ATMPs prepared under hospital exemption: European Blood Alliance position paper

Poorly controlled pain is a global public health issue. The personal, familial and societal costs are immeasurable. Only a minority of European patients have access to a comprehensive specialist pain clinic. More commonly the responsibility for chronic pain management and initiating opioid therapy rests with the primary care physician and other non‐specialist opioid prescribers. There is much confusing and conflicting information available to non‐specialist prescribers regarding opioid therapy and a great deal of unjustified fear is generated. Opioid therapy should only be initiated by competent clinicians as part of a multi‐faceted treatment programme in circumstances where more simple measures have failed. Throughout, all patients must be kept under close clinical surveillance. As with any other medical therapy, if the treatment fails to yield the desired results and/or the patient is additionally burdened by an unacceptable level of adverse effects, the overall management strategy must be reviewed and revised. No responsible clinician will wish to pursue a failed treatment strategy or persist with an ineffective and burdensome treatment. In a considered attempt to empower and inform non‐specialist opioid prescribers, EFIC convened a European group of experts, drawn from a diverse range of basic science and relevant clinical disciplines, to prepare a position paper on appropriate opioid use in chronic pain. The expert panel reviewed the available literature and harnessed the experience of many years of clinical practice to produce these series of recommendations. Its success will be judged on the extent to which it contributes to an improved pain management experience for chronic pain patients across Europe.SignificanceThis position paper provides expert recommendations for primary care physicians and other non‐ specialist healthcare professionals in Europe, particularly those who do not have ready access to specialists in pain medicine, on the safe and appropriate use of opioid medications as part of a multi‐faceted approach to pain management, in properly selected and supervised patients.

The European Position Paper on Rhinosinusitis and Nasal Polyps 2012 is the update of similar evidence based position papers published in 2005 and 2007. The document contains chapters on definitions and classification, we now also proposed definitions for difficult to treat rhinosinusitis, control of disease and better definitions for rhinosinusitis in children. More emphasis is placed on the diagnosis and treatment of acute rhinosinusitis. Throughout the document the terms chronic rhinosinusitis without nasal polyps (CRSsNP) and chronic rhinosinusitis with nasal polyps (CRSwNP) are used to further point out differences in pathophysiology and treatment of these two entities. There are extensive chapters on epidemiology and predisposing factors, inflammatory mechanisms, (differential) diagnosis of facial pain, genetics, cystic fibrosis, aspirin exacerbated respiratory disease, immunodeficiencies, allergic fungal rhinosinusitis and the relationship between upper and lower airways. The chapters on paediatric acute and chronic rhinosinusitis are totally rewritten. Last but not least all available evidence for management of acute rhinosinusitis and chronic rhinosinusitis with or without nasal polyps in adults and children is analyzed and presented and management schemes based on the evidence are proposed. This executive summary for otorhinolaryngologists focuses on the most important changes and issues for otorhinolaryngologists. The full document can be downloaded for free on the website of this journal: http://www.rhinologyjournal.com.

Background and ObjectivesBlood Establishments (BE) within the European Union, are legally obliged to conduct self inspections, as defined in the Commission Directive 2005/62/EC[3]. These self inspections are considered to be an essential part of the Quality Management System, allowing the BE to continuously improve their processes. Furthermore different BE's have developed different self inspection schemes based on a wide range of regulations and standards. Implementing an efficient and effective self inspection scheme can be a challenge.Materials and MethodsClear references to self inspections within blood establishments are made in the national and international regulation, as well as in other commonly used international standards. Because the defined inspection criteria are different within these standards, the European Blood Inspection Project (EuBIS[9]) was initiated by the European Commission in collaboration with the European Blood Alliance, resulting in pan‐European standards and criteria for self inspections.ResultsBased on the EuBIS criteria, a self inspection scheme can be put in place as a tool to evaluate the adherence and the effectiveness of the Quality Management System (QMS) of a blood establishment. This self inspection scheme is incorporated in the QMS and focuses on continuous improvement, root cause analysis, process optimalisation and efficacy, finally resulting in the prevention of quality failures by introducing remedial actions where necessary.ConclusionAs an essential part of management review and QMS improvement, a solid self inspection scheme within blood establishments can detect areas for improvement within the organization.

The immediate causes for the study are discussions with staff from multiple European Universities, articles and position papers of advisory committees and professional organization. They all express their worries about both the decline of education of process safety in the curricula of Chemical Engineering and the decline of research in process safety subjects

An increased coexistence of gastroesophageal reflux disease (GERD) and chronic rhinosinusitis (CRS) has been reported in epidemiologic and register studies, and reflux has been shown more frequently in patients with CRS in studies using esophagus pH manometry compared to participants without CRS. A discussion is ongoing about whether there might be an association between these two diseases and, if so, whether the association is causal. The purpose of this study was to clinically investigate the prevalence and symptom severity scores of CRS among patients with GERD. The results were compared with those of a randomly assigned control group from the general Danish population. In this case-control study, 82 patients with GERD were examined for CRS using the European Position Paper on Rhinosinusitis and Nasal Polyps criteria, which combine patient history and anterior/posterior rhinoscopy results. Sinonasal-related quality of life was assessed by using the Sino-Nasal Outcome Test 22 (SNOT-22). These results were compared with those of a population-based control group examined for CRS in the same way. The prevalence of CRS among patients with GERD was 20.7% (95% confidence interval [CI], 12.0%-29.5%), significantly higher than the CRS prevalence of 8.5% (95% CI, 6.8%-10.2%) in the background population. Patients with GERD and CRS had an average SNOT-22 score of 43.8, whereas patients with CRS from the background population scored, on average, 28.1. Having GERD increased the mean SNOT-22 score in patients with CRS by 15.7 (95% CI, 6.5-24.9). The results of this study provide additional evidence of an association between GERD and CRS and indicate that GERD may play a role in the development of CRS. The results also show that sinonasal-related quality of life is decreased in patients with CRS who also suffer from GERD.

Chronic sinusitis is the most common routine presentation for a general ENT surgeon. The 2007 'Primary Care Guidelines: European Position Paper on the Primary Care Diagnosis and Management of Rhinosinusitis and Nasal Polyps' aimed to deliver evidence-based guidelines for the diagnosis and management of rhinosinusitis in specialist and primary care. The aim of this audit was to assess the information provided in the referral letters to the ENT department regarding patients with potential rhinosinusitis, and compare this to the information required for the rhinology care pathways. We evaluated one month of referrals to the ENT department. The quality of information in the referral letters was poor. Only 22 per cent of patient referrals included basic information about symptoms, duration and treatment. We plan to investigate why general practitioners are not complying with the pathway. In addition, the pathways will be more widely disseminated via the 'Map of Medicine' (an online resource for general practitioners). This should facilitate the receipt of the best evidence-based treatment for patients prior to referral to secondary care.

This study aimed to investigate the correlation between metabolic syndrome and chronic rhinosinusitis (CRS), with related risk factors for CRS according to data from the Korean National Health and Nutrition Examination Survey (KNHANES). The KNHANES surveyed individuals >19 years of age from January 2010 to December 2011. CRS encompassed "symptom-based CRS" as defined by the European Position Paper on Rhinosinusitis and Nasal Polyps 2012. Metabolic syndrome was diagnosed according to the American Heart Association/National Heart Lung and Blood Institute criteria. A χ2 analysis, univariate analysis, and multivariate analysis were conducted. A total of 12,015 individuals were analyzed in this study. The prevalence of CRS in the patients with metabolic syndrome (high triglyceride level, reduced high-density lipoprotein level, and elevated blood pressure) was significantly higher than that in patients without metabolic syndrome (14.15 versus 10.16%) (p < 0.05). Allergic rhinitis was the only significant risk factor for CRS found to be associated with metabolic syndrome (p < 0.05). CRS was more prevalent in patients with metabolic syndrome, especially those with allergic rhinitis, than in patients without metabolic syndrome. Accordingly, CRS should be considered in patients with metabolic syndrome and allergic rhinitis.

The SNOT-20 questionnaire, a valid disease related quality of life instrument for rhinosinusitis, was modified for use in secondary school children and became the Modified Sino Nasal Outcome Test -20 Young Person Questionnaire, MSYPQ. MSYPQ was evaluated in a pilot study of disease (rhinosinusitis) and non-disease according to criteria in the European Position Paper on Rhinosinusitis and Nasal polyposis (EPOS). Those children who were suffering from rhinosinusitis according to the EPOS criteria showed significantly high scores on MSYPQ, whereas those who did not have rhinosinusitis had very low to zero scores on the MSYPQ. This pilot study confirmed that the MSYPQ recognises rhinosinusitis symptoms in the 11-16 year age group with its effect on quality of life and is a suitable instrument to investigate the prevalence and impact of this problem in young people.

The European Position Paper on Rhinosinusitis and Nasal Polyps (EP3OS) incorporates symptomatic, endoscopic, and radiologic criteria in the clinical diagnosis of chronic rhinosinusitis (CRS), while in epidemiological studies, the definition is based on symptoms only. We aimed to assess the reliability and validity of a symptom-based definition of CRS using data from the GA(2) LEN European survey. On two separate occasions, 1700 subjects from 11 centers provided information on symptoms of CRS, allergic rhinitis, and asthma. CRS was defined by the epidemiological EP3OS symptom criteria. The difference in prevalence of CRS between two study points, the standardized absolute repeatability, and the chance-corrected repeatability (kappa) were determined. In two centers, 342 participants underwent nasal endoscopy. The association of symptom-based CRS with endoscopy and self-reported doctor-diagnosed CRS was assessed. There was a decrease in prevalence of CRS between the two study phases, and this was consistent across all centers (-3.0%, 95% CI: -5.0 to -1.0%, I(2) = 0). There was fair to moderate agreement between the two occasions (kappa = 39.6). Symptom-based CRS was significantly associated with positive endoscopy in nonallergic subjects, and with self-reported doctor-diagnosed CRS in all subjects, irrespective of the presence of allergic rhinitis. Our findings suggest that a symptom-based definition of CRS, according to the epidemiological part of the EP3OS criteria, has a moderate reliability over time, is stable between study centers, is not influenced by the presence of allergic rhinitis, and is suitable for the assessment of geographic variation in prevalence of CRS.

Severe uncontrolled chronic rhinosinusitis with nasal polyps (CRSwNP) is a challenging condition to treat. The European Position Paper on Rhinosinusitis and Nasal Polyps 2020 (EPOS2020) has the following criteria when considering biological therapy for severe uncontrolled CRSwNP: eosinophilia, need for oral corticosteroids (OCS), symptom score, loss of sense of smell and co-morbid asthma. This study aimed at finding associations of baseline factors with uncontrolled CRSwNP after endoscopic sinus surgery (ESS). Electronic health record data of CRSwNP patients (N = 137) undergoing ESS in 2002-17 were used. Endpoints of uncontrolled CRSwNP were revision ESS, purchased OCS and antibiotic courses during follow up. Baseline factors were chosen based on EPOS2020 and the data available: nasal polyp (NP) eosinophilia, peripheral blood eosinophilia, co-existing asthma and/or non-steroidal anti-inflammatory drug exacerbated respiratory disease (NERD), need for OCS during the previous year, previous ESS, endoscopic NP score, and Lund-Mackay score of sinus computed tomography scans. During the follow-up of 10.1 ± 3.1 (mean ± standard deviation) years, 35 (25.5%) individuals underwent revision ESS. The best predictive model was obtained by a sum of baseline (1) blood eosinophilia ≥ 250 cells/≥l and/or NP eosinophilia ≥ 30% (Eos), (2) asthma/NERD, and (3) ≥ 1 OCS/year. It was significantly associated with revision ESS, purchased doctor-prescribed OCS and antibiotic courses during follow-up. We identified similar predictive variables for uncontrolled CRSwNP that are used in the EPOS2020 indications of biological therapy, thus suggesting that these estimates are usable in clinical practice.

&lt;b&gt;Introduction:&lt;/b&gt; Primary chronic rhinosinusitis with nasal polyps (CRSwNP) is a severe, often uncontrolled disease whose pathomechanism involves type 2 inflammation (T2). Biologic drugs targeting interleukin 4 and 13 (dupilumab) receptors and blocking interleukin 5 (mepolizumab) have been approved for the treatment of the T2 endotype.&lt;b&gt;Aim:&lt;/b&gt; Presentation of the authors' suggestions that guided the choice of an appropriate biologic agent when initiating qualification for the treatment of patients with CRSwNP, based on the authors' experience and data from the literature related to biologic therapy.&lt;b&gt;Materials and methods:&lt;/b&gt; Patients with CRSwNP were qualified for biological treatment in accordance with the EPOS (European Position Paper on Rhinosinusitis) guidelines and the criteria of the B.156 drug program. The choice of an appropriate biologic was based on medical history data, such as the level of asthma control, presence of allergies, and the occurrence of N-ERD (nonsteroidal anti-inflammatory drug-exacerbated respiratory disease), as well as biomarker results: total IgE concentration and absolute blood eosinophil count.&lt;b&gt;Results:&lt;/b&gt; The study included 43 patients (23 treated with mepolizumab, 20 treated with dupilumab). Groups of patients were comparable in terms of age, sex, number of sinonasal surgeries, prevalence of asthma, NSAIDs (non-steroidal anti-inflammatory drugs) sensitivity, atopy and initial SNOT-22 (Sinonasal Outcome Test-22), VAS (Visual Analog Scale), NPS (Nasal Polyp Score), and L-K score (Lund-Kennedy score). Eosinophilia total range was 250-1000 cells/microL. Baseline peripheral blood eosinophil count was significantly higher in the mepolizumab-treated group. In the dupilumab-treated group, increases in eosinophil counts up to 3500 cells/μl were observed during therapy; however, no patient developed clinical features of hypereosinophilic syndrome.&lt;b&gt;Conclusions:&lt;/b&gt; When selecting a biologic drug for the treatment of CRSwNP, it is recommended to consider not only the values of available biomarkers, but also the degree of asthma control, the cumulative dose of oral corticosteroids (OCSs), the patient's age, and treatment convenience for the patient.

Mo1111 Night Time Acid Clearance Is Related to Sleep Disturbance in Gastroesophageal Reflux Disease

Acute rhinosinusitis (ARS) is one of the most frequent diagnoses in clinical practice. Common symptoms include anterior and/or posterior nasal drainage, nasal obstruction, and facial pain, pressure, or sensation of fullness. ARS etiology is more often viral than bacterial, and infection-initiated inflammation is the primary pathophysiologic mechanism responsible for symptoms. Because ARS is usually a self-limited process, the primary goal of treatment is symptom relief, which can be more effectively achieved by targeting the underlying inflammation. Intranasal steroids (INS) have been shown to reduce components of respiratory inflammation and increase symptom relief for ARS when used alone or combined with antibiotics. Based on current evidence in support of INS therapy, the European Position Paper on Rhinosinusitis and Nasal Polyps 2007 guidelines and a recent Cochrane meta-analysis recommend using INS in the treatment of ARS, both as monotherapy and as an adjunct to antibiotics.

Background: Computed tomography (CT) scans are performed by some clinicians in the belief that they are a useful primary investigation in patients with facial pain. Objective: To assess the appropriateness and outcome of sinuses CT scans in patients with facial pain based on the European Position Paper on Chronic Rhinosinusitis and Nasal Polyps (EPOS) 2007 guideline and International Headache Society (IHS) criteria for diagnosing and investigating rhinosinusitis. Methodology: The first cycle of audit was performed on 50 patients with facial pain who underwent CT scanning. The findings on nasal endoscopy, Lund-Mackay scores (LMS) of the scans and management of these patients were analysed. Following implementation of the IHS and EPOS criteria, 50 consecutive patients were re-audited. Results: In the first cycle, 16% of patients had positive nasal endoscopic findings. Thirty patients had LMS of 0 and only 9 showed significant changes (LMS ≥ 8) on their scans. In the second cycle, only 10 patients underwent CT imaging as per EPOS guideline and 4 of them showed significant changes. The remaining 80% of patients in this cycle were diagnosed and treated for non-sino- genic causes. Conclusion: Applying the IHS and EPOS criteria has reduced the number of inappropriate CT scans requests and allowed consideration of non-sinogenic aetiologies.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a prevalent condition that significantly impacts quality of life and places a burden on healthcare systems. The advent of biologics targeting type 2 immune pathways offers new therapeutic options for severe and/or uncontrolled CRSwNP. Initially, biologic use was guided by the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2020 and the European Forum for Research and Education in Allergy and Airway Diseases (EUFOREA) guidelines, despite limited data on clinical indications, response measures, and treatment duration. Since then, numerous studies and the EPOS/EUFOREA 2023 update have refined these guidelines. The update defines clinical indications for biologics based on type 2 inflammation markers by lowering the blood eosinophil threshold from 250 to 150 cells/μL. The response to biologics is now more simply categorized into three levels based on reductions in nasal polyp size, improvements in quality of life, and enhancement of smell. Treatment evaluation is recommended at 6 months with annual follow-up. Longer administration intervals, such as every four weeks, have also proven effective in well-controlled patients. Although specific guidelines for discontinuation or switching biologics remain lacking, clinical judgment is essential in determining when treatment should be stopped or adjusted. Additionally, regulatory updates support the use of biologics for CRSwNP, and novel agents such as tezepelumab (an anti-thymic stromal lymphopoietin monoclonal antibody) continue to show promise. Finally, in Korea, biologics for CRSwNP are not covered by national health insurance, leading to extended dosing intervals due to high costs. Despite this limitation, studies have shown that adjusted dosing can maintain subjective quality of life. Recent studies by Korean authors have also explored practical considerations such as dosing intervals and comparisons to surgery. Further research is needed to optimize treatment strategies, particularly regarding cost-effectiveness and prospective studies tailored to the Korean healthcare system.