Expert Opinion on Pharmacotherapy最新文献

Introduction: Pneumonia remains a significant global health challenge due to its high prevalence and mortality rate, and challenging treatment. This review explores the best strategies to optimize the antibiotic therapy for pneumonia in critically ill patients, focusing on pharmacokinetics, pharmacodynamics, and therapeutic data.

Areas covered: A review of scientific publications on severe pneumonia highlights the challenges of optimizing antibiotic use to improve lung diffusion, bacterial killing, and achieving PK/PD targets, emphasizing the need to understand microbiological epidemiology and MIC breakpoints. Key strategies like nebulization, therapeutic drug monitoring, and emerging technologies such as ELF TDM and nanomaterial-based drug delivery systems are essential for optimizing PK/PD outcomes and addressing antimicrobial resistance.

Expert opinion: Improving our understanding of pulmonary pharmacokinetics and optimizing their tissue diffusion are instrumental for achieving precision antibiotic therapy for severe pneumonia. By addressing current limitations and embracing interdisciplinary collaboration, we can pave the way for more efficient personalized approaches in infectious diseases management.

Introduction: Despite a rising incidence, biliary tract cancers (BTCs) are still considered a rare tumor entity. The disease's subtle clinical presentation and lack of effective early detection strategies often lead to a diagnosis at an advanced or unresectable stage, where curative options are limited.

Areas covered: This review provides an overview of current systemic therapies and emerging novel approaches for BTC. For decades, the combination of gemcitabine with cisplatin (GemCis) has been the standard of care for palliative treatment. However, since 2020, the diagnostic and therapeutic landscape for BTC has evolved considerably, not only in the first-line setting but also beyond, driven by the development of clinical trials exploring immunotherapy and molecularly targeted agents. Due to the high frequency of targetable genetic alterations in BTC patients, there is a growing emphasis on obtaining tissue or liquid biopsy samples to identify markers like microsatellite instability and other actionable oncogenic driver genes.

Expert opinion: Early initiation of systemic therapies in combination with multimodal approaches is essential for maximizing survival outcomes in patients with BTC.

Introduction: The concept that children are therapeutic orphans emerged in the 1960s, triggering eventually worldwide legislation to facilitate pediatric studies, called 'Pediatric Drug Development (PDD).' However, PDD's true aim is not better medicines for children but labels in minors; minors are not another species.

Areas covered: Absorption, distribution, metabolism, and excretion (ADME) differ in preterm newborns, but babies mature. With the exception of neonatology, the justifications for clinical, pharmacokinetic, and safety studies were and are exaggerated.

Expert opinion: PDD reflects an artificial regulatory challenge, reflecting mankind's transition into a world of effective new drugs compared to previous millennia when only materials taken from nature were available. Minors need dose assessment and proof of safety; there is a tendency to exaggerate the scope of pharmacokinetic and safety studies before and after the eighteenth birthday, potentially motivated not by industry's greed, but by researchers' desire for funding and regulatory authorities' desire for recognition, specifically as since 2007 the European Medicines Agency (EMA) augmented and expanded PDD: a new type of conflict of interest in medicines' administration and mainstream medical science.

Introduction: Desmoid tumor (DT) is a rare, locally aggressive, mesenchymal neoplasm that can arise at any site in the body. Medical therapies play a major role for DT's patients requiring treatment. A novel systemic approach has recently emerged with Nirogacestat, a γ-secretase inhibitor targeting the NOTCH signaling pathway.

Areas covered: Nirogacestat is the first drug in its class to receive approval from the Food and Drug Administration (FDA) and is the first FDA-approved treatment specifically for DTs. We reviewed the data leading to its discovery, including its mechanism of action, pharmacological properties, clinical efficacy, and its positioning within the current treatment armamentarium for DTs.

Expert opinion: High-quality evidence for systemic therapies in the management of DTs remains an unmet need. Nirogacestat now joins sorafenib as the only drugs with efficacy in DTs demonstrated by randomized phase 3 studies. Currently, there are no comparative trials of the available systemic therapies. Therefore, physicians should consider factors such as drug accessibility, cost, toxicity profile, comorbidities, and patient preferences when selecting treatment. Long-term efficacy and safety data will be essential for evaluating the duration of treatment response and monitoring late-onset side effects of Nirogacestat.

Introduction: Sleep dysfunction occurs in various forms and is a bothersome and intrusive non-motor symptom of Parkinson's disease (PD). Frequently undiagnosed, their poor management can have a great impact on the quality of life of PD patients and their caregivers.

Areas covered: This article covers the safety and efficacy of pharmacological strategies for the management of the most frequent sleep disturbances in Parkinson's disease. Non-pharmacological aspects are also discussed, but these are not the main focus. Literature searches using electronic databases (Medline, Cochrane Library) and systematic checking of references from review articles/other reports were performed.

Expert opinion: Melatonin and clonazepam are the most commonly used therapies for the management of REM sleep behavior disorder (RBD). The most used pharmacological wake-promoting agents in the treatment of excessive daytime sleepiness (EDS) are modafinil and caffeine. Poor nocturnal sleep quality is usually linked to EDS, thus proper sleep hygiene is recommended. As nocturnal motor symptoms are commonly associated with sleep fragmentation and early morning off, optimization of dopaminergic treatment during nighttime is highly recommended for the proper management of insomnia. Further interventions include eszopiclone and melatonin for the management of insomnia. Therapeutic options for restless legs syndrome (RLS) include calcium channel alpha-2-delta ligands and low-dose dopamine agonists (DA). Further confirmatory evidence is needed before the general recommendation of these treatments.

Introduction: Infertility related to polycystic ovary syndrome (PCOS) represents a significant challenge for women of reproductive age. Over the last few years, evidence-based medicine has driven new approaches for treating infertility in patients with PCOS, changing rapidly and deeply the clinical practice.

Areas covered: The authors provide an in-depth examination of recent developments in drug treatment strategies that have impacted the clinical practice and changed the previous approach to infertility in patients with PCOS.

Expert opinion: The authors identify four primary areas of interest that have impacted clinical practice in the last few years. Specifically, they discuss the current role of metformin administration in women with PCOS and infertility, the choice for using clomiphene citrate or letrozole as first-line treatment for ovulation induction, the use of new gonadotropin formulations for in vitro fertilization (IVF) program, and the elective embryo transfer in IVF cycles as golden standard treatment for patients with PCOS at high-risk for ovarian hyperstimulation syndrome.

Introduction: Acne vulgaris is a chronic inflammatory disease of the pilosebaceous unit that affects approximately 9.4% of the global population. Current treatment strategies aim to target as many pathogenic factors involved in the appearance of acne lesions and are centered on a systematic treatment escalation based on disease severity, extension, and treatment response, starting with topical treatments for mild cases and progressing over to systemic therapies in more severe cases. A literature search, which included clinical guidelines, clinical studies, and review articles on acne treatment and maintenance, was conducted to review the pharmacological approaches currently available to treat this disease.

Areas covered: Topical therapies such as topical retinoids, benzoyl peroxide, azelaic acid, salicylic acid, topical antibiotics, and clascoterone, as well as systemic treatments such as oral antibiotics and isotretinoin are discussed in detail. Combined oral contraceptives and spironolactone will not be discussed in this article.

Expert opinion: There is a need for a blockbuster acne drug that simultaneously targets the four main pathogenic factors involved in the appearance of acne lesions while presenting with minimal side effects. Until such a drug exists, combination therapy will remain the standard of treatment for most acne patients.

Introduction: Heterotopic ossification (HO), acquired or hereditary, is a diverse pathological condition defined by the production of extraskeletal bone in muscles, soft tissues, and connective tissues. Acquired HO is relatively prevalent and develops mostly in response to trauma, although its etiology is unknown. Genetic forms provide insight into the pathobiological mechanisms of this disorder. Fibrodysplasia ossificans progressiva (FOP) is a rare hereditary form of HO that can have a significant impact on affected individuals. FOP steadily weakens affected subjects and increases their risk of death.

Areas covered: The U.S. Food and Drug Administration has recently approved the retinoid palovarotene as the first compound to treat heterotopic ossification in patients with FOP. This review provides a comprehensive overview of current and potential future pharmacotherapeutic options and their modes of action. The online databases PubMed, Cochrane Library, Web of Science, and ClinicalTrials.gov were searched using the terms 'heterotopic ossification' and 'fibrodysplasia ossificans progressiva' or synonyms, with a special focus over the last 5 years of publications.

Expert opinion: Approval of palovarotene, as the first retinoid indicated for reduction in the volume of new HO, may revolutionize the therapeutic landscape. However, long-term safety and efficacy data for palovarotene are currently lacking.

Introduction: Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated.

Areas covered: The authors review the current status and possible future developments in HF pharmacotherapy.

Expert opinion: The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.