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Background: SB5 (adalimumab-bwwd) is an adalimumab biosimilar targeting tumor necrosis factor (TNF) for the treatment of chronic inflammatory diseases, including moderate-to-severe chronic plaque psoriasis., Objectives: To assess the four-year persistence associated with the effectiveness and safety of SB5 in patients with psoriasis in the UK and Ireland., Methods: This prospective study included 1195 SB5-treated patients using British Association of Dermatologists' Biologic Interventions Register (BADBIR) between 01 June 2018 and 31 August 2022. Persistence was defined as the time from biologic therapy initiation to discontinuation and Kaplan-Meier analysis was used to evaluate SB5 discontinuation rates. Cox regression was used to investigate the effect of covariates on the time-to-first-discontinuation of SB5 with the potential covariates., Results: SB5 one-, two-, three-, and four-year discontinuation rates were 26.5%, 37.2%, 41.9%, and 43.3%, respectively. Tested covariates such as switching, age, sex, body mass index (BMI), and duration of psoriasis did not significantly affect the discontinuation rate of SB5., Conclusions: Median persistence of SB5 in predominantly bio-naïve psoriasis patients was about 2.5 years in clinical practice. The results suggest that SB5 can be confidently used for patients with psoriasis, offering comparable outcomes to reference adalimumab.

Purpose: Topical treatments for mild-to-moderate (MM) atopic dermatitis (AD) include emollients, corticosteroids, calcineurin inhibitors, a Janus kinase inhibitor, and a phosphodiesterase 4 inhibitor, which differ in multiple ways. This study aimed to quantify the conditional relative importance (CRI) of attributes of topical treatments for MM AD among adult and adolescent patients and caregivers of children with MM AD. Materials and methods: A discrete-choice experiment (DCE) survey was administered to US adults and adolescents with MM AD and caregivers of children with MM AD. Each choice task comprised 2 hypothetical topical treatments characterized by efficacy, adverse events, vehicle, and application frequency. Data were analyzed using a random-parameters logit model to calculate the CRI of each attribute. Results and conclusions: 300 adults, 331 adolescents, and 330 caregivers completed the DCE. Avoiding changes in skin color (CRI 29.0) and time until itch improves (26.6) were most important to adults, followed by time until clear/almost clear skin (17.8). Application frequency (3.0) did not have a statistically significant impact on adults' choices. Adolescents were less concerned about changes in skin color than adults or caregivers; caregivers were less concerned about time until clear/almost clear skin than patients. Physicians should consider age-relevant aspects of preferences in treatment discussions with patients and caregivers.

This study aimed to explore the self-management strategies of Danish patients living with advanced Chronic Obstructive Pulmonary Disease (COPD), with a particular focus on their daily life and their interactions with the respiratory outpatient clinic. Data were collected through semi-structured interviews with 11 patients with COPD affiliated with a Danish respiratory outpatient clinic. The data were thematically analyzed as suggested by Braun & Clarke. The analysis revealed one overarching theme, three main themes, and six subthemes. The overarching theme 'In a strained healthcare system patients with COPD struggle to access needed support to be able to self-manage their disease' revolved around the challenges that patients face in an overburdened healthcare system as they seek support to effectively self-manage their condition. The three main themes were: (1) Only physical symptoms provide legal access to the respiratory outpatient clinic, (2) For patients, the measurements serve as indicators of their health status and overall well-being, (3) Healthcare professionals' skills and not the mode of contact matters to the patients. Healthcare professionals should be aware that the rhetoric surrounding a busy healthcare system with a stressed-out staff also affects patients. Patients with COPD may be particularly sensitive to this message and try to avoid burdening the healthcare system further by setting aside their own needs. However, this approach can lead to neglecting symptoms of deterioration and mental symptoms, which increase the risk of disease progression and subsequent risk of hospital admission.

Objective: Acute exacerbations (AEs) of asthma are heterogeneous in terms of triggers, outcomes, and treatment response. This study investigated biomarker defined infective and inflammatory AE phenotypes in hospitalized adult asthma patients, and their impact on clinical outcomes and phenotype stability at AE recurrence., Method: Patients with asthma admitted with an AE between January 2010 and December 2011 with a 3-year follow-up were retrospectively studied. AEs were categorized into infective (CRP >10 mg/L) vs non-infective, eosinophilic (blood eosinophils ≥ 0.2 × 10 9 cells/L) vs non-eosinophilic, and viral (CRP >10 to <40 mg/L) vs bacterial (CRP ≥40 mg/L) phenotypes. Clinical impact of the index AE, the risk and time to a second AE and AE phenotype stability were analyzed using Kaplan-Meier survival curves and McNamar's test., Result: 294 asthma patients were included: 47% had infective AE with a longer length of stay than non-infective AE (2.0 vs. 1.0 days, p  = 0.01). The proportion of patients with eosinophilic AEs was evenly distributed across infective and non-infective AE (40% vs. 46%), although more patients with viral had eosinophilia than bacterial AE (46% vs. 26%). During follow-up, 18% had recurrent AE; with a higher risk in viral AE than bacterial AE (25% vs. 8%, p  = 0.02). Both inflammatory and infective AE phenotype were stable at recurrent AE., Conclusion: AE phenotyping in hospitalized asthma patients, based on CRP and blood eosinophils, revealed prolonged hospital stay in infective AEs and a higher risk of recurrent AE requiring hospitalization in viral versus bacterial AEs. Moreover, infective, and inflammatory AE phenotypes were rather stable at recurrent AE. Our results suggest a role for biomarker guided phenotyping of AEs of asthma.

In the KEEPsAKE 1 (NCT03675308) and KEEPsAKE 2 (NCT03671148) phase 3 trials, risankizumab demonstrated greater efficacy compared with placebo in patients with active psoriatic arthritis (PsA). This post hoc integrated analysis evaluated achieving the following efficacy outcomes at weeks 24 and 52 by baseline demographics and clinical characteristics: ≥20%/50%/70% improvement in American College of Rheumatology response criteria (ACR20/50/70), ≥90% improvement in Psoriasis Area and Severity Index, minimal disease activity status, Low Disease Activity status (Disease Activity in Psoriatic Arthritis), and minimal clinically important difference in pain. Baseline demographics and clinical characteristics were similar between risankizumab ( n  = 707) and placebo ( n  = 700) groups. Numerically higher ACR20 response rates at week 24 (primary endpoint) were observed among the risankizumab (46.3%-60.1%) vs. placebo (15.5%-36.2%) cohorts, regardless of subgroups. At week 52, consistent proportions of patients randomized to risankizumab achieved ACR20 (48.6%-75.8%) while those initially randomized to placebo and switched to risankizumab experienced an improvement from week 24 (43.7%-63.9%), regardless of subgroups. Similar trends were observed for other efficacy measures assessing rigorous skin response criteria, composite measures of overall disease activity, and PsA-related symptoms. Risankizumab treatment was efficacious among patients with varying demographic and psoriatic disease characteristics through 52 weeks.

To overcome the challenges of a manual leukocyte differential count, we have developed FlowDiff, an 8-colour, single tube flow cytometry panel, and investigated whether it could potentially replace the manual differential in our laboratory. The instrument was set up in accordance with the EuroFlow settings, and the protocol comprised a stain-lyse no wash process, taking approximately 30 min of working time, without the addition of a toxic lysis reagent. We found a very good correlation for all leukocyte populations between FlowDiff and the Sysmex XN analyzer in 80 normal, non-flagged samples. In addition, FlowDiff showed a very good correlation with manual differential in 168 abnormal samples, as well as a high diagnostic accuracy. FlowDiff correctly identified all samples with acute leukemia ( N  = 13) and differentiated all B-lymphomas ( N  = 49) in samples with lymphocytosis. Moreover, FlowDiff detected an additional five samples with B-lymphocytosis without any prior hematological malignancy, which turned out to be a B-lymphoma. Our data suggest that FlowDiff, our 8-colour flow cytometry-based differential, is comparable to, and can successfully substitute the manual differential.

Objective: To examine challenges in return to work (RTW) for persons with persistent postconcussion symptoms (PPCS) experienced by the affected employees and their managers., Methods: A survey of employees (S-E) and two surveys of managers (S-M1, S-M2) executed 4 months apart to capture the time perspective. Inclusion: Adults aged 18-66 with PPCS > 4 weeks, employed at the time of mTBI who returned to work within the previous year. Managers involved in their RTW process., Outcome Measures: Work status, working hours, work functioning (Work Role Functioning Questionnaire, WRFQ), work productivity., Results: Ninety-two employees and 66 managers were recruited. Three-fourths of the employees had returned to work but only one-third worked under similar conditions. Weekly working hours decreased from 36,3 hours (SD = 10,5) before mTBI to 17,6 hours (SD = 9,7). Employees had difficulties with tasks 43% of time (WRFQ). They needed more breaks, struggled with multitasking and work speed. About 65.9% experienced affected work productivity. Managers reported lack of knowledge and difficulties assessing the number of working hours and suitable tasks., Conclusions: Most employees returned to work but only a minority worked under similar conditions as before mTBI. Employees and managers struggled to estimate workload. The affected employees and their workplaces need a long-term RTW support.

Objective: This study aimed to explore whether phenotypic characteristics of patients with chronic widespread pain (CWP) and fibromyalgia (FM) can be aggregated into definable clusters that may help to tailor treatments., Method: Baseline variables (sex, age, education, marital/employment status, pain duration, prior CWP/FM diagnosis, concomitant rheumatic disease, analgesics, tender point count, and disease variables derived from standardized questionnaires) collected from 1099 patients (93.4% females, mean age 44.6 years) with a confirmed CWP or FM diagnosis were evaluated by hierarchical cluster analysis. The number of clusters was based on coefficients in the agglomeration schedule, supported by dendrograms and silhouette plots. Simple and multiple regression analyses using all variables as independent predictors were used to assess the likelihood of cluster assignment, reported as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: Only one cluster emerged (Cluster 1: 455 patients). Participants in this cluster were characterized as working (OR 66.67, 95% CI 7.14 to 500.00), with a medium-term/higher education (OR 16.80, 95% CI 1.94 to 145.41), married/cohabiting (OR 14.29, 95% CI 1.26 to 166.67), and using mild analgesics (OR 25.64, 95% CI 0.58 to > 999.99). The odds of being an individual in Cluster 1 were lower when having a worse score on the PDQ (score ≥ 18) (OR < 0.001, 95% CI < 0.001 to 0.02)., Conclusion: We identified one cluster, where participants were characterized by a potentially favourable clinical profile. More studies are needed to evaluate whether these characteristics could be used to guide the management of patients with CWP and FM.

Purpose: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications., Patients and Methods: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p  < 0.05., Results: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%., Conclusion: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Objective: Autoantibodies directed against the intracellular protein bicaudal D2 (BICD2) have been identified as a specific marker of systemic sclerosis (SSc). Since autoantibodies are of value in predicting disease onset and identifying meaningful clinical subsets, as well as having prognostic value, this study aimed to establish the prevalence of BICD2 autoantibodies (anti-BICD2) in a cohort of patients with connective tissue disease and healthy controls., Method: In this cross-sectional study, 363 patients with connective tissue disease (121 SSc, 141 systemic lupus erythematosus, 101 myositis, and 100 blood donors) were tested for the presence of anti-BICD2. All SSc patients were tested for specific anti-nuclear antibodies (ANAs), and clinical and laboratory associations were evaluated in the SSc patients, stratified by anti-BICD2 status., Results: In the SSc cohort, 35 patients had autoantibodies directed against BICD2. The specificity of anti-BICD2 in SSc patients was 96.5%; however, the sensitivity was only 28.9%. Anti-BICD2 and centromere autoantibodies were present together in 91% of the anti-BICD2-positive SSc patients, and in none of the cases was anti-BICD2 the only antibody present. Anti-BICD2-positive patients had lower forced expiratory volume in 1 s (FEV 1 ) (p = 0.01) and lower carbon monoxide transfer coefficient (K CO ) (p = 0.01) than anti-BICD2-negative SSc patients, but they had higher forced vital capacity (p = 0.03)., Conclusion: Autoantibodies against BICD2 were highly specific for SSc patients. Reduced FEV 1 and K CO in anti-BICD2-positive patients may indicate that the presence of anti-BICD2 is associated with altered lung function in an unknown pathophysiological manner, which awaits further elucidation.

Objectives: The objectives were to explore the clinical retention rate of an e-Device aimed at empowering chronic arthritis patients using certolizumab pegol (CZP) and to analyse beliefs about medication in the Danish population., Method: Patients treated with CZP were recruited from the Netherlands, Denmark, and Sweden through rheumatology clinics at initiation of, or switching to, the e-Device. Patients were adults (aged 18-85 years) diagnosed with rheumatoid arthritis, axial spondyloarthritis, or psoriatic arthritis. Patients administered three consecutive self-injections at home. Descriptive statistics regarding baseline characteristics, retention rates, and reasons for withdrawal were assessed, along with the Beliefs about Medicines Questionnaire., Results: In total, 59 patients participated (Netherlands 25, Denmark 15, Sweden 19). Most subjects (71%) were women, with a mean ± sd age of 55 ± 16.2 years and mean disease duration 12 ± 8.8 years. Six patients (10%) started CZP de novo and the remaining patients switched device. The overall retention rate was 42% after 52 weeks, declining to 38% after 104 weeks. A sharp decline, 34%, was seen at week 8. Between weeks 32 and 112, only four patients (6.8%) withdrew from the study. The primary reason for withdrawal was the patient's request. Stratification by country showed significant differences for some outcomes., Conclusion: An initial large dropout was evident within the first 8 weeks, with almost no dropouts thereafter. The reasons for withdrawal were primarily patient requests. Thus, the injection experience must be tailored carefully when selecting patients for new autoinjector e-Devices to enhance retention rates and patient satisfaction.

Introduction: Urticaria, a mast cell-mediated skin disease, manifests as acute or chronic, with the latter divided into spontaneous and inducible types and requires individualized management, including identifying triggers and comorbidities. Antihistamines, particularly the second generation group, form the mainstay of primary treatment plans consisting of dosage adjustments and/or in combination with other treatment modalities depending on underlying disease control., Areas Covered: A literature search was conducted using 'antihistamines,' 'urticaria,' 'pharmacogenomics,' 'genomics,' 'biomarkers' and 'treatment response' as key words. In this review, we focus on the comprehensive understanding and application of antihistamines in managing adult and adolescent patients with chronic urticaria., Expert Opinion: Using antihistamines to treat urticaria is set to change significantly, focusing more on personalized medicine and identifying key biomarkers to enhance treatment response prediction. These changes aim to make treatments more specific and cost-effective by avoiding unnecessary tests. Applying new approaches in everyday clinical care faces challenges like proving the biomarkers' reliability, updating current guidelines, and incorporating individualized treatments into standard procedures. Efforts should now concentrate on finding easy-to-use biomarkers, improving access to pharmacogenomics, understanding why some patients are resistant to treatment, and creating more specific treatment options based on patient needs.

Hypothalamic-pituitary-adrenal (HPA)-axis hyperactivity measured by the combined dexamethasone-CRH test (DEX-CRH test) has been found in patients with major depressive disorder (MDD), whereas hypoactivity has been found in patients with work-related stress. We aimed to investigate the DEX-CRH test as a biomarker to distinguish between MDD and work-related stress (exhaustion disorder - ED). We hypothesized that there would be lower cortisol and ACTH response in participants with ED compared to MDD and healthy controls (HC). Also, we explored if the cortisol response of those patients interacted with robust markers of oxidative stress. Thirty inpatients with MDD and 23 outpatients with ED were recruited. Plasma cortisol and ACTH were sampled during a DEX-CRH test. The main outcome measure, area under the curve (AUC) for cortisol and ACTH, was compa-red between MDD vs. ED participants and a historical HC group. Secondary markers of oxidative stress urinary 8-oxodG and 8-oxoGuo; quality of sleep and psychometrics were obtained. Cortisol concentrations were higher in MDD and ED participants compared to HC, and no differences in AUC cortisol and ACTH were found between ED vs. MDD. Compared to ED, MDD participants had higher stress symptom severity and a lower sense of well-being. No differences in oxidative stress markers or quality of sleep between the groups were found. The result indicates that the patients with ED, like patients with MDD, are non-suppressors in DEX-CRH test and not hypocortisolemic as suggested.

Objective: The Brief Illness Perception Questionnaire (B-IPQ) is a frequently used measure of illness perception (IP). The aim of this study was to explore the psychometric properties of the questionnaire when used in elderly people with knee pain., Method: Based on data from the Frederiksberg Cohort on elderly people reporting knee pain (N = 836), the psychometric properties of the eight B-IPQ items (1 'Consequences', 2 'Timeline', 3 'Personal control', 4 'Treatment control', 5 'Identity', 6 'Concern', 7 'Coherence', and 8 'Emotions') were analysed using Rasch analysis to establish whether the questionnaire provides reliable and valid measures of IP., Results: Threshold disordering was found on the 1-10 rating scale in all items. When rescaling to a 0-2 rating scale, disordering was resolved in six items. Item goodness-of-fit analyses revealed that two items displayed underfit misfit and four items overfit misfit; hence, the B-IPQ does not present unidimensionality. The person separation index indicated that items separate respondents into only two IP levels. Finally, floor and ceiling effects were found, indicating that the B-IPQ may not fully describe the extent of IP in this population., Conclusion: The 1-10 rating scale used in the Danish B-IPQ targeting knee pain is suboptimal, while a 0-2 scale improves the psychometric properties of the scale. The B-IPQ does not present unidimensionality and the use of a sum score is therefore not recommended when assessing IP. The B-IPQ may not cover the extent of IP in elderly people with knee pain.

Objectives: Obesity and psoriatic arthritis (PsA) have a complicated relationship. While weight alone does not cause PsA, it is suspected to cause worse symptoms. Neutrophil gelatinase-associated lipocalin (NGAL) is secreted through various cell types. Our objective was to assess the changes and trajectories in serum NGAL and clinical outcomes in patients with PsA during 12 months of anti-inflammatory treatment., Method: This exploratory prospective cohort study enrolled PsA patients initiating conventional synthetic or biological disease-modifying anti-rheumatic drugs (csDMARDs/bDMARDs). Clinical, biomarker, and patient-reported outcome measures were retrieved at baseline, and 4 and 12 months. Control groups at baseline were psoriasis (PsO) patients and apparently healthy controls. The serum NGAL concentration was quantified by a high-performance singleplex immunoassay., Results: In total, 117 PsA patients started a csDMARD or bDMARD, and were compared indirectly at baseline with a cross-sectional sample of 20 PsO patients and 20 healthy controls. The trajectory in NGAL related to anti-inflammatory treatment for all included PsA patients showed an overall change of -11% from baseline to 12 months. Trajectories in NGAL for patients with PsA, divided into treatment groups, showed no clear trend in clinically significant decrease or increase following anti-inflammatory treatment. NGAL concentrations in the PsA group at baseline corresponded to the levels in the control groups. No correlation was found between changes in NGAL and changes in PsA outcomes., Conclusion: Based on these results, serum NGAL does not add any value as a biomarker in patients with peripheral PsA, either for disease activity or for monitoring.

Background: Available network meta-analyses (NMAs) comparing the efficacy of biologics in nail psoriasis (NP) have not included recently approved biologics such as bimekizumab nor have they provided comparisons up to 1 year., Objective: We conducted two NMAs that update and extend results from a previous NMA comparing biologics for achieving complete resolution of NP., Methods: Bayesian NMAs were performed using a generalized linear model with a logit link to model the binary outcome of nail clearance at weeks 24-28 and 48-52., Results: For the NMA at weeks 24-28, which included seven biologics and placebo, the absolute probability of achieving complete resolution of NP was highest for ixekizumab (46.4%; 95% credibility interval [CrI] 35.2-58.0), followed by brodalumab (37.1%; 95% CrI 17.1-62.2) and bimekizumab (30.3%; 95% CrI 12.7-53.9). For the NMA at weeks 48-52, which included six biologics, the absolute probability was highest for ixekizumab (77.2%; 95% CrI 51.1-93.4), followed by adalimumab (75.6%; 95% CrI 61.5-87.3) and brodalumab (71.9%; 95% CrI 38.4-93.2)., Conclusion: Among biologics included in these two NMAs, ixekizumab has the highest absolute probability of achieving complete resolution of NP. Results may help to inform treatment decisions for patients with NP.

Background: Baricitinib is an oral selective Janus kinase 1/2 inhibitor approved for moderate-to-severe atopic dermatitis (AD) in adults., Objectives: To evaluate absolute Eczema Area and Severity Index (EASI) and SCORing of Atopic Dermatitis (SCORAD) outcomes over 16 weeks and to link disease severity categories to quality of life (QoL) improvements., Methods: This post-hoc analysis included patients enrolled in Phase3 monotherapy (BREEZE-AD1/AD2) and topical corticosteroid (TCS) combination therapy (BREEZE-AD7) trials and analyzed baricitinib 2 and 4 mg vs. placebo. Categorical outcomes were analyzed using Fisher's exact test., Results: Significantly more baricitinib-treated patients reached EASI ≤ 7 and SCORAD < 25 as early as week 1 in monotherapy and week 2 in TCS combination therapy, compared to placebo. Significant response vs. placebo was sustained until week 16 for EASI ≤ 7 (AD1/2 [ p -value vs. placebo]: 2 mg = 19.9%, 4 mg = 25.4% [ p  = 0.001] and AD7: 2 mg = 40.4% [ p  = 0.087], 4 mg = 48.6% [ p  = 0.003]) and SCORAD < 25 (AD1/2: 2 mg = 12.2%, 4 mg = 19.4% [ p  = 0.001] and AD7: 2 mg = 30.3% [ p  = 0.025], 4 mg = 34.2% [ p  = 0.004]) severity categories. These effects were accompanied by rapid improvements in QoL., Conclusion: Baricitinib-treated patients rapidly achieved recommended absolute EASI and SCORAD treatment outcomes which were sustained until week 16. Improvements in QoL were greater than EASI severity categories reflected, indicating that physician-assessed scores do not necessarily correlate with patients' impression of AD severity.

For many patients including those with psoriasis, scientific manuscripts comprising clinical outcomes including psoriasis area severity index (PASI) and/or physician global assessment (PGA) may be difficult to understand. However, most patients can relate to images at baseline and follow-up, particularly for dermatological diseases. This study aimed to assess the proportion of shared clinical images in psoriasis trials. A systematic review adhering to the PRISMA guidelines was performed. The review was limited to randomized controlled trials, and among these, only investigations involving biological agents for treatment of psoriasis were included. The Embase, MEDLINE and Scopus databases were searched for eligible studies published from inception to October 26, 2021. In total, 152 studies were included. When combining these, 62,871 patients were randomized. Overall, 203 images were shared depicting 60 patients in the manuscripts yielding an overall sharing rate of 0.1%. Patient images are seldom incorporated in clinical trial manuscripts which impairs interpretation for patients. Inclusion of image material would strengthen the patients' perspective and understanding on what treatment effects that can be expected. As such, this systematic review should be an invitation to the pharmaceutical industry, other sponsors, and editorial offices to improve easy transfer of information to patients using image data.

Background: Baricitinib, a selective Janus kinase (JAK)1/JAK2 inhibitor, is approved for treatment of moderate-to-severe atopic dermatitis (AD) in adults., Objectives: We report integrated baricitinib safety data in patients with up to 3.9-years exposure., Methods: Three datasets from the integrated AD clinical trial program were analyzed: placebo-controlled, 2-mg-4-mg extended, and All-bari. Data cutoffs were up to 21-December-2021 for long-term extension studies. Proportions of patients with events and incidence rates (IR)/100 patient years (PY) at risk were calculated., Results: 2636 patients received baricitinib for 4628.4 PY. Discontinuation due to adverse events was low (IR = 3.4). IRs in All-bari were: serious adverse events, 5.2; infection, 67.2 (any infection), 6.7 (herpes simplex), 2.8 (herpes zoster), and 0.3 (opportunistic infections). Adverse events of special interest in All-bari included seven patients with positively adjudicated major adverse cardiovascular events (MACE) (IR = 0.15), three pulmonary emboli (PE) (IR = 0.06), 14 malignancies excluding nonmelanoma skin cancer (IR = 0.3), one gastrointestinal perforation (IR = 0.02), and four deaths (IR = 0.1). No deep vein thromboses (DVT) or tuberculosis were reported., Conclusion: In this analysis, baricitinib maintained a similar safety profile to earlier analyses with no new safety signals. Rates of MACE, DVT/PE, malignancies, and serious infections were within ranges of background rates in patients with AD., Clinicaltrials.gov: NCT02576938 (JAHG), NCT03334396 (JAHL; BREEZE-AD1), NCT03334422 (JAHM; BREEZE-AD2), NCT03334435 (JAHN; BREEZE-AD3), NCT03428100 (JAIN; BREEZE-AD4), NCT03435081 (JAIW; BREEZE-AD5), NCT03559270 (JAIX; BREEZE-AD6), NCT03733301 (JAIY; BREEZE-AD7).

Background: Patients who completed the originating studies, BREEZE-AD1 (NCT03334396), BREEZE-AD2(NCT03334422), and BREEZE-AD7 (NCT03733301), were eligible for enrollment in the multicenter,phase-3, long-term extension study BREEZE-AD3 (NCT03334435)., Methods: At week 52, responders and partial responders to baricitinib 4 mg were re-randomized (1:1) into the sub-study to dose continuation (4 mg, N = 84), or dose down-titration (2 mg, N = 84). Maintenance of response was assessed from week 52 to 104 of BREEZE-AD3. Physician-rated outcomes included vIGA-AD (0,1), EASI75, and mean change from baseline in EASI. Patient-reported outcomes included DLQI, P OEM total score, HADS, and from baseline: WPAI (presenteeism, absenteeism, overall work impairment, daily activity impairment) and change from baseline in SCORAD itch and sleep loss., Results: With continuous treatment with baricitinib 4 mg, efficacy was maintained up to week 104 in vIGA-AD (0,1), EASI75, EASI mean change from baseline, SCORAD itch, SCORAD sleep loss, DLQI, P OEM, HADS, and WPAI (all scores). Patients down-titrated to 2 mg maintained most of their improvements in each of these measures., Conclusion: The sub-study of BREEZE AD3 supports flexibility in baricitinib dosing regimens. Patients who continued treatment with baricitinib 4 mg and down-titrated to 2 mg maintained improvements in skin, itch, sleep, and quality of life for up to 104 weeks.

Background: Concurrent chronic diseases and treatment hereof in patients with cancer may increase mortality. In this population-based study we examined the individual and combined impact of multimorbidity and polypharmacy on mortality, across 20 cancers and with 13-years follow-up in Denmark., Materials and Methods: This nationwide study included all Danish residents with a first primary cancer diagnosed between 1 January 2005 and 31 December 2015, and followed until the end of 2017. We defined multimorbidity as having one or more of 20 chronic conditions in addition to cancer, registered in the five years preceding diagnosis, and polypharmacy as five or more redeemed medications 2-12 months prior to cancer diagnosis. Cox regression analyses were used to estimate the effects of multimorbidity and polypharmacy, as well as the combined effect on mortality., Results: A total of 261,745 cancer patients were included. We found that patients diagnosed with breast, prostate, colon, rectal, oropharynx, bladder, uterine and cervical cancer, malignant melanoma, Non-Hodgkin lymphoma, and leukemia had higher mortality when the cancer diagnosis was accompanied by multimorbidity and polypharmacy, while in patients with cancer of the lung, esophagus, stomach, liver, pancreas, kidney, ovarian and brain & central nervous system, these factors had less impact on mortality., Conclusion: We found that multimorbidity and polypharmacy was associated with higher mortality in patients diagnosed with cancer types that typically have a favorable prognosis compared with patients without multimorbidity and polypharmacy. Multimorbidity and polypharmacy had less impact on mortality in cancers that typically have a poor prognosis.

Background: The COVID-19 pandemic was a global health crisis with population-wide behavioural restrictions imposed worldwide to reduce transmission of infection and to limit the potential burden on the healthcare systems. We examined whether there was any change in the diagnosis or treatment of breast cancer during the pandemic as compared to previous years., Material and Methods: The study population comprised all women aged ≥18 years diagnosed with breast cancer in 2015-2021 with data obtained from the clinical quality registry of the Danish Breast Cancer Cooperative Group (DBCG). Data on socioeconomic factors were retrieved from Statistics Denmark. Prevalence ratios (PR) with 95% confidence intervals (CI) were estimated from a generalised linear model (GLM) with a log link for the Poisson family with robust standard errors (SE) of each outcome, using the COVID-19 pandemic period in Denmark as the exposure of interest., Results: In total, 30,598 breast cancers were diagnosed during the study period. There was a small decrease (4.5%) in the total number of breast cancer cases in 2020 compared with previous years. During the pandemic, a lower proportion of the patients diagnosed with breast cancer had a short educational level (28.5 vs. 26.9%; PR = 0.91; 95% CI: 0.88-0.95), a low income (20.5 vs. 19.0%; PR = 0.90; 0.85-0.95) and fewer than expected in the age group 60-69 years (27.8 vs. 25.3; PR = 0.90; 0.86-0.94) were diagnosed, as compared with the pre-pandemic period. No difference in type of surgery or tumour size was observed. A higher proportion of patients received neo-adjuvant chemotherapy (49.0 vs 55.0%; PR = 1.15; 1.06-1.24), whereas a lower proportion received adjuvant chemotherapy (93.5 vs 85.6%; PR = 0.92; 0.90-0.93) during the pandemic, compared with the pre-pandemic period., Conclusions: During the pandemic, a small decrease in the number of breast cancer diagnoses was observed particularly among socially disadvantaged groups. Overall, the quality of breast cancer treatment was maintained.

Background: Five-year tildrakizumab safety data have been reported as exposure-adjusted incidence rates (EAIRs) of patients with events per 100 patient-years (PYs) of exposure., Objectives: To present 5-year safety data from reSURFACE 1/2 phase 3 trials as EAIRs of events per 100 PYs of exposure, and the number needed to harm (NNH) for one adverse event of special interest (AESI) to occur., Methods: Pooled analysis from two randomized controlled trials in patients with moderate-to-severe plaque psoriasis ( n  = 1800). PSOLAR registry was used as safety reference data for NNH estimation., Results: Rates of AESI with tildrakizumab were comparable with rates reported in PSOLAR. The NNH for one-year severe infection occurrence was 412 with tildrakizumab 200 mg, and negative for tildrakizumab 100 mg due to lower rates in reSURFACE trials; the NNH for malignancy was 990 for one year with tildrakizumab 100 mg (negative for tildrakizumab 200 mg); and the NNH for major adverse cardiovascular events was 355 for one year with tildrakizumab 200 mg (negative for tildrakizumab 100 mg)., Conclusion: Tildrakizumab demonstrated a favorable safety profile over 5 years with low rates of AESI, comparable to those of the PSOLAR. Consequently, the NNH for AESI with tildrakizumab were very high or negative due to lower event rates for tildrakizumab.

Background: Plasma concentrations of glucagon, GLP-1 and GIP are reported in numerous clinical trials as outcome measures but preanalytical guidelines are lacking. We addressed the impact of commonly used blood containers in metabolic research on measurements of glucagon, GLP-1 and GIP in humans., Methods: Seventeen overweight individuals were subjected to an overnight fast followed by an intravenous infusion of amino acids to stimulate hormonal secretion. Blood was sampled into five containers: EDTA-coated tubes supplemented with DMSO (control), a neprilysin inhibitor, aprotinin (a kallikrein inhibitor) or a DPP-4 inhibitor, and P800 tubes. Plasma was kept on ice before and after centrifugation and stored at -80 Celsius until batch analysis using validated sandwich ELISAs or radioimmunoassays (RIA)., Results: Measures of fasting plasma glucagon did not depend on sampling containers, whether measured by ELISA or RIA. Amino acid-induced hyperglucagonemia was numerically higher when blood was collected into P800 tubes or tubes with aprotinin. The use of p800 tubes resulted in higher concentrations of GLP-1 by RIA compared to control tubes but not for measurements with sandwich ELISA. Plasma concentrations of GIP measured by ELISA were higher in control tubes and negatively affected by P800 and the addition of aprotinin., Conclusions: The choice of blood containers impacts on measurements of plasma concentrations of glucagon, GLP-1 and GIP, and based on this study, we recommend using EDTA-coated tubes without protease inhibitors or P800 tubes for measurements of glucagon, GLP-1 and GIP in clinical trials.

Objective: Patient education is recommended as an integral component of the therapeutic plan for the management of chronic widespread pain (CWP) and fibromyalgia (FM). The key purpose of patient education is to increase the patient's competence to manage his or her own health requirements, encouraging self-management and a return to desired everyday activities and lifestyle. The aim of this systematic review was to evaluate the evidence for the benefits and potential harms associated with the use of patient education as a stand-alone intervention for individuals with CWP and FM through randomized controlled trials (RCTs)., Method: On 24 November 2021 a systematic search of PubMed, MEDLINE, Embase, CENTRAL, PsycINFO, CINAHL, ClinicalTrials.gov, American College of Rheumatology, European League Against Rheumatism, and the World Health Organization International Clinical Trials Registry Platform identified 2069 studies. After full-text screening, five RCT studies were found to be eligible for the qualitative evidence synthesis., Results: Patient education as a stand-alone intervention presented an improvement in patients' global assessment (standardized mean difference 0.79, 95% confidence interval 0.13 to 1.46). When comparing patient education with usual care, no intervention, or waiting list, no differences were found for functioning, level of pain, emotional distress in regard to anxiety and depression, or pain cognition., Conclusion: This review reveals the need for RCTs investigating patient education as a stand-alone intervention for patients with FM, measuring outcomes such as disease acceptance, health-related quality of life, enhancement of patients' knowledge of pain, pain coping skills, and evaluation of prioritized learning outcomes.

Objectives: To evaluate the prevalence of survey-based criteria for fibromyalgia (FM) among newly referred patients in a rheumatic outpatient clinic, and to compare the use of secondary healthcare services between survey-based FM and non-FM cases., Method: Newly referred patients to an outpatient clinic were screened for the fulfilment of the 2011 FM survey criteria during a 6 month period in 2013 in this observational cohort study. Demographic data were obtained at baseline. Patients' medical files were evaluated and comparisons between groups were made regarding the use of hospital healthcare facilities during the 7 year observation period., Results: Out of 300 invited patients, 248 (83%) completed the questionnaire; 90 patients (36%) fulfilled survey-based criteria for FM at enrolment. FM cases were primarily women (80% vs 54% of non-FM cases), and received more medications (median 4 vs 3 drugs) and public economic support (62% vs 20%). At the 7 year follow-up, crude analyses showed that FM cases had a higher number of hospital courses (median 10 vs 8) and had undergone more invasive procedures (78% vs 60%). Neurologists (42% vs 28%), gastroenterologists (30% vs 13%), endocrinologists (40% vs 21%), pain specialists (13% vs 3%), psychiatrists (20% vs 7%), and abdominal surgeons (43% vs 30%) were consulted more often by FM than by non-FM cases., Conclusion: Fulfilment of FM survey criteria among newly referred patients to a rheumatic outpatient clinic is frequent. Our study findings show that FM continues to present a challenge for healthcare professionals as well as for patients., Research Highlights: ● Fulfilment of FM survey criteria among newly referred patients to a rheumatic outpatient clinic is frequent.● The burden on the secondary healthcare system for these patients is significant.● This study suggests the need for increased awareness about the diagnosis of FM among certain medical and surgical specialties.

Objective: To evaluate whether disease activity-guided tapering of biologics compared to continuation as usual care enables a substantial dose reduction while disease activity remains equivalent., Method: In this pragmatic, randomized, open-label, equivalence trial, adults with rheumatoid arthritis, psoriatic arthritis, or axial spondyloarthritis in low disease activity on stable-dose biologics for ≥ 12 months were randomized 2:1 into either the tapering group, i.e. disease activity-guided prolongation of the biologic dosing interval until flare or withdrawal, or the control group, i.e. maintaince of baseline biologics with a possible small interval increase at the patients request. The co-primary outcome in the intention-to-treat population was met if superiority in ≥ 50% biologic reduction at 18 months was demonstrated and disease activity was equivalent (equivalence margins ± 0.5)., Results: Ninety-five patients were randomized to tapering and 47 to control, of whom 37% (35/95) versus 2% (1/47) achieved ≥ 50% biologic reduction at 18 months. The risk difference was statistically significant [35%, 95% confidence interval (CI) 24%-45%], while disease activity remained equivalent [mean difference 0.05, 95% CI -0.12-0.29]. A statistically significant flare risk was observed [tapering 41% (39/95) vs control 21% (10/47), risk difference 20%, 95% CI 4%-35%]; but, only 1% (1/95) and 6% (3/47) had persistent flare and needed to switch to another biological drug., Conclusions: Disease activity-guided tapering of biologics in patients with inflammatory arthritis enabled one-third to achieve ≥ 50% biologic reduction, while disease activity between groups remained equivalent. Flares were more frequent in the tapering group but were managed with rescue therapy.

Background: This study aimed to investigate the impact of adjuvant chemotherapy on long-term survival in unselected patients with high-risk stage II colon cancer including an analysis of each high-risk feature., Materials and Methods: Data from the Danish Colorectal Cancer Group, the National Patient Registry and the Danish Pathology Registry from 2014 to 2018 were merged. Patients surviving > 90 days were included. High-risk features were defined as emergency presentation, including self-expanding metal stents (SEMS)/loop-ostomy as a bridge to resection, grade B or C anastomotic leakage, pT4 tumors, lymph node yield < 12 or signet cell carcinoma. Eligibility criteria for chemotherapy were age < 75 years, proficient MMR gene expression, and performance status ≤ 2. The primary outcome was 5-year overall survival. Secondary outcomes included the proportion of eligible patients allocated for adjuvant chemotherapy and the time to first administration., Results: In total 939 of 3937 patients with stage II colon cancer had high-risk features, of whom 408 were eligible for chemotherapy. 201 (49.3%) patients received adjuvant chemotherapy, with a median time to first administration of 35 days after surgery. The crude 5-year overall survival was 84.9% in patients receiving adjuvant chemotherapy compared with 66.3% in patients not receiving chemotherapy, p  < 0.001. This association corresponded to an absolute risk difference of 14%., Conclusion: 5-year overall survival was significantly higher in patients with high-risk stage II colon cancer treated with adjuvant chemotherapy compared with no chemotherapy. Adjuvant treatment was given to less than half of the patients who were eligible for it.

Background: Smoking cessation treatment is an important prognostic factor for survival after a cancer diagnosis, especially for tobacco-related cancers. After being diagnosed with lung cancer, approximately 50% of patients continue smoking or frequently relapse after a quit attempt. Given the importance of smoking cessation treatment for cancer survivors, the objective was to compare the effectiveness of a 6-week intensive smoking cessation intervention, the Gold Standard Program (GSP), among cancer survivors compared with smokers without cancer. Second, we compared successful quitting among socioeconomically disadvantaged cancer survivors with that among nondisadvantaged cancer survivors., Materials and Methods: This was a cohort study based on 38,345 smokers from the Danish Smoking Cessation Database (2006-2016). Linkage to the National Patient Register was used to identify cancer survivors undergoing the GSP after being diagnosed with cancer (except nonmelanoma skin cancer). Linkage to the Danish Civil Registration System was used to identify participants who died, went missing, or emigrated before the follow-up. Logistic regression models were applied to evaluate effectiveness., Results and Conclusion: Six percent (2438) of the included smokers were cancer survivors at the time they undertook the GSP. Their 6-month successful quitting showed no difference compared to that of smokers without cancer, neither before nor after adjustment; 35% versus 37% in crude rates and an aOR of 1.13 (95% CI: 0.97-1.32). Likewise, the results for disadvantaged compared to nondisadvantaged cancer survivors were not significantly different (32% versus 33% and an adjusted aOR of 0.87 (95% CI 0.69-1.11)). Overall, an intensive smoking cessation program seems effective in helping both people without cancer and cancer survivors become successful quitters.

Objective: The aim of this study was to evaluate the psychometric properties of the Danish version of the Fibromyalgia Impact Questionnaire - Revised (FIQR), when used to quantify the severity of disease burden in a Danish population of patients with chronic widespread pain (CWP), including fibromyalgia (FM)., Method: A total of 924 participants diagnosed with CWP and/or FM completed an electronic version of the FIQR via touchscreens in the clinic at referral for specialist care. Data were collected from 1 January 2018 to 3 September 2020. Rasch measurement methods were applied., Results: Rating scale analysis suggested multiple threshold disordering in the 0-10 category rating scale. A principal component analysis suggested assessment of a multidimensional construct. Thus, the Rasch analysis of the full FIQR was discontinued. Instead, Rasch analyses were performed on the two subscales: 'function' and 'symptoms'. By collapsing the rating scale to a 0-4 category scale, the remaining threshold disordering of both subscale was solved. Only the symptom subscale indicated multidimensionality. There was underfitting misfit of item 21 and overfitting misfit of item 12. No significant differential item functioning, defined by sex, ethnicity, or education, was found., Conclusion: The FIQR should be considered as an instrument consisting of three separate subscales representing 'function', 'overall impact', and 'symptoms'. We recommend calculating and reporting on both a 0-10 and a 0-4 category scale. Also, if using the total FIQR score as an outcome measure, this should be done with caution, until revision of the rating scale.

Objective: The aim of the study was to characterize the drug utilization and switch patterns of biological treatment of ulcerative colitis (UC) and Crohn's disease (CD)., Methods: Using Danish national registries, this nationwide study included individuals diagnosed with UC or CD, bio-naïve at the initiation of treatment with infliximab, adalimumab, vedolizumab, golimumab, or ustekinumab in 2015-2020. Hazard ratios of discontinuing the first treatment or switching to another biological treatment were explored using Cox regression., Results: Among 2995 UC patients and 3028 CD patients, infliximab was used as a first-line biologic treatment in 89% of UC patients and 85% of CD patients, followed by adalimumab with 6%, vedolizumab with 3%, and golimumab with 1% for UC, and adalimumab with 12%, vedolizumab with 2%, and ustekinumab with 0.4% for CD.When comparing adalimumab as the first treatment series to infliximab, there was a higher risk of treatment discontinuation (excluding switch) among UC patients (hazard ratio: 2.02 [95% confidence interval: 1.57; 2.60]) and CD patients (1.85 [1.52; 2.24]). When comparing vedolizumab to infliximab, there was a lower risk of discontinuation for UC patients (0.51 [0.29-0.89]), and for CD patients, although not significantly (0.58 [0.32-1.03]). We observed no significant difference in the risk of switching to another biologic treatment for any of the biologics., Conclusion: More than 85% of UC and CD patients initiating biologic therapy had infliximab as their first-line biologic treatment, in accordance with official treatment guidelines. Future studies should explore the higher incidence of treatment discontinuation of adalimumab as the first treatment series.Key summarySeveral biologic therapies are available in the treatment of ulcerative colitis and Crohn's disease.Clinical guidelines stipulate that infliximab should be the first-line biologic therapy.Drug utilization studies comparing biologic therapies head-to-head are sparse.In Denmark, during 2015-2020 infliximab remained the most widely used biologic treatment, with adalimumab being second.One in four patients experienced more than one biologic during the study period.The risk of discontinuation of biologic treatment (and not starting a new biologic) was higher for initiators of adalimumab.Clinical and social background factors available from the registers could not account for the observed risk difference in discontinuation.

Background: Microscopically positive margins to lymph node metastases (R1LNM) are associated with poorer oncological outcomes in patients with Stage 3 colon cancer. These poorer outcomes were seen despite a greater proportion of these patients receiving adjuvant chemotherapy when compared to those with microscopically negative (R0) margins. We sought to determine if differences in the type or duration of adjuvant chemotherapy could account for the differences in outcomes seen between patients with R0 and R1LNM margins., Methods: A multicentre retrospective study including patients undergoing surgery for Stage 3 colon cancer between 2016-2019 at specialist centres. Patients were stratified according to margins status (R0 vs R1LNM). Type/duration of chemotherapy and oncological outcomes were compared between groups., Results: 718 patients were included, of whom 100 had R1LNM margins (13.1%). Patients with R1LNM margins had significantly poorer 3-year distant metastases-free (R0 78.2% (95% CI 74.5-81.3) versus R1LNM 58.8% (95% CI 47.2-68.6), p  < 0.001) and disease specific survival (R0 88.3% (95% CI 85.2-90.9) versus R1LNM 78.5% (95% CI 68.0-85.8), p  < 0.001) when compared to those with R0 margins. No differences were noted in the proportion of patients who completed long-course chemotherapy or were treated with oxaliplatin-based combinations between the R1LNM and R0 groups. Differences in outcomes between R0 and R1LNM groups persisted even when only those patients who completed long-course chemotherapy were compared., Discussion: Differences in adjuvant chemotherapy do not appear to account for the poorer oncological outcomes seen in patients with R1LNM margins after surgery for Stage 3 colon cancer. This suggests that adjuvant chemotherapy may be less effective in this patient group. Further studies to elucidate a potential biological basis for this difference are warranted.

Background: The combined effectiveness of remdesivir and dexamethasone in subgroups of hospitalised patients with COVID-19 is poorly investigated., Methods: In this nationwide retrospective cohort study, we included 3826 patients with COVID-19 hospitalised between February 2020 and April 2021. The primary outcomes were use of invasive mechanical ventilation and 30-day mortality, comparing a cohort treated with remdesivir and dexamethasone with a previous cohort treated without remdesivir and dexamethasone. We used inverse probability of treatment weighting logistic regression to assess associations with progression to invasive mechanical ventilation and 30-day mortality between the two cohorts. The analyses were conducted overall and by subgroups based on patient characteristics., Results: Odds ratio for progression to invasive mechanical ventilation and 30-day mortality in individuals treated with remdesivir and dexamethasone compared to treatment with standard of care alone was 0.46 (95% confidence interval, 0.37-0.57) and 0.47 (95% confidence interval, 0.39-0.56), respectively. The reduced risk of mortality was observed in elderly patients, overweight patients and in patients requiring supplemental oxygen at admission, regardless of sex, comorbidities and symptom duration., Conclusions: Patients treated with remdesivir and dexamethasone had significantly improved outcomes compared to patients treated with standard of care alone. These effects were observed in most patient subgroups.

Purpose/aim of the Study: Osteogenesis imperfecta is a heritable bone disorder that is usually caused by mutations in collagen type I encoding genes. The impact of such mutations on tendons, a structure with high collagen type I content, remains largely unexplored. We hypothesized that tendon properties are abnormal in the context of a mutation affecting collagen type I. The main purpose of the study was to assess the anatomical, mechanical, and material tendon properties of Col1a1 Jrt/+ mice, a model of severe dominant OI., Materials and Methods: The Flexor Digitorum Longus (FDL) tendon of Col1a1 Jrt/+ mice and wild-type littermates (WT) was assessed with in vitro mechanical testing., Results: The results showed that width and thickness of FDL tendons were about 40% larger in WT (p < 0.01) than in Col1a1 Jrt/+ mice, whereas the cross-sectional area was 138% larger (p < 0.001) . The stiffness, peak- and yield-force were between 160% and 194% higher in WT vs. Col1a1 Jrt/+ mice. The material properties did not show significant differences between mouse strains with differences <15% between WT and Col1a1 Jrt/+ (p > 0.05) . Analysis of the Achilles tendon collagen showed no difference between mice strains for the content but collagen solubility in acetic acid was 66% higher in WT than in Col1a1 Jrt/+ (p < 0.001)., Conclusions: This study shows that the FDL tendon of Col1a1 Jrt/+ mice has reduced mechanical properties but apparently normal material properties. It remains unclear whether the tendon phenotype of Col1a1 Jrt/+ mice is secondary to muscle weakness or a direct effect of the Col1a1 mutation or a combination of both.

Objective: Poisonings contribute significantly to morbidity and mortality of patients. Some patients have numerous contacts to a poison information center, indicating repeated poisoning exposures. Information on the involved substances is necessary to explore methods to prevent self-harm and reduce mortality. The objective of this study was to characterize the patient population with repeated poison exposures in Denmark and identify the substances involved., Methods: This study was a retrospective cohort study of enquiries to the nationwide Danish Poison Information Centre and the Danish National Patient Registry. The databases were used to identify patients with more than five individual poisoning episodes within a 12-month-period between 1 January 2013, and 31 December 2017., Results: One hundred and thirty-seven patients and 995 patients met the inclusion criteria in the Danish Poison Information Centre and the Danish National Patient Registry, respectively. The majority were women (82.5% and 66.3% for the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively). The mean age was 24.7 and 29.5 years. Psychiatric comorbidities were frequent with 74.5% and 67.0% suffering from personality disorders and 70.1% and 54.5% from affective disorders in the Danish Poison Information Centre and the Danish National Patient Registry cohorts, respectively. One thousand seven hundred and fifty-two poisoning episodes were identified in the Danish Poison Information Centre database, and the most common types of substance were 'pharmaceuticals' (1,420 episodes). The most common medications ingested were quetiapine, paracetamol and cyclizine. Median number of contacts to the Danish Poison Information Centre was 10. Patients with one or more poisoning episodes involving cyclizine had on average 11.4 poisoning episodes involving cyclizine. In the Danish National Patient Registry cohort 80.9% were alive after 10 years compared to 97.7% in the background population., Conclusion and Implications: Most poisonings were intentional and occurred among younger women. Psychiatric comorbidity was frequent. Most often, pharmaceuticals were the toxic substance, mainly quetiapine, paracetamol and cyclizine. Changing the status of cyclizine from over the counter to prescription only medication, and implementing stricter rules for prescribing quetiapine, could limit future poisoning incidences.

Objectives: To examine the prevalence of sleep disturbances, quantified by the Pittsburgh Sleep Quality Index (PSQI), in patients with psoriatic arthritis (PsA), psoriasis (PsO) and healthy controls (HCs), explore associations between PSQI and clinical and patient-reported outcomes, and evaluate the effect of treatment on PSQI., Method: Patients were included from the Parker Institute's PsA patient cohort to evaluate the prevalence of sleep disturbances. Univariate and multivariate regression analyses were used to explore associations between sleep disturbance and outcome measures. Treatment effect in PsA patients was assessed with a mixed-effect model for repeated measures., Results: In total, 109 PsA patients, 20 PsO patients, and 20 HCs were included. Sleep disturbances were reported by 66.1% of PsA patients, 45.0% of PsO patients, and 15.0% of HCs. Univariate regression analyses revealed statistically significant associations (p < 0.001) between PSQI and Disease Activity Score (DAS28CRP), tender points, visual analogue scale (VAS) patient global and pain, Psoriatic Arthritis Impact of Disease fatigue, Health Assessment Questionnaire (HAQ), and painDETECT score. Multivariate regression analysis demonstrated VAS patient global, VAS pain, and tender points as being independently associated with PSQI. The mixed-effect model revealed no effect of treatment., Conclusion: More PsA patients than PsO patients and HCs reported sleep disturbances. Sleep disturbances were associated with inflammatory and non-inflammatory measures possibly explaining the limited effect of treatment. This demonstrates the need for interdisciplinary approaches to improve the management of sleep disturbance in PsA. Trial registration : ClinicalTrials.gov (NCT02572700).

Background: Patient education is a key element in the management of asthma., Aims: This study aimed to evaluate the popularity and usefulness of YouTube videos on asthma., Methods: Two authors screened and evaluated the 200 most popular videos. Data on likes, dislikes, views, comment, source of uploader, days since upload, and usefulness were recorded and included for analyses. The usefulness of the videos was categorized as follows: useful , misleading , or neutral . Misleading videos provided at least one scientifically incorrect detail, whereas useful videos contained scientifically correct information., Results: A total of 130 videos were included, and the total number of views was 100,290,242 with a total duration of 29 h and 8 min. While 26.6% of videos were uploaded by TV shows and YouTube channels, only 7.7% were uploaded by lung specialists. 65.4% of the videos contained scientifically correct information, whereas 18.5% contained misleading information. Although videos from medical professionals had a higher quality than videos from YouTube channels and TV shows, the latter were more popular. Misleading videos had numerically, but not statistically significant higher views compared with useful videos., Conclusions: YouTube videos on asthma are popular in terms of viewer interaction, and the popularity is not restricted to videos uploaded by professional sources. Although more than half of the videos were found to be useful, a non-negligible proportion of videos were assessed as misleading. The usefulness of YouTube videos on asthma is variable and initiatives should be taken to increase the potential of YouTube as an useful source in patient education.

Introduction: Paracetamol poisoning is a frequent cause of hospitalization in Denmark. On 30 September 2013, the Danish authorities restricted packages available without a prescription in pharmacy outlets to contain a maximum of 10 g of paracetamol. We aimed to investigate the effects of this regulation., Methods: This was a cross-sectional study of two groups of patients admitted consecutively to a Danish University Hospital due to poisoning with paracetamol in 365 days in 2012-13 before 30 September 2013, and a corresponding 365-day period in 2017-18. Data were extracted from patient records., Results: In 2012-2013 and 2017-18, 156 and 92 admissions in 127 and 78 unique patients, respectively, were identified. Ingestion of more than 20 g paracetamol occurred in a significantly higher proportion of cases in 2012-13 compared to 2017-18 (29% vs 13%, P  < 0.01). In accordance, there were no cases of international normalized ratio >1.5 or alanine aminotransferase activity >1000 U/L in the post-legislation period, and seven and five cases in the pre-legislation period, respectively. Females accounted for 80% and 78% of patients in the two periods, respectively, and were considerably younger than males (median [interquartile range]: 22 [17-40] vs. 47 [30-56], P  < 0.01 in 2012-13, and 23 [18-46] vs. 43 [27-49] years, P  = 0.02 in 2017-18). Furthermore, in 2012-13, intentional poisonings occurred in a higher proportion of females than males 2012-13 (97% vs 85%, P  < 0.01)., Conclusions: The present study demonstrated a lower number of paracetamol poisonings, a decreased proportion of poisonings involving ingestion of more than 20 g of paracetamol, and a lower occurrence of hepatotoxicity after the regulation. However, circumstances other than pack size restrictions, such as increased public awareness of the danger of paracetamol poisonings, may affect these associations. Furthermore, the study showed that females and males constitute two distinct groups in terms of age and intentional poisoning.

Background: In patients with cancer, sarcopenia is associated with treatment related complications, treatment cessation, poor quality of life and reduced overall survival. Despite this, there is limited knowledge about changes in skeletal muscle mass during chemotherapy. The aim of this systematic review and meta-analysis was to investigate the change of skeletal muscle mass and sarcopenia during chemotherapy treatment among patients with lung cancer., Methods: A systematic literature search was conducted in three databases, PubMed, EMBASE and Web of Science. Observational studies with patients with lung cancer were eligible for inclusion if skeletal muscle mass was measured before and after receiving chemotherapy treatment., Results: Ten cohort studies with a total of 867 participants met the inclusion criteria. During 5.2 ± 2.9 months of chemotherapy treatment, patients with lung cancer experienced a significant loss of skeletal muscle mass with a standardized mean difference (SMD) of: -0.25 (95% CI -0.47 to -0.03). The pretreatment prevalence of sarcopenia varied across studies from 35% to 74%. Only one study reported prevalence of sarcopenia both before and after chemotherapy treatment with an increase from 35% to 59%., Conclusion: The present data demonstrate a marked loss of skeletal muscle mass in patients with lung cancer undergoing chemotherapy treatment, as well as a high prevalence of sarcopenia. As sarcopenia is associated with poor clinical outcomes, it seems important to include and use assessments of skeletal muscle mass in clinical practice to identify patients in need for interventions. Moreover, interventional studies to hinder development of sarcopenia are needed.

Animal studies have shown that SGLT2 inhibition decreases oxidative stress, which may explain the cardiovascular protective effects observed following SGLT2 inhibition treatment. Thus, we investigated the effects of two and twelve weeks SGLT2 inhibition on DNA and RNA oxidation. Individuals with type 2 diabetes ( n  = 31) were randomized to two weeks of treatment with the SGLT2 inhibitor empagliflozin treatment (25 mg once daily) or placebo. The primary outcome was changes in DNA and RNA oxidation measured as urinary excretion of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) and 8-oxo-7,8-dihydroguanosine (8-oxoGuo), respectively. In another trial, individuals with type 2 diabetes ( n  = 35) were randomized to twelve weeks of dapagliflozin treatment (10 mg once daily) or placebo in a crossover study. Changes in urinary excretion of 8-oxodG and 8-oxoGuo were investigated as a posthoc analysis. Compared with placebo treatment, two weeks of empagliflozin treatment did not change urinary excretion of 8-oxodG (between-group difference: 0.3 nmol/24-hour (95% CI: -4.2 to 4.8)) or 8-oxoGuo (1.3 nmol/24-hour (95% CI: -4.7 to 7.3)). From a mean baseline 8-oxodG/creatinine urinary excretion of 1.34 nmol/mmol, dapagliflozin-treated individuals changed 8-oxodG/creatinine by -0.17 nmol/mmol (95% CI: -0.29 to -0.04) following twelve weeks of treatment, whereas placebo-treated individuals did not change 8-oxodG/creatinine (within-group effect: 0.10 nmol/mmol (95% CI: -0.02 to 0.22)) resulting in a significant between-group difference ( p  = 0.01). Urinary excretion of 8-oxoGuo was unaffected by dapagliflozin treatment. In conclusion, two weeks of empagliflozin treatment did not change DNA or RNA oxidation. However, a posthoc analysis revealed that longer-term dapagliflozin treatment decreased DNA oxidation. Clinicaltrials.gov: NCT02890745 and NCT02914691.HighlightsPlasma ferritin correlated with DNA and RNA oxidation in individuals with T2D.Twelve weeks dapagliflozin treatment decreased DNA oxidation.Dapagliflozin and empagliflozin treatment did not change RNA oxidation.Lipid peroxidation was unaffected by two weeks empagliflozin treatment.

Objective: A randomized controlled trial [Joint Resources - Sedentary Behaviour (JR-SB) intervention] aimed to reduce sedentary behaviour and increase light-intensity physical activity in patients with rheumatoid arthritis (RA) through motivational counselling and text messages. Since a large proportion of invited patients declined to participate, this study aims to compare sociodemographic, clinical, and lifestyle factors between included patients and patients declining to participate (non-participants) in the JR-SB study and to investigate which characteristics were associated with participation., Method: A register-based cross-sectional study was conducted. All patients invited to participate in the JR-SB study were identified in the DANBIO registry, from which patients' clinical and lifestyle data were also retrieved. Data on sociodemography and comorbidity were extracted from national registers. Differences between participants and non-participants were determined by an independent t-test or a chi-squared test. Logistic regression analyses adjusted for various confounders tested the association of patient characteristics with the likelihood of participation in the JR-SB study., Results: A total of 467 (58%) declined participation in the JR-SB study. Non-participants were older and less educated, more were smokers, fewer performed regular physical activity, and more had comorbidity compared to participants. Regression analyses showed that a higher educational level and absence of comorbidity in particular were associated with participation in the JR-SB study., Conclusion: Patients with RA who are less educated and with certain types of comorbidity are less motivated to participate in a physical activity intervention. The findings may inform the recruitment process and implementation of physical activity interventions in rheumatology clinical practice.

Introduction: Treatment with immune checkpoint inhibitors (ICI) has expanded into the adjuvant setting enhancing the importance of knowledge on the immune-related toxicities and their impact on health-related quality of life (HRQoL). Large phase 3 trials of patients with resected Stage III/IV melanoma found no effect on HRQoL during adjuvant immunotherapy. This study investigates how HRQoL was affected during and after adjuvant immunotherapy in a real-world setting., Methods: Patients with resected melanoma treated with adjuvant nivolumab from 2018 to 2021 in Denmark were identified using the Danish Metastatic Melanoma Database (DAMMED). The study was performed as a nationwide cross-sectional analysis as a questionnaire consisting of six different validated questionnaires on HRQoL, cognitive function, fatigue, depression, fear of recurrence, and decision regret was sent to all patients in March 2021. To evaluate HRQoL during and after adjuvant treatment, patients were divided into groups depending on their treatment status when answering the questionnaire; patients in active treatment for 0-6 months, patients in active treatment for >6 months, patients who ended treatment 0-6 months ago, and patients who ended treatment >6 months ago., Results: A total of 271/412 (66%) patients completed the questionnaire. Patients who ended therapy 0-6 months ago had the lowest HRQoL and had more fatigue. Patients in active treatment for >6 months had lower HRQoL and more fatigue than patients who started treatment 0-6 months ago. Patients ending therapy >6 months ago had higher HRQoL and less fatigue compared to patients who ended therapy 0-6 months ago. Multivariable analysis showed an association between HRQoL and treatment status, comorbidity, civil status, and employment status., Conclusions: Adjuvant nivolumab may affect some aspects of QoL, but the influence seems temporary. Patient characteristics, such as civil status, employment status, and comorbidity were associated with HRQoL.

Stress-related exhaustion is associated with cognitive deficits, measured subjectively using questionnaires targeting everyday slips and failures or more objectively as performance on cognitive tests. Yet, only weak associations between subjective and objective cognitive measures in this group has been presented, theorized to reflect recruitment of compensational resources during cognitive testing. This explorative study investigated how subjectively reported symptoms of cognitive functioning and burnout levels relate to performance as well as neural activation during a response inhibition task. To this end, 56 patients diagnosed with stress-related exhaustion disorder (ED; ICD-10 code F43.8A) completed functional magnetic resonance imaging (fMRI) using a Flanker paradigm. In order to investigate associations between neural activity and subjective cognitive complaints (SCCs) and burnout, respectively, scores on the Prospective and Retrospective Memory Questionnaire (PRMQ) and the Shirom-Melamed Burnout Questionnaire (SMBQ) were added as covariates of interest to a general linear model at the whole-brain level. In agreement with previous research, the results showed that SCCs and burnout levels were largely unrelated to task performance. Moreover, we did not see any correlations between these self-report measures and altered neural activity in frontal brain regions. Instead, we observed an association between the PRMQ and increased neural activity in an occipitally situated cluster. We propose that this finding may reflect compensational processes at the level of basic visual attention which could go unnoticed in cognitive testing but still be reflected in the experience of deficits in everyday cognitive functioning.

Objective: To determine prognostic factors for work ability and employment/educational status among young patients referred to outpatient neurorehabilitation clinics after an acquired brain injury., Methods: A nationwide cohort study of 471 15-30-year-old patients who attended an interdisciplinary clinical assessment and provided questionnaire data at baseline and after one year. The outcomes were the Work Ability Score (WAS, 0-10 (best)) and employment/educational status after one year. Prognostic performance was analyzed using univariable regression and multivariable Ridge regression in a five-fold cross-validated procedure., Results: Preinjury, 86% of the patients were employed, while the percentage had decreased to 55% at baseline and 52% at follow-up. The model, which included clinical measures of function, showed moderate prognostic performance with respect to WAS (R 2 =0.29) and employment/educational status (area under the curve (AUC)=0.77). Glasgow Outcome Scale Extended (R 2 =0.15, AUC=0.68) and the cognitive subscale of the Functional Independence Measure (R 2 =0.09, AUC=0.64), along with fatigue measured with the Multidimensional Fatigue Inventory (R 2 =0.15, AUC=0.60) were the single predictors with the highest predictive performance., Conclusion: Despite generally high scores in motor and cognitive tests, only about half of the patients were employed at baseline and this proportion remained stable. Global disability, cognitive sequelae and fatigue had the highest prognostic performance.

Papulopustular rosacea is notoriously a challenge to treat, and treatment options are scarce. Only limited data exist on the use of azithromycin in treatment of papulopustular rosacea. However, the unique pharmacokinetics of azithromycin may have several indications in the treatment of papulopustular rosacea. We here report a case of hard-to-treat papulopustular rosacea which was successfully treated with pulsed oral azithromycin in addition to maintenance isotretinoin.

Background: It is believed that clinical management of osteoarthritis should address muscle weakness to improve physical function and prevent disability and frailty., Objectives: This sub-study investigated the effects of supervised progressive resistance training (RT), supervised Nordic Walking (NW), and unsupervised home-based exercise (HBE) on muscle and functional performance; and associations between these exercise-induced changes in persons with hip osteoarthritis., Methods: Forty-two patients with hip osteoarthritis were recruited from a larger RCT (NCT01387867). All the groups (RT, n = 15; NW, n = 12; HBE, n = 15) exercised 1 h 3 times/week for 4 months. Quadriceps cross-sectional area (QCSA, MRI-determined); quadriceps strength (QMVC); leg extensor power (LEP); functional performance (chair stands (30sCS); stair climbs (TSC); and 6-minute walk (6MWT)) were assessed at baseline and 4 months., Results: Per protocol analyses (one-way ANOVA and Bonferroni test) showed significant between-group differences for improvements in QCSA in the most symptomatic leg favoring RT versus NW (2.3 cm 2 , 95% CI [0.6, 3.9]) and HBE (2.3 cm 2 [0.8, 3.9]); and 30sCS (1.8 repetitions [0.2-3.3]), and 6MWT (35.1 m [3.5-66.7]) favoring NW versus HBE. Associations existed between exercise-induced changes in QCSA and QMVC ( r = 0.366, p = .019) for the most symptomatic leg and between changes in 6MWT and QMVC ( r = 0.320, p = .04) and LEP ( r = 0.381, p = .01), respectively, for the least symptomatic leg., Conclusions: Resistance training appeared effective for improving muscle mass, but less effective for improving muscle strength, power, and functional performance. Only exercise-induced changes in muscle strength and power of the least symptomatic leg, not the most symptomatic leg, were related to changes in functional performance.

Objective: To evaluate the relationship between self-reported and performance-based measures of functioning in rheumatoid arthritis (RA), knee osteoarthritis (OA), and fibromyalgia (FM), and the influence of pain and fatigue., Method: Self-reported functioning was assessed by the Stanford Health Assessment Questionnaire, Fibromyalgia Impact Questionnaire, and Knee injury and Osteoarthritis Outcome Score. Performance-based measures of task-related physical activity included grip strength and Six-Minute Walk Test (6MWT). Assessment of Motor and Process Skills (AMPS) was used to obtain performance-based measures of activities of daily living (ADL) ability. Pain and fatigue were assessed by 100 mm visual analogue scales. Spearman's rho correlation and regression modelling were applied., Results: Correlations between self-reported functioning and performance-based measures of ADL ability were weak to moderate, and strongest in OA (r = 0.57, p = 0.002), and AMPS ADL ability measures did not enter regression models as explanatory factors for self-reported functioning. Correlations between AMPS ADL ability measures and measures of task-related physical activity were weak, except for a strong correlation between AMPS ADL motor ability and 6MWT in OA (r = 0.63, p = 0.000). The 6MWT was the only performance-based test explaining variance in AMPS motor ability (OA = 42%; FM = 11%). Pain explained variance in self-reported ability and contributed to variance in AMPS ADL motor ability measures in OA., Conclusion: Self-reported and observed measures of functioning assess partly different aspects of functioning, and both approaches may therefore be relevant in a structured assessment of patients with musculoskeletal disorders.

The association between ferritin and transferrin saturation (TS), respectively, and all-cause mortality is unclear. Furthermore, the influence of concurrent inflammation has not been sufficiently elucidated. We investigated these associations and the effect of concurrently elevated C-reactive protein (CRP), and accordingly report the levels associated with lowest all-cause mortality for females and males with and without inflammation.Blood test results from 161,921 individuals were included. Statistical analyses were performed in sex-stratified subpopulations, with ferritin or TS level as continuous exposure variables, and were adjusted for age, co-morbidity and inflammation status using CRP. An interaction was used to investigate whether the effect of ferritin or TS on all-cause mortality was modified by inflammation status (CRP ≥ 10 mg/L or CRP < 10 mg/L). Low and high ferritin and TS levels were respectively associated with increased all-cause mortality in females and in males. These associations persisted with concurrent CRP ≥ 10 mg/L. The ferritin level associated with lowest mortality was 60 µg/L for females and 125 µg/L for males with CRP < 10 mg/L. It was 52 µg/L for females and 118 µg/L for males with CRP ≥ 10 mg/L. The TS level associated with lowest mortality was 33.9% for females and 32.3% for males with CRP < 10 mg/L. It was 28.7% for females and 30.6% for males with CRP ≥ 10 mg/L.Our findings can nuance clinical interpretation and further aid in defining recommended ranges for ferritin and TS.

Objectives: Adult obesity may be positively associated with risks of rheumatoid arthritis (RA), but associations with early life body size are unknown. We examined whether birthweight, childhood body mass index (BMI), height, and changes in BMI and height were associated with risks of adult RA., Method: A cohort of 346 602 children (171 127 girls) from the Copenhagen School Health Records Register, born in 1930-1996, with measured weights and heights from 7 to 13 years of age, were included. Information on RA, including serological status, came from national registers from 1977 to 2017. Cox regressions were performed., Results: During a median of 35.1 years of observation time per person, 4991 individuals (3565 women) were registered with RA. Among girls, per BMI z-score, risks of RA and seropositive RA increased by 4-9% and 6-10%, respectively. Girls with overweight had higher risks of RA than girls without overweight. Girls who became overweight by 13 years of age had increased risks of RA compared to girls without overweight at 7 or 13 years (hazard ratio = 1.40, 95% confidence interval 1.19-1.66). For boys, associations between BMI and RA (including seropositive RA) were not statistically significant. Height was not associated with RA (any type) in girls. Taller boys had higher risks of RA, especially seropositive RA. Birthweight was not associated with RA., Conclusions: Among women, childhood adiposity was associated with increased risks of RA. Among men, childhood height was positively associated with risks of RA. These findings support the hypothesis that early life factors may be important in the aetiology of RA.

The aim of this study was to assess the possible association between P-Albumin and 30-day mortality in hip fracture patients. The study is based on information from a database of hip fracture patients, established and collected at Bispebjerg University Hospital (Copenhagen, Denmark). This database includes all femoral neck (DS720), pertrochanteric (DS721) and subtrochanteric fractures (DS722) admitted to Bispebjerg Hospital between 1996 and 2012. We further identified all surgically treated hip fracture patients aged >60 years with an available P-Albumin at admission. 1856 patients were eligible for inclusion in this study (73.7% female, 26.3% male). 11.8% of these had died within 30 days. Differences between continuous variables were tested using unpaired t -tests while differences in the distribution of categorical variables were tested using chi square tests. After adjusting for co-variates in a logistic regression model, the association between P-Albumin and 30-day mortality remained increased, (OR 1.09, 95% CI 1.05;1.11 ( p  < 0.0001)). This study shows an increased 30-day mortality risk among surgically treated hip fracture patients with decreasing levels of P-Albumin even after adjusting for age, sex, BMI, CCI and fracture type. Routine screening of patients for hypoalbuminemia at hospital admission may be beneficial in the management of hip fracture patients.