BACKGROUND:Oral and ocular medications are frequently used in the treatment of allergic rhinitis (AR). As part of the update of the Allergic Rhinitis and its Impact on Asthma (ARIA)-EAACI guidelines, this manuscript presents the ARIA-EAACI 2024-2025 recommendations for oral and ocular treatments. METHODS:The ARIA-EAACI 2024-2025 guideline panel issued recommendations following the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) evidence-to-decision framework. Several sources of evidence were used to inform panel judgements and recommendations, including systematic reviews, mHealth and pharmacovigilance data as well as a survey on costs. RESULTS:Eight guideline questions concerning oral treatments for AR and three questions concerning ocular treatments were addressed. These questions led to the recommendations. Overall, these questions concern the choice between different classes of medication. They also discuss the role of oral antihistamines (OAH), leukotriene receptor antagonists (LTRA), ocular antihistamines (OcAH) and ocular mast cell stabilisers. Four questions had not been previously evaluated in ARIA guidelines, while, for the other four, there was a change in the strength or directionality of the recommendations. Overall, these guidelines recommend using intranasal corticosteroids over OAH and using OAH over LTRA. Moreover, they suggest using OAH over OcAH and suggest being against adding LTRA to OAH. Finally, considerations for choosing between different individual OAHs are presented. CONCLUSION:This ARIA-EAACI 2024-2025 article supports patients, their caregivers and healthcare professionals in choosing oral and ocular treatments for AR. Decisions on treatment should consider the clinical variability of the disease, patients' values and the affordability of medications.
The WHO Regional Office for Europe conducted 9 country studies of migration of doctors and nurses. This paper identifies similarities and variations in migratory flows, factors that influence them, and related policy responses. The 9 countries include 4 that integrate the European Economic Area (EEA), Ireland, Malta, Norway, and Romania, and 5 non-EEA, Albania, Armenia, Georgia, Moldova, Tajikistan. Case writers used a common study template that covered international outflows and inflows, mobility push, and pull factors, and related policy interventions. Data sources include the WHO/Europe-OECD-Eurostat joint questionnaire and country databases. Emigration is motivated by low wages, dissatisfaction with working conditions, inadequate practice environment, excessive workloads and lack of opportunities for professional development. Flows for doctors and nurses vary in volume over time, and in countries of origin and destination. Pull factors include the free circulation of persons within the EEA for citizens of member states, easy access to work permits, common or easily learned language, and the presence of a diaspora in a destination country. Policies to improve retention include increasing the number of training places, making remuneration and working conditions more attractive and compulsory service. All countries have some health workforce development plan, but implementation is a challenge everywhere. Policies should be tailored to country labour market conditions, migration trends, and institutional capacity. Better understanding of migration flows will improve the effectiveness of policy responses.
Chronic myeloid leukemia (CML) has undergone a significant shift over the past two decades, transitioning from a fatal malignancy to a chronic, highly manageable disease with near-normal life expectancy for most patients. This transformation has been driven by the development of BCR-ABL1-targeted tyrosine kinase inhibitors (TKIs), which have enabled durable disease control and deep molecular responses (DMRs) in the majority of patients with chronic-phase CML. As long-term survival outcomes have plateaued across available agents, contemporary management has shifted beyond disease suppression toward optimizing long-term safety, quality of life, and the achievement of treatment-free remission (TFR). This review summarizes current evidence on molecular monitoring strategies, the comparative efficacy and toxicity profiles of first-, second-, and third-generation TKIs, and emerging advances in response assessment. Patient-centered TKI selection is discussed in the context of cardiovascular risk, comorbidities, treatment tolerability, and survivorship goals, reflecting the growing emphasis on individualized therapy in chronic-phase CML. Molecular monitoring strategies are examined in parallel, highlighting the clinical importance of early and sustained DMRs in guiding therapeutic decisions and TFR eligibility. Although RT-qPCR remains the standard for molecular monitoring, emerging high-sensitivity techniques such as digital droplet PCR and next-generation sequencing provide complementary value by improving the detection of low-level residual disease, refining risk stratification, and enabling earlier identification of resistance. Emerging therapeutic strategies and advances in response assessment further highlight ongoing efforts to enhance the depth and durability of remission while minimizing long-term toxicity. These developments support a more precise, individualized, and outcome-driven approach to modern CML management.
Abstract Background/Purpose Heart failure with preserved ejection fraction (HFpEF) is increasingly recognized as a systemic metabolic and mitochondrial disorder, yet current diagnostic and prognostic tools rely largely on non-specific cardiac biomarkers. Circulating mitochondrial and metabolic biomarkers may better capture underlying energetic failure and improve risk stratification, but their clinical utility remains unclear. Methods We conducted a PRISMA 2020-compliant systematic review registered with PROSPERO. We searched PubMed, Embase, Scopus, and Cochrane Library from January 1, 2020 to November 1, 2025, for case-control, cross-sectional, and RCT-based biomarker analyses in adults with HFpEF (ejection fraction > 50% or study-defined).We used HFpEF, biomarker, mitochondrial, and metabolomics MeSH terms. Risk of bias was assessed using tool-specific approaches according to study design. Randomized controlled trials were evaluated using the Cochrane Risk of Bias 2 (RoB 2) tool, while non-randomized observational studies were assessed using the Risk Of Bias In Non-randomized Studies of Interventions (ROBINS-I) tools. Results Of 336 records, 41 studies were included. Two randomized trials (RoB 2) had overall low risk of bias, although some biomarker analyses were unplanned and may have been selectively reported. Most observational studies (ROBINS-I) had moderate overall risk, mainly due to residual confounding, missing data, and selective reporting. Mitochondrial and metabolic biomarkers such as lactate, circulating mtDNA, branched-chain amino acids, and acylcarnitines were consistently linked to congestion, reduced exercise capacity, and incident heart failure; for example, higher cell-free mtDNA was independently associated with congestion (OR 3.33, 95% CI 1.02–10.90). A nine-metabolite plasma panel including acylcarnitines and amino acid derivatives distinguished HFpEF from hypertensive controls with an AUC of 0.98, 94% sensitivity, and 100% specificity. Proteomic and inflammatory panels identified high-risk HFpEF clusters with nearly twofold higher cardiovascular events, while SERPINA3 and remodeling markers differentiated HFpEF from other phenotypes. Lipidomic, transcriptomic, and metabolomic markers (ceramide ratios, GATA3/IFNG, 9-metabolite panel) showed good diagnostic and prognostic performance, supporting a robust multi-omic HFpEF profile. Conclusion Circulating mitochondrial, metabolic, and other omics-based biomarkers provide information beyond natriuretic peptides to distinguish HFpEF, flag higher-risk patients, and reflect congestion and reduced exercise capacity. Together, they support biomarker-based HFpEF subtyping and provide a practical framework for designing targeted trials and improving individual risk assessment.
