Expert Opinion on Pharmacotherapy最新文献

Introduction: Irritable bowel syndrome (IBS) and functional abdominal pain - not otherwise specified (FAP-NOS) are amongst the most common disorders affecting children worldwide, often associated with a lower quality of live, anxiety, and depression. The underlying mechanisms of these conditions remain poorly understood, posing significant challenges to effective treatment. Consequently, many children receive inadequate care. This highlights the urgent need for accessible and effective treatment strategies.

Area covered: Data were identified using CENTRAL, MEDLINE, and PUBMED databases up to 1 December 2024. This review will explore existing treatment approaches, from first-line reassurance to a spectrum of non-pharmacological and pharmacological interventions. We also discuss emerging therapies and future directions.

Expert opinion: IBS and FAP-NOS are now named disorders of gut-brain interaction in the Rome IV criteria, highlighting the complex interplay between central and peripheral gastrointestinal alterations. Psychological interventions, such as cognitive behavior therapy and gut hypnotherapy, have proven to be the most successful therapies in pediatric IBS and FAP-NOS, whilst the evidence for the efficacy of pharmacological interventions is mostly lacking due to poor quality of available studies and high placebo responses. Future studies are needed to investigate the value of novel treatment strategies such as fecal microbiota transplantation and open label placebo's.

Introduction: The development of B-cell lymphoma-2 (BCL-2) inhibitors has totally revolutionized the management of acute myeloid leukemia (AML). These highly effective, small molecules trigger apoptosis in leukemia cells by specifically targeting the BCL-2 protein. Notably, venetoclax, an extremely high-affinity BCL-2 inhibitor, stands out particularly for its high therapeutic index, especially when combined with hypomethylating agents like azacytidine and decitabine, among older patients and even young patients with comorbidities that preclude intensive chemotherapy regimens. Once more, because the new AML model is evolving, venetoclax is being used more with high-intensity chemotherapy even in young patients, at any age.

Areas covered: This review summarizes the progress in AML targeting the intrinsic apoptosis pathway with current and developing BCL-2 inhibitors, as well as their clinical applications in combination therapies.

Expert opinion: While venetoclax has made significant progress in treating AML, ongoing clinical research is moving this agent into first-line combination treatments. Notably, the lack of response to this agent and the development of acquired resistance remain significant concerns. Although specific gene mutations strongly predict clinical response, research is ongoing into predictive biomarkers and new drug combinations that work synergistically. Emerging therapies targeting BCL-2 also aim to maximize treatment benefits and address issues related to venetoclax resistance.

Introduction: Remimazolam is a novel, ultra-short-acting benzodiazepine that enhances inhibitory transmission at the GABA-A receptor to produce sedation, anxiolysis, and amnesia. Its organ-independent metabolism by nonspecific tissue esterases enables rapid onset and offset. These characteristics make it particularly suited to high-risk populations where hemodynamic stability and predictable recovery are particularly important.

Areas covered: The review evaluates the pharmacological properties, clinical efficacy, and safety of remimazolam, drawing on data from Phase I - III clinical trials and major comparative trials. A systematic literature search was conducted using PubMed for English-language articles published between January 2015 and September 2025, incorporating both MeSH and non-MeSH terms. Key studies comparing remimazolam with midazolam, propofol, dexmedetomidine, and etomidate were analyzed, with a focus on pharmacokinetics, pharmacodynamics, pharmacoeconomic developments, and clinical outcomes.

Expert opinion: Remimazolam offers a favorable balance between efficacy and safety, with advantages in hemodynamic stability, reduced respiratory depression, and rapid recovery. While higher acquisition costs may limit widespread adoption, potential efficiencies in procedural throughput and patient safety support its growing role in modern anesthetic practice. Although higher acquisition cost and limited availability remain barriers, its procedural efficiency and safety profile support its growing role in anesthesia and sedation practice.

Introduction: Abdominal pain remains a major challenge in inflammatory bowel disease (IBD), due to its frequency and relative impact on healthcare costs and patient well-being. Although significant steps have been taken to better understand pain and how to manage this important symptom, a great deal is still unknown regarding the nature of abdominal pain, including in IBD.

Areas covered: In this critical perspective, we review current major issues related to abdominal pain in IBD, along with the contemporary strategies utilized to address this symptom. Additionally, we discuss approaches that can be taken now to optimize pain control in IBD, while also providing suggestions to significantly improve management of this issue in the future.

Expert opinion: IBD patients are still frequently plagued by abdominal pain, and their providers are often unable to adequately and/or safely manage this symptom. In order to significantly improve our approach in this regard, we need to utilize evidence-based strategies that are still practical, while also avoiding unhelpful (and potentially dangerous) analgesic choices. Additionally, more resources and research are necessary to take advantage of what is already known, and to further optimize our understanding of this challenging symptom.

Introduction: Anticoagulation in patients with liver disease presents a complex clinical challenge due to complex changes in hemostasis seen in hepatic dysfunction. Historically underrepresented in clinical trials, anticoagulation in this population remains a topic of uncertainty.

Areas covered: This review examines the current evidence regarding efficacy and safety of anticoagulation in liver disease. Comparative study between anticoagulants is summarized, with a focus on direct oral anticoagulants (DOACs) and vitamin K antagonists (VKAs). Key factors influencing outcomes are discussed, including liver disease severity, timing of therapy initiation, thrombus characteristics, and pre-anticoagulation variceal management.

Expert opinion: Current evidence suggests that DOAC therapy is at least as effective as VKA for stroke prevention in atrial fibrillation (AF) and treatment of portal venous thrombosis (PVT) in patients with liver disease, possibly with a superior safety profile. Guidelines support DOAC use in Child-Pugh class A cirrhosis and cautious use in Child-Pugh B. There is a lack of controlled trial data, especially in patients with moderate to severe liver disease. Observational studies often report low bleeding rates with anticoagulation, possibly due to selection bias and pre-anticoagulation variceal treatment. Future research should prioritize controlled trials and explore DOAC use in moderate to severe liver disease.

Areas covered: Drawing on recent clinical trials, expert consensus, and emerging data presented at hematology meetings (2018-2025), we highlight established cytoreductive strategies - hydroxyurea, interferon-α (including pegylated formulations), and anagrelide - and evaluate emerging targeted agents. Key trials include the phase 2 LSD1 inhibitor bomedemstat trial showing significant platelet-count reduction and mutation-burden improvement the phase 3 SURPASS-ET trial comparing ropeginterferon alfa-2b versus anagrelide, ongoing investigations of JAK - STAT pathway modulators, and emerging data on the anti-calreticulin (CALR) monoclonal antibody INCA033989, which selectively targets mutCALR progenitors to suppress malignant hematopoiesis while sparing normal hematopoiesis.

Expert opinion: Future advances in ET management hinge on integrating molecular risk stratification into treatment algorithms, optimizing combination regimens to deepen molecular remissions, and prioritizing agents with favorable safety profiles. Personalized approaches leveraging allele-burden dynamics and symptom-control metrics are likely to define the next era of ET pharmacotherapy.

Introduction: For the first time in history, a medication - tirzepatide, has been approved by the United States Food and Drug Administration (FDA) for the treatment of obstructive sleep apnea (OSA). This approval adds to the current array of therapeutic options and raises many issues regarding the future of treatment for OSA; in particular, the role of glucagon-like peptide-1 receptor agonists (GLP-1 RAs) in the chronic management of patients with OSA.

Areas covered: This review aims to summarize the impact of GLP-1 RAs for the treatment of OSA in the context of the recent FDA approval of tirzepatide following the SURMOUNT-OSA trial.

Expert opinion: The FDA approval of tirzepatide for OSA represents a major shift from symptom-based management with continuous positive airway pressure (CPAP) toward a weight-centered, disease-modifying strategy. Questions remain about whether benefits from GLP-1 RAs are purely weight-mediated, or whether they involve direct respiratory effects as well. Moving forward, pharmacotherapy could transform OSA management into a more individualized framework which views the condition as a chronic metabolic disease rather than solely a mechanical airway disorder.

Introduction: Antiplatelet therapy is key for secondary prevention in patients with atherosclerotic cardiovascular disease, particularly those undergoing percutaneous coronary intervention (PCI). While aspirin has historically been the standard of care agent, oral P2Y₁₂ inhibitors - namely clopidogrel, prasugrel and ticagrelor - have emerged as key adjunctive therapies as well as treatment alternatives. Given their differing pharmacodynamic, pharmacogenomic, and safety - efficacy profiles, the optimal selection of these agents remains an area of investigation.

Areas covered: This review provides a comprehensive overview of the pharmacologic profiles of oral P2Y₁₂ inhibitors, clopidogrel, prasugrel and ticagrelor, and their comparative effects when used with or without aspirin. MEDLINE, Cochrane, Web of Science, and Scopus were searched until August 5, 2025. Special attention is given to high-risk subgroups (e.g. clopidogrel poor-responders, diabetics, East Asians, females, and patients requiring concomitant oral anticoagulation), and to strategies involving platelet function or genetic testing.

Expert opinion: The selection of oral P2Y₁₂ inhibiting therapy should be tailored to the individual patient, taking into consideration clinical, procedural, demographic, and genetic factors, as well as the dynamic nature of ischemic and bleeding risks over time. Specific considerations are warranted for certain patient subgroups, as well as those with clopidogrel poor responsiveness, or patients with contraindications to ticagrelor or prasugrel.

Introduction: Sepsis is a clinical syndrome that occurs due to dysregulated host response to infection. Septic shock is the presence of cardiovascular dysfunction in the context of sepsis. Pediatric septic shock is an important cause of morbidity and mortality globally. Early recognition and prompt treatment has been shown to improve outcomes.

Areas covered: A comprehensive literature search was conducted using PubMed and Embase. Key search terms included 'Paediatric,' sepsis,' 'shock,' 'neonatal,' 'antimicrobial,' and 'adjunctive therapy' from 1965 to date.

Expert opinion: The primary focus underlying management of neonatal and pediatric septic shock is rapid recognition and timely antibiotic and fluid therapy, with initiation of supportive treatments. Disappointingly, this management paradigm has not significantly changed in the last 20 years, despite efforts to develop novel adjunctive therapies.What has changed is the recognition that 'bundles of care' including rapid diagnosis, appropriate antibiotics, fluid resuscitation, and initiation of supportive care can significantly improve outcomes.Molecular diagnostics have significantly improved the ability for effective antimicrobial stewardship. Initiatives such as the Surviving Sepsis Campaign have highlighted evidence-based practice. However, few new adjunctive therapies have been translated from research into clinical practice, but there are several potential advances in treatment modalities that will be discussed.