulations that ensure quality and safety, and patient-oriented flexibility in design, formulation, and production. This approach is further reinforced by the standardisation of a broad range of formulations and procedures across primary, secondary and tertiary care, as well as by continuous research-driven innovation to develop new medicines, formulations, and production methods. Full article

Heart failure with preserved ejection fraction (HFpEF) is a heterogeneous syndrome with increasing prevalence and substantial morbidity and mortality. Recent advances in pharmacotherapy have transformed its management. This review summarizes current evidence supporting the use of sodium–glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and glucagon-like peptide-1 receptor agonists, alongside selected use of angiotensin receptor–neprilysin inhibitors. Emphasis is placed on early initiation of disease-modifying therapies, phenotypic tailoring, and comorbidity-targeted strategies, especially in obese and diabetic patients. Together, these approaches define a new era of guideline-directed, personalized care for patients with HFpEF. Full article

According to the World Health Organization, musculoskeletal injuries affect more than 1.71 billion people around the world. These injuries are a major public health issue and the leading cause of disability. There has been a recent interest in hydrogels as a potential biomaterial for musculoskeletal tissue regeneration. This is due to their high water content (70–99%), ECM-like structure, injectability, and controllable degradation rates. Recent preclinical studies indicate that they can enhance regeneration by modulating the release of bioactive compounds, growth factors, and stem cells. Composite hydrogels that combine natural and synthetic polymers, like chitosan and collagen, have compressive moduli that are advantageous for tendon–bone healing. Some of these hydrogels can even hold up to 0.8 MPa of tensile strength. In osteoarthritis models, functionalized systems such as microspheres responsive to matrix metalloproteinase-13 have demonstrated disease modulation and targeted drug delivery, while intelligent in situ hydrogels have exhibited a 43% increase in neovascularization and a 50% enhancement in myotube production. Hydrogel-based therapies have been shown to restore contractile force by as much as 80%, increase myofiber density by 65%, and boost ALP activity in bone defects by 2.1 times in volumetric muscle loss (VML) models. Adding TGF-β3 or MSCs to hydrogel systems improved GAG content by about 60%, collagen II expression by 35–50%, and O’Driscoll scores by 35–50% in cartilage regeneration. Full article

Background/Objectives: The aim of this study was to systematically assess Adverse Events Following Immunization (AEFI) among children following administration of the human papillomavirus (HPV) vaccine (Cervarix^®) included in the Dutch National Immunization Program (NIP) and to characterize the pattern and recurrence risk of AEFI after HPV revaccination. Methods: A longitudinal cohort event monitoring study, using patient-reported outcomes was used among recipients of the HPV vaccine at 10 years of age. Data were available for 3063 children following the first HPV vaccination and for 2209 children following the second HPV vaccination. Results: The most commonly reported AEFI following HPV vaccination were injection site reactions—reported by 46.5% of participants after the first dose and 31.9% after the second dose—followed by headache (8.2% and 3.9%, respectively) and joint pain (4.5% and 3.7%, respectively). Participants who received both HPV vaccine doses reported more AEFI after the first dose than after the second. Among girls, 61.2% reported at least one AEFI following the first dose, compared to 44.2% after the second dose. For boys, these percentages were 55.3% and 38.5%, respectively. This difference was statistically significant (p = 0.002). For some AEFI, such as injection site reactions, there appears to be a potential increased risk of recurrence following the second dose. Conclusions: This prospective longitudinal cohort event monitoring study showed that AEFI were more frequent after the first HPV dose and more frequent for girls compared to boys. An increased risk of recurrence was seen for AEFI, such as injection site reactions and headache. Furthermore, this study provides insight into the course of AEFI and the extent to which children were affected by these symptoms based on real-world data. Full article

Knowing the superior biochemical defense mechanisms of sessile organisms, it is not hard to believe the cure for any human sickness might be hidden in nature—we “just” have to identify it and make it safely available in the right dose to our organs and cells that are in need. For decades, green tea catechins (GTCs) have been a case in point. Because of their low redox potential and favorable positioning of hydroxyl groups, these flavonoid representatives (namely, catechin—C, epicatechin—EC, epicatechin gallate—ECG, epigallocatechin—EGC, epigallocatechin gallate—EGCG) are among the most potent plant-derived (and not only) antioxidants. The proven anti-inflammatory, neuroprotective, antimicrobial, and anticarcinogenic properties of these phytochemicals further contribute to their favorable pharmacological profile. Doubtlessly, GTCs hold the potential to “cope” with the majority of today‘s socially significant diseases, yet their mass use in clinical practice is still limited. Several factors related to the compounds’ membrane penetrability, chemical stability, and solubility overall determine their low bioavailability. Moreover, the antioxidant-to-pro-oxidant transitioning behavior of GTCs is highly conditional and, to a certain degree, unpredictable. The nanoparticulate delivery systems represent a logical approach to overcoming one or more of these therapeutic challenges. This review particularly focuses on the lipid-based nanotechnologies known to be a leading choice when it comes to drug permeation enhancement and not drug release modification nor drug stabilization solely. It is our goal to present the privileges of encapsulating green tea catechins in either vesicular or particulate lipid carriers with respect to the increasingly popular trends of advanced phytotherapy and functional nutrition. Full article

Hypertrophic cardiomyopathy (HCM) is a prevalent and often underdiagnosed genetic cardiac disorder characterized by left ventricular hypertrophy and, in many cases, dynamic left ventricular outflow tract obstruction (LVOTO). The development of cardiac myosin inhibitors (CMIs) represents an emerging therapeutic approach in the pharmacological management of obstructive HCM (oHCM). This review offers an integrated and up-to-date synthesis of the cardiac myosin inhibitor class, with a focus on mavacamten, aficamten, and the broader landscape of emerging agents. It also highlights recent clinical trial outcomes, pharmacokinetic and pharmacogenetic considerations, and potential future directions in therapy. Furthermore, we incorporate the most recent data up to May 2025, including late-breaking trial results and real-world safety findings, aiming to provide clinicians with a practical and comprehensive perspective on this evolving drug class. A narrative review was conducted by systematically searching PubMed, Scopus, Google Scholar, and ClinicalTrials.gov for English-language articles and trials published between January 2016 and May 2025. Keywords included “cardiac myosin inhibitor”, mavacamten”, “aficamten”, “MYK-224”, and “hypertrophic cardiomyopathy.” Inclusion criteria encompassed clinical trials and comprehensive reviews specifically addressing CMIs in cardiac applications. CMIs such as mavacamten and aficamten have demonstrated significant clinical benefits in reducing LVOT gradients, improving exercise capacity, and alleviating symptoms in patients with oHCM. Mavacamten is currently approved for clinical use, while aficamten is in advanced regulatory review. Comparative data suggest potential advantages of aficamten in the onset of action, pharmacokinetic profile, and tolerability. Emerging evidence supports the exploration of CMIs in pediatric populations, heart failure with preserved ejection fraction (HFpEF), and non-obstructive HCM (nHCM), although results are still preliminary. Cardiac myosin inhibitors offer a novel, pathophysiology-targeted approach to managing oHCM. While mavacamten has established efficacy, next-generation agents like aficamten may offer improved safety and versatility. Further long-term studies are needed to clarify their role across broader patient populations. Full article