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To investigate the incidence and prevalence of rheumatoid arthritis (RA) in the adult Danish population. In this nationwide register-based cohort study, patients with incident RA between 1998 and the end of 2018 were identified using Danish administrative registries. The age- and sex-standardized incidence rate (IR), incidence proportion (IP), lifetime risk (LR), and point prevalence (PP) of RA were calculated. RA was defined as a first-time RA diagnosis registered in the Danish National Patient Registry combined with a redeemed prescription of a conventional synthetic disease-modifying anti-rheumatic drug in the following year. In addition, three different case definitions of RA were explored. The overall age- and sex-standardized IR of RA from 1998 to 2018 was 35.5 [95% confidence interval (CI) 35.1–35.9] per 100 000 person-years while the IP was 35.2 (95% CI 34.8–35.5) per 100 000 individuals. The IR was two-fold higher for women than for men. The LR of RA ranged from 2.3% to 3.4% for women and from 1.1% to 1.5% for men, depending on the RA case definition used. The overall PP of RA was 0.6% (95% CI 0.5–0.6%) in 2018: 0.8% (95% CI 0.7–0.8%) for women and 0.3% (95% CI 0.3–0.4%) for men. The prevalence increased about 1.5-fold from 2000 to 2018. The IR and PP were approximately two-fold higher for women than for men. The prevalence of RA in Denmark increased significantly from 2000 to 2018. The RA case definition had more impact on the results than the choice of denominator. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to investigate the effects of marine n-3 polyunsaturated fatty acids (PUFAs) on disease activity, use of analgesics, and inflammatory biomarkers in patients with psoriatic arthritis (PsA).Method: Patients with established PsA (n = 145) were investigated in a randomized, double-blind, placebo-controlled study. The participants received a supplement of 3 g n-3 PUFA/day or 3 g olive oil/day (control) for 24 weeks. Outcome measures for disease activity, use of analgesics, and leukotriene formation from activated granulocytes were assessed at baseline and at study end.Results: In total, 145 patients were included and 133 completed the study. After 24 weeks, the n-3 PUFA group showed a decrease in Disease Activity Score (DAS28-CRP), 68 tender joint count, enthesitis score, and psoriasis area and severity index, although not significantly different from the controls. There was a significant reduction in non-steroidal anti-inflammatory drug (NSAID) and paracetamol use compared with controls (p = 0.04). In addition, the participants in the n-3 PUFA group had significantly lower formation of leukotriene B4 (p = 0.004) from stimulated granulocytes and significantly higher formation of leukotriene B5 (p < 0.001) compared with controls.Conclusion: The n-3 PUFA-supplemented group showed improvement in outcome measures for disease activity, although the difference between the groups was not statistically significant. However, use of NSAIDs and paracetamol was significantly reduced in the n-3 PUFA group compared to the control group. Finally, there was a significant decrease in leukotriene B4 formation in the n-3 PUFA group compared with controls. [ABSTRACT FROM AUTHOR]

BACKGROUND: Lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) is an emerging independent risk factor for cardiovascular disease (CVD). Lp-PLA(2) can be modified by lipid lowering drugs, but it is unknown whether diet can reduce plasma levels of Lp-PLA(2). AIM OF THE STUDY: The aim of the trial was to study the effect of marine n-3 polyunsaturated fatty acids (PUFA) on plasma Lp-PLA(2) levels in healthy subjects. METHODS: Sixty healthy subjects were randomized to a moderate dose (2 g) of n-3 PUFA, a high dose (6.6 g) of n-3 PUFA or olive oil (control) daily for 12 weeks. Plasma Lp-PLA(2) was measured at baseline and after the interventions. RESULTS: Plasma Lp-PLA(2) levels were unchanged in all three groups before and after the supplements. Neither did the results differ between groups. There was no correlation between the content of n-3 PUFA in platelets or granulocytes or plasma Lp-PLA(2). CONCLUSION: Marine n-3 PUFA had no effect on plasma levels of Lp-PLA(2) in healthy adults and relatively young people. [ABSTRACT FROM AUTHOR]

Background: The aim of this study was to investigate the relation between low-grade inflammation and autonomic dysfunction, both of which may be risk markers for sudden cardiac death.Methods: A total of 269 subjects referred for elective coronary angiography because of clinically suspected coronary heart disease were included in the study. Of these 27% had a previous myocardial infarction and 70% had significant coronary stenoses. A 24-hour Holter-recording was obtained from all subjects, and time-domain heart rate variability indices were analyzed. C-reactive protein was measured using a high-sensitivity assay.Results: Mean SDNN was significantly higher in the lower compared to the upper hs-CRP quartile (140 +/- 34 ms vs 113 +/- 29 ms; P < 0.001). Similar results were found for SDNNindex (54 +/- 16 ms vs 46 +/- 12 ms; P = 0.002) and SDANN (125 +/- 33 ms vs 101 +/- 31 ms; P < 0.001). The association was strongest for subjects with a previous myocardial infarction, subjects with significant coronary stenoses, and males. In a linear regression analysis, hs-CRP remained an independent determinant of each of these three heart rate variability indices (all P < 0.001).Conclusion: C-reactive protein and heart rate variability are independently associated. This may support a link between low-grade inflammation and autonomic dysfunction. [ABSTRACT FROM AUTHOR]

BACKGROUND: Dietary intake of long-chain n-3 polyunsaturated fatty acids (PUFA) may protect against sudden cardiac death, an event that may be predicted by measurement of heart rate variability (HRV). OBJECTIVE: The objectives of this study were to 1) examine the correlations between the content of fatty acids in blood cell membranes (platelets and granulocytes) and HRV in healthy subjects, and 2) assess the effect on HRV of dietary intervention with n-3 PUFA in different doses. DESIGN: Sixty healthy volunteers (25 women and 35 men) were randomly assigned to 3 treatment groups in a double-blind design. Subjects received a daily supplement of either 6.6 g n-3 PUFA, 2.0 g n-3 PUFA, or placebo (olive oil). A 24-h Holter recording was obtained for each subject before supplementation and after 12 wk of supplementation; the 24-h HRV was then related to the content of fatty acids in granulocytes and platelets. RESULTS: Before supplementation, positive correlations were observed in men between the content of docosahexaenoic acid in cell membranes and HRV indexes (r = 0.50, P < 0.01), whereas such correlations were not found in women. Dietary intervention revealed a dose-dependent effect of n-3 PUFA on HRV in men, whereas no effect was found in women. CONCLUSION: The study showed a beneficial effect of n-3 PUFA on HRV in healthy men, suggesting an antiarrhythmic effect of n-3 PUFA. No such effect was observed in healthy women. [ABSTRACT FROM AUTHOR]

Background: Uraemia and chronical haemodialysis are associated with an abnormal growth hormone (GH)-insulin-like growth factor (IGF) axis which may contribute to malnutrition and renal bone disease. Short-term studies have shown a beneficial effect of treatment with recombinant human growth hormone (rhGH) on nutritional status in patients on haemodialysis. In the present study, we evaluated the effect of rhGH on bone and mineral metabolism. [ABSTRACT FROM PUBLISHER]

BACKGROUND: Dietary intake of the marine long-chain n-3 polyunsaturated fatty acids (PUFA) may reduce mortality after a myocardial infarction (MI). This may partly be attributed to their anti-inflammatory properties. AIM OF THE STUDY: To investigate the effect of n-3 PUFA on C-reactive protein (CRP) in patients with a previous MI. METHODS: In a double-blind design, forty-one patients (mean age 63 +/- 7 years) were randomized to receive daily supplements with 5.2 g of n-3 PUFA or olive oil (control). Serum CRP was measured with a highly sensitive assay (hs-CRP) before and after 12 weeks supplements. Compliance was monitored by measuring the incorporation of n-3 PUFA into platelets. RESULTS: The content of n-3 PUFA in platelets increased significantly in the n-3 PUFA supplemented group, whereas no changes were seen in controls. There was a minor increase in hs-CRP in the n-3 PUFA group (2.46 vs. 2.70 mg/l) and a small decrease in hs-CRP in the control group (2.52 vs. 1.67 mg/l). The changes, however, were not statistically significant (P = 0.30 and 0.43, respectively). CONCLUSION: Supplementation with 5.2 g of n-3 PUFA for 12 weeks had no hs-CRP lowering effect in patients with a previous MI. [ABSTRACT FROM AUTHOR]

Risk of cardiovascular disease (CVD) in patients with classical Hodgkin lymphoma (cHL) undergoing contemporary treatment is unclear. cHL patients ≥ 18 years at diagnosis treated with doxorubicin-containing chemotherapy between 2000 and 2022 were matched 1:5 with comparators on birth year, sex, and Charlson Comorbidity Index at time of matching (score of 0 or ≥ 1). Cause-specific cumulative incidence of a composite of CVDs with corresponding 95% confidence intervals (CIs) were computed with death and lymphoma relapse as competing events (i.e., by censoring individuals at such occurrences) using the Aalen-Johansen estimator. A total of 1905 patients and 9525 comparators with a median follow-up of 10 years (interquartile range, [IQR]: 5.9-17.4). Median age was 39 years (IQR: 27-56), median cumulative doxorubicin dose was 250 mg/m 2 (IQR: 200-300). The CVD cumulative incidences were 4.7% (95% CI: 3.6-5.7) for patients versus 2.6% (95% CI: 2.3-2.9) for comparators at 5 years, 8.9% (95% CI: 7.2-10.5) versus 5.5% (95% CI: 4.9-6.0) at 10 years, and 17.0% (95% CI: 14.1-19.9) versus 8.2% (95% CI: 7.4-9.0) at 15 years. CVD remains a substantial effect after contemporary treatment for cHL, suggesting that awareness of symptoms and a low threshold for referral to diagnostic examination are still important measures during survivorship., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Wastewater treatment plants (WWTPs) often fail to fully remove organic micro-pollutants (OMPs), necessitating advanced treatment methods. This study examines the potential of an agricultural waste-derived adsorbent, rice husk (RH) - silica, for removing a complex mixture of 20 OMPs in MilliQ water and wastewater effluent. While RH-silica shows potential for OMP removal, its performance with multicomponent mixtures in real wastewater has yet to be investigated. Batch experiments demonstrated the efficacy of RH-silica in removing cationic, neutral, polar, and non-polar OMPs across various pH levels, with no adsorption of anionic OMPs. Column elution studies revealed that only positively charged compounds did not reach a breakthrough after 300 specific bed volumes (BVs), even when the filtration velocity was increased fivefold (3.8 m/h) and lower adsorbent-to-volume ratios (0.5 g/L) were employed. This indicates that electrostatic interactions via deprotonated silanol groups are the primary adsorption mechanism. RH-silica's ability to retain cationic pollutants regardless of their hydrophilicity degree highlights its potential as a novel adsorbent targeting positively charged persistent and mobile organic compounds (PMOCs). Moreover, the adsorption efficiency remained high in experiments with real wastewater effluent. Considering practical applications, a RH-silica column could be used to enhance removal of cationic polar compounds. This approach not only improves pollutant removal efficiency but also contributes to sustainability in WWTPs by using agricultural waste resources. Despite significant operational and end-of-life challenges for large-scale implementation, this study represents a crucial advancement in the investigation of RH-silica as an adsorbent., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Alba Rodriguez-Otero reports financial support was provided by European Union. If there are other authors, they 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. Published by Elsevier Ltd.)

Contaminants of emerging concern receive increasing attention in the Arctic environment. The aim of this study was to screen for chemicals of emerging Arctic concern (CEACs) in different types of Arctic samples including biota, air and human serum. We used a combination of gas chromatography (GC) and liquid chromatography (LC) with high resolution mass spectrometry (HRMS) for suspect and non-target screening (NTS). Suspect screening of 25 CEACs was based on published in-silico approaches for the identification of CEACs and revealed tetrabromophthalic anhydride (TBPA) in pilot whale and air, albeit with low detection frequencies (17 and 33%, respectively). An NTS workflow detected 49, 42, 31 and 30 compounds in pilot whale, ringed seal, air, and human serum, respectively, at confidence level 2 and 3. Although legacy POPs still dominated the samples, 64 CEACs were tentatively identified and further assessed for persistence (P), bioaccumulation (B), mobility (M), toxicity (T), and long-range transport potential (LRTP). While four PBT compounds were identified, 37 PMT substances dominated among these 64 compounds. Our study indicated that many chemicals of potential risk might be present in Arctic samples and would benefit from confirmation and further studies of their transport to and accumulation in the Arctic environment., 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 Authors. Published by Elsevier Ltd.. All rights reserved.)

Nontargeted screening (NTS) utilizing liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI/HRMS) is increasingly used to identify environmental contaminants. Major differences in the ionization efficiency of compounds in ESI/HRMS result in widely varying responses and complicate quantitative analysis. Despite an increasing number of methods for quantification without authentic standards in NTS, the approaches are evaluated on limited and diverse data sets with varying chemical coverage collected on different instruments, complicating an unbiased comparison. In this interlaboratory comparison, organized by the NORMAN Network, we evaluated the accuracy and performance variability of five quantification approaches across 41 NTS methods from 37 laboratories. Three approaches are based on surrogate standard quantification (parent-transformation product, structurally similar or close eluting) and two on predicted ionization efficiencies (RandFor- IE and MLR- IE ). Shortly, HPLC grade water, tap water, and surface water spiked with 45 compounds at 2 concentration levels were analyzed together with 41 calibrants at 6 known concentrations by the laboratories using in-house NTS workflows. The accuracy of the approaches was evaluated by comparing the estimated and spiked concentrations across quantification approaches, instrumentation, and laboratories. The RandFor- IE approach performed best with a reported mean prediction error of 15× and over 83% of compounds quantified within 10× error. Despite different instrumentation and workflows, the performance was stable across laboratories and did not depend on the complexity of water matrices.

Wastewater is a major reservoir for chemical contaminants, both anthropogenic and biogenic. Recent chemical and toxicological analysis reveals the abundance and impact of these compounds, often termed contaminants of emerging concern (CECs). Concurrently, incomplete removal of these compounds in wastewater treatment plants sets a precedent for detailed characterisation and monitoring of such substances. Although liquid chromatography (LC) is frequently used for analysis of CECs in wastewater, gas chromatography (GC) maintains its significance for non-polar to mid-polar analytes. GC offers advantages such as increased separation efficiency, fewer matrix effects, and greater availability and reliability of reference mass spectra compared to LC. Comprehensive two-dimensional gas chromatography (GC × GC) delivers unmatched peak capacity and separational capabilities, critical in the resolution of diverse compound groups present within wastewater. When coupled with high resolution mass spectrometry, it provides a powerful identification tool with spectral databases and both 1st and 2nd dimensional retention indices, and has allowed for the separation, reliable annotation and characterisation of diverse CECs within wastewater in recent years. Herein, on the basis of recent studies from the last fifteen years, we outline cutting-edge methodologies and strategies for wastewater analysis using GC × GC. This includes sample preparation, derivatization of polar analytes, instrumental setup, and data analysis, ultimately providing the reader a framework for future non-targeted analysis of wastewater and other complex environmental matrices., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Jason Devers reports financial support was provided by Innovation Fund Denmark. Jason Devers reports financial support was provided by Horizon Europe. Jan H Christensen reports financial support was provided by Innovation Fund Denmark. Jan H Christensen reports financial support was provided by Horizon Europe. If there are other authors, they 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 Authors. Published by Elsevier B.V. All rights reserved.)

Background: Transportation noise has been linked with cardiometabolic outcomes, yet whether it is a risk factor for atrial fibrillation (AF) remains inconclusive. We aimed to assess whether transportation noise was associated with AF in a large, pooled Nordic cohort., Methods: We pooled data from 11 Nordic cohorts, totaling 161,115 participants. Based on address history from five years before baseline until end of follow-up, road, railway, and aircraft noise was estimated at a residential level. Incident AF was ascertained via linkage to nationwide patient registries. Cox proportional hazards models were utilized to estimate associations between running 5-year time-weighted mean transportation noise (L den ) and AF after adjusting for sociodemographics, lifestyle, and air pollution., Findings: We identified 18,939 incident AF cases over a median follow-up of 19.6 years. Road traffic noise was associated with AF, with a hazard ratio (HR) and 95% confidence interval (CI) of 1.02 (1.00-1.04) per 10-dB of 5-year mean time-weighted exposure, which changed to 1.03 (1.01-1.06) when implementing a 53-dB cut-off. In effect modification analyses, the association for road traffic noise and AF appeared strongest in women and overweight and obese participants. Compared to exposures ≤40 dB, aircraft noise of 40.1-50 and > 50 dB were associated with HRs of 1.04 (0.93-1.16) and 1.12 (0.98-1.27), respectively. Railway noise was not associated with AF. We found a HR of 1.19 (1.02-1.40) among people exposed to noise from road (≥45 dB), railway (>40 dB), and aircraft (>40 dB) combined., Interpretation: Road traffic noise, and possibly aircraft noise, may be associated with elevated risk of AF., Funding: NordForsk., Competing Interests: All other authors declare no competing interests., (© 2024 The Author(s).)

Objectives: The study compared the utility of two approaches for collecting real-world listening experiences to predict hearing-aid preference: a retrospective questionnaire (Speech, Spatial, and Qualities of Hearing Scale [SSQ]) and in-situ Ecological Momentary Assessment (EMA). The rationale being that each approach likely provides different and yet complementary information. In addition, it was examined how self-reported listening activity and hearing-aid data-logging can augment EMAs for individualized and contextualized hearing outcome assessments., Design: Experienced hearing-aid users (N = 40) with mild-to-moderate symmetrical sensorineural hearing loss completed the SSQ questionnaire and gave repeated EMAs for two wear periods of 2-weeks each with two different hearing-aid models that differed mainly in their noise reduction technology. The EMAs were linked to a self-reported listening activity and sound environment parameters (from hearing-aid data-logging) recorded at the time of EMA completion. Wear order was randomized by hearing-aid model. Linear mixed-effects models and Random Forest models with five-fold cross-validation were used to assess the statistical associations between listening experiences and end-of-trial preferences, and to evaluate how accurately EMAs predicted preference within individuals., Results: Only 6 of the 49 SSQ items significantly discriminated between responses made for the end-of-trial preferred versus nonpreferred hearing-aid model. For the EMAs, questions related to perception of the sound from the hearing aids were all significantly associated with preference, and these associations were strongest in EMAs completed in sound environments with predominantly low SNR and listening activities related to television, people talking, nonspecific listening, and music listening. Mean differences in listening experiences from SSQ and EMA correctly predicted preference in 71.8% and 72.5% of included participants, respectively. However, a prognostic classification of single EMAs into end-of-trial preference with a Random Forest model achieved a 93.8% accuracy when contextual information was included., Conclusions: SSQ and EMA predicted preference equally well when considering mean differences, however, EMAs had a high prognostic classifications accuracy due to the repeated-measures nature, which make them ideal for individualized hearing outcome investigations, especially when responses are combined with contextual information about the sound environment., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2024 The Authors. Ear & Hearing is published on behalf of the American Auditory Society, by Wolters Kluwer Health, Inc.)

Purpose: Childhood incontinence is stigmatized and underprioritized, and a basic understanding of its pathogenesis is missing. Our goal was to identify risk-conferring genetic variants in daytime urinary incontinence (DUI)., Materials and Methods: We conducted a genome-wide association study in the Danish iPSYCH2015 cohort. Cases (3024) were identified through DUI diagnosis codes and redeemed prescriptions for DUI medication in individuals aged 5 to 20 years. Controls (30,240), selected from the same sample, were matched to cases on sex and psychiatric diagnoses, if any, and down-sampled to a 1:10 case:control ratio. Replication was performed in the Icelandic deCODE cohort (5475 cases/287,773 controls). Single-nucleotide polymorphism heritability was calculated using the genome-based restricted maximum likelihood method. Cross-trait genetic correlation was estimated using linkage disequilibrium score regression. Polygenic risk scores generated with LDpred2-auto and BOLT-LMM were assessed for association., Results: Variants on chromosome 6 (rs12210989, odds ratio [OR] 1.24, 95% CI 1.17-1.32, P = 3.21 × 10 -12 ) and 20 (rs4809801, OR 1.18, 95% CI 1.11-1.25, P = 3.66 × 10 -8 ) reached genome-wide significance and implicated the PRDM13 and RIPOR3 genes. Chromosome 6 findings were replicated ( P = .024, OR 1.09, 95% CI 1.01-1.16). Liability scale heritability ranged from 10.20% (95% CI 6.40%-14.00%) to 15.30% (95% CI 9.66%-20.94%). DUI and nocturnal enuresis showed positive genetic correlation ( r g = 1.28 ± 0.38, P = .0007). DUI was associated with attention-deficit/hyperactivity disorder (OR 1.098, 95% CI 1.046-1.152, P < .0001) and BMI (OR 1.129, 95% CI 1.081-1.178, P < .0001) polygenic risk., Conclusions: Common genetic variants contribute to the risk of childhood DUI, and genes important in neuronal development and detrusor smooth muscle activity were implicated. These findings may help guide identification of new treatment targets.

Due to the decoupling of the first ( 1 D) and second ( 2 D) dimension in pulsed elution-LC × LC (PE-LC × LC), method development is more flexible and straightforward compared to fast comprehensive LC × LC where the dependencies of key parameters between the two dimensions limits its flexibility. In this study we present a method for pulse generation, which is based on a switching valve alternating between one pump that delivers the gradient and a second pump that delivers low eluotrophic strength for the pause state. Consequently, the dwell volume of the system was circumvented and 7.5, and 3.75 times shorter pulse widths could be generated at flow rates of 0.2, and 0.4 mL/min with satisfactory accuracies between programmed and observed mobile phase composition (relative deviation of 6.0 %). We investigated how key parameters including pulse width and step height, 2 D gradient time and flow rate affected the peak capacity in PE-LC × LC. The conditions yielding the highest peak capacity for the PE-LC × LC- high-resolution mass spectrometry (HRMS) system were applied to a wastewater effluent sample. The results were compared to a one dimensional (1D)-LC-HRMS chromatogram. The peak capacity increased with a factor 34 from 112 for the 1D-LC run to 3770 for PE-LC × LC-HRMS after correction for undersampling. The analysis time for PE-LC × LC-HRMS was 12.1 h compared to 67.5 min for the 1D-LC-HRMS run. The purity of the mass spectra improved for PE-LC × LC-HRMS by a factor 2.6 (p-value 3.3 × 10 -6 ) and 2.0 (p-value 2.5 × 10 -3 ) for the low and high collision energy trace compared to the 1D-LC-HRMS analysis. Furthermore, the signal-to-noise ratio (S/N) was 4.2 times higher (range: 0.06-56.7, p-value 3.8 × 10 -2 ) compared to the 1D-LC-HRMS separation based on 42 identified compounds. The improvements in S/N were explained by the lower peak volume obtained in the PE-LC × LC-HRMS., 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. Published by Elsevier B.V.)

Late toxicities can impact survivorship in patients with classical Hodgkin lymphoma (cHL) with pulmonary toxicity after bleomycin-containing chemotherapy being a concern. The incidence of pulmonary diseases was examined in this Danish population-based study. A total of 1474 adult patients with cHL treated with ABVD (doxorubicin, bleomycin, vinblastine and dacarbazine) or BEACOPP (bleomycin, vincristine, etoposide, doxorubicin, cyclophosphamide, procarbazine and prednisone) between 2000 and 2018 were included along with 7370 age- and sex-matched comparators from the background population. Median follow-up was 8.6 years for the patients. Patients with cHL had increased risk of incident pulmonary diseases (HR 2.91 [95% CI 2.30-3.68]), with a 10-year cumulative risk of 7.4% versus 2.9% for comparators. Excess risks were observed for interstitial lung diseases (HR 15.84 [95% CI 9.35-26.84]) and chronic obstructive pulmonary disease (HR 1.99 [95% CI 1.43-2.76]), with a 10-year cumulative risk of 4.1% and 3.5% respectively for patients. No excess risk was observed for asthma (HR 0.82 [95% CI 0.43-1.56]). Risk factors for interstitial lung diseases were age ≥60 years, the presence of B-symptoms and low albumin. These findings document a significant burden of pulmonary diseases among patients with cHL and emphasize the importance of diagnostic work-up of pulmonary symptoms., (© 2024 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

Background: A standard of care and optimal duration of therapy have not been established for patients with multiply relapsed or refractory follicular lymphoma. The aim of this study was to evaluate epcoritamab, a novel CD3 × CD20 bispecific antibody, in the third-line and later setting of follicular lymphoma., Methods: EPCORE NHL-1 is a multicohort, single-arm, phase 1-2 trial conducted at 88 sites across 15 countries. Here, we report the primary analysis of patients with relapsed or refractory follicular lymphoma in the phase 2 part of the trial, which included the pivotal (dose expansion) cohort and the cycle 1 optimisation cohort. Eligible patients were aged 18 years or older, had relapsed or refractory CD20 + follicular lymphoma (grade 1-3A), an Eastern Cooperative Oncology Group performance status of up to 2, and had received at least two previous lines of therapy (including an anti-CD20 monoclonal antibody and an alkylating agent or lenalidomide). Patients were treated with subcutaneous epcoritamab 48 mg in 28-day cycles: weekly in cycles 1-3, biweekly in cycles 4-9, and every 4 weeks until disease progression or unacceptable toxicity. To mitigate the risk and severity of cytokine release syndrome, in the pivotal cohort, cycle 1 consisted of a step-up dosing regimen of a 0·16-mg priming dose on day 1 and a 0·80-mg intermediate dose on day 8, followed by subsequent 48-mg full doses and prophylactic prednisolone 100 mg; in the cycle 1 optimisation cohort, a second intermediate dose of 3 mg on day 15, adequate hydration, and prophylactic dexamethasone 15 mg were evaluated during cycle 1 to further reduce risk and severity of cytokine release syndrome. Primary endpoints were independently reviewed overall response rate for the pivotal cohort and the proportion of patients with grade 2 or worse and any-grade cytokine release syndrome for the cycle 1 optimisation cohort. Analyses were done in all enrolled patients who had received at least one dose of epcoritamab. This study is registered with ClinicalTrials.gov, NCT03625037, and is ongoing., Findings: Between June 19, 2020, and April 21, 2023, 128 patients (median age 65 years [IQR 55-72]; 49 [38%] female and 79 [62%] male) were enrolled and treated in the pivotal cohort (median follow-up 17·4 months [IQR 9·1-20·9]). The overall response rate was 82·0% (105 of 128 patients; 95% CI 74·3-88·3), with a complete response rate of 62·5% (80 of 128; 95% CI 53·5-70·9). The most common grade 3-4 treatment-emergent adverse event was neutropenia in 32 (25%) of 128 patients. Grade 1-2 cytokine release syndrome was reported in 83 (65%) of 128 patients; grade 3 cytokine release syndrome was reported in two (2%). Immune effector cell-associated neurotoxicity syndrome was reported in eight (6%) of 128 patients (five [4%] grade 1; three [2%] grade 2). Between Oct 25, 2022, and Jan 8, 2024, 86 patients (median age 64 years [55-71]; 37 [43%] female and 49 [57%] male) were enrolled and treated in the cycle 1 optimisation cohort. The incidence of cytokine release syndrome was 49% (42 of 86 patients; eight [9%] grade 2; none of grade 3 or worse), with no reported immune effector cell-associated neurotoxicity syndrome., Interpretation: Epcoritamab monotherapy showed clinically meaningful activity in patients with multiply relapsed or refractory follicular lymphoma, and had a manageable safety profile., Funding: Genmab and AbbVie., Competing Interests: Declaration of interests KML declares being a member of the Epcoritamab Global Council on behalf of Genmab; a consulting or advisory role for AbbVie, BeiGene, BMS, Genmab, Kite/Gilead, and Roche; participation in speakers bureaus from AbbVie and BMS; research funding (paid to institution) from AbbVie, ADC Therapeutics, AstraZeneca, BeiGene, BMS, CellCentric, Genmab, Janssen, Kite/Gilead, MorphoSys, MSD, Nurix, Regeneron, Roche, Step Pharma, and Viracta; and travel expenses from BMS. UV declares participation on an advisory board for AbbVie, Bayer, Genmab, Gilead, and Novartis; and lecture fees from AbbVie, Incyte, Janssen, Regeneron, Roche, and Servier. WJ declares research funding and consultancy fees from AbbVie and Roche. PJL declares research grants from Takeda and Servier; advisory honoraria from BMS, Roche, Takeda, Genmab, AbbVie, Incyte, Regeneron, and Sandoz; and consultancy honoraria from Y-mAbs Therapeutics. EG declares congress or travel fees or hospitality from AbbVie, Amgen, Gilead, Roche, and Sanofi; research funding from MSD, Novartis, Sandoz, and Sanofi; is a coordinating investigator for industry-sponsored studies for Astellas, Pharmacyclics, and Roche; and has received honoraria from Alexion, BMS, EUSA Pharma, Gilead, Jazz Pharma, Novartis, Pfizer, Roche, Sandoz, and Sanofi. AS declares consultancy for Takeda, BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, Kite, and Mundipharma; honoraria from Takeda, BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, and Kite; membership on board of directors or advisory committee for Takeda, BMS, Novartis, Janssen, Amgen, Bluebird, Sanofi, and Kite; travel expenses from Takeda, BMS, and Roche; research funding from Takeda; and participation in speakers bureaus for Takeda, BMS, Novartis, Janssen, MSD, Amgen, GSK, Sanofi, and Kite. BH declares membership on board of directors or advisory committee for ADC Therapeutics and BMS. HT declares membership on board of directors or advisory committee for ADC Therapeutics, BMS, and Roche; honoraria from Roche; and research funding from Roche. RC declares consultancy for AbbVie, Janssen, AstraZeneca, Kite, BMS, Genmab, Roche, Takeda, Kyowa Kirin, BeiGene, and Lilly; participation in speakers bureaus for AbbVie, Janssen, AstraZeneca, Kite, BMS, Roche, and Takeda; and research funding from Pfizer. DJL declares participation on advisory boards and consultancy for Janssen, Lilly, Roche, BeiGene, and Kite. MH declares participation on scientific advisory boards for AbbVie, BMS, Genmab, Janssen, Roche, and Takeda; and research support (paid to institution) from BMS, Genentech, Genmab, Incyte, Janssen, Novartis, Roche, and Takeda. MRC declares consultancy for AbbVie, Janssen, Gilead, AstraZeneca, Genmab, and Incyte; participation on advisory boards for AbbVie, Janssen, Gilead, and Genmab; and travel expenses from AbbVie, Janssen, AstraZeneca, Genmab, Roche, and Pfizer. J-MS declares consultancy or an advisory role for AbbVie, BeiGene, BMS, Gilead/Kite, Incyte, Janssen, Lilly, Miltenyi Biomedicine, Novartis, and Roche; and speaker honoraria from AbbVie, BeiGene, BMS, Gilead/Kite, Incyte, Janssen, Lilly, Novartis, and Roche. TC declares research funding from BeiGene; and participation in a speakers bureau for Janssen-Cilag. SL declares membership on board of directors or advisory committee for BeiGene, Genmab, Gilead, Incyte, Novartis, Orion, and Roche; research funding (paid to institution) from Bayer, BMS, Genmab, Hutchmed, Novartis, Nordic Nanovector, and Roche; and honoraria from Gilead, Incyte, and Novartis. MEDC declares consultancy for AbbVie, Novartis, and Sanofi; and research funding from BMS, Gilead, and Genmab. DG, YL, DH, and EF are current employees of Genmab. IA and TA are current employees of Genmab and hold stock or options in Genmab. MHD is a current employee of AbbVie. BE is a current employee of Genmab and holds patents and royalties (P158-US-PSP3). CT declares research funding from BMS, Hospira, and Roche; consultancy for AbbVie, Amgen, BMS, Cellectis, Gilead, Kite, Novartis, and Roche; honoraria from AbbVie, Amgen, Bayer, Cellectis, Gilead, Incyte, Janssen, Kite, Novartis, and Takeda; membership on board of directors or advisory committee for AbbVie, Amgen, BMS, Cellectis, Gilead, Incyte, Janssen, Kite, Novartis, Roche, and Takeda; and travel expenses from AbbVie, Amgen, BMS, Cellectis, Gilead, Kite, Novartis, and Roche. JMV declares research funding from Epizyme, Genmab, and Loxo; and consultancy for Adaptive, Genmab, and Ono. All other authors declare no competing interests., (2024 Elsevier Ltd. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

Aims: We provide an overview of nationwide environmental data available for Denmark and its linkage potentials to individual-level records with the aim of promoting research on the potential impact of the local surrounding environment on human health., Background: Researchers in Denmark have unique opportunities for conducting large population-based studies treating the entire Danish population as one big, open and dynamic cohort based on nationally complete population and health registries. So far, most research in this area has utilised individual- and family-level information to study the clustering of disease in families, comorbidities, risk of, and prognosis after, disease onset, and social gradients in disease risk. Linking environmental data in time and space to individuals enables novel possibilities for studying the health effects of the social, built and physical environment., Methods: We describe the possible linkage between individuals and their local surrounding environment to establish the exposome - that is, the total environmental exposure of an individual over their life course., Conclusions: The currently available nationwide longitudinal environmental data in Denmark constitutes a valuable and globally rare asset that can help explore the impact of the exposome on human health ., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.