Expert Opinion on Pharmacotherapy最新文献

Introduction: Insomnia is very common among individuals with Opioid Use Disorder [OUD] and can interfere with successful treatment. However, no pharmacotherapies with consistent efficacy for treating insomnia in this population have been identified.

Areas covered: A selection of medications, including trazodone and mirtazapine, have been studied as treatments for insomnia among individuals with OUD. Results have been mixed and require interpretation in the context of small sample sizes and/or clinical trial design. Dual orexin-receptor antagonists [DORAs] have shown some promise as treatments for insomnia that could also attenuate drug seeking behaviors. Future pharmacotherapies will need to address the underlying mechanisms driving insomnia among individuals with OUD, including dysregulated hypothalamic - pituitary - adrenal [HPA] axis activity in which excessive and/or aberrant cortisol release in early treatment drives hypervigilance and wakefulness, as well as potential sleep disturbances mediated by mu-opioid agonist therapies.

Expert opinion: There is an absence of clear guidance on how to address insomnia among individuals with OUD. Improved pharmacotherapies targeting this pathology are critical not only for enhancing quality of life but also the success of OUD treatment outcomes. Large, rigorous clinical trials are sorely needed to improve sleep medication prescribing guidelines in this population.

Introduction: Distal pulmonary arterial remodeling in pulmonary arterial hypertension (PAH) is driven by abnormal proliferation of endothelial cells, smooth muscle cells, and fibroblasts, coupled with apoptosis resistance and impaired bone morphogenetic protein receptor-2 (BMPR2) signaling. Growth factor pathways such as platelet-derived growth factor (PDGF) further promote vascular remodeling. These insights support the view of PAH as a cancer-like-disease and highlight the potential of emerging targeted therapies, including Transforming growth factor-beta (TGF-β) and PDGF receptor inhibitors, to move beyond vasodilation toward true disease-modifying strategies.

Areas covered: This article examines the concept of PAH as a cancer-like disease, emphasizing shared pathological mechanisms such as unchecked cellular proliferation, apoptosis resistance, genomic instability, and dysregulated growth factor signaling, mirroring oncogenic processes. Evidence from preclinical studies and clinical trials underscores that targeting these cancer-like mechanisms can attenuate vascular remodeling.

Expert opinion: The discovery of novel signaling pathways - such as the TGF-β superfamily, growth factors, and tyrosine kinases - has advanced the understanding of PAH and opened opportunities for disease-modifying therapies. Targeting these pathways, including BMPR2 restoration, TGF-β inhibition, and tyrosine kinase blockade, has shown encouraging results beyond the vasodilator-focused standard of care. These innovations may reshape PAH management by improving outcomes, and potentially altering disease progression.

Introduction: Ciprofol (cipepofol) is a new anesthetic with a phenol structure similar to propofol. It has a rapid onset and offset and may have fewer side effects than propofol. Our study aims to explore the effective dosage of ciprofol in different patient groups and to evaluate the optimal usage in various clinical settings.

Methods: We conducted a systematic search of studies evaluating the effective dose of ciprofol, including the median effective dose (ED50) and the dose required for 95% of the population (ED95) in different populations, and identified 13 clinical trials. The up and down method and sequential allocation design were the dose-finding strategies used in trials included in the review. Protocol registration: https://www.crd.york.ac.uk/prospero identifier is CRD420251026457.

Results: The studies we included encompass different patient groups, such as healthy adults, the elderly, children, obese patients, and critically ill patients. The calculated ciprofol ED50 and ED95 values varied among patient subgroups. In the included studies, the lowest reported ED50 for ciprofol was 0.18 mg·kg^-1, and the highest was 0.67 mg·kg^-1, whereas fewer studies reported ED95 values.

Conclusions: The minimum effective dose of ciprofol varies depending on the type of patient and clinical setting. Age, weight, BMI, drug interactions, differences in anesthesia induction and maintenance, physiological status and complications can influence the effective dose.

Introduction: Effective postoperative pain is a significant challenge for clinicians. Suboptimal pain management can lead to delayed recovery and increased risk of chronic pain. Multimodal analgesia strategies are increasingly adopted but variably implemented.

Areas covered: This review evaluates current and emerging pharmacologic agents for postoperative pain, from established drugs like acetaminophen, NSAIDs, and ketamine to off label and adjunct agents like vitamin C and duloxetine. It also critically appraises novel formulations of local anesthetics, opioids, and emerging agents with promising potential. The review highlights clinical implementation barriers including costs, provider familiarity, and real-world evidence.

Expert opinion: Despite an ever-expanding pharmacologic arsenal, postoperative pain control continues to be hindered by systemic, clinical, and institutional barriers. Although several new agents show promising results in reducing opioid consumption and improving recovery, their widespread adoption is limited by high costs and lack of robust long-term data. Bridging the gap between innovation and clinical practice requires coordinated efforts in research, education, and policy development.

Introduction: Pediatric fever often causes significant parental anxiety, or 'fever phobia,' leading to the inappropriate use of antipyretics. This narrative review synthesizes current evidence to support clinical decision-making, framing fever as a regulated physiological host defense mechanism, not a disease. The primary therapeutic goal is improving the child's overall comfort, rather than simply normalizing body temperature.

Areas covered: This review dispels common misconceptions, clarifying that fever height and response to antipyretics are poor predictors of illness severity. We cover evidence-based approaches to temperature measurement and the pharmacological management of symptoms, focusing on paracetamol and ibuprofen as first-line agents. Non-pharmacological strategies, such as hydration and comfort care, are described. Ultimately, we underscore the importance of clinical judgment over isolated temperature readings to guide appropriate management.

Expert opinion: The management of pediatric fever is shifting from a temperature-centric paradigm to a child-centric approach focused on comfort and reducing medication misuse. Future progress hinges on harmonizing inconsistent clinical guidelines and developing advanced point-of-care diagnostics to better stratify the risk of serious bacterial infections. Overcoming 'fever phobia' remains a key challenge, requiring education and scalable digital tools. Key research priorities include validating novel biomarkers, clarifying the long-term effects of antipyretics, and implementing effective educational programs.

Introduction: As medicines for adults are often not suitable for children, pediatric formulations must be specifically provided. Micropellets and mini-tablets are ideal platform technologies for APIs challenging in terms of solubility and taste, enabling products not only for the pediatric but also for the adult and the geriatric population.

Areas covered: Micropellets offer a great variety of oral drug products, administrations and flexible dosage strengths covering the palatability issue adequately. Dispensed into capsules, stick packs or sachets, micropellets can be directly administered into the mouth, sprinkled on food or dispersed in a liquid allowing for an even broader administration spectrum than mini-tablets. Personalized medicine, including combinations of different APIs and dosage strengths, can be compounded easily.

Expert opinion: To provide pediatric medicines also in developing countries at viable cost, a harmonization of pediatric product development and supply is suggested by WHO's GAP-f approach. Close cooperation between the different stakeholders supports a focused pediatric drug development and supply concept. A specialized pediatric CDMO (PedExpert CDMO) focusing on challenging APIs could mean an important step forward toward the goal 'Medicine for the children of the world.'

Introduction: Recurrent urinary tract infections (rUTIs) remain a significant clinical challenge, particularly in women, due to limited treatment options and increasing antimicrobial resistance (AMR).

Areas covered: This narrative review summarizes nonantibiotic and alternative management strategies to reduce recurrence and antibiotic exposure. Nonantibiotic options such as cranberry products, D-mannose, methenamine hippurate, probiotics, and vaginal estrogen demonstrate varying efficacy, though evidence remains mixed. Immunoprophylactic approaches, including sublingual and oral vaccines (e.g. MV140, OM-89), show promise in reducing infection rates among high-risk patients. Intravesical therapies - both antibiotic and nonantibiotic - offer localized treatment with favorable safety and reduced systemic resistance risk. Conventional antibiotic strategies, including continuous, postcoital, or self-start prophylaxis, remain widely used but require cautious monitoring due to AMR and adverse effects.

Expert opinion: Multidisciplinary management, including consultation with infectious disease and allergy specialists, is essential for complex, refractory infections. In rare, severe cases unresponsive to other therapies, cystectomy may be considered. Ultimately, individualized treatment based on risk factors, microbiological patterns, and tolerance is critical to improving outcomes and quality of life in women with rUTIs.

Introduction: Pediatric reflux esophagitis (RE) lies within the gastroesophageal reflux disease (GERD) spectrum but differs from adults in pathophysiology, presentation, and therapy risk - benefit. Clear, age-aware guidance is needed.

Areas covered: This narrative review synthesizes guidelines and studies on diagnosis and management of pediatric RE. We outline indications for endoscopy with biopsy and ambulatory monitoring (pH for acid burden; pH-impedance for nonacid reflux and symptom association, especially under acid suppression or in infants). First-line care prioritizes feeding optimization, thickeners, targeted allergy evaluation, and safe positional advice. Pharmacotherapy is summarized with emphasis on efficacy and safety: proton-pump inhibitors for documented esophagitis in children ≥1 year; H2-receptor antagonists for short-term or step-down use; alginates for post-prandial symptoms or mild disease; emerging potassium-competitive acid blockers under pediatric evaluation; and selective prokinetics/baclofen in refractory, dysmotility-predominant cases. Surgical options are addressed for proven, complicated, or refractory disease. Literature was identified in PubMed/Embase through 2025 using predefined pediatric GERD/RE, diagnostics, pharmacotherapy, safety, and surgery keywords.

Expert opinion: An age-aware, stepwise strategy - non-pharmacologic first, time-limited proton pump inhibitors with planned step-down, and cautious adjuncts - optimizes outcomes while minimizing harm. Priorities include pediatric trials for potassium-competitive acid blockers (P-CABs) and alginates, validated deprescribing pathways, noninvasive biomarkers, and scalable care models.

Introduction: Candida species produce a wide array of infections ranging from mucocutaneous to systemic infections. Candida albicans remains the most common species identified; however, the non-albicans Candida species have continued to increase as the diagnosis and therapeutic regimens have progressed.

Areas covered: This review with discussion of the various Candida species, especially the non-albicans species, some of the important mechanisms of resistance, and newer in vitro and clinical studies describing the recent and novel antifungal options such as rezafungin, ibrexafungerp, and oteseconazole, along with a novel antifungal, fosmanogepix.

Expert opinion: Initial antifungal therapy is frequently obsolete due to the expansion of antifungal resistance. This is especially true with C. glabrata, C. krusei, and most recently with C. auris. The newer and novel antifungals discussed here will add valuable tools to our antifungal armamentarium to be able to appropriately and adequately treat and manage these difficult infections. Each of the antifungals has unique and novel properties that will expand the arsenal useful to treat these fungal infections in the years to come.