Advances in Therapy最新文献

Keratoconus is a progressive corneal disorder characterized by thinning and steepening of the cornea, leading to visual impairment and reduced quality of life. Although epithelium-off corneal cross-linking has emerged as the gold-standard therapy, it can be associated with postoperative pain, delayed healing, and increased risk of complications due to removal of the corneal epithelium. To overcome these limitations, epithelium-on cross-linking was developed as a less invasive alternative. In epithelium-on cross-linking, three essential components must be present to maximize the photochemical reaction: oxygen, riboflavin formulation with permeation enhancers, and high-irradiance pulsed ultraviolet-A (UV-A) light. Oxygen plays an especially critical rate-limiting role, as it interacts with riboflavin and UV-A irradiation to produce the reactive oxygen species (ROS) that promote covalent cross-links, thereby strengthening the corneal stroma. Given that the intact epithelium during epithelium-on cross-linking can act as a barrier to oxygen diffusion, in addition to riboflavin penetration, enhancing oxygen availability during epithelium-on cross-linking has been shown to improve treatment outcomes. Oxygen-enriched epithelium-on cross-linking is poised to emerge as a mainstay therapy for keratoconus. This narrative review examines the influence of oxygen supplementation, a key rate-limiting factor, in enhancing the efficacy of epithelium-on cross-linking.

Introduction: Spinal muscular atrophy (SMA) is a progressive neuromuscular disorder associated with respiratory complications and reduced quality of life (QOL). Although disease-modifying therapies have altered the clinical course of SMA, the role of home-based respiratory physiotherapy as an adjunct to pharmacologic treatment remains underexplored. The aim of this study is to evaluate the impact of a 1-year home-based respiratory physiotherapy program on QOL and pulmonary function in nusinersen-treated patients with SMA types 2 and 3.

Methods: This mixed prospective interventional and retrospective analytical study assessed the impact of weekly home-based, personally tailored respiratory physiotherapy sessions in addition to standard multidisciplinary care. Group allocation was determined by patient or parental willingness to participate and geographical feasibility for weekly home visits. Pulmonary function tests (PFTs) were performed at baseline and after 12 months. QOL was assessed with the SF-36 questionnaire and the Global Rating of Change (GROC) scale.

Results: Twenty-nine patients with spinal muscular atrophy (SMA) types 2 and 3 receiving nusinersen were included. The intervention group (n = 15) and the control group (n = 14) were comparable at baseline. Objective respiratory parameters remained stable in both groups with no significant differences at the end of the intervention (forced vital capacity % predicted: 72.7 ± 25.1 in the intervention group vs. 69.4 ± 26.5 in the control group, p = 0.7). In contrast, the intervention group demonstrated significantly higher scores in multiple SF-36 domains, including physical functioning and energy/fatigue (41.3 ± 43.7 vs. 2.1 ± 3.7 and 71.7 ± 16.9 vs. 51.4 ± 14.5, respectively; p < 0.05). The median GROC score in the intervention group was 3.0, indicating a clinically meaningful perceived benefit in QOL by exceeding the minimal clinically important difference threshold.

Conclusion: Home-based respiratory physiotherapy was associated with stable pulmonary indices as well as significant improvements in perceived health status and QOL in patients with SMA treated with nusinersen.

Renin-angiotensin-aldosterone system inhibitor (RAASi) therapies are a cornerstone of guideline-directed medical therapy in the management of cardiorenal disease, including chronic kidney disease and heart failure. Management guidelines state that these therapies should be prescribed at the maximum licensed or tolerated dose in order to prevent disease progression and adverse events. However, both cardiorenal disease and RAASi therapies increase the risk of hyperkalaemia. When hyperkalaemia occurs, clinicians often down-titrate or discontinue these important RAASi therapies, leaving patients at risk of adverse cardiorenal outcomes. Eleven cardiorenal experts considered how hyperkalaemia can act as a barrier to optimised RAASi therapy in patients with cardiorenal disease and how these issues could be mitigated. Four key areas of suboptimal and variable clinical practice were identified: optimisation of RAASi therapy; definition and management of acute hyperkalaemia; secondary to primary care communications; and patient education. In this podcast article, two of the experts discuss the clinical challenges and principles of optimal care for each of the four areas identified. The experts agreed that hyperkalaemia should be considered a predictable and manageable condition, requiring a pre-emptive and long-term approach. When hyperkalaemia occurs, down-titrating or discontinuing RAASi therapy should be a last resort, after all other management approaches have been employed. Healthcare professionals in secondary and primary care must communicate and collaborate to ensure effective, consistent management of patients with cardiorenal disease. Finally, patients should be educated to understand their cardiorenal disease and its management and the importance of optimal RAASi therapy. Supplementary file1 (MP4 173853 KB).

Introduction: Bipolar disorder (BD) is a chronic and heterogeneous condition associated with global and specific cognitive deficits, including but not limited to impaired executive function, memory, and processing speed. As cognitive impairment represents a therapeutic target, this systematic review aims to synthesize available evidence investigating the association between clinical markers of illness progression and cognitive decline in adults with BD.

Methods: A systematic search was conducted in PubMed, OVID (PsycINFO), and Scopus from inception to September 27, 2025. Eligible studies included adults (≥ 18 years) with BD (I, II, or mixed) that reported a direct comparison between subgroups of illness progression markers (illness duration and/or number of mood episodes). The primary outcome was cognitive function assessed by validated neuropsychological tests. Eligible study designs were cross-sectional, longitudinal, case-control, cohort, or baseline clinical trial data.

Results: Available evidence from cross-sectional studies suggest that a higher number of mood episodes or longer illness duration was associated with decreased cognitive function, particularly in domains of executive function and verbal/visual memory. In contrast, several longitudinal studies reported no significant change in cognitive outcomes over time in persons with BD relative to healthy controls.

Conclusion: Findings on the influence of illness progression markers on cognitive decline in BD is mixed. Future research should prioritize large-scale longitudinal designs and integrate biomarker and neuroimaging methods to investigate underlying mechanisms that may contribute to cognitive worsening in individuals with BD.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive, often fatal disease characterized by an elevation in pulmonary arterial pressure and pulmonary vascular resistance (PVR). Oral treprostinil is indicated for the treatment of PAH and has been shown to delay disease progression and to improve exercise capacity.

Methods: The purpose of this report is to examine and summarize the data on the use of oral treprostinil in patients already on dual therapy with an endothelin receptor antagonist (ERA) and phosphodiesterase type-5 inhibitor (PDE-5i), using data from the FREEDOM-C study, FREEDOM-C2 study, and a retrospective chart review.

Results: In this analysis, background monotherapy versus dual therapy did not have an impact on clinical parameters (6-min walk distance). Additionally, the number of background therapies did not have an impact on the dose of oral treprostinil achieved at week 16 or measures typically used to assess clinical efficacy in patients with PAH (change in 6MWD at week 16 and NT-proBNP).

Conclusion: Oral treprostinil is a safe and efficacious treatment option and has been shown to further improve clinical parameters and risk status in patients with PAH on background dual therapy.

Trial registry: ClinicalTrials.gov identifier, NCT00325442 and NCT00887978.

Introduction: Atopic dermatitis (AD), a chronic type 2 inflammatory disease, often requires long-term therapeutic intervention. Understanding the long-term safety profile of dupilumab treatment is crucial for clinicians and patients, especially regarding laboratory parameters.

Methods: LIBERTY AD OLE, a phase 3, multicenter, open-label extension (OLE) study, evaluated clinical laboratory findings in adults with moderate-to-severe AD treated with dupilumab for up to 5 years.

Results: In total, 2677 patients entered the OLE study. At the time of database lock, 238 patients completed up to week 272 and 1297 patients completed treatment or the end-of-study visit. There were no clinically meaningful changes from baseline values in mean hematology or serum chemistry parameters. Few laboratory abnormalities were reported as treatment-emergent adverse events (TEAEs), most of which were not serious and did not lead to permanent drug discontinuation. Five serious laboratory-related TEAEs occurred in one patient each (number of patients [nP]/100 patient-years [PY], 0.02): febrile neutropenia, hemolytic anemia, thrombocytopenia, hypokalemia, and hematuria. Six laboratory-related TEAEs led to permanent treatment discontinuation: one case each (nP/100 PY, 0.02) of increased alanine aminotransferase, increased aspartate aminotransferase, increased blood creatine phosphokinase, and increased transaminases and two cases of thrombocytopenia (nP/100 PY, 0.03); although rare, some were related to the study drug. Serious laboratory-related TEAEs and TEAEs leading to study discontinuation were generally lower in our study than in the placebo arm of the 1-year LIBERTY AD CHRONOS study, which was included for comparison. Most of these TEAEs were considered unrelated to the study drug and were recovered/resolved during the study period. No deaths due to laboratory-related TEAEs were reported.

Conclusions: Treatment with dupilumab for up to 5 years showed no clinically meaningful changes in mean laboratory parameters. Continuous long-term use of dupilumab in adults with moderate-to-severe AD does not require laboratory testing before initiating or during the treatment.

Trial registration: ClinicalTrials.gov identifiers NCT01949311 and NCT02260986.

Introduction: There is an increasing demand for information on the environmental impact of medical devices from decision-makers in healthcare. Performing 'comprehensive' life cycle assessments (LCA) can be time and resource intensive to undertake. We present a screening LCA approach (scLCA) to streamline the LCA process for device manufacturers, intended to provide comparable results to more comprehensive assessments.

Methods: The scLCA is similar to the 'comprehensive' LCA in scope (cradle to grave) and methodology. In the scLCA two key changes are made to the LCA methodology: the use of standardized models for transport and product end-of-life. Furthermore, result interpretation is via a hotspot analysis and the validation process does not include an external review. The application of scLCAs is presented here with examples from three dialysis machines, where the functional unit is the production and operation of one dialysis machine over its lifetime.

Results: All three dialysis machines showed similar hotspots, with the main drivers of environmental impact being water and electricity consumption during use. Using the scLCA is an efficient approach to perform environmental assessments on multiple products. The results of the scLCA provide an informative hotspot analysis that can be used to target improved sustainability of the device's manufacturing and distribution process.

Conclusion: The scLCA makes performing environmental assessments more feasible for manufacturers while generating results comparable to 'comprehensive' LCAs.

Pulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular remodeling and a deficiency of endogenous prostacyclin, a potent vasodilator with antiproliferative effects. Prostacyclin analogues (PCAs) target this deficiency and are integral to the PAH treatment algorithm. Parenteral PCA therapy is recommended for patients at intermediate-high and high risk, and early initiation-particularly in combination regimens-is associated with improved survival in real-world and post hoc analyses.The 2002 approval of the parenteral PCA treprostinil (Remodulin®) marked a significant advancement in PCA therapy. Compared with epoprostenol, treprostinil offers greater chemical stability at room temperature and a longer half-life, enabling subcutaneous (SC) infusion and minimizing the complications and challenges associated with intravenous delivery. Despite robust evidence demonstrating its benefits on morbidity and mortality and risk-based guideline recommendations, parenteral PCA therapy remains underutilized. Contributing factors include concerns about the complexity and perceived burden of pump-based delivery systems.Here we review the place for parenteral prostacyclin in PAH therapy, and the evolution of SC PCA pumps over time, with a focus on recent enhancements intended to overcome practical limitations of older devices and thereby improve usability. Key features such as simplified cassette filling, automated priming, a larger and more intuitive touchscreen remote, and expanded flow rate options aim to reduce the perceived challenges of SC therapy and support broader adoption among patients and prescribers. The article also provides perspectives and practical guidance from experienced practitioners on the initiation and maintenance of SC PCA therapy, emphasizing how improvements in pump technology can help overcome barriers to use. Addressing these challenges through improved design, education, and support may help bridge the gap between evidence-based recommendations and real-world practice.Graphical abstract available for this article.