Drugs in Context最新文献

The management of chronic obstructive lung diseases, particularly severe asthma, chronic obstructive pulmonary disease (COPD) and non-cystic fibrosis bronchiectasis, is complicated by frequent overlap syndromes such as asthma-bronchiectasis overlap and bronchiectasis-COPD overlap syndrome. These overlapping phenotypes are characterized by severe symptoms, frequent exacerbations, accelerated lung function decline and increased mortality, driven by a common, destructive endotype: persistent, neutrophil-dominant airway inflammation. This inflammation is fuelled by the overactivity of neutrophil serine proteases, notably neutrophil elastase, which drives the self-perpetuating 'vicious vortex' of structural damage and infection. Traditional therapies, including inhaled corticosteroids and type 2 (T2) inflammation-targeted biologics, are often ineffective against this non-T2, neutrophilic inflammation. Brensocatib, a first-in-class, oral, reversible inhibitor of dipeptidyl peptidase 1 (DPP1), offers a novel, targeted strategy. By inhibiting DPP1 - the master activator of neutrophil serine proteases in the bone marrow - brensocatib effectively 'disarms' neutrophils before they reach the lungs. The phase III ASPEN trial in non-cystic fibrosis bronchiectasis demonstrated its disease-modifying potential, showing a significant reduction in the annualized rate of exacerbations and, critically, a statistically significant slowing of the decline in forced expiratory volume in 1 second in the 25 mg arm (a benefit not observed with the 10 mg dose). Subgroup analysis confirmed consistent efficacy in the high-risk bronchiectasis-COPD overlap syndrome population. These findings validate DPP1 inhibition as a first potential disease-modifying therapy. This strategy is poised to fundamentally shift clinical focus from symptom control to the preservation of lung function for patients with severe, neutrophilic-driven neutrophilic overlap syndromes.

Background: Acute ischaemic heart disease (AIHD) and atherothrombotic stroke are amongst the leading causes of mortality and disability worldwide, sharing pathogenic mechanisms. Quality indicators (QIs) are essential tools for evaluating and optimizing clinical management. The aim of this article is to develop an integrated organizational model for the care of AIHD and atherothrombotic stroke, incorporating validated and measurable QIs to improve patient outcomes and care coordination.

Methods: A multidisciplinary panel of cardiologists, neurologists, internists, primary care physicians and nursing staff reached a consensus through structured meetings. After reviewing the literature and scientific recommendations, the most relevant QIs were selected. When clear standards were lacking, the panel established criteria by consensus. The selected QIs were integrated into a care pathway covering the pre-hospital phase through long-term follow-up.

Results: Sixteen key QIs were identified for each process, covering intervention times, secondary prevention, patient satisfaction, rehabilitation, follow-up and clinical outcomes. The model highlights the importance of rapid diagnosis, timely interventions and coordinated discharge planning. Early initiation of intensive lipid-lowering therapy and systematic monitoring of targets such as LDL-c and mortality are emphasized.

Conclusion: The proposed QIs and organizational model can be valuable tools for optimizing care and coordination for patients with AIHD and atherothrombotic stroke. They enable the monitoring and improvement of critical aspects of the care process.

Moist wound healing, an established paradigm in the management of wounds, accelerates healing by maintaining an optimal microenvironment. Hydrogels, such as the Dermatix^® Wound Care (DWC) gel, possess fluid-retentive and absorptive properties and provide a moist environment for wound healing. We examined the effectiveness of DWC gel in acute and chronic wounds across various aetiologies, alone and in combination with other modalities, through a series of case studies. DWC gel promoted granulation, epithelialization, pain relief and patient adherence due to its ease of application. It is an effective and safe treatment for acute and chronic wounds; further comparative trials and research on its anti-infective and anti-inflammatory properties are warranted.

Osteoarthritis (OA) is increasingly understood as a complex, inflammatory disease rather than a purely mechanical disorder. Apremilast, a selective phosphodiesterase 4 inhibitor approved for psoriatic arthritis, is amongst several new treatment alternatives that target one of the most important inflammatory pathways involved in OA. Apremilast decreases pro-inflammatory cytokines, such as TNF, IL-1 and IL-6, which are central to cartilage degradation and synovial inflammation. This review explores the mechanistic rationale and available evidence supporting the repurposing of apremilast in OA. We highlight its potential to reduce pain and slow structural progression. Although the data are currently scarce, there remains a strong rationale for its repurposing for the treatment of OA based on its safety profile, oral route of administration and positive treatment adherence. Nevertheless, clinical investigation remains limited. Further research is needed to clarify its therapeutic potential and identify patient populations most likely to benefit.

Ulcerative colitis (UC) is a chronic inflammatory bowel disorder with a relapsing and remitting course often necessitating the use of advanced therapy to maintain disease control. Sphingosine-1-phosphate receptor modulators (S1PRMs) represent a new class of oral small molecules approved for the management of moderate-to-severe UC. Evidence from pivotal trials shows promising results for the induction and maintenance of remission in UC. This comprehensive review of S1PRMs explores their mechanism of action, key clinical trial data, real-world insights, and an overview of their safety, including considerations for special populations and comparative effectiveness. S1PRMs offer distinct advantages, including oral administration and a lack of immunogenicity, positioning them as valuable additions to the UC treatment landscape. However, future research will be required to understand their position in the evolving UC treatment paradigms.

Background: Invasive disease-free survival in adjuvant treatment of HR⁺/HER2^- early-stage breast cancer is improved by the use of CDK4/6 inhibitors. However, to date, minimal data are available on their safety and effectiveness in older patients (≥70 years old).

Methods: A retrospective, multi-centre cohort study was conducted in two oncology centres in Pavia, Italy. Patients had to have received at least 3 months of therapy with adjuvant abemaciclib (a CDK4/6 inhibitor). Data on demographics, toxicity, dose reductions and clinical outcomes were analysed. Analyses were descriptive, with continuous variables reported as median (IQR) and categorical variables as counts and percentages.

Results: Fifty-four patient records were reviewed (median age 55; six patients ≥70 years (older-age subgroup). Adverse events of any grade were reported in 53/54 patients (98.1%), most commonly haematological and gastrointestinal. Dose reductions occurred more frequently and earlier in the older-age subgroup (66.7% versus 45.8%; median 4.2 versus 8.3 months). Toxicities were generally of low-moderate grade and manageable.

Conclusion: During adjuvant abemaciclib, low-moderate-grade toxicities were common, particularly haematological and gastrointestinal events. Older patients showed a numerically higher rate of dose reductions, suggesting a potential need for personalized dosing and early monitoring in this subgroup. These findings should be considered hypothesis-generating and warrant confirmation in larger prospective studies.

Rupatadine is a modern, long-acting, non-sedating antihistamine that targets the H₁ receptor and exhibits additional strong antagonist activity toward platelet-activating factor (PAF) receptors as well as exerting other anti-inflammatory effects. All these properties have positioned rupatadine as a remarkable treatment option for adults and children with various allergic and skin disorders, including allergic rhinitis and urticaria of different causes. This case series shows the real-world effectiveness and safety of off-label rupatadine use in paediatric patients with clinically relevant complex allergy-related and dermatology-related conditions, whose underlying pathogenetic mechanisms were successfully addressed by the pharmacological profile of rupatadine.

Although mild upper respiratory tract infections (MURTIs) are typically self-limiting and benign, they can substantially impair a patient's quality of life. The wide range of pathogens causing MURTIs often necessitates a symptomatic treatment approach rather than a pathogen-specific treatment. The present article introduces a patient-centred classification system that distinguishes between self-care-oriented, pharmacist-oriented and physician-oriented patients. Building on this framework, we propose a 360° holistic care model that considers contextual factors and addresses the whole person, under the premise that the effectiveness, safety and suitability of the treatment are tailored to the individual's symptoms and circumstances. To support practical implementation, a stepwise guide for MURTI management is presented, encompassing all steps from initial patient assessment to pharmacological and non-pharmacological treatment approaches, lifestyle advice, patient education, and follow-up care. This structured approach not only facilitates symptom resolution but also promotes long-term health by empowering patients with the knowledge, tools and support they need to maintain their well-being. By shifting the focus from isolated symptom management to comprehensive care, our 360° holistic care model may enhance the overall treatment experience and outcome for patients affected by MURTIs.

Background: Oxidative modifications of low-density lipoproteins (LDL) have been reported in patients with β-thalassaemia/haemoglobin E (HbE) and are related to cardiovascular complications. Deferiprone (L1) is an iron chelator that decreases iron overload and, consequently, reduces oxidative stress. This study assesses the protective effect of L1 on the oxidative status of LDL in patients with β-thalassaemia/HbE.

Methods: Twenty-nine patients with β-thalassaemia/HbE treated with L1 were recruited. The study included a 4-week washout period followed by 4 and 12 weeks of L1 treatment. Non-transferrin-bound iron (NTBI) levels and oxidative stress markers, including thiobarbituric acid reactive substances and α-tocopherol, were monitored at each visit. The rate and content of lipid radical formation following Cu²⁺-induced LDL oxidation in vitro were detected by NBD-Pen, a specific fluorescence probe.

Results: L1 was shown to prevent the depletion of α-tocopherol, decrease thiobarbituric acid reactive substances and preserve the levels of lipid components in LDL. A negative correlation between serum NTBI and LDL α-tocopherol indicated that the circulating non-redox-active NTBI can lead to the depletion of α-tocopherol. LDL from the washout period showed the highest oxidative susceptibility when evaluated by NBD-Pen.

Conclusion: Iron chelation therapy with L1 improves the oxidative status of LDL in patients with β-thalassaemia/HbE.

Advances in the understanding of the pathophysiology of psoriasis have led to the development of biologic therapies that target key components of the immune system involved in the inflammatory cascade of psoriasis, revolutionizing the management of moderate-to-severe cases. Alongside biologics, small molecules have emerged as promising treatment options. However, despite significant progress, several challenges remain. Additionally, long-term safety data for many newer agents are still lacking, necessitating ongoing surveillance and real-world evidence collection. This narrative review, performed by analysing the existing medical literature using PubMed, Ovid, Scopus, Embase and Cochrane Library databases up to 30 June 2025, explores new systemic therapies for psoriasis, including both approved and emerging biologics and small molecules, highlighting future directions in treatment. Despite advancements in psoriasis treatment, unmet needs persist, including specific clinical phenotypes such as pustular psoriasis, paradoxical reactions, patient comorbidities, treatment resistance or inefficacy, and high costs, underscoring the need for novel and emerging therapies. In the future, advances in pharmacogenetics and artificial intelligence could revolutionize psoriasis management. Artificial intelligence-driven models integrating clinical data, laboratory findings and biomarkers could enhance precision medicine by optimizing treatment selection and establishing standardized therapeutic algorithms, ensuring that patients receive the right drug at the right time.