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Trond Bliksvær,1 Tilde Marie Bertelsen,2 Merete Kvamme Fabritius,1 Morten Balle Hansen,2 Bente Vibecke Lunde,3 Ragnhild Holmen Waldahl1 1Nordland Research Institute, Bodø, Norway; 2Center for Organization, Management and Administration (COMA), Department of Politics and Society, Aalborg University, Aalborg, Denmark; 3Faculty of Social Sciences, Nord University, Bodø, NorwayCorrespondence: Trond BliksværNordland Research Institute, Pb 1490, Bodø, 8049, NorwayTel +47 95075408Email tbl@nforsk.noIntroduction: Home-based reablement (HBR) has achieved significant international prominence in recent years. In the Nordic countries, HBR has been introduced as an innovative care model within the municipal health care sector that answers the need for better and more effective service delivery. But knowledge about how innovations can be spread in the municipal health care sector is scarce. We also know little about what role first-line managers (FLMs) may play for the diffusion of innovations.Purpose: To describe and explain adoption of HBR in municipalities in Norway and to explore if there is a relationship between early/late adoption and the FLM’s perception of innovativeness in their organization. Such knowledge is valuable for the understanding of the role of FLM for the diffusion of innovations in the health care sector.Methods: A cross-sectional national online survey was carried out among FLM in the eldercare sector in 422 Norwegian municipalities. The response rate was 64%. The analysis was based on univariate and bivariate techniques, factor analysis, and multiple linear regression.Results: A bivariate analysis revealed that early adoption is associated with a high score on perception of innovativeness among FLMs. Innovators and early adopters scored highest (5.65) on perception of innovativeness, followed by early majority (5.31) and late majority (5.18). The lowest score was found among Laggards. A multiple regression analysis revealed that a substantial part of the positive relationship between early adoption and perception of innovativeness can be explained by FLMs’ length of service in the organization and their educational level. Wealth of the municipality does not have an effect on innovativeness.Conclusion: An implication of the results is that mature and stable personnel in key positions in the organization, and personnel with higher education, can be positive for innovativeness in the municipal health care sector.Keywords: restorative care, innovativeness, diffusion of innovations, health care service, elderly care

Mogens Groenvold,1,2 Mathilde Adsersen,1 Maiken Bang Hansen1 1The Danish Palliative Care Database (DPD) Secretariat, Research Unit, Department of Palliative Medicine, Bispebjerg Hospital, 2Department of Public Health, University of Copenhagen, Copenhagen, Denmark Aims: The aim of the Danish Palliative Care Database (DPD) is to monitor, evaluate, and improve the clinical quality of specialized palliative care (SPC) (ie, the activity of hospital-based palliative care teams/departments and hospices) in Denmark. Study population: The study population is all patients in Denmark referred to and/or in contact with SPC after January 1, 2010. Main variables: The main variables in DPD are data about referral for patients admitted and not admitted to SPC, type of the first SPC contact, clinical and sociodemographic factors, multidisciplinary conference, and the patient-reported European Organisation for Research and Treatment of Cancer Quality of Life Questionaire-Core-15-Palliative Care questionnaire, assessing health-related quality of life. The data support the estimation of currently five quality of care indicators, ie, the proportions of 1) referred and eligible patients who were actually admitted to SPC, 2) patients who waited

Cutaneous T-cell lymphoma is characterized by malignant T cells proliferating in a unique tumor microenvironment dominated by keratinocytes (KCs). Skin colonization and infection by Staphylococcus aureus are a common cause of morbidity and are suspected of fueling disease activity. In this study, we show that expression of HLA-DRs, high-affinity receptors for staphylococcal enterotoxins (SEs), by KCs correlates with IFN-γ expression in the tumor microenvironment. Importantly, IFN-γ induces HLA-DR, SE binding, and SE presentation by KCs to malignant T cells from patients with Sézary syndrome and malignant and nonmalignant T-cell lines derived from patients with Sézary syndrome and mycosis fungoides. Likewise, preincubation of KCs with supernatant from patient-derived SE-producing S aureus triggers proliferation in malignant T cells and cytokine release (including IL-2), when cultured with nonmalignant T cells. This is inhibited by pretreatment with engineered bacteriophage S aureus-specific endolysins. Furthermore, alteration in the HLA-DR-binding sites of SE type A and small interfering RNA-mediated knockdown of Jak3 and IL-2Rγ block induction of malignant T-cell proliferation. In conclusion, we show that upon exposure to patient-derived S aureus and SE, KCs stimulate IL-2Rγ/Jak3-dependent proliferation of malignant and nonmalignant T cells in an environment with nonmalignant T cells. These findings suggest that KCs in the tumor microenvironment play a key role in S aureus-mediated disease activity in cutaneous T-cell lymphoma., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Autoantibodies against cytokines (c-aAb) have been implicated in the pathophysiology of autoimmune diseases, and a variety of infections. In addition, several independent studies have detected elevated titers of c-aAb in the circulation of healthy individuals. To further understand their impact on immune responses, we measured c-aAb against IFN-α, IFN-γ, CSF2, IL-1α, IL-6, and IL-10 in the plasma of 1000 healthy individuals of the Milieu Intérieur (MI) cohort. Focusing on donors above a defined positive cut-off we observed significant age effects for c-aAb against IL-1α, but no major environmental or lifestyle associated factors were identified. Using TruCulture stimulation data from the MI cohort, we observed a strong association between induced IL-1α and c-aAb levels after LPS stimulation. For several other stimuli, c-aAb against IL-1α and IL-10 were associated with decreased or increased proinflammatory gene expression, respectively. Finally, TruCulture assays supplemented with plasma containing high-titer c-aAb showed a strong influence of anti-IFN-α and anti-IL-6 c-aAb on both baseline and induced gene expression. In summary, this study shows a widespread prevalence of anti-cytokine autoantibodies in healthy donors with impacts on diverse immune responses, suggesting a significant contribution of c-aAb to interindividual immune heterogeneity., (© 2024 The Author(s). European Journal of Immunology published by Wiley‐VCH GmbH.)

During the last three decades, an increased amount of research on errors in health care has been conducted. Studies show that physicians find it challenging to handle errors because of the blame and guilt that errors cause. Communicating with colleagues has been identified as vital for coping with errors and for creating a just culture; however, many physicians do not usually discuss their errors. Knowledge about how junior doctors experience errors is vital to ensure that they both receive emotional support and learn from errors. To capture junior doctors' perceptions and experiences, we used a qualitative, exploratory design based on virtual focus groups. We conducted seven virtual focus groups with 22 junior doctors from 11 specialties. We defined three main themes: (1) how the junior doctors conceptualized medical errors, (2) how they experienced talk about errors among colleagues, and (3) the context in which this talk took place. The participants experienced errors as challenging elements in their working life; however, they struggled to define it. They described inconsistencies regarding the reasons for discussing errors within the learning environment, with some being experienced as constructive (providing education and support) and some as destructive (involving blame and shame). There was a discrepancy between the wish to normalize error and the lack of sharing between colleagues. Our study shows that error in health care is a complex phenomenon that challenges junior doctors' navigation in clinical practice. Despite efforts to implement an open and just culture, this has not yet been achieved., Competing Interests: Declaration of Conflicting InterestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Cytokine autoantibodies (c-aAb) have been associated with pulmonary diseases, including severe novel coronavirus disease 2019 (COVID-19) and pulmonary alveolar proteinosis. This study aimed to determine c-aAb association with community-acquired pneumonia (CAP) etiology (SARS-CoV-2, influenza, or bacteria) and c-aAb associations with CAP-related clinical outcomes and pulmonary comorbidities., Methods: In a cohort of 665 patients hospitalized with CAP, c-aAb targeting interferon α (IFNα), IFNβ, IFNγ, interleukin-1α (IL-1α), IL-6, IL-10, and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured in plasma samples. Associations between c-aAb and baseline characteristics, pulmonary comorbidities, pathogen, intensive care unit (ICU) transferal, time to clinical stability, and mortality were estimated, with results stratified by sex., Results: More men infected with SARS-CoV-2 were had high-titer type 1 IFN c-aAb compared to other pathogens. Among patients with CAP, asthma and bronchiectasis comorbidities were associated with high-titer GM-CSF c-aAb in men, and men with high-titer IFNβ c-aAb had increased odds for ICU transferal. High-titer IL-10 c-aAb were associated with faster clinical stability in women., Conclusion: In men with CAP, various c-aAb-including type 1 IFN and GM-CSF c-aAb-were associated with adverse clinical events and comorbidities, whereas c-aAb targeting an autoinflammatory cytokine were associated with a positive outcome in women. This suggests that the potentially immunomodulatory effects of c-aAb depend on pathogen, autoantibody specificity, comorbidity, and sex., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Von Stemann, Dungu, Laguarda, Ryrsø, Hegelund, Faurholt-Jepsen, Krogh-Madsen, Hansen, Lindegaard and Ostrowski.)

Background: The primary cause of antimicrobial resistance is excessive and non-indicated antibiotic use., Aim: To evaluate the impact of a multifaceted intervention aimed at various healthcare professionals (HCPs) on antibiotic prescribing and dispensing for common infections., Design and Setting: Before-and-after study set in general practice, out-of-hours services, nursing homes, and community pharmacies in France, Greece, Lithuania, Poland, and Spain., Methods: Following the Audit Project Odense method, HCPs from these four settings self-registered encounters with patients related to antibiotic prescribing and dispensing before and after an intervention (February-April 2022 and February-April 2023). Prior to the second registration, the HCPs undertook a multifaceted intervention, which included reviewing and discussing feedback on the first registration's results, enhancing communication skills, and providing communication tools. Indicators to identify potentially unnecessary prescriptions and non-first-line antibiotic choices were developed, and the results of the two registrations were compared., Results: A total of 345 HCPs registered 10 744 infections in the first registration period and 10 207 infections in the second period. In general practice, participants showed a significant 9.8% reduction in unnecessary antibiotic prescriptions in the second period, whereas limited or no effect was observed in out-of-hours services and nursing homes (0.8% reduction and 4.5% increase, respectively). Pharmacies demonstrated an 18% increase in safety checks, and correct advice in pharmacies rose by 17%., Conclusion: External factors like COVID-19, antibiotic shortages, and a streptococcal epidemic impacted the intervention's benefits. Despite this, the intervention successfully improved antibiotic use in both settings., (© The Author(s) 2024. Published by Oxford University Press.)

Introduction: Opioids used to manage severe pain in acute pancreatitis (AP) might exacerbate the disease through effects on gastrointestinal and immune functions. Methylnaltrexone, a peripherally acting µ-opioid receptor antagonist, may counteract these effects without changing analgesia., Methods: This double-blind, randomized, placebo-controlled trial included adult patients with AP and systemic inflammatory response syndrome at 4 Danish centers. Patients were randomized to receive 5 days of continuous intravenous methylnaltrexone (0.15 mg/kg/d) or placebo added to the standard of care. The primary end point was the Pancreatitis Activity Scoring System score after 48 hours of treatment. Main secondary outcomes included pain scores, opioid use, disease severity, and mortality., Results: In total, 105 patients (54% men) were randomized to methylnaltrexone (n = 51) or placebo (n = 54). After 48 hours, the Pancreatitis Activity Scoring System score was 134.3 points in the methylnaltrexone group and 130.5 points in the placebo group (difference 3.8, 95% confidence interval [CI] -40.1 to 47.6; P = 0.87). At 48 hours, we found no differences between the groups in pain severity (0.0, 95% CI -0.8 to 0.9; P = 0.94), pain interference (-0.3, 95% CI -1.4 to 0.8; P = 0.55), and morphine equivalent doses (6.5 mg, 95% CI -2.1 to 15.2; P = 0.14). Methylnaltrexone also did not affect the risk of severe disease (8%, 95% CI -11 to 28; P = 0.38) and mortality (6%, 95% CI -1 to 12; P = 0.11). The medication was well tolerated., Discussion: Methylnaltrexone treatment did not achieve superiority over placebo for reducing the severity of AP., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of The American College of Gastroenterology.)

Background: People with type 2 diabetes (T2D) and chronic kidney disease (CKD) are at high risk for heart failure (HF) and premature death from cardiovascular (CV) causes. The FLOW (Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease), which enrolled participants with T2D and CKD, demonstrated that semaglutide, a glucagon-like peptide-1 receptor agonist, reduced the incidence of the primary composite outcome (persistent ≥50% decline in estimated glomerular filtration rate, persistent estimated glomerular filtration rate <15 mL/min/1.73 m 2 , kidney replacement therapy, and kidney or CV death) by 24%., Objectives: This prespecified analysis examined the effects of semaglutide on HF outcomes in this high-risk population., Methods: Participants were randomized (1:1) to once-weekly subcutaneous semaglutide 1 mg or placebo. The prespecified main outcome was a composite of HF events (new onset or worsening of HF leading to an unscheduled hospital admission or an urgent visit, with initiation of or intensified diuretic/vasoactive therapy) or CV death. HF data were collected by the investigator. CV death was adjudicated by an independent committee., Results: A total of 3,533 randomized participants were followed for a median of 3.4 years. HF was present at baseline in 342 participants (19.4%) in the semaglutide group and 336 (19.0%) in the placebo group. In the overall trial population, semaglutide increased time to first HF events or CV death (HR: 0.73; 95% CI: 0.62-0.87; P = 0.0005), HF events alone (HR: 0.73; 95% CI: 0.58-0.92; P = 0.0068), and CV death alone (HR: 0.71; 95% CI: 0.56-0.89; P = 0.0036). The risk reduction for the composite HF outcome was similar in those with (HR: 0.73; 95% CI: 0.54-0.98; P = 0.0338) and without (HR: 0.72; 95% CI: 0.58-0.89; P = 0.0028) HF at baseline. The risk of HF outcomes (HF events or CV death) was generally higher in participants categorized as NYHA functional class III and those with the HF reduced ejection fraction subtype, regardless of treatment., Conclusions: Semaglutide substantially reduced the risk of time to first composite outcome of HF events or CV death, as well as HF events and CV death alone, in a high-risk population with T2D and CKD. These effects were consistent regardless of history of HF. (A Research Study To See How Semaglutide Works Compared to Placebo in People With Type 2 Diabetes and Chronic Kidney Disease [FLOW]; NCT03819153)., Competing Interests: Funding Support and Author Disclosures The FLOW trial was funded by Novo Nordisk A/S. Dr Pratley has received speaker fees paid to his employer, AdventHealth (through December 31, 2023) from Eli Lilly, Lilly USA LLC, and Novo Nordisk; has received consulting fees directed to his institution from AbbVie, AstraZeneca, Bayer AG, Bayer HealthCare Pharmaceuticals, Corcept Therapeutics, Dexcom, Endogenex, Gasherbrum Bio, Genprex, Getz Pharma, Hanmi Pharmaceutical, Hengrui (USA) Ltd, Intas Pharmaceuticals, Eli Lilly, Lilly USA LLC, Merck, Novo Nordisk, Pfizer, Rivus Pharmaceuticals, Scholar Rock, and Sun Pharmaceutical Industries; has received grants directed to his institution from Biomea Fusion, Carmot Therapeutics, Dompe, Endogenex, Fractyl, Eli Lilly, Novo Nordisk, and Sanofi; and has received personal fees (from January 1, 2024) from AdventHealth, a nonprofit entity. Dr Tuttle has received support from National Institutes of Health research grants R01MD014712, U2CDK114886, UL1TR002319, U54DK083912, U01DK100846, OT2HL161847, UM1AI109568, and OT2OD032581, and from Centers for Disease Control and Prevention project numbers 75D301-21-P-12254 and 75D301-23-C-18264; has received investigator-initiated grant support from Travere, Bayer, and the Doris Duke Foundation outside of the submitted work; has received consulting fees from Boehringer Ingelheim, Eli Lilly, and Novo Nordisk; and has received speaker fees from Novo Nordisk. Dr Rossing has received grants from Bayer, AstraZeneca, and Novo Nordisk; has received honoraria paid to the Steno Diabetes Centre Copenhagen from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer; and has received consulting fees from AstraZeneca, Astellas, Boehringer Ingelheim, Gilead, Novo Nordisk, Merck, Mundipharma, Sanofi, and Bayer. Dr Perkovic has received honoraria for steering committee, data monitoring committee, or advisory board roles or for scientific presentations from AstraZeneca, Bayer, Boehringer Ingelheim, Chinook, GSK, Janssen, Novo Nordisk, Novartis, Otsuka, Travere, Tricida, and UptoDate; and is Board Director for George Clinical, St Vincent’s Health Australia and several independent medical research institutes. Dr Mann has received grants from Novo Nordisk, the European Union, and McMaster University, Hamilton, Canada; has received consulting fees from Novo Nordisk, AstraZeneca, Bayer, and Boehringer Ingelheim; has received honoraria from Novo Nordisk, AstraZeneca, Bayer, and Novartis; and has participated on a data safety monitoring board or advisory board for AstraZeneca, Bayer, Sanofi, and Boehringer Ingelheim, as well as a leadership role in the Kidney Disease: Improving Global Outcomes group. Dr MacIsaac was a FLOW trial investigator and member of the FLOW global expert panel; has received research grants from Novo Nordisk, Servier, Medtronic, The Rebecca Cooper Medical Research Foundation, St Vincent’s Research Foundation, The Juvenile Diabetes Research Foundation, Grey Innovations, The Diabetes Australia Research Trust/Program, and The National Health and Medical Research Council of Australia; has received honoraria for lectures from Eli Lilly, Novo Nordisk, Sanofi, AstraZeneca, MSD, Novartis, and Boehringer Ingelheim; has been on the advisory boards for Novo Nordisk, Boehringer Ingelheim-Eli Lilly Diabetes Alliance, AstraZeneca, and MSD; has received travel support from Novo Nordisk, Sanofi, Boehringer Ingelheim, and AstraZeneca; and has been a principal investigator for industry-sponsored clinical trials run by Novo Nordisk, Sanofi, Bayer, Johnson-Cilag, and AbbVie. Dr Kosiborod has received research grant support from AstraZeneca and Boehringer Ingelheim; has served as a consultant or on an advisory board for Amgen, Applied Therapeutics, AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Esperion Therapeutics, Janssen, Merck (Diabetes and Cardiovascular), Novo Nordisk, Sanofi, and Vifor Pharma; has received other research support from AstraZeneca; and has received honoraria from AstraZeneca, Boehringer Ingelheim, and Novo Nordisk. Dr Kamenov has received speaker fees from Actavis, AstraZeneca, Bayer-Schering, Berlin Chemie, Boehringer Ingelheim, Eli Lilly, KRKA, Merck, MLD, MSD (Merck), Mundipharma, Mylan, Novartis, Novo Nordisk, Pfizer, Sandoz, Sanofi, Servier, TEVA Pharmaceuticals, Valentis, Vedra, and Viatris. Dr Hadjadj has received grants from Asdia, Asten, AstraZeneca, Homeperf, LVL, Nestle Home Care, Pierre Fabre, and VitalAire; has received consulting fees from AstraZeneca, Bayer, Boehringer Ingelheim, Eli Lilly, Novo Nordisk, Sanofi, Servier, and Valbiotis; has received speaker fees from Abbott, AstraZeneca, Boehringer Ingelheim, Bayer, Dino Santé, Eli Lilly, Novartis, Novo Nordisk, Pierre Fabre, Sanofi, Servier, and Valbiotis; and has received meeting invitations from AstraZeneca, Abbott, Dino Santé, Eli Lilly, and Novo Nordisk. Dr Bakris has received consulting fees from Bayer, KBP Biosciences, Ionis, Alnylam, AstraZeneca, Quantum Genomics, Novo Nordisk, and Dia Medica Therapeutics. Dr Mahaffey has received grants from the American Heart Association, Apple, Bayer, California Institute Regenerative Medicine, CSL Behring, Eidos, Ferring, Gilead, Google (Verify), Idorsia, Johnson and Johnson, Luitpold, Novartis, PAC-12, Precordior, and Sanifit; and has received consulting fees from Applied Therapeutics, Bayer, Bristol Myers Squibb, BridgeBio, CSL Behring, Elsevier, Fosun Pharma, Human, Johnson and Johnson, Moderna, Myokardia, Novartis, Novo Nordisk, Otsuka, PhaseBio, Portola, Quidel, and Theravance; and holds equity in Human, Medeloop, Precordior and Regencor. Drs Rasmussen, Nielsen, Idorn, Hansen, and Baeres are employees of and shareholders in Novo Nordisk., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Patients with non-cancer disease are less likely to receive specialized palliative care than cancer patients. To be able to provide the best specialized palliative care, it is important to understand palliative care needs of non-cancer patients and whether the type and level of needs differ from those of cancer patients. Large studies including both cancer and non-cancer patients, using validated needs-assessment-tools, are needed to understand differences in palliative care needs at admittance to specialized palliative care., Aims: To compare palliative care needs at the start of palliative care for cancer and non-cancer disease., Design: Six-year nationwide register-based study., Setting/participants: This study included patients from all Danish specialized palliative care services (hospice care, hospital-based palliative care, home-based palliative care, or consultation) who completed a need-assessment-questionnaire. Ordinal logistic regression was performed to study the association between diagnosis and needs., Results: Cancer patients had a higher probability of receiving specialized palliative care. Of the 44,315 palliative care admissions included in this study, 93.3% were on cancer patients. Independent of diagnosis patients experienced on average six needs and high levels of fatigue and impaired physical functioning. Non-cancer patients had significantly higher odds of insomnia, fatigue and impaired emotional functioning, physical functioning, and quality of life whereas cancer patients had higher odds of pain (except for patients with neurological disease)., Conclusions: The higher levels of several symptoms/problems among non-cancer patients compared to cancer patients suggests that referral to specialized palliative care should be improved for non-cancer patients perhaps by improving identification of palliative needs., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

A widespread strategy to increase the transport of therapeutic peptides across cellular membranes has been to attach lipid moieties to the peptide backbone (lipidation) to enhance their intrinsic membrane interaction. Efforts in vitro and in vivo investigating the correlation between lipidation characteristics and peptide membrane translocation efficiency have traditionally relied on end-point read-out assays and trial-and-error-based optimization strategies. Consequently, the molecular details of how therapeutic peptide lipidation affects it's membrane permeation and translocation mechanisms remain unresolved. Here we employed salmon calcitonin as a model therapeutic peptide and synthesized nine double lipidated analogs with varying lipid chain lengths. We used single giant unilamellar vesicle (GUV) calcein influx time-lapse fluorescence microscopy to determine how tuning the lipidation length can lead to an All-or-None GUV filling mechanism, indicative of a peptide mediated pore formation. Finally, we used a GUVs-containing-inner-GUVs assay to demonstrate that only peptide analogs capable of inducing pore formation show efficient membrane translocation. Our data provided the first mechanistic details on how therapeutic peptide lipidation affects their membrane perturbation mechanism and demonstrated that fine-tuning lipidation parameters could induce an intrinsic pore-forming capability. These insights and the microscopy based workflow introduced for investigating structure-function relations could be pivotal for optimizing future peptide design strategies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Hand hygiene (HH) among health care workers (HCWs) is crucial in preventing infections in nursing homes. However, HH compliance (HHC) among HCWs remains low. This study aimed to investigate the effect of feedback lights on HCWs' HHC., Methods: A 5-month interventional study was conducted in 3 wards in a nursing home in Denmark. During the intervention period, a green light with a smiley appeared on the alcohol-based hand rub (ABHR) dispensers when HCWs used the ABHR, acknowledging HCWs for using the ABHR. HHC was monitored using an automatic HH monitoring system (AHHMS)., Results: A total of 64 HCWs were enrolled. The AHHMS collected 23,696 HH opportunities in apartments and dirty utility rooms. Overall, HHC in the apartments increased from 50% at baseline (95% CI: 48, 53) to 56% (95% CI: 54, 58) during the intervention. However, the increased HHC level was not sustained during follow-up., Conclusions: The AHHMS enabled the assessment of the intervention. We found a significant effect of light-guided feedback in the apartments. However, the increased HHC was not sustained after the light was switched off., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Follicular helper T (Tfh) cells and their interplay with B cells likely contribute to the pathogenesis of relapsing-remitting multiple sclerosis (RRMS). Tfh cells are enriched in cerebrospinal fluid (CSF) in RRMS, but effects of anti-CD20 therapy are unknown. We investigated Tfh cells in controls, untreated and anti-CD20-treated patients with RRMS using flow cytometry. CSF Tfh cells were increased in untreated patients. Compared to paired blood samples, CD25 - Tfh cells were enriched in CSF in RRMS, but not in controls. Contrast-enhancing brain MRI lesions and IgG index correlated with CSF CD25 - Tfh cell frequency in untreated patients with RRMS. Anti-CD20 therapy reduced the numbers of circulating PD1 + Tfh cells and CD25 - Tfh cells, and the frequency of CSF CD25 - Tfh cells. The study suggests that CD25 - Tfh cells are recruited to the CSF in RRMS, associated with focal inflammation, and are reduced by anti-CD20 therapy., Competing Interests: Declaration of competing interest Outside the submitted work, SEM has received speaker honoraria and non-financial support for conference participation from Merck. MH has received non-financial support for conference participation from Merck and Sanofi. MBH, VHH and HBS report no conflicting interests. MRM has received non-financial support for conference participation from Merck. JRC has received speaker honoraria from Biogen. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Lundbeck, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. MRvE has received speaker honoraria from Merck., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Danish Palliative Care Database comprises five quality indicators: (1) Contact with specialised palliative care (SPC) among referred patients, (2) Waiting time of less than 10 days, (3) Proportion of patients who died from (A) cancer or (B) non-cancer diseases, and had contact with SPC, (4) Proportion of patients completing the patient-reported outcome measure at baseline (EORTC QLQ-C15-PAL), and (5) Proportion of patients discussed at a multidisciplinary conference., Purpose: To investigate changes in the quality indicators from 2010 until 2020 in cancer and non-cancer patients. Patients/material: Patients aged 18+ years who died from 2010 until 2020., Method: Register-based study with the Danish Palliative Care Database as the main data source. Indicator changes were reported as percentage fulfilment., Results: From 2010 until 2020, the proportion of patients with non-cancer diseases in SPC increased slightly (2.5-7.2%). In 2019, fulfilment of the five indicators for cancer and non-cancer were: (1) 81% vs. 73%; (2) 73% vs. 68%; (3A) 50%; (3B) 2%; (4) 73% vs. 66%; (5) 73% vs. 65%. Whereas all other indicators improved, the proportion of patients waiting less than 10 days from referral to contact decreased. Differences between type of unit were found, mainly lower for hospice., Interpretation: Most patients in SPC had cancer. All indicators except waiting time improved during the 10-year period. The establishment of the Danish Palliative Care Database may have contributed to the positive development; however, SPC in Denmark needs to be improved, especially regarding a reduction in waiting time and enhanced contact for non-cancer patients.

Background: Elderly nursing home residents are vulnerable to infection from micro-organisms. Hand hygiene is considered one of the most important measures to prevent transmission., Aim: To determine the effect of increased accessibility to alcohol-based hand rub (ABHR) in nursing home wards by monitoring hand hygiene compliance (HHC) among healthcare workers (HCWs)., Methods: An 11-month intervention study was conducted in a Danish six-ward nursing home. Data were collected using an automatic hand hygiene monitoring system (AHHMS). After a baseline period, one extra ABHR dispenser was placed in each of the 150 apartments. Baseline HHC was compared with the HHC during an immediate intervention period and a long-term intervention period., Findings: A total of 159 HCWs were included. The AHHMS registered 341,078 hand hygiene opportunities. Overall baseline HHC was 31% (95% confidence interval: 30-32). A significant +18% absolute immediate effect (first five months) (95% CI: 17-19; P < 0.0001) and +13 percentage points (95% CI: 11-14; P < 0.0001) long-term effect (another four months) were recorded. HCWs working day shifts and short-term employees had a higher baseline HHC than HCWs working evening/night shifts. However, HCWs working night shifts achieved the greatest long-term effect with a mean +27 percentage point difference (P < 0.0001)., Conclusion: Placing an additional ABHR dispenser strategically within staff workflow significantly increased HHC among HCWs, demonstrating a noteworthy effect. The study is the first to report the effect on nursing home dispenser accessibility as a single intervention and to show a significant unmet potential., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: To evaluate the added value of MR dynamic susceptibility contrast (DSC)-perfusion-weighted imaging (PWI)-derived tumour microvascular and oxygenation information with cerebral blood volume (CBV) to distinguish pseudoprogression from true progression (TP) in post-treatment glioblastoma., Methods: This retrospective single-institution study included patients with isocitrate dehydrogenase (IDH) wild-type glioblastoma and a newly developed or enlarging measurable contrast-enhancing mass within 12 weeks after concurrent chemoradiotherapy. CBV, capillary transit time heterogeneity (CTH), oxygen extraction fraction (OEF), and cerebral metabolic rate of oxygen (CMRO 2 ) were obtained from DSC-PWI. Predictors were selected using univariable logistic regression, and performance was measured with adjusted diagnostic odds with tumour volume and area under the curve (AUC) of receiver operating characteristics analysis., Results: A total of 103 patients were included (mean age, 59.6 years; 59 women), with 67 cases of TP and 36 cases of pseudoprogression. Pseudoprogression exhibited higher CTH (4.0 vs. 3.4, p = .019) and higher OEF (12.7 vs. 10.7, p = .014) than TP, but a similar CBV (1.48 vs. 1.53, p = .13) and CMRO 2 (7.7 vs. 7.3s, p = .598). Independent of tumour volume, both high CTH (adjusted odds ratio [OR] 1.52; 95% confidence interval [CI]: 1.11-2.09, p = .009) and high OEF (adjusted OR 1.17; 95% CI:1.03-1.33, p = .016) were predictors of pseudoprogression. The combination of CTH, OEF, and CBV yielded higher diagnostic performance (AUC 0.71) than CBV alone (AUC 0.65)., Conclusion: High intratumoural capillary transit heterogeneity and high oxygen extraction fraction derived from DSC-PWI have enhanced the diagnostic value of CBV in pseudoprogression of post-treatment IDH-wild type glioblastoma., Clinical Relevance Statement: In the early post-treatment stage of glioblastoma, pseudoprogression exhibited both high oxygen extraction fraction and high capillary transit heterogeneity and these dynamic susceptibility contrast-perfusion weighted imaging derived parameters have added value in cerebral blood volume-based noninvasive differentiation of pseudoprogression from true progression., Key Points: • Capillary transit time heterogeneity and oxygen extraction fraction can be measured noninvasively through processing of dynamic susceptibility contrast imaging. • Pseudoprogression exhibited higher capillary transit time heterogeneity and higher oxygen extraction fraction than true progression. • A combination of cerebral blood volume, capillary transit time heterogeneity, and oxygen extraction fraction yielded the highest diagnostic performance (area under the curve 0.71)., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The oral bioavailability of therapeutic peptides is generally low. To increase peptide transport across the gastrointestinal barrier, permeation enhancers are often used. Despite their widespread use, mechanistic knowledge of permeation enhancers is limited. To address this, we here investigate the interactions of six commonly used permeation enhancers with lipid membranes in simulated intestinal environments. Specifically, we study the interactions of the permeation enhancers sodium caprate, dodecyl maltoside, sodium cholate, sodium dodecyl sulfate, melittin, and penetratin with epithelial cell-like model membranes. To mimic the molecular composition of the real intestinal environment, the experiments are performed with two peptide drugs, salmon calcitonin and desB30 insulin, in fasted-state simulated intestinal fluid. Besides providing a comparison of the membrane interactions of the studied permeation enhancers, our results demonstrate that peptide drugs as well as intestinal-fluid components may substantially change the membrane activity of permeation enhancers. This highlights the importance of testing permeation enhancement in realistic physiological environments and carefully choosing a permeation enhancer for each individual peptide drug., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Author(s). Published by Elsevier B.V. All rights reserved.)

( S )-Atenolol (( S )-2-(4-(2-Hydroxy-3-(isopropylamino)propoxy)phenyl)acetamide) has been synthesized in >99% enantiomeric excess ( ee ) with the use of Candida antarctica lipase B from Syncozymes (Shanghai, China), in a kinetic resolution of the corresponding racemic chlorohydrin. A catalytic amount of base was used in deprotonation of the phenol building block. The enantiopurity of the chlorohydrin building block remained unchanged upon subsequent amination to yield the final drug. All four steps in the synthesis protocol have been optimized compared to previously reported methods, which makes this new protocol more sustainable and in accordance with green chemistry principles. The overall yield of ( S )-atenolol was 9.9%, which will be further optimized.

Objective: To explore the Nordic municipal health and care services' ability to promote principal goals within care for older people during the COVID-19 pandemic., Design and Setting: Two surveys were conducted among managers of municipal health care services for older people in Denmark, Finland, Norway and Sweden; the first around 6 months into the pandemic (survey 1), and the second around 12 months later (survey 2). Data were analysed through descriptive statistics, and multiple regression (OLS)., Subjects: 1470 (survey 1, 2020) and 745 (survey 2, 2021) managers. 32% in home care, 51% in nursing homes, 17% combined., Results: In all countries the pandemic seems to have had more negative impact on eldercare services' ability to promote an active and social life, than on the ability to promote or enhance older people's mental and physical health. The regression analysis indicates that different factors influence the ability to promote these goals. Managers within nursing homes reported reduced ability to promote mental and physical health and an active social life to a significantly lower degree than managers of home care. The effect of three prevention strategies (lock down, testing, and/or organisational change), were explored. Organisational change (reorganize staff and practice, restrict use of substitutes) tended to impact the units' ability to promote a social life in a positive direction, while lock down (areas, buffets etc) tended to impact both the ability to promote mental/physical health and a social life in a negative direction., Conclusion: Measures that can improve opportunities for an active and social life during a pandemic should have high priority, particularily within home care.

Purpose: Since 2010, a comprehensive symptom/problem (S/P) assessment has been carried out in Danish specialist palliative care using the EORTC QLQ-C15-PAL questionnaire and the open-ended "Write In three Symptoms/Problems" (WISP) instrument. On WISP patients can report up to three S/Ps not included in the EORTC QLQ-C15-PAL. However, little is known about which S/Ps patients with non-cancer diseases report using WISP. Therefore, we investigated the prevalence and severity of S/Ps reported on WISP by non-cancer patients in specialist palliative care and compared these S/Ps with those previously reported by cancer patients., Methods: This register-based study collected data from the Danish Palliative Care Database. We included adult patients with non-cancer diseases answering the EORTC QLQ-C15-PAL at admittance to specialist palliative care between 2016 and 2021. WISP responses were qualitatively categorized, and their prevalence and severity calculated., Results: Of the 2323 patients with non-cancer diseases answering the EORTC QLQ-C15-PAL, 812 (34.9%) reported at least one S/P using WISP. A total of 1340 S/Ps were reported on WISP, of which 56.7% were not included in the EORTC QLQ-C15-PAL (i.e., were new). Edema, existential problems, dizziness, cough, and dysphagia were the most prevalent new S/Ps. Overall, 88.7% of the S/Ps were scored as moderate-severe. The prevalence of S/Ps reported on WISP did not significantly differ between cancer and non-cancer patients, except for existential problems, dysphagia, myoclonus, speaking problems, sweats, and vomiting., Conclusion: The similarities and differences in the prevalence of the most common S/Ps reported on WISP confirm that WISP improves symptom assessment regardless of patient diagnosis., (© 2024. The Author(s).)

Background: Achieving high hand hygiene compliance among health care workers is a challenge, requiring effective interventions. This study investigated the impact of individualized feedback on hand hygiene compliance using an electronic monitoring system., Methods: A quasi-experimental intervention design with pretest-post-test was conducted in an orthopedic surgical ward. Participants served as their own controls. A 3-month baseline was followed by a 3-month intervention period. Hand hygiene events were recorded through sensors on dispensers, name tags, and near patient beds. Health care workers received weekly email feedback reports comparing their compliance with colleagues., Results: Nineteen health care workers (17 nurses, 2 doctors) were included. Hand hygiene compliance significantly improved by approximately 15% (P < .0001) across all rooms during the intervention. The most substantial improvement occurred in patient rooms (17%, P < .0001). Compliance in clean and contaminated rooms increased by 10% (P = .0068) and 5% (P = .0232). The average weekly email open rate for feedback reports was 46%., Conclusions: Individualized feedback via email led to significant improvements in hand hygiene compliance among health care workers. The self-directed approach proved effective, and continuous exposure to the intervention showed promising results., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Early and accurate diagnosis of neurocognitive disorders including neurodegenerative dementia remains challenging. This study explores the impact of biological factors on serum neurofilament light chain (NfL) levels and clinical usefulness for the detection of neurocognitive disorders in a mixed memory clinic., Methods: Serum samples and clinical data were obtained from 1188 patients who underwent diagnostic investigations for memory complaints between January 2018 and September 2019. Serum NfL was measured using single molecule array technology., Results: NfL exhibited a moderate association with age, estimated glomerular filtration rate (eGFR), and Fazekas score. NfL was able to differentiate between patients with neurocognitive disorders and those without with a sensitivity and specificity of 80%. NfL could, however, not distinguish between different dementia etiologies., Discussion: Serum NfL could aid early diagnostic triage by identifying patients requiring further diagnostic procedures and therefore aid in a more focused use of health-care resources., Competing Interests: The authors declare that the study was carried out without any commercial or financial affiliations that could potentially be seen as a conflict of interest. AHS, HSG, CSM, SGH, MBH, HBS report no conflicts of interest. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation, or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche, and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche, and Sanofi Genzyme. Author disclosures are available in the supporting information., (© 2023 The Authors. Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Objectives: This study aimed to examine the symptomatology of patients with advanced cancer at admittance to palliative care services and to investigate how the symptomatology changed during the first month, and whether these changes were associated with various patient characteristics., Methods: In a longitudinal study in Chile, outpatients with advanced cancer completed the questionnaires European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 15 Palliative Care and the Hospital Anxiety and Depression Scale. Prevalence and severity of symptoms and problems (S/Ps) at baseline were calculated. Differences in S/P scores from baseline to follow-up were calculated overall and according to patient characteristics. Multiple linear regression was used to study the associations between patient characteristics and changes in S/P scores., Results: At baseline, 201 patients answered the questionnaires and 177 completed the follow-up. Fatigue, pain and sleeping difficulties were the most prevalent S/Ps reported, and also had the highest mean scores at baseline. S/P scores at baseline varied significantly according to sex, age, civil status, residence, children, prior and current antineoplastic treatment. Emotional functioning, pain, sleeping difficulties, constipation and anxiety improved significantly during the first month of palliative care. Residence, cohabitation status, diagnosis and current antineoplastic treatment were associated with changes in S/P scores., Conclusions: Patients reported moderate-to-severe levels of S/Ps at admittance to palliative care. Several S/Ps improved the first month. Certain patient characteristics were associated with changes in S/P scores. This information may guide clinicians to more effective interventions that can improve the quality of life of patients receiving palliative care., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hospital-acquired infections are the most frequent adverse events in health care and can be reduced by improving the hand hygiene compliance (HHC) of health care workers (HCWs). We aimed to investigate the effect of nudging with sensor lights on HCWs' HHC., Methods: An 11-month intervention study was conducted in 2 inpatient departments at a university hospital. An automated monitoring system (Sani Nudge TM ) measured the HHC. Reminder and feedback nudges with lights were displayed on alcohol-based hand rub dispensers. We compared the baseline HHC with HHC during periods of nudging and used the follow-up data to establish if a sustained effect had been achieved., Results: A total of 91 physicians, 135 nurses, and 15 cleaning staff were enrolled in the study. The system registered 274,085 hand hygiene opportunities in patient rooms, staff restrooms, clean rooms, and unclean rooms. Overall, a significant, sustained effect was achieved by nudging with lights in relation to contact with patients and patient-near surroundings for both nurses and physicians. Furthermore, a significant effect was observed on nurses' HHC in restrooms and clean rooms. No significant effect was found for the cleaning staff., Conclusions: Reminder or feedback nudges with light improved and sustained physicians' and nurses' HHC, and constitute a new way of changing HCWs' hand hygiene behavior., (Copyright © 2023 Association for Professionals in Infection Control and Epidemiology, Inc. Published by Elsevier Inc. All rights reserved.)

Background: Hand hygiene (HH) by healthcare workers (HCWs) is one of the most important measures to prevent hospital-acquired infections. However, HCWs struggle to adhere to HH guidelines. We aimed to investigate the effect of a non-resource intensive intervention with group and individual feedback on HCWs HH in a real-life clinical practice during the COVID-19 pandemic., Methods: In 2021, an 11-month prospective, interventional study was conducted in two inpatient departments at a Danish university hospital. An automated hand hygiene monitoring system (Sani Nudge™) was used to collect data. HH opportunities and alcohol-based hand rub events were measured. Data were provided as HH compliance (HHC) rates. We compared HHC across 1) a baseline period, 2) an intervention period with weekly feedback in groups, followed by 3) an intervention period with weekly individual feedback on emails, and 4) a follow-up period., Results: We analyzed data from physicians ( N =65) and nurses ( N =109). In total, 231,022 hygiene opportunities were analyzed. Overall, we observed no significant effect of feedback, regardless of whether it was provided to the group or individuals. We found a trend toward a higher HHC in staff restrooms than in medication rooms and patient rooms. The lowest HHC was found in patient rooms., Conclusions: The automated hand hygiene monitoring system enabled assessment of the interventions. We found no significant effect of group or individual feedback at the two departments. However, other factors may have influenced the results during the pandemic, such as time constraints, workplace culture, and the degree of leadership support., (© 2023 The Authors.)

Objectives: Smerteinfo.dk is a freely accessible Danish website containing research-based, up-to-date knowledge on chronic pain, written in lay language, with a focus on information, guidance and self-management tools, developed in collaboration between health professionals and persons with high-impact chronic pain. This mixed-method study explored experiences, perceived usability, and challenges of Smerteinfo among patients with high-impact chronic pain., Methods: Semi-structured interviews enabling thinking-aloud and participant observation while using Smerteinfo were performed in 11 patients with high-impact chronic pain. Survey data were collected three months after being invited to use Smerteinfo among 200 patients on waiting-list at a Pain Center in Denmark., Results: Three themes captured the depth and variation in patterns of experiences, usability and challenges using Smerteinfo during interviews: 1) Appreciated easy access to new knowledge yet strived for more personalized information, 2) Experienced incentives as well as challenges when navigating the website, and 3) Suggested earlier introduction to the website. Challenges concerned the unknown update frequency of the website, information consisting of mostly text and many links, lack of material to improve self-management and too general information. Survey data revealed that 87 % found the language in the articles easy to understand and 73 % could recognize themselves and their challenges in the articles. A proportion of the respondents reported improved understanding of their pain condition (56 %), improved coping (33 %), and that they had made changes in their everyday life after reading on the website (33 %)., Conclusions: Patients with high-impact chronic pain found Smerteinfo valuable. The results suggest attention towards spreading knowledge of the website to general practitioners, who could introduce the site at an earlier stage of illness. Continuously improving the site and expand the applicable tools based on scientific evidence and in collaboration with end-users are crucial to ensure the usability of the website in the future., (© 2023 the author(s), published by De Gruyter, Berlin/Boston.)

Cerebrospinal fluid (CSF) soluble CD27 (sCD27) is a sensitive biomarker of intrathecal inflammation. Although generally considered a biomarker of T cell activation, CSF sCD27 has been shown to correlate with biomarkers of B cell activity in multiple sclerosis. We analyzed CSF from 40 patients with relapsing-remitting multiple sclerosis (RRMS) and nine symptomatic controls using flow cytometry and multiplex electrochemiluminescence immunoassays. CSF sCD27 levels were increased in RRMS and correlated with IgG index, soluble B cell maturation antigen, cell count, B cell frequency and CD8 + T cell frequency. We provide new data indicating that CSF sCD27 is associated with CD8 + T cells and B cells in RRMS., Competing Interests: Declaration of Competing Interest SEM reports non-financial support from Merck for congress participation. SRH, SB, MRM, MBH and SC have nothing to disclose. MRvE has received speaker honoraria from Merck. FS has served on scientific advisory boards for, served as consultant for, received support for congress participation or received speaker honoraria from Alexion, Biogen, Bristol Myers Squibb, Merck, Novartis, Roche and Sanofi Genzyme. His laboratory has received research support from Biogen, Merck, Novartis, Roche and Sanofi Genzyme. JRC has received speaker honoraria from Biogen., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: The demand for RT-PCR testing has been unprecedented during the SARS-CoV-2 pandemic. Fully automated antigen tests (AAT) are less cumbersome than RT-PCR, but data on performance compared to RT-PCR are scarce., Methods: The study consists of two parts. A retrospective analytical part, comparing the performance of four different AAT on 100 negative and 204 RT-PCR positive deep oropharyngeal samples divided into four groups based on RT-PCR cycle of quantification levels. In the prospective clinical part, 206 individuals positive for and 199 individuals negative for SARS-CoV-2 were sampled from either the anterior nasal cavity (mid-turbinate) or by deep oropharyngeal swabs or both. The performance of AATs was compared to RT-PCR., Results: The overall analytical sensitivity of the AATs differed significantly from 42% (95% CI 35-49) to 60% (95% CI 53-67) with 100% analytical specificity. Clinical sensitivity of the AATs differed significantly from 26% (95% CI 20-32) to 88% (95% CI 84-93) with significant higher sensitivity for mid-turbinate nasal swabs compared to deep oropharyngeal swabs. Clinical specificity varied from 97% to 100%., Conclusion: All AATs were highly specific for detection of SARS-CoV-2. Three of the four AATs were significantly more sensitive than the fourth AAT both in terms of analytical and clinical sensitivity. Anatomical test location significantly influenced the clinical sensitivity of AATs., Competing Interests: Declaration of Competing Interest None of the authors have any personal conflict of interests to report. The project received a participation fee from each of the participating companies to cover the cost of the project., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background and Purpose: The response to cluster headache treatments has a high interindividual variation. To date, treatment response has only been assessed by a candidate gene approach and no investigations into metabolic pathways have been performed. Our aim was to investigate the association between the polygenetic risk of cluster headache and treatment response to first-line cluster headache treatments as well as known functional variants of CYP3A4 and the response to verapamil. Further, it was aimed to replicate previous single nucleotide polymorphisms found to be associated with treatment response in cluster headache and/or migraine., Methods: In, 508 cluster headache patients diagnosed according to the International Classification of Headache Disorders were genotyped and participated in a semi-structured interview to evaluate treatment response. Polygenetic risk scores were calculated by the effect retrieved from a meta-analysis of the latest two genome-wide association studies on cluster headache., Results: Inferior treatment response to oxygen, triptans and verapamil is associated with chronicity of cluster headache were confirmed but no evidence was found that a response could be predicted by a high genetic risk of cluster headache. Likewise, verapamil response was not associated with functional variants of CYP3A4. No support of the genetic variants previously reported to be associated with treatment response to triptans or verapamil was found., Conclusion: The clinically relevant variation in treatment response for cluster headache was not influenced by genetic factors in the present study., (© 2023 The Authors. European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)